May 21, 2021
LYRICS: Can’t escape disappointment Can’t avoid the delay But I don’t have to make feeling down and defeated the place that I stay Gonna rise to the moment Gonna speak to the waves Gonna push back the doubt that keeps dragging me down when I can’t find the way Don’t need to see it (eyes on You) To believe it (for my breakthrough) Before You even move or make a way I will stand in faith (eyes on You) Walk by faith (for my breakthrough) Live by faith (before You move) I believe, I believe, I believe Stand in faith (eyes on You) See by faith (for my breakthrough) Receive by faith (before You move) I believe, I believe, I believe It’s a season for healing It’s a season for change To see miracles happen that no one can fathom as heaven invades It’s more than a feeling And it’s anchored in praise And when it’s the darkest it reaches the farthest and opens the way This is how blind men get their sight This is how dead men start to rise This is how small things multiply Nothing’s impossible Nothing’s impossible This is where oceans have to part This is where light cuts through the dark This is where I see who You are Nothing’s impossible Nothing’s impossible Stir my faith Stir my faith
#DannyGokey #StandInFaith #LyricVideo #Official Music video by Danny Gokey performing Stand In Faith (Lyric Video). Sparrow Records; © 2021 Danny Gokey, under exclusive license to Capitol Christian Music Group, Inc.
JUNE 6, 2022 AT 7:00 AM EDT
Interim Analysis Findings Support Continued Evaluation of Both Monotherapy and Combination Therapy
Encouraging Efficacy Results Include Independently Confirmed Responses in Both KRAS Mutant and KRAS Wild-Type Tumors with No New Safety Signals Observed
Substantial Majority (~80%) of Patients Remain on Therapy; Timing of Go Forward Treatment Regimen Selection Driven by Data Maturity
BOSTON--(BUSINESS WIRE)--Jun. 6, 2022-- Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for people living with cancer, today announced an update from an interim analysis of its international Phase 2 RAMP 201 trial evaluating VS-6766 ± defactinib in recurrent low-grade serous ovarian cancer (LGSOC), regardless of KRAS status.
Verastem recently completed a planned interim analysis of its RAMP 201 trial with the goal of selecting a go forward treatment regimen of either VS-6766 monotherapy or VS-6766 in combination with defactinib. The analysis indicated encouraging efficacy results with confirmed responses by independent review in patients treated with VS-6766 monotherapy and patients treated with VS-6766 in combination with defactinib. The findings also include confirmed responses by independent review in both KRAS mutant and KRAS wild-type LGSOC. To date, there have been no additional safety signals with a continued favorable safety profile in both the monotherapy and combination treatment arms with approximately 6% of patients discontinuing due to adverse events.
With a substantial majority (approximately 80%) of patients remaining on study treatment with a median duration of follow-up of four months, the Company has concluded that the data from the interim analysis are not mature enough to make a final decision on the go forward treatment regimen at this time and the trial will continue with all four cohorts (VS-6766 ± defactinib in KRAS mutant and KRAS wild type patient populations).
“We are encouraged by the positive anti-tumor activity that we have seen to date in the RAMP 201 trial in patients with both KRAS mutant and KRAS wild-type tumors. We look forward to evaluating a more mature data set and expect to provide an update on progress once the go forward treatment regimen has been determined,” said Brian Stuglik, Chief Executive Officer, Verastem Oncology. “This interim analysis adds to our optimism about the potential for VS-6766 with or without defactinib and our commitment to advancing the first new treatment specifically developed and approved for women with low-grade serous ovarian cancer where a high medical need remains.”
The Company plans to complete enrollment of all four cohorts of the trial in the second half of this year. Each cohort is expected to have approximately 36 patients for a total of 144 patients.
Both VS-6766 and defactinib are in late-stage development and the combination has received Breakthrough Therapy Designation by the U.S. Food and Drug Administration for the treatment of all patients with recurrent low-grade serous ovarian cancer regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy.
About the VS-6766/Defactinib Combination
VS-6766 is a RAF/MEK clamp that induces inactive complexes of MEK with ARAF, BRAF and CRAF potentially creating a more complete and durable anti-tumor response through maximal RAS pathway inhibition. In contrast to currently available MEK inhibitors, VS-6766 blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK. This unique mechanism allows VS-6766 to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other inhibitors. The combination of VS-6766 and FAK inhibitor, defactinib provides RAF/MEK vertical blockade and FAK parallel inhibition to overcome key resistance mechanisms. Both VS-6766 and defactinib are in late-stage development.
Verastem Oncology is conducting Phase 2 registration-directed trials of VS-6766 alone and with defactinib in patients with recurrent LGSOC and in patients with recurrent KRAS G12V-mutant NSCLC as part of its RAMP (Raf And Mek Program) clinical trials, RAMP 201 and RAMP 202, respectively (www.ramp201study.com and www.ramp202study.com). Verastem Oncology has also established clinical collaborations with Amgen, Inc. and Mirati Therapeutics, Inc. to evaluate LUMAKRAS™ (sotorasib) and adagrasib in combination with VS-6766 in KRAS G12C-mutant NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively.
About Verastem Oncology
Verastem Oncology (Nasdaq: VSTM) is a development-stage biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition. For more information, please visit www.verastem.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220606005303/en/
Source: Verastem Oncology
Jun. 06, 2022 8:10 AM ET
By: Ravikash, SA News Editor
Verastem Oncology (NASDAQ:VSTM) said interim analysis of a mid-stage study of VS-6766 standalone therapy and in combination with defactinib showed encouraging efficacy with confirmed responses in patients with recurrent low-grade serous ovarian cancer (LGSOC), regardless of KRAS mutation.
MAINZ, Germany and CHICAGO, June 5, 2022 (GLOBE NEWSWIRE) – BioNTech SE (Nasdaq: BNTX, “BioNTech”) today announced initial data from an ongoing investigator-initiated first-in-human Phase 1 study evaluating the safety and tolerability of the mRNA-based individualized neoantigen specific immunotherapy (iNeST) autogene cevumeran (also known as BNT122, RO7198457) in combination with anti-PD-L1 immune checkpoint inhibitor atezolizumab and chemotherapy in patients with resected pancreatic ductal adenocarcinoma (PDAC). Feasibility of the process of profiling each patient’s tumor to inform individualized vaccine design and on-demand manufacturing of iNeST in a clinically relevant timeframe was confirmed. The preliminary results showed a favorable safety profile as well as encouraging signs of clinical activity. The data have been presented at the American Society of Clinical Oncology (“ASCO”) Annual Meeting 2022 by Vinod Balachandran, M.D., at Memorial Sloan Kettering Cancer Center. Autogene cevumeran is the lead candidate from BioNTech’s iNeST platform, which is jointly developed together with Genentech, a member of the Roche Group, in multiple solid tumor indications.
The data presented at the ASCO Annual Meeting include a total of 19 patients who underwent surgery and received atezolizumab. 16 out of these 19 patients (84%) received autogene cevumeran at 9.4 weeks (median; 95% CI 9–10) after surgery. The preliminary data readout from these 16 vaccinated patients revealed that autogene cevumeran in combination with atezolizumab was well-tolerated. Only 1 of 16 patients (6%) developed a vaccine-related Grade 3 fever and hypertension, no other Grade 3 or higher adverse events were observed. In addition, the treatment induced de-novo, neoantigen-specific T cell response in half (8/16) of these patients from undetectable levels to large fractions of all blood T cells (median 2.9%). At an early median follow-up of 18 months, patients with de-novo immune response (n=8) had a significantly longer recurrence-free survival (RFS) as compared to those without vaccine-induced immune responses (n=8) (median not reached vs. 13.4 months, HR 0.08, 95% CI 0.01-0.4, P = 0.003). Based on these data, BioNTech and Genentech are planning a randomized study to further evaluate the efficacy and safety of autogene cevumeran in combination with atezolizumab and chemotherapy in patients with resected PDAC.
“With only under 5 percent of patients responding to current treatment options, PDAC is one of the highest unmet medical need cancers. We are committed to take up this challenge by leveraging our long-standing research in cancer vaccinology and are trying to break new ground in the treatment of such hard-to-treat tumors,” said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. “The results of this Phase 1 study are encouraging. We look forward to further evaluating these early results in a larger randomized study.”
The investigator-initiated, single-center, Phase 1 trial (NCT04161755) was designed to evaluate the treatment of the companies’ individualized immunotherapy candidate autogene cevumeran in combination with the anti-PDL-1 immune checkpoint inhibitor atezolizumab as an add-on to the standard-of-care regimen with adjuvant chemotherapy mFOLFIRINOX in patients with resected PDACs. The primary objective of the study is to assess the safety. Secondary objectives include the efficacy of the treatment measured as the 18-month RFS, the immunogenicity as well as the feasibility of the treatment regimen.
“Pancreatic cancer remains one of the deadliest cancers as it is resistant to all treatments, including immunotherapies. Conventional thinking has been that, as pancreatic cancers have few mutations, the immune system is unlikely to recognize mutation-derived neoantigens,” said Vinod Balachandran, M.D., surgeon-scientist at Memorial Sloan Kettering Cancer Center and Principal Investigator of the study. “Our research, and now the results from this study show that the immune system can recognize neoantigens in pancreatic cancer, and that we can use mRNA vaccines to stimulate T cells to recognize neoantigens in pancreatic cancer patients. We now look forward to further investigating these results in a larger randomized trial.”
BioNTech’s iNeST platform previously demonstrated encouraging results with a tolerable safety profile of autogene cevumeran as single agent and in combination with atezolizumab in a heterogenous patient population with advanced and heavily pretreated solid tumors. In a Phase1a/b trial autogene cevumeran revealed robust CD8+ and CD4+ T cell responses and a manageable safety profile (NCT03289962). In October 2021, BioNTech announced that the first patient was dosed in a randomized Phase 2 trial (NCT04813627) of autogene cevumeran in the adjuvant treatment of post-operative circulating tumor DNA (ctDNA) positive, surgically resected colorectal cancer. BioNTech and Genentech are also conducting a Phase II proof-of-concept study, which is designed to evaluate autogene cevumeran plus pembrolizumab in the first-line treatment of advanced melanoma (NCT03815058).
The abstract is available under the following link:
Title: Phase I Trial of adjuvant autogene cevumeran, an Individualized mRNA Neoantigen Vaccine, for Pancreatic Ductal Adenocarcinoma
About iNeST (individualized Neoantigen Specific immunoTherapy)
iNeST immunotherapies are individualized cancer therapies tailored to a specific patient’s tumor. They contain unmodified, pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens, identified using real-time next generation sequencing and bioinformatic neoantigen discovery. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells and are recognized by immune cells. The mRNA is encapsuled in BioNTech’s proprietary intravenous RNA-lipoplex delivery formulation which is designed to enhance stability as well as enable targeted delivery to dendritic cells. By analyzing each patient’s tumor, BioNTech is able to identify the cancer mutations that may act as neoantigens. Each individual cancer vaccine encodes for neoantigen candidates with the highest likelihood to help the immune system to recognize the cancer. For this purpose, BioNTech has developed a first of its kind, on-demand manufacturing process, following Good Manufacturing Practice (GMP) conditions.
Biopharmaceutical New Technologies (BioNTech) is a next generation immunotherapy company pioneering novel therapies for cancer and other serious diseases. The Company exploits a wide array of computational discovery and therapeutic drug platforms for the rapid development of novel biopharmaceuticals. Its broad portfolio of oncology product candidates includes individualized and off-the-shelf mRNA-based therapies, innovative chimeric antigen receptor T cells, bispecific checkpoint immuno-modulators, targeted cancer antibodies and small molecules. Based on its deep expertise in mRNA vaccine development and in-house manufacturing capabilities, BioNTech and its collaborators are developing multiple mRNA vaccine candidates for a range of infectious diseases alongside its diverse oncology pipeline. BioNTech has established a broad set of relationships with multiple global pharmaceutical collaborators, including Genmab, Sanofi, Genentech, a member of the Roche Group, Regeneron, Genevant, Fosun Pharma and Pfizer.
For more information, please visit www.BioNTech.com
Jun. 06, 2022 6:15 AM ET
BioNTech (NASDAQ:BNTX) and Roche's (OTCQX:RHHBY) (OTCQX:RHHBF) Genentech said on June 5 that data from an ongoing early stage study of their mRNA-based individualized neoantigen specific immunotherapy (iNeST) autogene cevumeran, showed that vaccine-induced immunity significantly correlates with delayed tumor recurrence in patients with a type of pancreatic cancer.
Jun 1, 2022< Go BackDownload PDF
WATERTOWN, Mass., June 01, 2022 (GLOBE NEWSWIRE) -- Kymera Therapeutics, Inc. (NASDAQ: KYMR), a clinical-stage biopharmaceutical company advancing targeted protein degradation to deliver novel small molecule protein degrader medicines, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to KT-333 for the treatment of Peripheral T-cell Lymphoma (PTCL). KT-333 is a first-in-class degrader of the transcriptional regulator STAT3. STAT3 activation has been shown to be a key modulator of disease in PTCL, and there are currently no approved therapies for PTCL that target this pathway.
“The Orphan Drug Designation highlights the potential of this first-in-class heterobifunctional degrader to transform the treatment of PTCL by targeting STAT3, a protein that has historically been undruggable,” said Nello Mainolfi, PhD, Co-Founder, President and CEO, Kymera Therapeutics. “We look forward to working with the lymphoma community to rapidly advance KT-333 as a potential treatment for PTCL while we continue to expand clinical investigation of this novel mechanism in other cancers both in the hematological and in the solid tumor space.”
The FDA's Orphan Drug Designation program provides orphan status to drugs defined as those intended for the treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States. Orphan drug designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and seven-year marketing exclusivity upon FDA approval.
KT-333 is currently being evaluated in an ongoing Phase 1 trial in adult patients with relapsed/refractory liquid and solid tumors, including aggressive lymphomas. KT-333 is a potent and selective heterobifunctional small molecule protein degrader which can mediate degradation of the STAT3 protein.
Normally, the STAT3 protein is activated by cytokines and growth factors, resulting in transcriptional regulation of many important cellular functions. In diseases including cancer, STAT3 activity becomes dysregulated, resulting in persistent activation of STAT3.
About Peripheral T-cell Lymphoma
PTCL, a subtype of non-Hodgkin’s lymphoma, is a heterogenous group of tumors that arise from mature white blood cells (T-cells) in the lymphoid tissues in areas such as the lymph nodes, lungs, gastrointestinal tract and skin. Approximately 13,000 PTCL patients are diagnosed in the U.S. each year, and PTCL accounts for 15% to 20% of aggressive lymphomas in the United States. PTCLs carry a poorer prognosis than other non-Hodgkin’s lymphomas since they are less responsive to standard chemotherapy regimens.
About Kymera Therapeutics
Kymera Therapeutics (Nasdaq: KYMR) is a biopharmaceutical company pioneering the field of targeted protein degradation, a transformative approach to address disease targets and pathways inaccessible with conventional therapeutics. Kymera’s Pegasus platform is a powerful drug discovery engine, advancing novel small molecule therapies that harness the body’s innate protein recycling machinery to degrade dysregulated, disease-causing proteins. With a focus on undrugged nodes in validated pathways, Kymera is advancing a pipeline of novel therapeutics designed to address the most intractable pathways and provide new treatments for patients. Kymera’s initial programs target IRAK4, IRAKIMiD, and STAT3 within the IL-1R/TLR or JAK/STAT pathways, providing the opportunity to treat patients with a broad range of immune-inflammatory diseases, hematologic malignancies, and solid tumors. For more information, visit www.kymeratx.com.
Founded in 2016, Kymera is headquartered in Watertown, Mass. Kymera has been named a “Fierce 15” biotechnology company by Fierce Biotech and has been recognized by the Boston Business Journal as one of Boston’s “Best Places to Work.” For more information about our people, science, and pipeline, please visit www.kymeratx.com or follow us on Twitter or LinkedIn.
Jun. 01, 2022 9:43 AM ET
By: Dulan Lokuwithana, SA News Editor
Deucravacitinib showed statistically significant efficacy at primary endpoint of Systemic Lupus Erythematosus (SLE) Responder Index-4 (SRI(4)) responses versus placebo at Week 32
Secondary endpoints demonstrated clinically meaningful improvements at Week 48
Safety profile of deucravacitinib was consistent with previously reported studies in patients with psoriasis and psoriatic arthritis with no new safety signals observed
Data demonstrated favorable risk-benefit profile supportive of progressing into Phase 3
PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) announced positive results from the Phase 2 PAISLEY study evaluating deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor, compared to placebo in patients with moderate to severe systemic lupus erythematosus (SLE). The study met the primary endpoint of achieving SLE Responder Index-4 (SRI(4)) responses, a composite endpoint used in SLE clinical trials to assess disease activity, at Week 32. A significantly greater proportion of patients on deucravacitinib 3 mg twice daily (BID) and 6 mg BID achieved SRI(4) at 32 weeks versus placebo (deucravacitinib 3 mg BID: 58.2%, P=0.0006; deucravacitinib 6 mg BID: 49.5%, P=0.0210; placebo: 34.4%). While the 12 mg once daily (QD) group had numerically higher SRI(4) responses relative to placebo at 32 weeks, the results did not reach statistical significance on multiplicity adjustment. SRI(4) responses were sustained across all deucravacitinib groups up to Week 48. These data are being presented as a late-breaking abstract (#LB0004) at the European Alliance of Associations for Rheumatology (EULAR) 2022 Congress, taking place June 1-4, 2022, in Copenhagen, Denmark.
“There is an urgent need for new systemic lupus treatments. As many as half of patients may not respond adequately to current treatment options and a new oral therapy has not been approved in decades,” said Eric F. Morand, MD, PhD, Head of the School of Clinical Sciences, Monash University, Australia. “These clinically meaningful results represent a huge potential step forward in the development of a new lupus therapy to help meet the immense need for patients living with this disease.”
Secondary endpoints demonstrated clinically meaningful improvements at Week 48, including SRI(4), British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), decrease of ≥50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI-50) and change in active joint count.
“Based on the consistent and positive findings from this trial, we are advancing deucravacitinib into Phase 3 studies for systemic lupus erythematosus and will continue to further explore its development in our ongoing programs in psoriatic arthritis, lupus and inflammatory bowel disease, as well as other immune-mediated diseases with high unmet needs,” said Jonathan Sadeh, MD, MSc, senior vice president of Immunology and Fibrosis Development, Bristol Myers Squibb. “We have been paving the way in rheumatology for more than 20 years and will continue to build upon our heritage with our strong Immunology franchise and deep pipeline that have the potential to transform outcomes for patients living with immune-mediated diseases.”
Deucravacitinib was well tolerated, with the safety profile consistent with earlier trials in psoriasis and psoriatic arthritis and with no evidence of laboratory abnormalities characteristic of Janus kinase (JAK) 1/2/3 inhibitors, despite substantial concomitant use of antimalarials, corticosteroids and immunosuppressants.
Bristol Myers Squibb would like to thank the patients and investigators who were involved in the PAISLEY study.
Deucravacitinib (pronounced doo-krav-a-sih-ti-nib) is an oral, selective, allosteric tyrosine kinase 2 (TYK2) inhibitor with a unique mechanism of action, representing a new class of small molecules. It is the first selective TYK2 inhibitor in clinical studies across multiple immune-mediated diseases. Bristol Myers Squibb scientists designed deucravacitinib to selectively target TYK2, thereby inhibiting signaling of cytokines, such as interleukin (IL)-23, IL-12 and Type 1 interferons (IFN), that are involved in the pathogenesis of multiple immune-mediated diseases. Deucravacitinib achieves a high degree of selectivity by binding to the regulatory domain of TYK2, resulting in allosteric inhibition of TYK2 and its downstream functions. Deucravacitinib selectively inhibits TYK2 at physiologically relevant concentrations. At therapeutic doses, deucravacitinib does not inhibit JAK1, JAK2 or JAK3.
Deucravacitinib is being evaluated in global clinical trials in multiple immune-mediated diseases, including psoriasis, psoriatic arthritis, active discoid and/or subacute cutaneous lupus erythematosus and inflammatory bowel diseases. Deucravacitinib is under regulatory review with global health authorities, including the U.S. Food and Drug Administration (FDA) and European Medical Association (EMA) for the treatment of moderate to severe plaque psoriasis and Japan's Ministry of Health, Labour and Welfare for the treatment of adults with moderate to severe plaque psoriasis, generalized pustular psoriasis and erythrodermic psoriasis.
About the Phase 2 PAISLEY Trial
PAISLEY was a one-year, randomized, double-blind, placebo-controlled, global Phase 2 trial. More information can be found at www.clinicaltrials.gov (NCT03252587).
Eligible patients had a systemic lupus erythematosus (SLE) diagnosis for at least 24 weeks before screening, met the Systemic Lupus International Collaborating Clinics (SLICC) classification criteria, were seropositive and had a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥6 and ≥1 British Isles Lupus Assessment Group (BILAG) index A or ≥2 BILAG B manifestations, at least 1 of which had to be from the musculoskeletal or mucocutaneous domain. Patients on standard background medications were randomized 1:1:1:1 to oral deucravacitinib 3 mg twice daily (BID), 6 mg BID, 12 mg once daily (QD) or placebo BID. Of 363 patients randomized, 275 (76.0%) completed 48 weeks of treatment (deucravacitinib 3 mg BID, 71/91 [78%]; 6 mg BID, 76/93 [82%]; 12 mg QD, 62/89 [70%]; placebo, 66/90 [73%]).
The primary endpoint was the proportion of patients achieving SLE Responder Index 4 SRI(4) at Week 32 by non-responder imputation (NRI). Secondary endpoints included SRI(4), BILAG-based Composite Lupus Assessment (BICLA), Lupus Low Disease Activity State (LLDAS), decrease of ≥50% from baseline Cutaneous Lupus Erythematosus Disease Area and Severity Index Activity score (CLASI-A) and change from baseline in active (tender and swollen) joint response at Week 48.
Source: Bristol Myers Squibb
Jun. 01, 2022 8:39 AM ET
By: Ravikash, SA News Editor
– Phase 1 clinical study of PSMA-TRACTr (JANX007) expected to initiate in 2H 2022 –
SAN DIEGO--(BUSINESS WIRE)-- Janux Therapeutics, Inc. (Nasdaq: JANX) (Janux), a biopharmaceutical company developing a broad pipeline of novel immunotherapies by applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms, today announced that the U.S. Food and Drug Administration (FDA) has cleared the Company’s investigational new drug (IND) application for its lead product candidate, JANX007, a PSMA-TRACTr in development for the treatment of metastatic castration-resistant prostate cancer (mCRPC). JANX007 is the Company’s lead novel T cell engager (TCE) therapeutic from its TRACTr platform. Janux plans to initiate a Phase 1 clinical trial for JANX007 in the second half of 2022.
“We are proud to announce today the clearance of Janux’s first IND – a critical milestone for our TRACTr platform and for the Company as we advance a broad pipeline of next generation immunotherapies to address unmet needs and improve the treatment of cancer,” said David Campbell, Ph.D., President and CEO of Janux. “JANX007 is uniquely designed to overcome the clinical limitations of existing TCE approaches, potentially providing mCRPC patients a safer therapeutic option, while also generating potent anti-tumor activity by enabling the delivery of a higher concentration of active drug. With this IND acceptance, we are on track to advance JANX007 into the clinic in the second half of this year.”
Unlike existing TCE approaches to prostate cancer that have been limited to-date by dose-limiting toxicities, poor pharmacokinetic (PK) profiles and attenuated efficacy, JANX007 is designed as a safer, highly potent anti-tumor approach to mCRPC. In preclinical studies, JANX007 was well tolerated in non-human primates with limited healthy tissue toxicities and cytokine release syndrome and exhibited enhanced safety and PK properties relative to unmasked TCEs. These data along with the superior manufacturability properties of JANX007 support its further development as an attractive mCRPC therapeutic.
About Janux Therapeutics
Janux Therapeutics is an innovative biopharmaceutical company developing next-generation therapeutics based on applying its proprietary technology to its Tumor Activated T Cell Engager (TRACTr) and Tumor Activated Immunomodulator (TRACIr) platforms to better treat patients suffering from cancer. Janux’s initial focus is on developing a novel class of T cell engagers (TCEs), and its lead product candidates are designed to target clinically validated drug targets. While TCE therapeutics have displayed potent anti-tumor activity in hematological cancers, developing TCEs to treat solid tumors have faced challenges due to the limitations of prior TCE technologies, namely (i) overactivation of the immune system leading to cytokine release syndrome, (ii) on-target, healthy tissue toxicities, and (iii) poor pharmacokinetics leading to short half-life. Janux is using its TRACTr platform technology to engineer product candidates designed to overcome these limitations by offering accuracy, stability, activity, modularity, and manufacturability. Janux is developing a broad pipeline with lead TRACTr programs targeting prostate-specific membrane antigen (PSMA), epidermal growth factor receptor (EGFR), and trophoblast cell surface antigen 2 (TROP2). For more information, please visit www.januxrx.com.
Source: Janux Therapeutics, Inc.
May 31, 2022 9:20 AM ET
Janux Therapeutics (NASDAQ:JANX) on Tuesday said the U.S. Food and Drug Administration had cleared the company's investigational new drug (IND) application for its lead product candidate JANX007 for the treatment of prostate cancer.
May 26, 2022PDF Version
NEW YORK, May 26, 2022 (GLOBE NEWSWIRE) -- Y-mAbs Therapeutics, Inc. (the “Company” or “Y-mAbs”) (Nasdaq: YMAB) a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, today announced that Dr. Shakeel Modak, MD from Memorial Sloan Kettering (“MSK”) will present results from the naxitamab-based chemoimmunotherapy trial in patients with chemoresistant high-risk neuroblastoma (“HR-NB”), at the American Society of Clinical Oncology (“ASCO”) Annual Meeting to be held June 3-7, 2022.
This clinical trial studied the combination of Humanized anti-GD2 antibody naxitamab, Irinotecan, Temozolomide and Sargramostim (GM-CSF), (“HITS”) protocol, and included cohort of patients that were treated at MSK in a phase 2 protocol, and at Hospital Sant Joan de Déu (“HJSD”) per protocol on compassionate use basis. Health authorities have not established the safety and efficacy of the HITS protocol, as it is investigational and has not been approved by health authorities.
Eligibility criteria included evaluable or measurable chemoresistant disease. Prior anti-GD2 or irinotecan/temozolomide therapy was permitted. Each cycle, administered 3-5 weeks apart, comprised irinotecan, temozolomide, naxitamab and GM-CSF. The primary endpoint of the phase 2 trial at MSK was complete response (“CR”) and partial response (“PR”) after 4 cycles.
Of 90 previously heavily treated patients, (38 at MSK in the phase 2 trial, and 52 at HJSD), eight had HR-NB refractory to induction chemotherapy and 82 had up to six prior relapses.
The primary endpoint was reached in the MSK phase 2 trial: Objective Response Rate (“ORR”) according to the International Neuroblastoma Response Criteria (“INRC”) of 30.6 %, with a lower boundary of 20.4%. In the entire cohort, responses were 26% for CR, 11% for PR, 9% for mixed response, 27% for stable disease and 27% for progressing disease (“PD”). In the MSK phase 2 trial, the ORR was 64% for all patients, with soft tissue (48%) and skeletal MIBG uptake (66%). CR in bone marrow was seen in 57% of the patients. The ORR in patients with MYCN-amplification was 25%, in patients with refractory disease 100%, and in patients with relapsed disease 61%. Moreover, in patients who had previously received irinotecan/temozolomide or naxitamab, the ORR was 64% and 68%, respectively. In patients who had previously received dinutuximab/irinotecan/temozolomide, the ORR was 42% (five out of 12 patients).
Toxicities included myelosuppression and diarrhea as expected with irinotecan/temozolomide, pain and hypertension as expected with naxitamab, plus febrile neutropenia. No other >grade 2 unexpected toxicities occurred, and the treatment was outpatient. In this trial, human anti-human antibody did not develop in any of the 50 patients providing samples for testing.
“We are very pleased to present data for the HITS protocol,” stated Thomas Gad, Founder, President and Interim CEO. “Responses in patients with relapsed or progressive high-risk neuroblastoma are challenging, as chemo-resistant disease is considered an obstacle, so we are excited to see this study met its primary endpoint. This further demonstrates the potential role for DANYELZA in HR-NB. No other GD2 antibody has been studied in such a heavily pre-treated patient population.”
Researchers at Memorial Sloan Kettering Cancer Center MSK developed naxitamab, which is exclusively licensed by MSK to Y-mAbs. As a result of this licensing arrangement, MSK has institutional financial interests in the compound.
Y-mAbs is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic cancer products. In addition to conventional antibodies, the Company’s technologies include bispecific antibodies generated using the Y-BiClone platform and the SADA platform. The Company’s broad and advanced product pipeline includes one FDA-approved product, DANYELZA® (naxitamab-gqgk), which targets tumors that express GD2, and one product candidate at the registration-stage, OMBLASTYS® (omburtamab), which targets tumors that express B7-H3.
DANYELZA®, OMBLASTYS® and Y-mAbs® are registered trademarks of Y-mAbs Therapeutics, Inc.
Source: Y-mAbs Therapeutics, Inc
May 26, 2022 4:52 PM ET
By: Jonathan Block, SA News Editor
May 26, 2022
Friedreich’s Ataxia is a Rare, Progressive, Life-Shortening, Neuromuscular Disease that Affects Approximately 5,000 Patients in the United States
Application Assigned a PDUFA Date of November 30, 2022
If Approved, Omaveloxolone Would Become the First Approved Therapy for Friedreich’s Ataxia in the United States
PLANO, Texas--(BUSINESS WIRE)-- Reata Pharmaceuticals, Inc. (Nasdaq: RETA) (“Reata,” the “Company,” “our,” “us,” or “we”), a clinical-stage biopharmaceutical company, today announced that the U.S. Food and Drug Administration (“FDA”) has accepted for filing and granted Priority Review of its New Drug Application (“NDA”) for omaveloxolone for the treatment of patients with Friedreich’s ataxia. The FDA indicated that at this time it has not identified any potential review issues. The NDA is supported by the efficacy and safety data from the MOXIe Part 2 trial and additional supporting data from the MOXIe Part 1 and MOXIe Extension trials. Omaveloxolone received Fast Track Designation in November 2021 and Rare Pediatric Disease Designation in May 2022.
The FDA grants Priority Review to medicines that may offer significant improvements in the treatment, diagnosis, or prevention of a serious condition. This Designation shortens the FDA’s review of the NDA to eight months from the time of submission, versus a standard review timeline of 12 months. The FDA has assigned a Prescription Drug User Fee Act (“PDUFA”) target action date of November 30, 2022. The FDA indicated it is currently planning to hold an advisory committee meeting to discuss the application.
“We are pleased with the FDA’s decision to grant Priority Review to our NDA for omaveloxolone for the treatment of patients with Friedreich’s ataxia in the United States,” said Warren Huff, Reata’s Chief Executive Officer. “With the FDA’s acceptance of our NDA for filing, omaveloxolone is now one step closer to potentially providing a treatment option for patients with Friedreich’s ataxia, a rare, genetic, debilitating, and degenerative neuromuscular disorder with no approved therapies. We look forward to working with the FDA during the review process, and if approved, we are looking forward to a commercial launch in early 2023.”
Omaveloxolone is an investigational, oral, once-daily activator of Nrf2, a transcription factor that induces molecular pathways that promote the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling. The FDA has granted Orphan Drug, Fast Track, and Rare Pediatric Disease Designations to omaveloxolone for the treatment of Friedreich’s ataxia. The European Commission has granted Orphan Drug Designation in Europe to omaveloxolone for the treatment of Friedreich’s ataxia.
Reata is a clinical-stage biopharmaceutical company that develops novel therapeutics for patients with serious or life-threatening diseases by targeting molecular pathways involved in the regulation of cellular metabolism and inflammation. Reata’s two most advanced clinical candidates, omaveloxolone and bardoxolone methyl (“bardoxolone”), target the important transcription factor Nrf2 that promotes the resolution of inflammation by restoring mitochondrial function, reducing oxidative stress, and inhibiting pro-inflammatory signaling. Omaveloxolone and bardoxolone are investigational drugs, and their safety and efficacy have not been established by any agency.
Source: Reata Pharmaceuticals, Inc.
May 26, 2022 7:12 AM ET
By: Ravikash, SA News Editor
May 19, 2022 2:49 PM ET
Date Designated: 05/19/2022
May 19, 2022Download PDF
CAMBRIDGE, Mass., May 19, 2022 (GLOBE NEWSWIRE) -- Mersana Therapeutics, Inc. (NASDAQ: MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation to XMT-2056, the company’s lead Immunosynthen STING-agonist ADC, for the treatment of gastric cancer.
According to the American Cancer Society, gastric cancer (also referred to as stomach cancer) accounts for approximately 1.5 percent of all new cancers diagnosed in the United States each year, with an estimated 26,560 new cases reported in 2021. The FDA grants orphan drug designation to a drug or biologic intended to treat a rare disease or condition impacting fewer than 200,000 individuals in the United States. This designation qualifies Mersana for potential incentives, including tax credits for certain trials, exemption from user fees and the potential for seven years of market exclusivity following approval (if granted).
“The FDA’s decision to grant orphan drug designation to XMT-2056 for the treatment of gastric cancer is an important recognition of its potential in this area of high unmet medical need,” said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. “We are eager to bring XMT-2056 and its unique mechanism of action into the clinic mid-year to investigate its safety, tolerability and anti-tumor activity in gastric and other cancers.”
XMT-2056 is designed to offer a differentiated and complementary therapeutic approach to existing and emerging solid tumor treatments. The company developed XMT-2056 leveraging a differentiated antibody that binds to a novel HER2 epitope, providing the opportunity, as demonstrated in preclinical studies, for treatment both as monotherapy and in combination with a variety of agents, including other anti-HER2 therapies. Mersana plans to initiate a Phase 1 trial of XMT-2056 in a range of HER2 expressing tumors, such as breast, gastric and non-small-cell lung cancers, in mid-2022.
Mersana Therapeutics was recently named among the 2021 Top Places to Work in Massachusetts by The Boston Globe. Mersana routinely posts information that may be useful to investors on the “Investors and Media” section of its website at www.mersana.com.
May 19, 2022 7:29 AM ET
By: Dulan Lokuwithana, SA News Editor
May 16, 2022
– All Clinical Studies Evaluating Injectable Lenacapavir to Resume –
– Decision Based on Review of Vial Compatibility Data –
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced the U.S. Food and Drug Administration (FDA) has lifted the clinical hold placed on the company’s Investigational New Drug Application (IND) to evaluate injectable lenacapavir for HIV treatment and HIV pre-exposure prophylaxis (PrEP). As previously announced, the FDA had placed a clinical hold on the use of injectable lenacapavir in borosilicate vials due to a vial compatibility issue. FDA removed the clinical hold following the agency’s review of Gilead’s comprehensive plan and corresponding data on the storage and compatibility of lenacapavir injection with an alternative vial made from aluminosilicate glass.
Following today’s decision from the FDA, all activity can resume in the clinical studies evaluating injectable lenacapavir for HIV treatment and HIV PrEP. During the clinical hold, screening and enrollment of study participants and the dosing of injectable lenacapavir were not permitted across all lenacapavir studies. Other study activities, including the monitoring of participants, the dosing of participants in comparator arms, and the dosing of oral formulations of lenacapavir continued according to the relevant study protocol. Gilead will now work with study site investigators to fully resume the lenacapavir clinical development programs as quickly as possible.
“We are pleased to have identified an alternative vial for lenacapavir, and to now advance the robust clinical program for this potential first-in-class long-acting option for HIV treatment and prevention,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “Today’s news brings us one step closer to our goal of offering therapeutic options for the diverse communities affected by HIV as we work to end the epidemic for everyone, everywhere.”
In May 2019, the FDA granted Breakthrough Therapy Designation for the development of lenacapavir for the treatment of HIV infection in heavily treatment-experienced patients with multi-drug resistance in combination with other antiretroviral drugs. Lenacapavir recently received a complete response letter (CRL) for its new drug application (NDA) in this population due to vial compatibility. Gilead is working with the FDA to discuss next steps for the potential use of lenacapavir for the treatment of HIV in this population. Lenacapavir is an investigational compound and is not approved by any regulatory authority for any use and its safety and efficacy are not established. There is no cure for HIV or AIDS.
Lenacapavir is Gilead’s potential first-in-class, investigational long-acting HIV-1 capsid inhibitor in development for the treatment and prevention of HIV-1 infection. Lenacapavir’s multi-stage mechanism of action is distinguishable from currently approved classes of antiviral agents and is designed to provide a new avenue for the development of long-acting therapy options for people living with or at risk for HIV-1. While most antivirals act on just one stage of viral replication, lenacapavir is designed to inhibit HIV-1 at multiple stages of its lifecycle and has no known cross resistance to other existing drug classes. If approved, lenacapavir would be the only HIV-1 treatment option administered twice yearly.
The safety, efficacy and dosing of Gilead’s investigational, long-acting HIV-1 capsid inhibitor lenacapavir are being evaluated in multiple ongoing clinical studies, including CAPELLA, a Phase 2/3, double-blinded, placebo-controlled global multicenter study designed to evaluate the antiviral activity of lenacapavir administered every six months as a subcutaneous injection in heavily treatment-experienced people with multi-drug resistant HIV-1 infection. The New England Journal of Medicine published the primary outcome results of the CAPELLA trial in its May 11, 2022 issue.
(Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection). Through week 26, lenacapavir was generally well tolerated in CAPELLA, with no serious adverse events related to lenacapavir as determined by the study investigator. The most common adverse event observed in the trial was injection-site reactions.
GILEAD and the GILEAD logo are trademarks of Gilead Sciences, Inc.
For more information about Gilead, please visit the company’s website at www.gilead.com , follow Gilead on Twitter (@Gilead Sciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220516005696/en/
Source: Gilead Sciences, Inc.
May 17, 2022 7:27 AM ET
SAN DIEGO, May 12, 2022 /PRNewswire/ -- Neurocrine Biosciences, Inc. (Nasdaq: NBIX) today announced that it has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for valbenazine as a treatment for Huntington disease (HD). The treatment of chorea associated with HD is within the scope of this Orphan Drug Designation. In December 2021, Neurocrine Biosciences reported top-line data from its Phase 3 KINECT-HD study evaluating the efficacy, safety and tolerability of valbenazine, a selective vesicular monoamine transporter 2 (VMAT2) inhibitor being investigated as a once-daily treatment in adults with chorea associated with HD.
"Receiving an FDA Orphan Drug Designation validates our continued commitment to developing new treatment options that could benefit the lives of patients living with rare diseases, including those impacted by HD," said Kevin Gorman, Ph.D., Chief Executive Officer. "We are in the process of completing data analysis from the KINECT-HD and the ongoing KINECT-HD2 studies, which will form the basis of our supplemental new drug application (sNDA) for submission to the FDA later this year."
Enrollment is ongoing in the KINECT-HD2 open-label study to evaluate the long-term safety and tolerability of valbenazine for the treatment of chorea in Huntington Disease.
About the KINECT-HD Study
KINECT-HD is a Phase 3, randomized, double-blind, placebo-controlled study designed to: evaluate the efficacy of valbenazine as a once-daily treatment to reduce chorea associated with Huntington disease (HD) and evaluate the safety and tolerability of valbenazine in patients with HD. The study enrolled 128 adults 18 to 75 years of age who have been diagnosed with motor manifest HD and who have sufficient chorea symptoms to meet study protocol criteria. For more information on this KINECT-HD study, please visit www.huntingtonstudygroup.org.
KINECT-HD2 is an open-label study to evaluate the long-term safety and tolerability of valbenazine in patients with chorea associated with Huntington disease (HD). The 112-week study will enroll up to 150 adults 18 to 75 years of age who have been diagnosed with motor manifest HD and who have sufficient chorea symptoms to meet study protocol criteria. For more information on the KINECT-HD2 study, please visit www.huntingtonstudygroup.org. or clinicaltrials.gov.
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SOURCE Neurocrine Biosciences, Inc.
May 13, 2022 6:08 AM ET
By: Ravikash, SA News Editor
COPENHAGEN, Denmark, May 10, 2022 (GLOBE NEWSWIRE) -- Evaxion Biotech A/S (NASDAQ: EVAX), a clinical-stage biotechnology company specializing in the development of AI-driven immunotherapies to improve the lives of patients with cancer and infectious diseases, announced today that it has successfully produced all batches of personalized cancer immunotherapies for all patients enrolled in the Phase 1/2a clinical trial of EVX-02 in adjuvant melanoma.
Birgitte Rønø, Chief Scientific Officer of Evaxion, said: “I am extremely proud that the team behind EVX-02 has shown that this complex production chain is feasible and that we can provide truly unique, personalized DNA vaccines within a critical time window. And we are delighted that we mastered all steps in the production process. Every cancer is unique, as is every immune system, and this is why we create cancer therapies that are one size fits one – and only one.”
She continues: “With the release of the final batch, we confirmed our manufacturing process, which we believe will allow us to progress our DNA cancer immunotherapy programs into larger global trials to explore the clinical benefits of the compounds further. We have again demonstrated our capabilities to timely deliver personalized cancer treatment tailored to the unique cancer profile of every patient in a clinical trial.”
The production process of the personalized drug product consists of multiple steps. The sequencing of the tumor DNA is followed by AI-powered identification of the most promising therapeutic targets developed by Evaxion's proprietary PIONEER™ technology. This leads to designing the personalized multi-target vaccine drug product, which is then manufactured, released to the clinical sites, and administered to the patient.
This is the second time Evaxion has conducted a clinical trial with personalized cancer immunotherapy, having previously used a peptide-based treatment.
Our EVX-02 program (NCT04455503) treats adjuvant melanoma patients with our patented DNA-based immunotherapy in combination with standard of care. The patients are fully resected before the trial, meaning that their tumors have been successfully removed (surgically). In the study, the focus of the therapy is to prevent disease relapse. The EVX-02 program is a multicenter study conducted in Australia. There are currently 16 patients enrolled in the trial.
Evaxion Biotech A/S is a clinical-stage AI-immunology™ platform company decoding the human immune system to discover and develop novel immunotherapies to treat cancer, bacterial diseases, and viral infections. Based on its proprietary and scalable AI-immunology core technology, Evaxion is developing a broad pipeline of novel product candidates, including three patient-specific cancer immunotherapies.
Source: Evaxion Biotech
May 10, 2022 8:26 AM ET
By: Dulan Lokuwithana, SA News Editor
May 2, 2022 at 7:01 AM EDTDownload PDF
Incidence of Grade 3 esophagitis substantially reduced in patients treated with avasopasem compared to literature
No Grade 4 or 5 esophagitis in patients treated with avasopasem
MALVERN, Pa, May 02, 2022 (GLOBE NEWSWIRE) -- Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy in cancer, today announced topline results from the six-week, Phase 2a, open-label, single-arm AESOP trial of avasopasem evaluating its ability to reduce the incidence of severe acute radiation-induced esophagitis in patients with lung cancer receiving concurrent chemoradiotherapy.
The multicenter Phase 2a trial enrolled 39 patients (62 screened) with unresectable Stage 3A/3B or post-operative Stage 2B non-small cell (NSCLC) or limited-stage small cell (SCLC) lung cancers. Thirty-five patients completed treatment with 60 gray of intensity-modulated radiation therapy (IMRT) plus chemotherapy over six weeks. Of these 35 patients, 29 received at least five weeks of 90 mg of avasopasem on the days they underwent IMRT. These 29 patients were evaluated as the pre-specified per protocol population. Patients enrolled in this trial were considered at high risk for developing esophagitis due to the amount of radiation planned to be delivered to the esophagus.1 Patients were assessed and classified according to NCI-CTCAE criteria.2
Incidence of esophagitis by grade and timepoint in the AESOP trial (per protocol, n=29):
Avasopasem manganese (avasopasem, or GC4419) is a selective small molecule dismutase mimetic in development for the reduction of radiation-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) and for the reduction of radiation-induced esophagitis in patients with lung cancer. The FDA has granted Fast Track and Breakthrough Therapy designations to avasopasem for the reduction of SOM induced by radiotherapy, with or without systemic therapy.
About the Phase 2a AESOP Trial
The AESOP trial is an open-label, multicenter trial designed to evaluate the ability of avasopasem to reduce the incidence of radiotherapy-induced esophagitis in patients receiving chemoradiotherapy for unresectable Stage 3A/3B or post-operative Stage 2B non-small cell lung cancer, or small cell lung cancer treatable with chemoradiotherapy. For more information, please visit https://clinicaltrials.gov/ct2/show/NCT04225026.
Galera is headquartered in Malvern, PA. For more information, please visit www.galeratx.com.
May 02, 2022 8:35 AM ET
By: Ravikash, SA News Editor
Apr 27, 2022 6:00 AM
CAMBRIDGE, Mass. & BASEL, Switzerland & BEIJING--(BUSINESS WIRE)-- BeiGene (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, today announced the Independent Data Monitoring Committee (IDMC) determined at a pre-planned interim analysis that RATIONALE 306, a global Phase 3 trial of tislelizumab in combination with chemotherapy, had met the study’s primary endpoint of overall survival (OS) in patients with previously untreated advanced or metastatic esophageal squamous cell carcinoma (ESCC). The safety and tolerability profile for tislelizumab in combination with chemotherapy at this interim analysis was consistent with previous trials and no new safety signals were identified.
“ESCC is a difficult to treat disease that imposes a significant symptom burden on patients. We are encouraged by the survival benefit seen in the tislelizumab and chemotherapy group in RATIONALE 306. We have designed an expansive clinical development program, with a global scope, to investigate tislelizumab as a potential treatment for solid tumors, and it is rewarding to deliver the seventh positive Phase 3 pivotal trial to demonstrate benefit with tislelizumab treatment,” said Mark Lanasa, M.D., Chief Medical Officer, Solid Tumors at BeiGene. “Combined with the overall survival benefit seen in RATIONALE 302, the second-line evaluation of tislelizumab versus chemotherapy in ESCC, the results from 306 add to the body of evidence supporting tislelizumab as a potential standard of care for patients suffering from this disease. We are grateful to the more than 1,100 patients with ESCC who chose to participate in these two pivotal Phase 3 studies and look forward to sharing the RATIONALE 306 study results with the community at a future scientific conference.”
Tislelizumab is currently under review by the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for advanced or metastatic ESCC after prior chemotherapy. The EMA is also reviewing tislelizumab for advanced or metastatic non-small cell lung cancer (NSCLC) after prior chemotherapy, and in combination with chemotherapy for previously untreated advanced or metastatic NSCLC. In January 2021, BeiGene announced a collaboration with Novartis to accelerate the clinical development and marketing of tislelizumab in North America, Europe, and Japan.
Tislelizumab is approved by the China National Medical Products Administration (NMPA) as a treatment for eight indications, including a recent approval for use in patients with locally advanced or metastatic ESCC who have disease progression or are intolerant to first-line standard chemotherapy. Tislelizumab is not approved for use outside of China.
About RATIONALE 306
RATIONALE 306 (NCT03783442) is a randomized, placebo-controlled, double-blind, global Phase 3 study to evaluate the efficacy and safety of tislelizumab in combination with chemotherapy as a first-line treatment in patients with advanced or metastatic ESCC. The primary endpoint of the trial is overall survival (OS). Secondary endpoints include progression free survival, overall response rate, and duration of response per RECIST v1.1, as well as health-related quality of life measures and safety.
The trial enrolled 649 patients at research centers across Asia-Pacific, Europe, and North America. Patients were randomized 1:1 to receive either tislelizumab plus chemotherapy or placebo plus chemotherapy.
About Esophageal Squamous Cell Carcinoma
There are two main types of esophageal cancer, based on the cells where cancer develop: squamous cell carcinoma (ESCC) and adenocarcinoma (EAC). ESCC is the most common subtype of esophageal cancer, accounting for more than 85% of esophageal cancers worldwide.i,ii Because many patients are diagnosed with ESCC at later stages of disease, management of ESCC is challenging and the overall prognosis remains poor.iii,iv,v
Tislelizumab is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping to aid the body’s immune cells to detect and fight tumors. In pre-clinical studies, binding to Fcγ receptors on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells.
Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
BeiGene has initiated or completed more than 20 potentially registration-enabling clinical trials in 35 countries and regions, including 17 Phase 3 trials and four pivotal Phase 2 trials. More information on the clinical trial program for tislelizumab can be found at: https://www.beigene.com/en-us/science-and-product-portfolio/pipeline
To learn more about BeiGene, please visit www.beigene.com and follow us on Twitter at @BeiGeneGlobal.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220427005497/en/
Apr. 27, 2022 6:47 AM ET
By: Dulan Lokuwithana, SA News Editor
RESEARCH TRIANGLE PARK, N.C., April 27, 2022 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced the European Medicines Agency (EMA) has granted access to the Priority Medicines (PRIME) scheme for BCX9250, a novel, oral activin receptor-like kinase-2 (ALK-2) inhibitor discovered and developed by BioCryst for the treatment of fibrodysplasia ossificans progressiva (FOP).
PRIME is a program launched by the EMA to enhance support for the development of medicines that target an unmet medical need. This voluntary program is based on enhanced interaction and early dialogue with developers of promising medicines and is designed to optimize development plans and speed up evaluation so these medicines can potentially reach patients earlier. According to the EMA, developers of medicines that are eligible for PRIME can expect additional opportunities for scientific advice and be eligible for accelerated assessment at the time of application for a marketing authorization.
“Promising results from non-clinical data and the first-in-human Phase 1 safety, tolerability and pharmacokinetics study in healthy subjects formed the basis of the application for PRIME eligibility. We are pleased with the EMA’s decision to grant PRIME eligibility to BCX9250 – the first investigational drug for this indication to receive this designation – based on the early evidence of the potential of BCX9250 to address the unmet need for patients living with FOP. We look forward to applying the benefits available to us through PRIME as we continue to advance our ALK-2 inhibitor program,” said Dr. Helen Thackray, chief research and development officer of BioCryst.
FOP is an ultra-rare, severely disabling genetic disorder characterized by the irregular formation of bone outside the normal skeleton, also known as heterotopic ossification (HO). HO can occur in muscles, tendons, ligaments and other connective tissues. Patients with FOP become bound by this irregular ossification over time, with restricted movement and fused joints, resulting in deformities, restricted mobility and premature mortality.
BCX9250 is designed to inhibit the ALK-2 enzyme, which is a part of the normal signaling pathway for bone formation and responds to binding its specific ligands (bone morphogenic proteins, BMPs) by stimulating normal bone growth and renewal in healthy children and adults. Specific activating mutations of the ALK-2 gene are seen in all cases of FOP. An activating mutation in ALK-2 is necessary for the disease to occur, making the ALK-2 enzyme an ideal drug target for treatment of FOP.
In a Phase 1 clinical trial in healthy subjects, BCX9250 was safe and well tolerated at all doses studied, with linear and dose-proportional exposure supporting the potential for once-daily dosing.
For more information, please visit the company’s website at www.biocryst.com.
Apr. 27, 2022 8:04 AM ET
By: Ravikash, SA News Editor
Apr 23, 2022PDF Version
Nektar and Collaborators Present Preclinical Data on NKTR-255, a Novel IL-15 Receptor Agonist, in combination with CAR Cell Therapies at the 2022 Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT™ and CIBMTR®
SAN FRANCISCO, April 23, 2022 /PRNewswire/ -- Nektar Therapeutics (Nasdaq: NKTR) announced that collaborators from the Cairo Laboratory at New York Medical College today presented data from several preclinical studies demonstrating the potential of NKTR-255 to enhance the anti-tumor activities of different CAR-T therapies in a variety of cancer preclinical models. Presentations include an oral presentation by Wen Luo, Ph.D., assistant professor of pediatrics at NYMC, on in vivo and in vitro efficacy of NKTR-255 combined with anti-MCAMa CARb modified Natural Killer (NK) cells in several tumor models, and a poster presentation by Yaya Chu, Ph.D., assistant professor of pediatrics at NYMC, presenting studies of NKTR-255 in combination with ex vivo expanded anti-CD19 CAR NK cells and anti-CD20 or anti-CD79 antibodies in models of Burkitt Lymphoma (BL).
"Our research builds on the body of knowledge for the role of an agent which activates the full IL-15 biology pathway in the field of cell therapy," said Mitchell S. Cairo, M.D., director of the Cairo Laboratory, chief of pediatric hematology, oncology and stem cell transplantation, director of the Children and Adolescent Cancer and Blood Diseases Center, associate chairman of the Department of Pediatrics and professor of pediatrics, medicine, pathology, microbiology and immunology and cell biology and anatomy at NYMC. "My lab's findings show that NKTR-255's ability to expand and proliferate NK cells resulted in the enhancement of the efficacy of two different CAR therapies in our preclinical models."
The oral presentation will be virtually live streamed on Saturday April 23rd, 2022 at 3:00 PM MT and is accessible through the meeting organizer's website at https://www.astct.org/attend/tandem-meetings. These presentations are available for download at http://www.nektar.com/science/scientific-posters.
Key details and takeaways from the two collaborator presentations include:
Abstract 27: "Targeting Ewing sarcoma, Osteosarcoma and Neuroblastoma with Anti-MCAM Chimeric Antigen Receptor Modified Natural Killer Cells" Luo, W., et al.
Presentation Type: Oral Presentation
Presenting Author: Wen Luo, Ph.D.
Session: Oral Abstract - Session C - Immune and Gene Therapy
Virtual Live Stream of the presentation will begin at 3:00 PM MT on Saturday April 23rd, 2022
Abstract 201: "Optimizing Chimeric Antigen Receptor (CAR) Engineered NK Cell- Mediated Cytotoxicity Combined with anti-CD20 or anti-CD79 Therapeutic Antibodies and NKTR-255 in Burkitt Lymphoma (BL)" Chu, Y., et al.
Presentation Type: Poster
NKTR-255 is an investigational IL‐15 receptor agonist designed to boost the immune system's natural ability to fight cancer. NKTR-255 increases the proliferation and survival of cancer-killing natural killer (NK) cells and memory CD8+ T cells. NKTR-255 engages the entire IL-15 receptor complex (IL‐15Rα/IL‐15Rβγ) to enhance the formation of long-term immunological memory, which may lead to sustained antitumor immune response.
NKTR-255 is specifically engineered using Nektar's expertise in polymer chemistry to mimic the natural biological activity of the body's own IL-15, resulting in optimal activation of the IL-15 pathway. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15, which has to be given in high doses due to rapid clearance from the body, limiting its utility due to toxicity and lack of convenience and use.
Further information about the company and its drug development programs and capabilities may be found online at http://www.nektar.com.
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SOURCE Nektar Therapeutics
Apr. 25, 2022 7:49 AM ET
Nektar Therapeutics (NASDAQ:NKTR) and its collaborators at the New York Medical College (NYMC) said on Monday that the company’s IL‐15 receptor agonist NKTR-255, in combination with different CAR-T therapies, boosted the activity of Natural Killer (NK) cells in preclinical models.
BriaCell Receives FDA Fast Track Approval for Targeted Breast Cancer Immunotherapy
PHILADELPHIA and VANCOUVER, British Columbia, April 13, 2022 (GLOBE NEWSWIRE) -- BriaCell Therapeutics Corp. (Nasdaq: BCTX, BCTXW) (TSX: BCT) (“BriaCell” or the “Company”) , a clinical-stage biotechnology company specializing in targeted immunotherapies for cancer, announces that the U.S. Food and Drug Administration (FDA) has granted Fast Track status to BriaCell’s lead candidate, Bria-IMT™, for the treatment of metastatic breast cancer (breast cancer that has spread beyond the breast).
The Fast Track designation will apply to patients with metastatic breast cancer. BriaCell is developing Bria-IMT™ in combination with immune checkpoint inhibitors in a clinical trial listed in ClinicalTrials.gov as NCT03328026 . BriaCell is currently enrolling and dosing advanced breast cancer patients in its Phase I/IIa combination study of Bria-IMT™ with Incyte’s checkpoint inhibitor, retifanlimab, and its immunomodulator, epacadostat under corporate collaboration with Incyte.
Initial data on patient survival in this study was first presented at the San Antonio Breast Cancer Symposium in December 2021 and was over 12 months (average of 9 prior regimens) compared with 7-10 months in a study in 3 rd line breast cancer patients (those who failed 2 prior regimens for metastatic breast cancer) 1 . Other patient subsets with possible survival benefit included those who match Bria-IMT™ at 1 or more HLA type and those with grade I (well differentiated) or grade II (moderately differentiated) breast cancer.
“We are grateful for the opportunity to accelerate the development of our novel immunotherapy in advanced breast cancer. We continue to move forward with the clinical evaluation of Bria-IMT™ towards a potential registration study to bring hope to patients living with this deadly disease,” said Dr. Del Priore, BriaCell’s Chief Medical Officer.
1 Kazmi S et al, 2020 Breast Cancer Res Treat. 2020 Aug 17
Bria-IMT™ is a cell-based immunotherapy designed to selectively destroy tumor cells without harming the normal cells.
To view the schematic video showing the mechanism by which Bria-IMT™ destroys tumor cells in patients with advanced breast cancer, please visit: https://briacell.com/moa/ .
About Phase I/IIa Clinical Trial of Bria-IMT Combination
The clinical trial evaluates safety and efficacy of Bria-IMT™, in combination with Incyte’s checkpoint inhibitor, retifanlimab, and its immunomodulator, epacadostat, in patients with advanced breast cancer. The combination study is listed in ClinicalTrials.gov as NCT03328026 .
About BriaCell Therapeutics Corp.
BriaCell is an immuno-oncology focused biotechnology company developing targeted and effective approaches for the management of cancer. More information is available at https://briacell.com/ .
Apr. 13, 2022 8:54 AM ET
By: Anuron Mitra, SA News Editor
April 12, 2022
- Navitoclax is being studied in myelofibrosis, a rare, difficult-to-treat blood cancer
- Results are from an exploratory analysis of 34 myelofibrosis patients who received at least one dose of navitoclax in combination with ruxolitinib after suboptimal response or disease progression with ruxolitinib monotherapy
- Median overall survival was not reached for patients who had a ≥ 1 grade improvement in bone marrow fibrosis or ≥ 20% variant allele frequency reduction
- At the time of analysis with > 2 year follow up the survival estimate was 100% in patients who had improvements in bone marrow fibrosis or variant allele frequency
- Results were presented at the American Association for Cancer Research annual meeting
NORTH CHICAGO, Ill., April 12, 2022 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced new data from a Phase 2 trial of navitoclax in combination with ruxolitinib in patients with myelofibrosis. The results were presented at the American Association for Cancer Research annual meeting (AACR 2022, abstract #LB108). Navitoclax is an investigational, first-in-class, oral BCL-XL/BCL-2 inhibitor that is designed to activate programmed cell death (apoptosis) in cancer cells. Navitoclax and its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies.
"Myelofibrosis is a cancer that originates in the bone marrow, leading to fibrosis. Currently, available therapies do not address the underlying disease biology and have not shown a consistent effect on both biomarkers of disease modification and overall survival. Disease control with reversal of bone marrow fibrosis is a key objective for improving patient outcomes," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology clinical development at AbbVie. "That's why we are especially pleased about these early results of navitoclax in combination with ruxolitinib that indicate its novel mechanism of action of inducing cell death may cause reversal of bone marrow fibrosis and extend survival for patients who respond to treatment."
Myelofibrosis is a rare, difficult-to-treat blood cancer that results in excessive scar tissue formation (fibrosis) in the bone marrow. Anti-fibrosis activity, measured by reversal of bone marrow fibrosis (BMF) and reduction in driver gene variant allele frequency (VAF) have been suggested as potential biomarkers to measure disease modification in myelofibrosis, but their association with a survival benefit have not been widely described.1 These data build on AbbVie's history of transforming standards of care in blood cancers with significant unmet needs.
The results presented at AACR 2022 were from REFINE (NCT03222609) – a Phase 2 trial evaluating navitoclax in combination with ruxolitinib (a JAK1/2 inhibitor), which included patients with myelofibrosis who had progressed on or had a suboptimal response to at least 12 weeks of ruxolitinib monotherapy. Median exposure to prior ruxolitinib was 91 weeks (range: 19 weeks – 391 weeks) in the first 34 patients enrolled earlier in the trial.
In the exploratory analysis of 32 patients who were evaluable for improvements in BMF, 12 (38%) had a ≥1 grade improvement during any time point in the study. For driver gene VAF reduction, 26 patients were evaluable and 6 (23%) achieved a ≥20% reduction at week 24. Five patients achieved both BMF and VAF responses.
Median overall survival (OS) for all patients was not reached as presented previously by Harrison2 et al. For patients who had a ≥1 grade improvement BMF median OS was not reached compared with 28.5 months for patients who did not experience an improvement. Similarly, median OS was also not reached for patients who achieved a ≥20% driver gene VAF reduction versus 28.5 months for patients who did not.
All 34 patients (100%) experienced at least one adverse event (AE), and 15 (44%) experienced a serious adverse event (SAE).2 The most common AEs of any grade were thrombocytopenia (n= 30, 88%), diarrhea (n= 24, 71%), fatigue (n= 21, 62%), and nausea (n= 13, 38%). The most common SAEs were pneumonia (n= 4, 12%) and splenic infarction (n= 2, 6%).2 There were no SAEs of bleeding and thrombocytopenia was manageable and reversible with dose reduction/interruption of navitoclax and/or ruxolitinib.2 REFINE was a dose-finding study and the target dose of navitoclax was reduced subsequent to these findings.
"Data obtained from this exploratory analysis holds promise for potential future clinical research," said Jacqueline S. Garcia, M.D., Dana-Farber Cancer Institute, assistant professor of medicine at Harvard Medical School. "What is most notable in this analysis is the overall survival among patients who demonstrate VAF and BMF responses and all patients were alive at time of analysis. Patients in this Phase 2 trial had suboptimal response to ruxolitinib at time of study entry and then had navitoclax added to ruxolitinib on the trial. VAF and BMF responses occurred despite the presence of high molecular risk mutations, which suggests the potential efficacy of combination navitoclax and ruxolitinib could be independent of underlying risk factors."
Navitoclax is an investigational, oral BCL-XL/BCL-2 inhibitor. The BCL-2 family of proteins are known regulators of the apoptosis pathway.3 Navitoclax is not approved by the U.S. Food and Drug Administration (FDA). Its safety and efficacy are under evaluation as part of ongoing Phase 2 and registrational Phase 3 studies.
AbbVie is currently recruiting for two Phase 3 trials of navitoclax (TRANSFORM-1 and TRANSFORM-2) in combination with ruxolitinib for the treatment of myelofibrosis that will enroll more than 500 patients. The company anticipates pivotal trial readouts and regulatory submission for navitoclax in 2023.
About the REFINE Study
REFINE is a Phase 2, open-label, multicenter study evaluating the tolerability and efficacy of navitoclax alone or when added to ruxolitinib in patients with myelofibrosis.1 The primary outcome measure is the percentage of patients who achieve Spleen Volume Reduction of greater than or equal to 35% (SVR35) from baseline to Week 24. Secondary outcomes measures include percentage of participants achieving 50% reduction in Total Symptom Score from baseline to Week 24 and change in grade of bone marrow fibrosis assessed according to the European Consensus Grading System. More information can be found on www.clinicaltrials.gov (NCT03222609).
Apr. 12, 2022 8:53 AM ET
Iovance Biotherapeutics Announces Regulatory and Clinical Updates for Lifileucel in Melanoma
Positive FDA Feedback on Potency Assay Matrix to Support BLA Submission
Further Defines Frontline Melanoma Strategy for Lifileucel in Combination with Pembrolizumab
SAN CARLOS, Calif., April 05, 2022 (GLOBE NEWSWIRE) -- Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies, today announced that the U.S. Food and Drug Administration (FDA) has provided feedback on April 1, 2022 regarding Iovance’s proposed matrix of potency assays for its upcoming Biologics License Application (BLA) for lifileucel in metastatic melanoma. Iovance received positive feedback from the FDA on both its potency assay matrix and its proprietary cell co-culture assay included in the potency assay matrix. Based on this response, Iovance expects to request a pre-BLA meeting in July 2022 and to complete a BLA submission for lifileucel by August 2022.
Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, “The favorable feedback received from the FDA on our potency assays and assay matrix brings Iovance a step closer to our submission of a BLA for lifileucel in metastatic melanoma. We look forward to bringing lifileucel to the market quickly to offer melanoma patients a new option following anti-PD-1 therapy.”
In addition, Iovance today announced plans to open a Phase III study for lifileucel in combination with pembrolizumab for the treatment of immune checkpoint inhibitor (ICI) naïve frontline metastatic melanoma in late 2022. Updated data from the combination cohort of lifileucel and pembrolizumab in ICI naïve patients (Cohort 1A in the IOV-COM-202 study, n=12) demonstrated an overall response rate (ORR) of 67%. Eight out of 12 patients had a confirmed objective response per RECIST 1.1, including three complete responses and five partial responses. Six of the eight responders had ongoing response at the time of the last data cut, and five responders had a duration of response of more than one year. The FDA previously granted Fast Track Designation for lifileucel in combination with pembrolizumab for the treatment of ICI naïve metastatic melanoma based on the unmet medical need and potential advantages for this combination over available care.
Management will host a conference call and live audio webcast to discuss these updates at 8:00 a.m. Eastern time on April 6, 2022. To participate in the conference call, please dial 1-844-646-4465 (domestic) or 1-615-247-0257 (international) and reference the access code 3734669. The live webcast can be accessed in the Investors section of the Company’s website at www.iovance.com. The archived webcast will also be available for one year in the Investors section at www.iovance.com.
For more information, please visit www.iovance.com.
Source: Iovance Biotherapeutics, Inc.
Apr. 05, 2022 4:26 PM ET
By: Dania Nadeem, SA News Editor
March 28, 2022 at 7:30 AM EDT
CAMBRIDGE, Mass. and CARLSBAD, Calif. , March 28, 2022 (GLOBE NEWSWIRE) -- Biogen Inc. (Nasdaq: BIIB) and Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced topline results from the Phase 1 study of BIIB078 (IONIS-C9Rx), an investigational antisense oligonucleotide (ASO) for people with C9orf72-associated amyotrophic lateral sclerosis (ALS).
In this Phase 1 study, BIIB078 was generally well-tolerated. The adverse events (AEs) were mostly mild to moderate in severity and occurred at a similar rate across BIIB078 and placebo groups. The most common AEs were fall, procedural pain and headache.
BIIB078 did not meet any secondary efficacy endpoints and it did not demonstrate clinical benefit. In the dose cohorts up to 60 mg there were no consistent differences between the BIIB078 group and the placebo group. Participants in the BIIB078 90 mg dose cohort trended toward a greater decline than those in the placebo group across secondary endpoints. Based on these results, the BIIB078 clinical development program will be discontinued, including its ongoing open-label extension study.
“We are incredibly grateful for the selfless commitment of the individuals with ALS who participated in the study, and the community’s dedication to advancing research for this devastating disease,” said Toby Ferguson, M.D., Ph.D., Vice President and Head of the Neuromuscular Development Unit at Biogen. “While these were not the results we were hoping for, they are clear and will inform future research across our broad pipeline of investigational ALS therapies. We remain focused on pioneering new treatments that will positively impact people living with this debilitating disease.”
“C9orf72-associated ALS is a complex genetic form of ALS and there are multiple mechanisms by which the scientific community believes the C9orf72 gene causes disease. We designed BIIB078 to test the prevailing hypothesis that the mechanisms of disease for C9orf72-associated ALS were caused by toxicity associated with the repeat containing RNA and corresponding dipeptides. Unfortunately, this Phase 1 study did not support the hypothesis, suggesting that the disease mechanism is much more complex. While these results do not support further development of BIIB078, we anticipate they will provide valuable learnings that lead to a deeper understanding of this form of ALS,” said C. Frank Bennett, Executive Vice President, Chief Scientific Officer and Franchise Leader for Neurological Programs at Ionis.
This Phase 1 study was a randomized, placebo-controlled, dose-escalating trial to evaluate BIIB078 administered intrathecally to adults (n=106) with C9orf72-associated ALS. Within each of the six study treatment cohorts, participants were randomized to receive BIIB078 or placebo (3:1 ratio). The primary objective of the study was to assess safety and tolerability. Secondary efficacy endpoints included ALS Functional Rating Scale–Revised, Slow Vital Capacity, Hand-Held Dynamometry, and the Iowa Oral Pressure Instrument.
The companies will present the BIIB078 Phase 1 data at a future scientific forum.
The company routinely post information that may be important to investors on our website at www.biogen.com. To learn more, please visit www.biogen.com and follow Biogen on social media – Twitter, LinkedIn, Facebook, YouTube.
To learn more about Ionis, visit www.ionispharma.com and follow us on Twitter @ionispharma.
March 31, 2022 08:00 ET | Source: Longeveron
Results Support Further Exploration of Therapeutic Potential of Lomecel-B to Slow Cognitive Decline, Improve Quality of Life for Alzheimer’s Patients
Phase 2 Trial Recently Launched With First Patient Treated
MIAMI, March 31, 2022 (GLOBE NEWSWIRE) -- Longeveron Inc. (NASDAQ: LGVN), a clinical-stage biopharma company developing cellular therapies for aging-related illnesses, chronic disorders, and other specific life-threatening conditions, announced the publication of results from a Phase 1 trial testing Lomecel-B on patients with mild Alzheimer’s disease (AD) in Alzheimer’s & Dementia®: The Journal of the Alzheimer’s Association. The trial met its primary endpoint, demonstrating that Lomecel-B was well tolerated in this patient population. In addition, the data provided indications supporting further exploration of Lomecel-B, particularly the therapeutic potential to slow cognitive decline and improve quality of life in patients with AD.
“We are pleased and encouraged by the publication of our study in this high-impact journal,” said Geoff Green, CEO of Longeveron. “The Lomecel-B study was funded by two competitive Part the Cloud Neuroinflammation Challenge grants awarded to Longeveron from the Alzheimer’s Association, for which we are extremely grateful.”
The article, titled “Results and Insights from a Phase 1 Clinical Trial of Lomecel-B for Alzheimer’s disease,” details the study findings on Longeveron’s lead investigational product, Lomecel-B, an allogeneic bone marrow-derived medicinal signaling cell (MSC) product, given to patients with mild Alzheimer’s disease.
“What makes this study unique is the use of a cellular therapy that may potentially target multiple pathological features of Alzheimer’s disease simultaneously,” said Dr. Mark Brody, lead author of the manuscript. “Not only did the study meet its primary endpoint of safety, but it also suggests the potential that Lomecel-B could have in treating patients with Alzheimer’s disease. We found data suggesting that Lomecel-B could have effects ranging from increasing blood vessel health to reducing inflammation, which could yield promising results.”
The double-blinded, randomized, placebo-controlled trial was conducted on thirty-three patients at four clinical sites. Each patient received a single intravenous infusion of low- or high-dose Lomecel-B, or a placebo. The findings from this study are being tested in a new larger Phase 2 study, which commenced in December 2021, and has already treated the first patient and continues to enroll others. The new trial is double-blinded, randomized, and placebo-controlled, and is designed to evaluate single versus multiple doses of Lomecel-B for mild Alzheimer’s disease.
The major findings of the Phase 1 study as reported in Alzheimer’s & Dementia are as follows:
“We are encouraged by these results,” said Dr. Anthony Oliva, Senior Scientist at Longeveron, and principal investigator on the grants. “With a single dose of Lomecel-B, we observed several lines of preliminary evidence supporting multiple mechanisms of action of Lomecel-B, and most importantly, the data supports the potential of Lomecel-B as disease modifying for Alzheimer’s.”
The results of this study could have important implications for combatting this devastating disease that is also taking a significant toll on healthcare systems. According to a recent report by the Alzheimer’s Association, an estimated 6.5 million Americans age sixty-five and older are living with dementia due to Alzheimer’s disease. Seventy-three percent are age seventy-five or older. Of the total U.S. population, about 1 in 9 people (11.3%) age sixty-five and older has dementia due to Alzheimer’s disease.
Additional information about the Company is available at http://www.longeveron.com/.
Apr. 01, 2022 9:29 AM ET
By: Dulan Lokuwithana, SA News Editor
Mar 9, 2022
CAMBRIDGE, Mass., March 09, 2022 (GLOBE NEWSWIRE) -- Intellia Therapeutics, Inc. (NASDAQ:NTLA), a leading clinical-stage genome editing company focused on developing potentially curative therapeutics leveraging CRISPR-based technologies, today announced that the U.S. Food and Drug Administration (FDA) has granted orphan drug designation for Intellia’s ex vivo investigational T cell receptor (TCR)-T cell therapy, NTLA-5001, for the treatment of acute myeloid leukemia (AML).
NTLA-5001 is an autologous TCR-T cell therapy designed to target the Wilms’ Tumor (WT1) antigen, which is highly expressed in AML and many other hematologic and solid tumors. NTLA-5001 is currently being evaluated in a Phase 1/2a study in adults with persistent or recurrent AML who have previously received first-line therapy.
“The FDA’s decision to grant orphan drug designation for NTLA-5001 reflects the serious need for novel treatment options for people living with AML, a disease with notably poor long-term survival,” said Intellia President and Chief Executive Officer John Leonard, M.D. “As part of our full-spectrum genome editing strategy, we seek to leverage our proprietary CRISPR/Cas9-based platform to engineer differentiated cell therapies targeting cancers for which there are currently limited or no treatment options. We look forward to advancing our investigational TCR-T cell therapy, NTLA-5001, through the clinic in hopes of improving future treatment options for patients in need.”
The FDA's Orphan Drug Designation program provides orphan status to drugs defined as those intended for the treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States. Orphan drug designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user-fee exemptions and seven-year marketing exclusivity upon FDA approval.
About the NTLA-5001 Clinical Program
The Phase 1/2a study will evaluate the safety, tolerability, cell kinetics and anti-tumor activity of a single dose of NTLA-5001 in adults who have detectable AML after having received standard first-line therapy. The study includes a dose escalation and expansion phase, with up to 54 total participants. The dose-escalation phase of the study includes two independent arms of up to three cohorts each: Arm 1 consists of adults with AML with lower disease burden, defined as those with less than 5% blasts in bone marrow, while Arm 2 consists of adults with AML with higher disease burden, defined as those with greater than or equal to 5% blasts in bone marrow. Once a dose is identified in each arm, two expansion cohorts will be opened for further safety assessment. Visit clinicaltrials.gov (NCT05066165) for more details.
NTLA-5001 is an investigational CRISPR/Cas9-engineered T cell receptor (TCR)-T cell therapy in development for the treatment of all genetic subtypes of acute myeloid leukemia (AML). This autologous cell therapy candidate is designed for AML patients with the HLA-A*02:01 allele and whose tumors carry the Wilms’ Tumor 1 (WT1) antigen, which is widely overexpressed in AML and other cancers. NTLA-5001 is Intellia’s first wholly owned ex vivo therapeutic candidate, developed using its proprietary cell engineering platform for the treatment of cancer. NTLA-5001 utilizes a WT1-targeting TCR identified in collaboration with IRCCS Ospedale San Raffaele. Based on preclinical results, Intellia believes its proprietary cell engineering platform will result in a pipeline of more efficacious and safer cell-based cancer therapies.
Source: Intellia Therapeutics, Inc.
Mar. 09, 2022 12:14 PM ET
The FDA has granted Orphan Drug Designation to an Intellia Therapeutics' (NTLA +2.9%) CRISPR treatment for acute myeloid leukemia.
Mar 8, 2022 at 1:31 PM CET
COPENHAGEN, Denmark; March 8, 2022
Genmab A/S (Nasdaq: GMAB) announced today that the U.S. Food and Drug Administration (FDA) has granted orphan-drug designation to the investigational medicine, epcoritamab (DuoBody®-CD3xCD20), for the treatment of follicular lymphoma (FL). Epcoritamab is being co-developed by Genmab and AbbVie (NYSE: ABBV).
Orphan drug status is designated by the FDA to medicines and biologics that are defined as those intended for the prevention, diagnosis, or treatment of a rare disease or condition affecting less than 200,000 people in the U.S.i
Approximately 2.7 per 100,000 people in the U.S. are newly diagnosed with follicular lymphoma (FL)ii every year and the median age of patients at diagnoses with FL is 63.iii,iv,v FL is typically a slow-growing or indolent form of non-Hodgkin’s lymphoma (NHL) that arises from B-lymphocytes.vi Although FL is an indolent lymphoma, patients who relapse or become refractory are incurable with conventional therapy and there is a need for additional treatment options.vii,viii Globally, FL is the second most common form of NHL, accounting for approximately 25 percent of adult NHL.ix
“This orphan drug designation is an important milestone for epcoritamab,” said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab. “With AbbVie, we remain committed to further developing epcoritamab in this patient population, as well as in patients diagnosed with other B-cell hematologic malignancies.”
Epcoritamab is currently being evaluated as a treatment option for patients with FL in several clinical trials, including the phase 1/2 EPCORE™ NHL-1 evaluating the efficacy and safety of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (B-NHL), including diffuse large B-cell Lymphoma (DLCBL), follicular lymphoma (FL), and mantle cell lymphoma (MCL) (NCT: 03625037). Additional trials evaluating epcoritamab in patients with FL include a phase 1b/2, open-label, multinational, interventional trial to evaluate the safety and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents across different lines of therapy in patients with DLBCL or FL (NCT: 04663347) and a phase 1/2 trial evaluating the safety and efficacy of epcoritamab in Japanese patients with relapsed/refractory B-NHL (NCT: 04542824).
Epcoritamab is an investigational IgG1-bispecific antibody created using Genmab’s proprietary DuoBody technology. Genmab’s DuoBody-CD3 technology is designed to direct cytotoxic T cells selectively to tumors to elicit an immune response towards malignant cells. Epcoritamab is designed to simultaneously bind to CD3 on T cells and CD20 on B cells and induces T cell mediated killing of lymphoma B cells.x CD20 is a clinically validated therapeutic target, and is expressed on many B-cell malignancies, including diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma and chronic lymphocytic leukemia.xi,xii Epcoritamab is an investigational medicine not currently approved by the FDA. Epcoritamab is being co-developed by Genmab and AbbVie as part of the companies’ broad oncology collaboration.
Genmab is headquartered in Copenhagen, Denmark with locations in Utrecht, the Netherlands, Princeton, New Jersey, U.S. and Tokyo, Japan. For more information, please visit Genmab.com and follow us on Twitter.com/Genmab.
Mar. 08, 2022 7:56 AM ET
By: Dulan Lokuwithana, SA News Editor
March 7, 2022
SOUTH SAN FRANCISCO, Calif., March 07, 2022 (GLOBE NEWSWIRE) -- Harpoon Therapeutics, Inc. (NASDAQ: HARP), a clinical-stage immunotherapy company developing novel T cell engagers, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation for HPN328, a delta like ligand 3- (DLL3) targeting TriTAC®, for the treatment of small cell lung cancer (SCLC). A Phase 1/2 clinical trial is currently ongoing for HPN328 in the SCLC patient population.
“Orphan Drug Designation for HPN328 is a significant milestone that underscores the need for additional treatments for patients suffering from small cell lung cancer and HPN328’s potential to contribute to this unmet medical need,” stated Julie Eastland, President and CEO, Harpoon Therapeutics. “We are pleased with the clinical progress of HPN328 and remain focused on dose escalation with the goal to determine the recommended Phase 2 dose by the end of this year.”
The FDA's Orphan Drug Designation program provides orphan status to drugs defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases that affect fewer than 200,000 people in the United States. Orphan Drug Designation qualifies the sponsor of the drug for certain development incentives, including tax credits for qualified clinical testing, prescription drug user fee exemptions and potential eligibility for seven-year marketing exclusivity upon FDA approval.
About the Phase 1/2 Trial for HPN328
HPN328 is a TriTAC that binds to human and non-human primate DLL3, CD3ε, and albumin with similar affinities. The Phase 1/2 trial is an open-label study of HPN328 as monotherapy to assess the safety, tolerability and pharmacokinetics in patients with advanced cancers associated with expression of DLL3. The first part of the trial is designed to determine a dose for additional clinical investigations.
As of the December 13, 2021 clinical update provided by Harpoon, 15 patients had been enrolled in dose cohorts ranging from 15 µg to 7200 µg per week using both fixed and step dose administration once weekly by intravenous infusion. Enrolled patients had a median of 2 lines (range 1 to 5) of prior therapy and included small cell lung cancer patients who had relapsed after platinum chemotherapy and patients with other malignancies with high grade neuroendocrine tumors associated with DLL3 expression. HPN328 has been well tolerated with Grade 1-2 cytokine release syndrome (CRS) reported in 33% of patients, no DLTs observed and MTD had not been reached. Among four patients with small cell lung cancer receiving the two highest doses tested to date, 1215 µg fixed dose and 3600-7200 µg step dose, three had target lesion reduction, including 1 confirmed RECIST partial response. The patient with a cPR experienced a target lesion reduction of 53% at week 10.
Following dose escalation, Harpoon may further evaluate the safety and efficacy of HPN328 in additional parallel cohorts. The primary outcome measure will be to determine efficacy for the Phase 2 dose based on the overall response rate as determined by RECIST. For additional information about the trial, please visit clinicaltrials.gov using the identifier NCT04471727.
For additional information about Harpoon Therapeutics, please visit www.harpoontx.com.
Source: Harpoon Therapeutics
Mar. 07, 2022 7:52 AM ET
By: Dulan Lokuwithana, SA News Editor
The clinical-stage immunotherapy company, Harpoon Therapeutics (NASDAQ:HARP) announced on Monday that the U.S. Food and Drug Administration (FDA) granted the Orphan Drug Designation for its investigational product, HPN328, for the treatment in small cell lung cancer (SCLC).
AC Immune ACI-35.030 Phase 1b/2a Trial Interim Data Confirm Consistent Safety and Potent Immunogenicity of pTau Alzheimer’s Vaccine in High-dose CohortFebruary 15, 2022
Observed strong induction of antibodies specific for pathological forms of Tau with ACI-35.030 treatment
ACI-35.030 continues to be well tolerated with no clinically relevant safety concerns observed in low-, mid- or high-dose cohorts to date
Interim data support plans for further late-stage development
LAUSANNE, Switzerland, Feb. 15, 2022 (GLOBE NEWSWIRE) -- AC Immune SA (NASDAQ: ACIU), a Swiss-based, clinical-stage biopharmaceutical company with a broad pipeline focused on neurodegenerative diseases, today announced new interim 10-week data from the high-dose cohort of a placebo-controlled Phase 1b/2a trial evaluating ACI-35.030, a first-in-class phosphorylated-Tau (pTau) vaccine candidate in participants with early Alzheimer’s disease (AD). The Company previously reported interim data from low-dose and mid-dose cohorts.
ACI-35.030, based on AC Immune’s SupraAntigen® platform, is the first AD vaccine candidate designed to generate antibodies targeting pathological pTau in the brain. New interim data from the Phase 1b/2a trial show that the high-dose of ACI-35.030 led to the strong induction of antibodies selective for pTau and its aggregated form, enriched paired helical filaments (ePHF). These data are consistent with those previously announced for the trial’s mid-dose cohort that showed median anti-pTau antibody titers increasing from baseline by two orders of magnitude at week 2 after a first injection.
Additional key findings from the high-dose interim analysis include:
As previously announced, the ongoing Phase 1b/2a study has been expanded to include a total of 24 AD participants in the mid-dose sub-cohort. This expansion was designed to generate additional immunogenicity and safety data.
Prof. Andrea Pfeifer, CEO of AC Immune SA, commented: “These latest interim results add to the robust clinical dataset supporting plans for continued late-stage development. The observed antibody response also shows a preference for pathological pTau, which is present in AD years before Tau accumulation can be detected via brain imaging. With these results we believe ACI-35.030 holds significant promise as a first-in-class therapeutic that could shift the AD treatment paradigm towards earlier treatment and prevention, especially when used alongside cutting-edge pTau diagnostics as part of a precision medicine approach. We look forward to the continued development of ACI-35.030.”
About the Phase 1b/2a pTau AD Vaccine Trial
The Phase 1b/2a study is a randomized, multicenter, double-blind, placebo-controlled clinical study with a primary objective to assess the safety, tolerability, and immunogenicity of different dosages of ACI-35.030 and JACI-35.054 in participants with early AD. Secondary objectives will assess additional immunogenicity parameters, while exploratory endpoints will include notable biomarkers of progression of AD as well as clinical assessments. This Phase 1b/2a study evaluating ACI-35.030 and JACI-35.054 was initiated in Q3 2019 and is currently ongoing.
The pTau vaccine candidate is being developed in collaboration with Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson.
About AC Immune SA
AC Immune SA is clinical-stage biopharmaceutical company that aims to become a global leader in precision medicine for neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and NeuroOrphan indications driven by misfolded proteins. The Company’s two clinically validated technology platforms, SupraAntigen® and Morphomer®, fuel its broad and diversified pipeline of first- and best-in-class assets, which currently features ten therapeutic and three diagnostic candidates, six of which are currently in clinical trials. AC Immune has a strong track record of securing strategic partnerships with leading global pharmaceutical companies including Genentech, a member of the Roche Group, Eli Lilly and Company, and Janssen Pharmaceuticals, Inc., resulting in substantial non-dilutive funding to advance its proprietary programs and >$3 billion in potential milestone payments.
SupraAntigen® is a registered trademark of AC Immune SA in the following territories: AU, EU, CH, GB, JP and RU. Morphomer® is a registered trademark of AC Immune SA in CN, CH, GB, JP, and NO.
AC Immune (NASDAQ:ACIU) reported interim 10-week data from a high-dose cohort of a phase 1b/2a trial evaluating ACI-35.030, a phosphorylated-Tau (pTau) vaccine candidate in people with early Alzheimer’s disease (AD).
February 9, 2022 at 7:00 AM ESTPDF Version
On track to complete the BLA submission in the first half of 2022
BOSTON--(BUSINESS WIRE)--Feb. 9, 2022-- Gamida Cell Ltd. (Nasdaq: GMDA), an advanced cell therapy company committed to cures for cancer and other serious diseases, today announced that it has initiated the Biologics License Application (BLA) rolling submission process with the U.S. Food and Drug Administration for omidubicel, a potentially life-saving treatment for patients with blood cancers in need of stem cell transplant. The company remains on track to complete the BLA submission in the second quarter of 2022.
“We are pleased to reach this important milestone for omidubicel and bring this potential therapy one step closer to reaching patients in need,” said Julian Adams, Ph.D., Chief Executive Officer of Gamida Cell. “In the Phase 3 study, omidubicel achieved a statistically significant reduction in time to neutrophil engraftment, reduced hospitalization time, decreased risk of infection and shorter time to platelet engraftment. Based on this positive data, we believe omidubicel has the potential to address the existing unmet needs in allogeneic transplant, offering a new standard of care and the opportunity to treat even more patients.”
Omidubicel has the potential to be the first FDA approved advanced cell therapy product for allogeneic stem cell transplant. For patients with hematologic malignancies that are deemed eligible for an allogeneic stem cell transplant, the procedure is their best chance for a potential cure. In the U.S., there are approximately 8,000 patients above the age of 12 with hematologic malignancies who undergo an allogeneic stem cell transplant each year and we believe that number of patients may grow over time1. Unfortunately, there are approximately 1,000 patients each year, who are above the age of 12 and are deemed eligible for an allogeneic stem cell transplant but cannot find an appropriate donor2. Based on its encouraging clinical data and less stringent matching criteria, omidubicel has the potential to improve outcomes for allogeneic stem cell transplant patients compared to other donor sources and expand access for patients who cannot find a suitable donor.
Omidubicel is an advanced cell therapy under development as a potential life-saving allogeneic hematopoietic stem cell (bone marrow) transplant solution for patients with blood cancers. Omidubicel is the first stem cell transplant donor source to receive Breakthrough Therapy Designation from the U.S. FDA and has also received Orphan Drug Designation in the U.S. and EU. Gamida Cell has completed an international, multi-center, randomized Phase 3 study (NCT0273029) evaluating the safety and efficacy of omidubicel in patients with hematologic malignancies undergoing allogeneic bone marrow transplant compared to a comparator group of patients who received a standard umbilical cord blood transplant. That study achieved its primary endpoint, demonstrating a highly statistically significant reduction in time to neutrophil engraftment, a key milestone in a patient’s recovery from a stem cell transplant. The Phase 3 study also achieved its secondary endpoints of reduced time to platelet engraftment, reduced infections and shorter days of hospitalization. For more information about omidubicel, please visit https://www.gamida-cell.com.
Omidubicel is an investigational therapy, and its safety and efficacy have not been established by the FDA or any other health authority.
For additional information, please visit www.gamida-cell.com or follow Gamida Cell on LinkedIn, Twitter, Facebook or Instagram at @GamidaCellTx.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220209005257/en/
Source: Gamida Cell Ltd.
Feb. 09, 2022 3:05 PM ET
By: Jonathan Block, SA News Editor
February 9, 2022 at 11:36 AM EST
ROCKVILLE, Md., Feb. 9, 2022 /PRNewswire/ --
REGENXBIO Inc. (Nasdaq: RGNX) today announced positive interim data are being presented at the 18th Annual WORLDSymposium™ from five patients in the ongoing Phase I/II trial and one patient from a single-patient Investigational New Drug (IND) application of RGX-111 for the treatment of severe Mucopolysaccharidosis Type I (MPS I).
"This marks our first data presentation from the Phase I/II trial evaluating RGX-111 as a potential one-time gene therapy delivered directly to the central nervous system (CNS) for the treatment of severe MPS I. We are encouraged to see that RGX-111 has been well-tolerated with emerging evidence of CNS biomarker activity and improvements in neurodevelopmental function, which suggest biological activity in the CNS following one-time administration of RGX-111. We also saw emerging evidence of biomarker activity outside of the CNS," said Steve Pakola, M.D., Chief Medical Officer of REGENXBIO. "We plan to enroll additional patients in the Phase I/II trial and look forward to providing additional updates."
"MPS I is a rare inherited disorder caused by a mutation in the gene that encodes human α-l-iduronidase (IDUA), an enzyme needed by cells to break down long chains of sugar molecules known as mucopolysaccharides. Current treatment options for MPS I have limitations and can be associated with significant morbidity and mortality," said Ray Wang, M.D., Campbell Foundation Director of the Multidisciplinary Lysosomal Program, Division of Metabolic Disorders, CHOC Children's Hospital / Department of Pediatrics, University of California, Irvine, CA. "Initial data indicate encouraging CNS and systemic biomarker activity following RGX-111 administration."
RGX-111 is an investigational one-time gene therapy designed to deliver the gene that encodes the IDUA enzyme using the AAV9 vector. RGX-111 is administered directly to the CNS. The primary endpoint of the trial is to evaluate the safety of RGX-111. Secondary and exploratory endpoints include biomarkers of α-l-iduronidase (IDUA) enzyme activity in the cerebrospinal fluid (CSF), serum and urine, neurodevelopmental assessments, and caregiver reported outcomes. Patients were treated across two dose cohorts: 1.0x1010 genome copies per gram (GC/g) of brain mass (n=2) and 5.0x1010 GC/g of brain mass (n=3). In the single-patient IND for RGX-111, a severe MPS I patient was dosed with 1x1010 GC/g of brain mass.
REGENXBIO plans to immediately expand enrollment of patients in Cohort 2 of the Phase I/II trial based on support from MPS I treating-physicians and the Independent Data Monitoring Committee, to enroll up to six additional patients.
Data Summary and Safety Update
As of December 20, 2021, RGX-111 is reported to be well-tolerated in the five patients enrolled in the Phase I/II clinical trial with no drug-related serious adverse events (SAEs). Time of post-administration follow-up ranges from three weeks to 56 weeks. One patient in Cohort 1 has completed the 48-week immunosuppression regimen per the study protocol. Two patients were not receiving enzyme replacement therapy (ERT) at the time of enrollment, and they continue to not receive ERT.
RGX-111 continues to be well-tolerated in the single-patient IND with no drug-related SAEs as of December 20, 2021. Time of post-administration follow-up is 87 weeks. This patient has completed the 48-week immunosuppression regimen, per the study protocol, and continues to receive weekly ERT.
The study findings presented at the WORLDSymposium are available under the Presentations & Publications page in the Media section of the company's website located at www.regenxbio.com.
RGX-111 is designed to use the AAV9 vector to deliver the α-l-iduronidase (IDUA) gene to the central nervous system (CNS). Delivery of the IDUA gene within the cells in the central nervous system (CNS) could provide a permanent source of secreted IDUA beyond the blood-brain barrier, allowing for long-term cross-correction of cells throughout the CNS. By providing rapid IDUA delivery to the brain, RGX-111 could potentially help prevent the progression of cognitive deficits that otherwise occurs in MPS I patients. RGX-111 has received orphan drug product, rare pediatric disease and Fast Track designations from the U.S. Food and Drug Administration.
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SOURCE REGENXBIO Inc.
Feb. 09, 2022 12:52 PM ET
By: Dulan Lokuwithana, SA News Editor
Announcing initial data from its Phase I/II trial for RGX-111 in severe Mucopolysaccharidosis Type I (MPS I), REGENXBIO (NASDAQ:RGNX) suggested there was systemic and CNS biomarker activity following the gene therapy.
February 7, 2022 at 6:00 PM ESTPDF Version
- Isaralgagene civaparvovec, or ST-920, continued to be generally well tolerated across three dose cohorts in the five treated patients
- In the first two dose cohorts, all four patients exhibited above normal α-Gal A activity, ranging from 3-fold to 15-fold above mean normal; patients in the first dose cohort have maintained elevated activity for one year and are now in the long-term follow-up study
- In the third dose cohort, the fifth patient exhibited activity within mean normal α-Gal A levels at week 2 and the sixth patient was recently dosed
- Lyso-Gb3 levels remain significantly reduced in the patient who exhibited high baseline levels of this biomarker
BRISBANE, Calif.--(BUSINESS WIRE)--Feb. 7, 2022-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced updated preliminary results from the Phase 1/2 STAAR clinical study evaluating isaralgagene civaparvovec, or ST-920, a wholly owned gene therapy product candidate for the treatment of Fabry disease. These latest data show that, as of the November 9, 2021 cutoff date, the investigational treatment continued to be well tolerated and that the four longest treated patients continued to exhibit elevated alpha-galactosidase A (α-Gal A) activity. These data are being presented at the 18th Annual WORLDSymposiumTM in a platform presentation on February 8, 2022 during the 1:30 p.m. Eastern Time session and in a poster presentation available on February 7, 2022 at 6:00 p.m. Eastern Time. These data are available on the Events & Presentations page of Sangamo’s website.
“These updated preliminary results demonstrate the potential of isaralgagene civaparvovec gene therapy to address the most challenging symptoms of Fabry disease with a favorable tolerability and safety profile,” said Jaya Ganesh, MD, at The Icahn School of Medicine at Mount Sinai and investigator of the Phase 1/2 study. “Now with two patients dosed in the third cohort, we are eager to see if the favorable trends exhibited by patients in the first two dose cohorts continue as we follow these patients and learn more about the emerging profile of this potential treatment.”
As of the cutoff date, elevated α-Gal A activity was maintained for the four patients treated in the first two dose cohorts (0.5e13 vg/kg and 1e13 vg/kg) ranging from 3-fold to 15-fold above mean normal at last measurement. For the two patients on enzyme replacement therapy (ERT), α-Gal A activity measured at ERT trough was 15-fold above mean normal at week 52 (Cohort 1) and 10-fold above mean normal at week 25 (Cohort 2). For the two ERT pseudo-naïve patients, α-Gal A activity was 3-fold above mean normal at week 52 (Cohort 1) and 4-fold above mean normal at week 40 (Cohort 2). The two patients in the first dose cohort have now begun the long-term follow-up study. For the first patient in the third dose cohort (3e13 vg/kg), α-Gal A activity has increased into mean normal range at week 2. Withdrawal from ERT has been completed for one patient and is planned for the other patient on ERT, based on the stability of their α-Gal A activity following treatment.
As of the cutoff date, isaralgagene civaparvovec was generally well tolerated across three dose cohorts in the five treated patients. There were no treatment-related adverse events higher than Grade 1 (mild) and no treatment-related serious adverse events. No patients experienced liver enzyme elevations requiring steroid treatment.
About the STAAR Study
The Phase 1/2 STAAR study is a global open-label, single-dose, dose-ranging, multicenter clinical study designed to evaluate the safety and tolerability of isaralgagene civaparvovec, or ST-920, a gene therapy product candidate in patients with Fabry disease. Isaralgagene civaparvovec requires a one-time infusion without preconditioning. The STAAR study is enrolling patients who are on ERT, are ERT pseudo-naïve (defined as having been off ERT for six or more months), or who are ERT-naïve. The age range of the five patients dosed as of the cutoff date is 22 to 48 years. The U.S. Food and Drug Administration has granted Orphan Drug designation to isaralgagene civaparvovec, which has also received Orphan Medicinal Product designation from the European Medicines Agency.
For more information about Sangamo, visit www.sangamo.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220207005059/en/
Source: Sangamo Therapeutics, Inc.
Feb. 08, 2022 6:59 AM ET
Friday, February 04, 2022 - 05:52am
• Dose selection complete for planned Phase 3 trial, expected to be initiated in 3Q2022
• Sub-analysis compared the immunogenicity of VLA15 in adults 18-65 years of age after administration of two or three primary series doses
• Stronger immune response observed in adult participants who received three priming doses vs. two priming doses; pediatric study ongoing with initial data expected in 1H2022
• Three-dose priming schedule selected for use in adults moving forward
Saint-Herblain (France) and New York, February 4, 2022 – Valneva SE (Nasdaq: VALN; Euronext Paris: VLA), a specialty vaccine company, and Pfizer Inc. (NYSE: PFE) today reported further positive Phase 2 data for their Lyme disease vaccine candidate, VLA15. Based on these new results, Valneva and Pfizer plan to proceed with a three-dose primary series vaccination schedule in a planned Phase 3 clinical trial. The trial will evaluate VLA15 in adults and pediatric subjects 5 years of age and above and is expected to be initiated in 2022, subject to regulatory approval.
The Phase 2 trial, VLA15-221, compared the immunogenicity of VLA15 after administration of two (at months 0 and 6) or three (at months 0, 2 and 6) primary series doses in groups aged 5-11, 12-17 and 18-65 years. In the sub-analysis of adult participants (18-65 years old) who received VLA15 in either the two-dose schedule (N=90) or the three-dose schedule (N=97), performed one month after the last vaccination dose, VLA15 was found to be immunogenic with both vaccination schedules tested. These data are consistent with the strong immunogenicity profile observed for this age group in previous Phase 2 studies. However, the induction of anti-OspA IgG (anti-outer surface protein A immunoglobulin G) antibody titers was higher in participants who received the three-dose primary series compared to those who received the two-dose primary series, supporting the use of a three-dose primary series schedule in the planned Phase 3 clinical trial. The VLA15-221 trial is ongoing to assess the safety and immunogenicity of VLA15 in 5-17 year olds. Initial pediatric data are expected in the first half of 2022.
The analysis was also consistent with the acceptable safety and tolerability profile observed in previous studies of VLA15. No vaccine-related serious adverse events (SAEs) were observed.
VLA15 is the only Lyme disease vaccine candidate currently in clinical development. This investigational multivalent protein subunit vaccine uses an established mechanism of action for a Lyme disease vaccine that targets the outer surface protein A (OspA) of Borrelia burgdorferi, the bacteria that cause Lyme disease. OspA is one of the most dominant surface proteins expressed by the bacteria when present in a tick. The vaccine covers the six OspA serotypes expressed by Borrelia burgdorferi sensu lato species that are prevalent in North America and Europe. VLA15 has demonstrated strong immunogenicity and safety data in pre-clinical and clinical studies so far. The program was granted Fast Track designation by the U.S. Food and Drug Administration (FDA) in July 20171. Valneva and Pfizer entered into a collaboration agreement in April 2020 to co-develop VLA15.2
About Clinical Study VLA15-221
VLA15-221 is a randomized, observer-blind, placebo-controlled Phase 2 study. It is the first clinical study with VLA15 that enrolls a pediatric population aged 5 years and older.
294 healthy adult participants received VLA15 at two different immunization schedules (month 0-2-6 [N=97] or month 0-6 [N=90]) or three doses of placebo (month 0-2-6 [N=107]). Vaccine recipients received VLA15 at a dose of 180 µg, which was selected based on data generated in the two previous Phase 2 studies. The main safety and immunogenicity readout in adults was performed at month 7. A subset of participants will receive a booster dose of VLA15 or placebo at month 18 (booster phase) and will be followed for three additional years to monitor antibody persistence. The VLA15-221 trial is ongoing to assess the safety and immunogenicity of VLA15 in a pediatric population aged 5 years and above.
VLA15 is tested as an alum-adjuvanted formulation and administered intramuscularly. The study is conducted at sites located in areas where Lyme disease is endemic and has enrolled volunteers with a cleared past infection with Borrelia burgdorferi as well as Borrelia burgdorferi-naïve volunteers.
Feb. 04, 2022 9:25 AM ET
By: Jonathan Block, SA News Editor
Jan 31, 2022
HOUSTON, Jan. 31, 2022 (GLOBE NEWSWIRE) -- Aravive, Inc. (Nasdaq: ARAV), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, today announced that the Company has dosed the first patient in the Phase 2 portion of the Phase 1b/2 study of batiraxcept for the treatment of clear cell renal cell carcinoma (ccRCC).
“Safety and preliminary activity data from the Phase 1b study of batiraxcept in combination with cabozantinib in patients with 2L+ ccRCC gives us confidence to initiate the Phase 2 portion of the trial and expand the study to additional cohorts,” said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. “I’m grateful to our team for their diligence and dedication to expedite the ccRCC program. The data reported to date shows clinically relevant benefit of adding batiraxcept to the current standard of care in ccRCC without adding to the toxicity profile. We will continue to update the ongoing Phase 1b portion of the study as data mature and anticipate providing clinical activity and safety updates of the P2 portion of the study throughout 2022.”
The Phase 2 portion of the Phase 1b/2 clinical trial of batiraxcept in ccRCC is an open-label study in which 55 patients are anticipated to enroll across three parts. Part A is expected to enroll approximately 25 patients and will investigate batiraxcept 15 mg/kg in combination with cabozantinib in 2L+ ccRCC patients. Part B is expected to enroll approximately 20 patients and evaluate batiraxcept 15 mg/kg in combination with standard of care nivolumab and cabozantinib in first-line ccRCC patients. Part C is expected to evaluate batiraxcept 15 mg/kg monotherapy in approximately 10 patients with ccRCC who are not eligible for curative intent therapies. The primary endpoint of each part of the Phase 2 portion of the trial is objective response rate (“ORR”) and key secondary endpoints include duration of response (“DOR”), progression free survival (“PFS”), and overall survival (“OS”). Additional information on the trials: NCT04300140.
About Batiraxcept (AVB-500)
Batiraxcept is a therapeutic recombinant fusion protein that has been shown to neutralize GAS6 activity by binding to GAS6 with very high affinity in preclinical models. In doing so, batiraxcept selectively inhibits the GAS6-AXL signaling pathway, which is upregulated in multiple cancer types including ovarian, renal and pancreatic. In preclinical studies, GAS6-AXL inhibition has shown anti-tumor activity in combination with a variety of anticancer therapies, including radiation therapy, immuno-oncology agents, and chemotherapeutic drugs that affect DNA replication and repair. Increased expression of AXL and GAS6 in tumors has been correlated with poor prognosis and decreased survival and has been implicated in therapeutic resistance to conventional chemotherapeutics and targeted therapies. Batiraxcept is currently being evaluated in multiple clinical trials and has been granted Fast Track designation by the U.S. Food and Drug Administration and orphan drug designation by the European Commission in platinum resistant recurrent ovarian cancer.
Additional information at www.aravive.com.
Jan. 31, 2022 9:19 AM ET
By: Ravikash, SA News Editor
Vaccinex Reports Two Complete Responses in First Three Patients Enrolled in the Phase 1b/2 KEYNOTE-B84 Study of Pepinemab in Combination with KEYTRUDA (pembrolizumab) in Patients with Recurrent or Metastatic Head and Neck Cancer
ROCHESTER, N.Y., Jan. 26, 2022 (GLOBE NEWSWIRE) -- Vaccinex, Inc. (Nasdaq: VCNX, Vaccinex, the Company), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease through the inhibition of semaphorin 4D (SEMA4D), today reported positive interim response data in the Phase Ib segment of the KEYNOTE-B84 study of Vaccinex’s pepinemab in combination with Merck’s (known as MSD outside of the United States and Canada) anti-PD-1 therapy KEYTRUDA (pembrolizumab) in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).
Among the three patients enrolled in the Phase1b safety segment of the study, two patients have been observed to experience a complete response (CR), as per RECIST v.1.1. Biomarker analysis revealed that tumors in both responders expressed low levels of PD-L1 biomarker (CPS<20), a subset of HNSCC patients who have historically low response rates to anti-PD-1/L1 antibodies administered as single agents.
KEYNOTE-B84 Study (NCT04815720)
The Phase 1b safety observation segment of KEYNOTE-B84 enrolled 3 patients to assess potential Dose Limiting Toxicity (DLT) for pepinemab, Vaccinex’s monoclonal antibody inhibitor of SEMA4D, in combination with KEYTRUDA (pembrolizumab), Merck’s anti-PD-1 therapy (pembrolizumab), in R/M HNSCC. The trial’s Data Safety Monitoring Boarddetermined that the recommended phase 2 dose of pepinemab (20 mg/kg Q3W), in combination with KEYTRUDA (200 mg Q3W), appeared to be well-tolerated. Treatment was continued following the 28-day Safety Observation Period, and, as per protocol, an on-treatment biopsy of a target lesion was obtained at week 5, and scans for tumor response assessments were performed week 9 and every 6-weeks thereafter. Two of these initial three patients have been observed to experience a complete response (CR), as per RECIST v.1.1.
Case Study: #1, Complete Response (Confirmed)
Case Study: #2. Complete Response (pending confirmation by repeat scan)
The third patient in this group who had cancer of the tongue was deemed by investigator to have clinical progression and withdrew from the study at Week 6, which was prior to the first radiologic tumor response assessment at Week 9, and was, therefore, non-evaluable for tumor response. Patient also suffered serious adverse events (SAE) including dehydration and hyperglycemia that were attributed to a pre-existing co-morbidity (diabetes and other complications) unrelated to treatment.
Maurice Zauderer, Ph.D., President and Chief Executive Officer of Vaccinex, remarked, “We believe there is a strong rationale for continued development of pepinemab in combination with KEYTRUDA in HNSCC because these tumors are known to express high levels of SEMA4D and preclinical studies by Vaccinex and others have indicated that SEMA4D induces increased numbers and activity of myeloid suppressor cells that inhibit immune responses. Notably, pepinemab in combination with KEYTRUDA does not include administration of chemotherapy. The KEYNOTE-B84 study is accruing patients in the now open expansion phase which will enroll up to an additional 62 patients in approximately equal groups of patients with CPS <20 and CPS ≥20 across 18 U.S. trial sites. We look forward to sharing further results at a medical conference as the study progresses, with interim analysis around the midpoint of enrollment (2H 2022).”
Vaccinex has global commercial and development rights to pepinemab, and is sponsor of the KEYNOTE-B84 study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc. Kenilworth, NJ, USA. Additional information about the study is available at: clinicaltrials.gov link.
KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA.
Pepinemab is a humanized IgG4 monoclonal antibody that inhibits SEMA4D, which regulates chronic inflammation in the tumor microenvironment. Preclinical and clinical data show that pepinemab promotes infiltration/activation of dendritic cells/ CD8+ T-cells and reverses immunosuppression within the tumor.
Results of a Phase 1b/2 study to evaluate the combination of pepinemab with checkpoint inhibitor, BAVENCIO®, avelumab (Merck KGaA) were presented at ASCO 2020 and were highlighted in the July 2021 publication of Clinical Cancer Research. Vaccinex reported that results of this Phase 1b/2 CLASSICAL-Lung trial showed a 25-33% Overall Response Rate (ORR) for patients with difficult to treat PD-L1 low/negative tumors treated with the combination. The study report also indicated that pepinemab did not increase immune-related toxicities of BAVENCIO but increased penetration of cytotoxic T cells. The publication is available electronically at: Clinical Cancer Research.
Jan. 26, 2022 9:03 AM ET
By: Mamta Mayani, SA News Editor
SAN DIEGO, Jan. 21, 2022 /PRNewswire/ -- Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical-stage targeted oncology company, today announced positive results from a Phase 2 cohort of the KRYSTAL-1 study evaluating adagrasib at the 600mg BID dose in patients with pretreated pancreatic ductal adenocarcinoma and other gastrointestinal (GI) tumors harboring a KRASG12C mutation, including cancers of the biliary tract, appendix, small bowel, gastro-esophageal junction, and esophagus. Results showed that adagrasib demonstrated significant clinical activity and broad disease control. The findings (Abstract # 519) will be presented today at 10:00 a.m. ET during a rapid abstract session at the 2022 American Society for Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium.
Dr. Tanios S. Bekaii-Saab, an investigator of the KRYSTAL-1 study, commented, "Gastrointestinal cancers are some of the most common cancers and continue to be associated with poor survival outcomes despite recent advances, especially in patients with GI tumors harboring a KRASG12C mutation. New clinical data presented at ASCO GI show that adagrasib, an inhibitor of KRASG12C, demonstrated promising clinical activity in patients with pancreatic cancer and other GI tumors. These findings build on the previously reported positive adagrasib clinical data in colorectal and pancreatic cancers, and are highly encouraging, warranting further investigation of adagrasib in this setting."
Summary of Clinical Results
"We believe adagrasib has a differentiated molecular profile, and the data presented at ASCO GI further support its potential best-in-class profile," said Charles M. Baum, M.D., Ph.D., founder, president and head of research and development, Mirati Therapeutics, Inc. "The results demonstrated positive clinical activity in patients with KRASG12C-mutated GI cancers treated with single agent adagrasib, particularly in those with pancreatic cancer where options are limited. We continue to aggressively evaluate adagrasib as a single agent and in combination with other cancer medicines in a broad development plan to help more people living with cancer."
About Adagrasib (MRTX849)
Adagrasib is an investigational, highly selective, and potent oral small-molecule inhibitor of KRASG12C that is optimized to sustain target inhibition, an attribute that could be important to treat KRASG12C-mutated cancers, as the KRASG12C protein regenerates every 24−48 hours. Adagrasib is a being evaluated as monotherapy and in combination with other anti-cancer therapies in patients with advanced KRASG12C-mutated solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer. For more information visit Mirati.com/science.
For more information about Mirati Therapeutics, visit us at Mirati.com or follow us on Twitter and LinkedIn.
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SOURCE Mirati Therapeutics, Inc.
Jan. 21, 2022 11:22 AM ET
By: Ravikash, SA News Editor
Jan 21, 2022
– Vutrisiran Met All 18 Month Secondary Endpoints, Including Statistically Significant Improvements in Neuropathy Impairment, Quality of Life (QoL), Gait Speed, Nutritional Status and Overall Disability, Relative to External Placebo –
– Vutrisiran Continued to Demonstrate Halting or Reversal of Polyneuropathy, with Improvements in Neuropathy Impairment and QoL Relative to Baseline –
– Exploratory Cardiac Data, Including Reduced Technetium Uptake Relative to Baseline in Majority of Assessable Patients, Continue to Support Potential for Vutrisiran to Reduce Cardiac Amyloid Burden and Improve Cardiac Manifestations of Disease –
– In Addition, Vutrisiran Continued to Demonstrate Encouraging Safety and Tolerability Profile –
– Alnylam to Host Conference Call Today at 8:30 am ET –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Jan. 21, 2022-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, announced today that the HELIOS-A Phase 3 study of vutrisiran, an investigational RNAi therapeutic in development for the treatment of transthyretin-mediated (ATTR) amyloidosis, met all secondary endpoints measured at 18 months in patients with hATTR amyloidosis with polyneuropathy, including statistically significant improvements in neuropathy impairment, quality of life (QoL), gait speed, nutritional status and overall disability, relative to placebo, and non-inferiority of serum TTR reduction relative to the within-study patisiran arm. The results were presented today in an oral session at the Société Francophone du Nerf Périphérique (SFNP) Annual Meeting.
In HELIOS-A, patients treated with vutrisiran also showed improvement in exploratory cardiac endpoints including NT-proBNP and echocardiographic parameters relative to placebo, as well as technetium uptake, relative to baseline, in a planned cohort of patients. Vutrisiran also continued to demonstrate an encouraging safety and tolerability profile consistent with the previously reported Month 9 results. Alnylam previously announced that HELIOS-A met its primary and secondary endpoints at 9 months and study results were presented at the 2021 American Academy of Neurology (AAN) Virtual Annual Meeting.
“These HELIOS-A results show that the improvement in neuropathy impairment and quality of life observed with vutrisiran at 9 months is maintained through Month 18, with the treatment effect increasing over time and an encouraging safety profile. Further, we are encouraged by the exploratory cardiac endpoint results, particularly new data indicating that 18 months of vutrisiran treatment resulted in reduced technetium uptake in the heart compared to baseline in the majority of patients who were in a planned cohort, suggesting the potential for amyloid regression. We look forward to seeing data from the APOLLO-B and HELIOS-B studies, which are investigating the potential of patisiran and vutrisiran, respectively, to treat the cardiac manifestations of disease in patients with ATTR amyloidosis with cardiomyopathy,” said Rena N. Denoncourt, Vice President, TTR Franchise Lead. “Vutrisiran is currently under review by multiple regulatory authorities around the world, bringing us a step closer to potentially making this low-dose, once-quarterly, subcutaneously administered treatment option available for patients living with the polyneuropathy of hATTR amyloidosis, and furthering our efforts to build an industry-leading franchise of medicines for the treatment of ATTR amyloidosis.”
HELIOS-A 18-Month Study Results
At 18 months, vutrisiran met all secondary endpoints in HELIOS-A, demonstrating statistically significant improvement in clinical endpoints compared to placebo and non-inferiority in serum TTR reduction compared to the within-study patisiran arm, specifically:
Vutrisiran demonstrated an encouraging safety profile in HELIOS-A at 18 months. There were three study discontinuations (2.5 percent) due to adverse events in the vutrisiran arm by Month 18, one due to a non-fatal event of heart failure and two due to deaths, neither of which was considered related to the study drug. During the 18-month treatment period there were two serious adverse events (SAEs) deemed related to vutrisiran by the study investigator, consisting of dyslipidemia and urinary tract infection. The two deaths and the two related SAEs were previously reported at Month 9.
Treatment emergent adverse events (AEs) occurring in 10 percent or more patients included fall, pain in extremity, diarrhea, peripheral edema, urinary tract infection, arthralgia and dizziness; with the exception of pain in extremity and arthralgia, each of these events occurred at a similar or lower rate as compared with external placebo. Injection site reactions (ISRs) were reported in five patients (4.1 percent) and were all mild and transient. There were no clinically significant changes in liver function tests (LFTs).
To view the data presented by Alnylam at SFNP, please visit, Capella
“The 18-month results of the HELIOS-A Phase 3 study build on the results observed at 9 months and continue to underscore the potential of vutrisiran as an attractive new treatment option that can be administered subcutaneously four times a year,” said David Adams, M.D., Ph.D., Department of Neurology, Bicetre hospital, Greater Paris University Hospitals, AP-HP, University Paris Saclay and Principal Investigator for the HELIOS-A trial. “The data presented today are exciting, demonstrating additional progress from ongoing research focused on meeting the needs of this diverse group of patients living with a progressive, life-threatening, multi-system disease, with a potential new option that may help simplify their treatment.”
Vutrisiran is an investigational, subcutaneously administered RNAi therapeutic in development for the treatment of ATTR amyloidosis, which encompasses both hATTR and wild-type ATTR (wtATTR) amyloidosis. It is designed to target and silence specific messenger RNA, potentially blocking the production of wild-type and variant transthyretin (TTR) protein before it is made. Quarterly, and potentially biannual, administration of vutrisiran may help to reduce deposition and facilitate the clearance of TTR amyloid deposits in tissues and potentially restore function to these tissues. Vutrisiran utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate delivery platform, designed for increased potency and high metabolic stability that may allow for infrequent subcutaneous injections. The safety and efficacy of vutrisiran have not been evaluated by the U.S. Food and Drug Administration, European Medicines Agency, or any other health authority.
About HELIOS-A Phase 3 Study
HELIOS-A (NCT03759379) is a Phase 3 global, randomized, open-label study to evaluate the efficacy and safety of vutrisiran. The study enrolled 164 patients with hATTR amyloidosis with polyneuropathy at 57 sites in 22 countries. Patients were randomized 3:1 to receive either 25mg of vutrisiran (N=122) via subcutaneous injection once every three months or 0.3 mg/kg of patisiran (N=42) via intravenous infusion once every three weeks (as a reference comparator) for 18 months. The efficacy results of vutrisiran in HELIOS-A are compared to the placebo group from the landmark APOLLO Phase 3 study, which evaluated the efficacy and safety of patisiran in a patient population similar to that studied in HELIOS-A. The primary endpoint is the change from baseline in mNIS+7 at 9 months. Secondary endpoints at 9 months are the change from baseline in the Norfolk QoL-DN score and the timed 10-MWT. Changes from baseline in NT-proBNP were evaluated as an exploratory endpoint at 9 months. Additional secondary endpoints at 18 months were evaluated in the HELIOS-A study, including change from baseline in mNIS+7, Norfolk QoL-DN, 10-MWT, modified body mass index (mBMI), Rasch-built Overall Disability Scale (R-ODS), and serum transthyretin (TTR) levels. Additional exploratory cardiac endpoint data at the 18-month time point include NT-proBNP, echocardiographic measures and cardiac amyloid assessments with technetium scintigraphy imaging. Following the 18-month treatment period, all patients are eligible to receive vutrisiran for an additional 18 months as part of the randomized treatment extension where they will receive either 25mg vutrisiran once quarterly or 50mg vutrisiran once every six months.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220121005075/en/
Source: Alnylam Pharmaceuticals, Inc.
Jan. 21, 2022 8:26 AM ET
By: Dulan Lokuwithana, SA News Editor
January 18, 2022PDF Version- DKN-01 plus tislelizumab demonstrated encouraging clinical activity in both first- and second-line advanced gastric or gastroesophageal junction cancer patients
- 10.7 months PFS in overall first-line population; higher 11.9 months PFS in DKK1-high patients
- Company to host conference call on Friday, January 21, 2022 at 1:00 p.m. ET
CAMBRIDGE, Mass., Jan. 18, 2022 /PRNewswire/ -- Leap Therapeutics, Inc. (Nasdaq:LPTX), a biotechnology company focused on developing targeted and immuno-oncology therapeutics, today announced the Company will be presenting updated data from the DisTinGuish study, a Phase 2a clinical trial evaluating Leap's anti-Dickkopf-1 (DKK1) antibody, DKN-01, in combination with tislelizumab, BeiGene's anti-PD-1 antibody, in patients with gastric or gastroesophageal junction cancer (G/GEJ), at the American Society of Clinical Oncology (ASCO) Gastrointestinal (GI) Cancers Symposium being held on January 20-22, 2022.
The Company will host a conference call with Dr. Samuel Klempner of Harvard Medical School and Massachusetts General Hospital on Friday, January 21, 2022 to discuss results from the study.
The latest results from Part A of the DisTinGuish study will be presented, representing first-line advanced G/GEJ patients treated with DKN-01 in combination with tislelizumab and chemotherapy. New data demonstrate compelling efficacy from this combination regimen, driven by enhanced clinical responses and survival benefit associated with high tumoral DKK1 expression that is independent of PD-L1 expression. Also to be presented are initial findings from the still-enrolling Part B of the clinical trial, studying DKN-01 and tislelizumab in second-line advanced G/GEJ patients with high tumoral DKK1 expression, showing the treatment is well tolerated with encouraging objective responses observed.
"The combination of DKN-01 with tislelizumab continues to demonstrate encouraging results in patients with gastric and gastroesophageal junction cancer, especially those in the DKK1-high subpopulation," said Samuel Klempner, MD, Associate Professor at Harvard Medical School who leads the gastric and esophageal cancer program at Massachusetts General Hospital Cancer Center and is a principal investigator on the DisTinGuish study. "The updated front-line results are encouraging in a difficult to treat cohort of primarily PD-L1 low patients, who are less likely to benefit from anti-PD-1 therapy. Together with encouraging initial findings from Part B, where DKN-01 and tislelizumab are used as a chemo-free second-line treatment of DKK1 high-expressing tumors, these results continue to support the therapeutic potential of DKN-01 and warrant exploration in a randomized clinical trial in first-line gastric and gastroesophageal junction patients."
About the DisTinGuish Study
The DisTinGuish study (NCT04363801) is a Phase 2a study of DKN-01 in combination with tislelizumab, an anti-PD-1 antibody, with or without chemotherapy as first-line or second-line therapy in patients with inoperable, locally advanced, G/GEJ adenocarcinoma. The study is being conducted in two parts in the United States and the Republic of Korea. Enrollment of Part A has been completed with 25 first-line HER2- G/GEJ cancer patients whose tumors express either high levels of DKK1 (DKK1-high) or low levels of DKK1 (DKK1-low). Part B of the study has enrolled 30 patients with second-line DKK1-high G/GEJ cancer and will continue to enroll up to 48 patients. Leap is conducting this combination study as part of an exclusive option and license agreement with BeiGene for the development of DKN-01 in Asia (excluding Japan), Australia, and New Zealand.
DKN-01 is a humanized monoclonal antibody that binds to and blocks the activity of the Dickkopf-1 (DKK1) protein. DKK1 modulates the Wnt/Beta-catenin and PI3kinase/AKT signaling pathways and has an important role in promoting tumor proliferation, metastasis, angiogenesis, and in mediating an immune suppressive tumor microenvironment through enhancing the activity of myeloid-derived suppressor cells and downregulating NK cell ligands on tumor cells. The U.S. Food and Drug Administration has granted DKN-01 Orphan Drug Designation for the treatment of gastric and gastroesophageal junction cancer and Fast Track Designation in combination with tislelizumab for the treatment of patients with gastric and gastroesophageal junction adenocarcinoma whose tumors express high DKK1 protein, following disease progression on or after prior fluoropyrimidine- and platinum- containing chemotherapy and if appropriate, human epidermal receptor growth factor (HER2)/neu-targeted therapy.
For more information about Leap Therapeutics, visit http://www.leaptx.com or view our public filings with the SEC that are available via EDGAR at http://www.sec.gov or via https://investors.leaptx.com/.
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SOURCE Leap Therapeutics, Inc.
Jan. 19, 2022 8:35 AM ET
By: Dulan Lokuwithana, SA News Editor
-- SEA-CD40 with Chemotherapy and an Anti-PD-1 Showed Evidence of Immune Activation, Preliminary Antitumor Activity, and an Acceptable Safety Profile --
BOTHELL, Wash.--(BUSINESS WIRE)-- Seagen Inc. (Nasdaq:SGEN) today announced data from a phase 1 clinical trial combining SEA-CD40 with chemotherapy and an anti-PD-1 in patients with metastatic PDAC at the ASCO GI annual meeting taking place in San Francisco, January 20 – 22, 2022. SEA-CD40 is a novel, investigational, nonfucosylated monoclonal receptor-agonistic antibody directed to CD40, which is expressed on antigen-presenting cells. In preclinical models, the combination of SEA-CD40 and chemotherapy resulted in antitumor activity which is further enhanced with anti-PD-1 treatment.
In the ongoing phase 1 trial, SEA-CD40 was combined with chemotherapy [gemcitabine and nab-paclitaxel (GnP)], and an anti-PD-1 (pembrolizumab), in 61 patients with untreated metastatic PDAC. Of these, 40 patients received 10 mcg/kg and 21 patients received 30 mcg/kg of SEA-CD40. Key endpoints include confirmed objective response rate (cORR) per RECIST v1.1 by investigator, progression-free survival (PFS) and overall survival (OS).
Activity of SEA-CD40 in combination with GnP and pembrolizumab was observed in both doses of SEA-CD40 tested. The overall (N = 61) cORR was 44 percent, median PFS was 7.4 months (95 percent CI: 5.6-9.0), and median OS was 15.0 months (95 percent CI: 7.8-19.9).
Follow-up for efficacy is ongoing.
The regimen demonstrated a manageable and tolerable safety profile. Overall, ≥ grade 3 treatment-emergent adverse events (TEAEs) were fatigue, nausea, neutropenia, infusion-related reaction, chills, diarrhea, and pyrexia.
This combination also showed evidence of immune activation consistent with the SEA-CD40 mechanism of action.
“Preliminary activity is encouraging based on historical chemotherapy outcomes. Further survival follow up is required to inform our next steps in pancreatic cancer,” said Roger Dansey, M.D., Chief Medical Officer at Seagen. “We are continuing to advance the ongoing phase 2 trial of SEA-CD40 in melanoma and in non-small cell lung cancer.”
View source version on businesswire.com: https://www.businesswire.com/news/home/20220118006157/en/
Source: Seagen Inc.
Jan. 18, 2022 5:41 PM ET
Trial Reaches Milestone of Over 1000 Patients Screened
Addition of New Interventions – Biohaven Pharmaceuticals’ Troriluzole and Vigeo Therapeutics’ VT1021
Planned Expansion of Trial to Include Sites in Europe and China
January 18, 2022 04:15 PM Eastern Standard Time
LOS ANGELES--(BUSINESS WIRE)--Global Coalition for Adaptive Research (GCAR) today announced an update on the progress of GBM AGILE (Glioblastoma Adaptive Global Innovative Learning Environment - NCT03970447). GBM AGILE is a revolutionary patient-centered, adaptive platform trial for registration that tests multiple therapies for patients with newly-diagnosed and recurrent glioblastoma (GBM) – the deadliest form of brain cancer.
GBM AGILE is an international, innovative platform trial designed to more rapidly identify and confirm effective therapies for patients with glioblastoma through response adaptive randomization and a seamless phase 2/3 design. The trial, conceived by over 130 key opinion leaders, is conducted under a master protocol, allowing multiple therapies or combinations of therapies from different pharmaceutical partners to be evaluated simultaneously. With its innovative design and efficient operational infrastructure, data from GBM AGILE can be used as the foundation for a new drug application (NDA) and biologics license application (BLA) submissions and registrations to the FDA and other health authorities.
Biohaven’s troriluzole is a novel, orally administered small molecule that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. Troriluzole is thought to restore glutamate homeostasis by enhancing glutamate cycling, decreasing presynaptic glutamate release, and augmenting the expression and function of excitatory amino acid transporters (i.e., EAAT2) located on glial cells that play a key role in clearing excess glutamate from the synapse. Troriluzole was selected for inclusion in GBM AGILE, based on compelling evidence showing deregulation of glutamate in glioblastoma. The therapeutic potential of troriluzole in glioblastoma and other oncology indications is supported by several recent clinical and translational research studies conducted with troriluzole and its active moiety.
About Global Coalition for Adaptive Research (GCAR)
The Global Coalition for Adaptive Research (GCAR) is a 501(c)(3) nonprofit organization uniting physicians, clinical researchers, advocacy and philanthropic organizations, biopharma, health authorities, and other key stakeholders in healthcare to expedite the discovery and development of treatments for patients with rare and deadly diseases by serving as sponsor of innovative and complex trials including master protocols and platform trials. GCAR is the sponsor of GBM AGILE, an adaptive platform trial for patients with GBM – the most common and deadliest of malignant primary brain tumors. Key strategic partners for the GBM AGILE trial effort include the National Brain Tumor Society, National Foundation for Cancer Research, and Asian Fund for Cancer Research, three nonprofit organizations that are working together to provide philanthropic support as well as assistance in communicating with patients and families and inviting all others to join in supporting this innovating approach to brain tumor treatment development.
Jan. 18, 2022 4:46 PM ET
By: Dulan Lokuwithana, SA News Editor
January 10, 2022
FOSTER CITY, Calif.--(BUSINESS WIRE)-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced it has entered into two clinical trial collaboration and supply agreements with Merck (known as MSD outside of the United States and Canada) to evaluate the combination of Gilead’s Trop-2 targeting antibody-drug conjugate (ADC) Trodelvy® (sacituzumab govitecan-hziy) and Merck’s anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in first-line metastatic non-small cell lung cancer (NSCLC). As part of the collaboration, Merck will sponsor a global Phase 3 clinical trial of Trodelvy in combination with KEYTRUDA as a first-line treatment for patients with metastatic NSCLC. Additionally, the companies recently established an agreement whereby Gilead will sponsor a Phase 2 signal-seeking study evaluating combinations that include pembrolizumab in first-line NSCLC.
“We’re excited to broaden our clinical collaborations with Merck to investigate Trodelvy in combination with KEYTRUDA in another cancer where there is tremendous need for novel combinations to help improve patient outcomes,” said Merdad Parsey, MD, PhD, Chief Medical Officer, Gilead Sciences. “This partnership builds on our ambition of providing alternatives to traditional chemotherapy with Trodelvy containing regimens across some of the most difficult-to-treat cancers.”
NSCLC is the most common type of lung cancer and accounts for up to 85% of cases. It is an aggressive disease with poor prognosis. Although there has been significant progress in recent years in the treatment of the disease, there is a still a major unmet need for patients with only 25% of patients surviving beyond five years.
Trodelvy is an antibody-drug conjugate that specifically targets Trop-2 expressing cells to enable local delivery of a cytotoxic payload that selectively kills the targeted cells. The combination of Trodelvy with an immune-stimulating agent such as KEYTRUDA could provide a new treatment option for a broader set of patients with first-line metastatic NSCLC.
The use of Trodelvy for the treatment of NSCLC is investigational, and the safety and efficacy for this use have not been established or approved by any regulatory agency globally. In the United States, Trodelvy is approved for the treatment of second-line metastatic triple-negative breast cancer (TNBC),and has additionally been approved under the accelerated approval pathway for the treatment of metastatic urothelial cancer (UC) in adults who have received certain prior therapies. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; please see below for additional Important Safety Information for Trodelvy.
Everest Medicines will also participate in the global Phase 3 study in Asia through its existing collaboration agreement with Gilead.
These agreements follow a collaboration, established in October 2021, to investigate Trodelvy in combination with KEYTRUDA as first-line treatment for people with locally advanced or metastatic triple-negative breast cancer (TNBC).
The use of Trodelvy for the treatment of NSCLC and the use of Trodelvy in combination with KEYTRUDA for any use is investigational, and the safety and efficacy for these uses have not been established or approved by regulatory agency globally.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
About Non-Small Cell Lung Cancer (NSCLC)
Lung cancer (including both NSCLC and small-cell lung cancer (SCLC)) is the second most common cancer in both men and women and is the leading cause of cancer death, making up approximately 25% of all cancer deaths. NSCLC is the most common type of lung cancer and accounts for up to 85% of cases. It is an aggressive disease with poor prognosis, and the relative five-year survival rate is 25%.
Trodelvy is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein overexpressed in multiple types of epithelial tumors, including metastatic TNBC and metastatic urothelial cancer (UC), where high expression is associated with poor survival and relapse. Trodelvy is approved for adults with second-line metastatic TNBC in the United States, the European Union, Australia, Canada, Great Britain and Switzerland. Trodelvy is also under multiple regulatory reviews worldwide, including in Singapore and China through our partner Everest Medicines. Trodelvy continues to be developed for potential use in other TNBC and metastatic UC populations and is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.
U.S. Indication for Trodelvy
In the United States, Trodelvy is indicated for the treatment of:
Please see full Prescribing Information , including BOXED WARNING.
U.S. Prescribing Information for Trodelvy including BOXED WARNING, is available at www.gilead.com.
Trodelvy, Gilead and the Gilead logo are trademarks of Gilead Sciences, Inc., or its related companies.
For more information about Gilead, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.
View source version on businesswire.com: https://www.businesswire.com/news/home/20220107005485/en/
Source: Gilead Sciences, Inc.
Jan. 10, 2022 8:30 AM ET
RESEARCH TRIANGLE PARK, N.C., Jan. 07, 2022 (GLOBE NEWSWIRE) -- BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced the enrollment of the first patient in the REDEEM-1 pivotal trial with its oral Factor D inhibitor, BCX9930, in patients with paroxysmal nocturnal hemoglobinuria (PNH).
REDEEM-1 is a randomized, open-label, active comparator-controlled comparison of the efficacy and safety of BCX9930 (500 mg bid) monotherapy in approximately 81 PNH patients with an inadequate response to a C5 inhibitor. In part 1 of this trial, patients who have not had an adequate response to a C5 inhibitor will be randomized 2:1 to discontinue their C5 inhibitor and receive BCX9930 as monotherapy or to continue receiving their C5 inhibitor for 24 weeks. All patients will receive BCX9930 in part 2 (weeks 25-52) to assess the long-term safety, tolerability and effectiveness of BCX9930. Patients who are randomized to C5 inhibitor therapy in part 1 will discontinue that therapy at the week 24 visit and start BCX9930 for part 2. The primary endpoint of REDEEM-1 is change from baseline in hemoglobin, as assessed at weeks 12 to 24.
“On the heels of recently beginning enrollment in our REDEEM-2 pivotal trial, today’s announcement marks another important milestone as we advance BCX9930 closer to registration for patients living with PNH,” said Dr. William Sheridan, chief medical officer of BioCryst. “Given the unmet need patients have related to the current standard of care, we aim to demonstrate in the REDEEM-1 pivotal trial the potential of BCX9930 as an oral monotherapy that could represent significant improvement for patients compared to their experiences with C5 inhibitor therapies.”
In a dose-ranging trial of BCX9930 in C5 inadequate response patients, the company previously reported that BCX9930 (at doses of 400 mg or 500 mg bid) increased hemoglobin from baseline by a mean of 2.7 g/dL through weeks 12 to 24 with 80 percent of patients being transfusion-free over the same period. BCX9930 was safe and generally well-tolerated in the trial.
BioCryst recently announced it had begun enrolling patients in the REDEEM-2 pivotal trial, a randomized, placebo-controlled trial to evaluate the efficacy and safety of BCX9930 (500 mg bid) as monotherapy versus placebo in approximately 57 PNH patients not currently receiving complement inhibitor therapy. Additionally, the company is initiating a proof-of-concept trial of BCX9930 in renal complement-mediated diseases including C3 glomerulopathy (C3G), IgA nephropathy (IgAN) and primary membranous nephropathy (PMN).
The U.S. Food and Drug Administration has granted both Fast Track status and Orphan Drug Designation to BCX9930 for PNH. For more information about REDEEM-1, visit ClinicalTrials.gov and search NCT number NCT05116774.
For more information, please visit the company’s website at www.biocryst.com.
Dusquetide Demonstrates Positive Anti-tumor Efficacy in Multiple Nonclinical Animal StudiesComplementary treatment with chemotherapy, radiation and targeted therapy supports development as potential anti-cancer agent
PRINCETON, N.J., Jan. 4, 2022 /PRNewswire/ -- Soligenix, Inc. (Nasdaq: SNGX) (Soligenix or the Company), a late-stage biopharmaceutical company focused on developing and commercializing products to treat rare diseases where there is an unmet medical need, announced today that dusquetide is effective at reducing tumor size in nonclinical xenograft models. Recent studies, recapitulating results from previously published studies, have confirmed the efficacy of dusquetide as a stand-alone and combination anti-tumor therapy, with radiation, chemotherapy and targeted therapy, in the context of the MCF-7 breast cancer cell line. Dusquetide previously demonstrated benefits in reducing the duration of severe oral mucositis (SOM) in a Phase 2 clinical trial and reduction in SOM rates in the per protocol population in a Phase 3 study. In addition to the reduction of severe oral mucositis, an acceleration in the clearance of tumor response and an increase in overall survival were also observed in the Phase 2 clinical study as an ancillary benefit to treating oral mucositis in patients receiving chemo-radiation for their head and neck cancer (HNC).
Based on the biological proof of principle shown both nonclinically and clinically with dusquetide, a novel synthetic peptide that modulates the body's innate immune system, Soligenix continues to explore product opportunities, both in the reduction of oral mucositis in HNC and as a potential anti-cancer treatment. Dusquetide binds to p62 or SQSTM-1, a scaffold protein implicated in a number of intracellular signaling networks implicated in tumor cell survival, including autophagy. The role of p62 is best characterized in multiple myeloma and breast cancer. All variants of breast cancer, including metastatic breast cancer, estrogen receptor positive (ER+), human epidermal growth factor receptor 2 high expressing (HER2+) and triple negative expressing cell lines, have demonstrated a significant role for p62 in tumorigenesis.
The MCF-7 cell line tested in the xenograft studies with dusquetide is both ER+ and responsive to anti-HER2 treatment. Treatment with dusquetide was effective not only as a stand-alone treatment (p<0.01 for tumor size), but also in conjunction with radiation (p<0.05 vs radiation only for survival), chemotherapy (paclitaxel) and targeted treatment (trastuzumab; p<0.001 vs. placebo only for tumor size), reducing tumor size and enhancing overall survival. Other tumor types also have been shown to be dependent on p62 expression, including multiple myeloma, liver cancer (hepatocellular carcinoma), lung cancer (non-small cell lung cancer, EGFR-TKI-resistant lung cancer), intestinal cancer (small intestinal adenocarcinoma and gastric cancer), and colorectal cancer and ovarian cancer (multi-drug resistant).
"Soligenix continues to pursue potential product opportunities with our new chemical entity dusquetide, including in oncology," stated Christopher J. Schaber, PhD, President and Chief Executive Officer of Soligenix. "With the supportive data from the Phase 2 and 3 oral mucositis trials, and the nonclinical anti-tumor efficacy demonstrated, we continue to pursue potential partnership for this novel molecule."
Dusquetide (the active ingredient in SGX942) is an innate defense regulator (IDR), a new class of short, synthetic peptides. It has a novel mechanism of action whereby it modulates the body's reaction to both injury and infection towards an anti-inflammatory, anti-infective and tissue healing response. IDRs have no direct antibiotic activity but, by modulating the host's innate immune system responses, increase survival after infections caused by a broad range of bacterial Gram-negative and Gram-positive pathogens. It also accelerates resolution of tissue damage following exposure to a variety of agents including bacterial pathogens, trauma and chemo- and/or radiation therapy. Preclinical efficacy and safety has been demonstrated in numerous animal disease models including mucositis, colitis, macrophage activation syndrome (MAS) as well as bacterial infections, including melioidosis. Potential anti-tumor activity has been demonstrated in in vitro and in vivo xenograft studies.
SGX942 has demonstrated safety and tolerability in a Phase 1 clinical study in 84 healthy human volunteers. Positive efficacy results were demonstrated in an exploratory Phase 2 clinical study (Study IDR-OM-01) in 111 patients with oral mucositis due to CRT for HNC, including potential long term ancillary benefits. The Phase 3 multinational, placebo-controlled, randomized study evaluated the impact of dusquetide on the duration of SOM in 268 subjects with squamous cell carcinoma of the oral cavity and oropharynx, scheduled to receive a minimum total cumulative radiation dose of 55 Gy with concomitant cisplatin chemotherapy. A clinically meaningful reduction in the duration of SOM was observed in the ITT population and a clinically and statistically significant reduction was observed in the per protocol population.
SGX942 has received Fast Track Designation from the FDA for the treatment of oral mucositis as a result of radiation and/or chemotherapy treatment in HNC patients, as well as Promising Innovative Medicine designation in the United Kingdom by the Medicines and Healthcare products Regulatory Agency for the treatment of severe oral mucositis in HNC patients receiving CRT. In addition, products containing the same active ingredient, dusquetide, have been granted Fast Track Designation as an adjunctive therapy with other antibacterial drugs, for the treatment of melioidosis and Orphan Drug Designations in the treatment of MAS and the treatment of acute radiation syndrome.
Soligenix has a strong intellectual property position in the IDR technology platform, including composition of matter for dusquetide and related analogs. Dusquetide was developed pursuant to discoveries made by Professors B. Brett Finlay, PhD and Robert Hancock, PhD of the University of British Columbia, Canada. Soligenix has received partial funding from NIH for its oral mucositis clinical studies. The Phase 2 study was supported with a Phase I SBIR grant (#R43DE024032) award, with the Phase 3 study being supported by a Phase II SBIR grant (#R44DE024032) award.
In addition, a high level review of the IDR technology platform is available here.
Jan. 04, 2022 8:06 AM ET
By: Dulan Lokuwithana, SA News Editor
Vaccinex Reports Phase Ib KEYNOTE B84 Combination Study of Keytruda® and Pepinemab in Patients with Advanced, Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) Passes Planned Interim Safety Analysis
Phase 1b segment evaluated safety and tolerability of the combination
Paves the way to expand and accelerate enrollment in the Phase 2 segment of the study
ROCHESTER, N.Y., Jan. 04, 2022 (GLOBE NEWSWIRE) -- Vaccinex, Inc. (Nasdaq: VCNX, Vaccinex, the Company), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and neurodegenerative disease through the inhibition of SEMA4D, today reported positive interim safety data in the Phase Ib “safety run-in” segment of the KEYNOTE B84 combination study of Keytruda® (Merck, NYSE: MRK, known as MSD outside of the United States and Canada) and pepinemab (Vaccinex) in patients with advanced, recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The Phase 2 segment of the study is now expected to begin enrollment and is expected to accelerate patient accrual.
The Phase Ib “safety run-in” segment of the trial (NCT04815720) was intended to evaluate the safety and tolerability of pepinemab (20 mg/kg) in combination with Keytruda (Merck’s anti-PD-1 therapy, pembrolizumab, 200 mg Q3W/every three weeks) to determine a recommended Phase 2 dose (RP2D) for the dose expansion phase of the study enrolling patients with R/M HNSCC. The interim safety analysis was completed by the Data Safety Monitoring Board and signals initiation of the Phase 2 expansion segment.
“We are very pleased that the interim KEYNOTE B84 safety data indicated that the combination of pepinemab and Keytruda appears to be well tolerated,” stated Maurice Zauderer, Ph.D., President and Chief Executive Officer. “Vaccinex hopes that the combination of pepinemab and an anti-PD-1 therapy for the treatment of advanced R/M HSNCC may result in improved patient benefits. There is strong rationale for development in HNSCC because these tumors express very high levels of SEMA4D and we believe that preclinical data indicated that this contributes to disease pathology. We look forward to progressing with the recruitment of the Phase 2 segment of the trial.”
About the KEYNOTE B84 Study:
The KEYNOTE B84 combination study of Keytruda® (Merck’s anti-PD-1 therapy, pembrolizumab) and pepinemab (Vaccinex’s monoclonal antibody inhibitor of SEMA4D) is being conducted for first line treatment of patients with advanced, recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study has two segments:
Secondary objectives of the study are to evaluate Progression-Free Survival (PFS) by RECIST 1.1, Overall Survival (OS), and Duration of Response (DOR).
The study is also expected to evaluate a number of exploratory measures including the pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of the combination and a number of biomarkers and genomic tumor signatures.
Additional information about the study is available at: the KEYNOTE B84 clinicaltrials.gov link. Vaccinex anticipates interim results for the primary efficacy endpoint, ORR, in the second half of 2022.
Vaccinex will sponsor the study which is being performed in collaboration with Merck Sharp & Dohme Corp, a subsidiary of Merck and Co, Inc.
Vaccinex has global commercial and development rights to pepinemab.
Keytruda® is a trademark of Merck.
Pepinemab is a humanized IgG4 monoclonal antibody that inhibits SEMA4D, which regulates chronic inflammation in the tumor microenvironment. Preclinical/clinical data show that pepinemab promotes infiltration/activation of dendritic cells/ CD8+ T-cells and reverses immunosuppression within the tumor.
Results of a Phase 1b/2 study to evaluate the combination of pepinemab with checkpoint inhibitor, BAVENCIO®, (with Merck KGaA) were presented by Dr. Shafique, MD, Assistant Professor Thoracic Oncology, Moffitt Cancer Center, in an oral poster and discussion section at ASCO 2020 and were highlighted in the July 2021 publication of Clinical Cancer Research. Vaccinex reported that results of the Phase 1b/2 CLASSICAL-Lung trial showed a 25-33% Overall Response Rate (ORR) for patients with difficult to treat PD-L1 low/negative tumors treated with the combination, while reported ORR for similar patients treated with anti-PD-L1 monotherapy is ~10-15%. The study report also indicated that pepinemab did not increase immune-related toxicities of BAVENCIO but increased penetration of cytotoxic T cells. The publication is available electronically at: Clinical Cancer Research.
Jan. 04, 2022 9:18 AM ET
By: Mamta Mayani, SA News Editor
Suzhou, China, January, 3, 2022 - CStone Pharmaceuticals (“CStone”, HKEX: 2616), a leading biopharmaceutical company focused on the research, development, and commercialization of innovative immuno-oncology therapies and precision medicines, today announced that the investigational new drug (IND) application of CS5001, a potential global best-in-class antibody-drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1) has received a STUDY MAY PROCEED (SMP) letter from the U.S. Food and Drug Administration (FDA). CS5001 will commence in the clinic as one of the three most advanced ROR1 ADCs globally, marking another important milestone for CStone’s Pipeline 2.0 strategy.
ROR1 is an oncofetal protein with low or no expression in adult tissues but high expression in a variety of cancers including various forms of leukemia and non-Hodgkin lymphoma, breast, lung, and ovarian cancers, making it an ideal ADC target. CS5001 is an ADC targeting ROR1 with multiple differentiated features including proprietary site-specific conjugation, tumor-selective cleavable linker and pro-drug technology. Results from pre-clinical studies showed that CS5001 exhibited potent and selective cytotoxicity to a variety of ROR1-expressing cancer cell lines and demonstrated remarkable in vivo antitumor activity in both hematological and solid tumor xenograft models.
Dr. Archie Tse, Chief Scientific Officer of CStone, said, “We are glad that the IND application of CS5001 received the SMP letter from the U.S. FDA in 2021. The preclinical pharmacology data were encouraging and demonstrated CS5001’s therapeutic potential in multiple hematological and solid malignancies. There are only three ROR1 ADCs including CS5001 in clinical development. The upcoming first-in-human Phase I study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity of CS5001 in advanced B cell lymphomas and solid tumors. We will make every effort to advance this clinical trial of CS5001, meanwhile we have already submitted the CTN application in Australia and plan to submit the IND application in China soon.”
About CS5001（ROR1 ADC）
In October 2020, CStone signed a licensing agreement with LegoChem Biosciences, Inc. (LCB) for the development and commercialization of CS5001 which was originally generated by collaboration of LCB and ABL Bio, both South Korea-based leading biotech companies. Under the agreement, CStone obtains the exclusive global right to lead development and commercialization of CS5001 outside the Republic of Korea.
CS5001 is now a clinical-stage antibody-drug conjugate (ADC) targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1). CS5001 has uniquely designed and LCB’s proprietary tumor-cleavable linker and pyrrolobenzodiazepine (PBD) prodrug. Only after reaching the tumor, the linker and prodrug are cleaved to release the PBD toxin, resulting in lethal DNA cross-links in cancer cells. The use of the linker plus PBD prodrug effectively helps addressing the toxicity problem associated with traditional PBD payloads, leading to a better safety profile. Additionally, CS5001 utilizes site-specific conjugation for a precise drug antibody ratio of 2 which enables homogeneous production and large-scale manufacturing.
For more information about CStone, please visit: www.cstonepharma.com.
Janssen Submits Biologics License Application to U.S. FDA Seeking Approval of Teclistamab for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma
RARITAN, N.J., December 29, 2021 – The Janssen Pharmaceutical Companies of Johnson & Johnson announced today the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of teclistamab for the treatment of patients with relapsed or refractory (R/R) multiple myeloma. Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both B-cell maturation antigen (BCMA) and CD3.
“Despite all the gains that have been made in treating multiple myeloma, the unmet need still remains very high. Our relentless pursuit of treatments for this disease continues with the same sense of urgency that we have always had,” said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. “We look forward to working with the FDA in their review of our teclistamab submission.”
The BLA submission for teclistamab is supported by data from MajesTEC-1 (NCT04557098, NCT03145181), an open-label, multicenter clinical trial evaluating the safety and efficacy of teclistamab in adults with R/R multiple myeloma. In the study, investigators assessed efficacy outcomes, including overall response rate, very good partial response and complete response using International Myeloma Working Group (IMWG) criteria, as well as the safety profile of teclistamab. Updated MajesTEC-1 data were recently presented at the American Society of Hematology annual meeting.
“The deep expertise, creativity and persistence of the entire Janssen R&D organization enabled the expeditious advancement of teclistamab for multiple myeloma,” said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. “Today’s submission is another important step in our commitment to bring to patients truly transformational medicines that profoundly impact their health.”
Multiple myeloma is an incurable blood cancer that affects white blood cells called plasma cells, which are found in the bone marrow and normally make antibodies which fight infection., When these plasma cells become malignant and develop into multiple myeloma, these myeloma cells proliferate and replace normal cells in the bone marrow. In 2021, it is estimated that nearly 35,000 people will be diagnosed and more than 12,000 will die from this disease in the U.S. While some patients with multiple myeloma initially have no symptoms, many patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels, kidney problems or infections.
Teclistamab is an investigational, off-the-shelf, T-cell redirecting, bispecific antibody targeting both BCMA (B-cell maturation antigen) and CD3, the T-cell receptor. BCMA is expressed at high levels on multiple myeloma cells.,,,, Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells.8
Teclistamab is currently being evaluated in several monotherapy and combination studies. In 2020, the European Commission and the U.S. FDA each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the U.S. FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimize drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need. The U.S. FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.
Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenUS and www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC is one of the Janssen Pharmaceutical Companies of Johnson & Johnson.
Dec. 29, 2021 8:29 AM ET
By: Dulan Lokuwithana, SA News Editor
SHANGHAI, China, and GAITHERSBURG, MD, December 27, 2021 - I-Mab (the “Company”) (Nasdaq: IMAB), a clinical-stage biopharmaceutical company committed to the discovery, development, and commercialization of novel biologics, announced that the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) has approved I-Mab’s IND submission for the initiation of a phase 2 trial in China for enoblituzumab (also known as TJ271) in combination with pembrolizumab (Keytruda®) in patients with solid tumors, including non-small cell lung cancer (NSCLC), urothelial carcinoma (UC), and other selected cancers. I-Mab has acquired exclusive rights to develop and commercialize enoblituzumab in Greater China from MacroGenics (Nasdaq: MGNX).
Enoblituzumab is a highly differentiated humanized monoclonal antibody directed against the immune regulator B7-H3, which plays a key role in regulating immune response against cancers and is widely expressed in multiple cancers. The presence of B7-H3 in tumors is associated with the poor efficacy of neoadjuvant therapies. Enoblituzumab enhances the antibody-dependent killing of cancer cells and has demonstrated strong anti-tumor activity in preclinical studies. Additional preclinical data generated by I-Mab and preliminary clinical evidence from MacroGenics support increased efficacy for the combination of enoblituzumab and a PD-1 antibody against cancers.
The phase 2 clinical trial in China will evaluate the efficacy of the combination of enoblituzumab and pembrolizumab. The trial is designed as a "basket" clinical trial in patients with NSCLC, UC, and other selected cancer types based on previous studies conducted by MacroGenics. These previous studies have indicated that combination therapy resulted in anti-tumor activity in recurrent or metastatic NSCLC and squamous cell carcinoma of the head and neck (SCCHN).
"The initiation of the phase 2 clinical trial will accelerate the clinical development of enoblituzumab in China," said Dr. Andrew Zhu, President of I-Mab. "Enoblituzumab has become a key player against various advanced cancers and one of the Company’s core clinical assets. We are excited about the initiation of this clinical study and expect to bring this valuable compound to cancer patients with critical unmet medical needs."
Currently, MacroGenics is conducting a phase 2 study of enoblituzumab in combination with retifanlimab (PD-1 antibody) or tebotelimab (PD-1 & LAG-3 bispecific DART® molecule) for first-line treatment of patients with recurrent or metastatic SCCHN.
Enoblituzumab is an investigational Fc-optimized monoclonal antibody that targets B7-H3, a member of the B7 family of immune regulator proteins. B7-H3 is widely expressed by many different tumor types and may play a key role in regulating the immune response to various types of cancer. Enoblituzumab has been or is currently being evaluated in clinical trials as a monotherapy or in combination with anti-PD-1-based therapies in patients with B7-H3-expressing cancers. I-Mab acquired the development and commercial rights from MacroGenics for Greater China.
Patritumab Deruxtecan Granted U.S. FDA Breakthrough Therapy Designation in Patients with Metastatic EGFR-Mutated Non-Small Cell Lung Cancer • First Breakthrough Therapy Designation for patritumab deruxtecan based on results of phase 1 trial • Seventh Breakthrough Therapy Designation granted by FDA across Daiichi Sankyo’s oncology portfolio Tokyo, Munich and Basking Ridge, NJ – (December 23, 2021) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation (BTD) to patritumab deruxtecan (HER3-DXd), a potential first-in-class HER3 directed antibody drug conjugate (ADC), for the treatment of patients with metastatic or locally advanced EGFR-mutated non-small cell lung cancer (NSCLC) with disease progression on or after treatment with a third-generation tyrosine kinase inhibitor (TKI) and platinum-based therapies. Lung cancer is the second most common cancer and the leading cause of cancer-related mortality worldwide, with 80% to 85% classified as NSCLC. 1,2,3 While the efficacy of targeted therapy with EGFR TKIs is wellestablished in the treatment of advanced EGFR-mutated NSCLC, which comprises approximately 30% of patients, the development of a broad range of resistance mechanisms commonly leads to disease progression. 4,5,6 After failure of an EGFR TKI, platinum-based chemotherapy haslimited efficacy with progression-free survival (PFS) of approximately 4.4 to 6.4 months. 7 Subsequent salvage therapies after EGFR TKI and platinum-based chemotherapy have PFS of 2.8 to 3.2 months. 8 The U.S. FDA’s BTD is designed to accelerate the development and regulatory review of potential new medicines that are intended to treat a serious condition and address a significant unmet medical need. The new medicine needs to have shown encouraging preliminary clinical results that demonstrate substantial improvement on a clinically significant endpoint over available medicines. The FDA granted the BTD based on data from the dose escalation portion and two expansion cohorts of a three-cohort phase 1 study of patritumab deruxtecan (cohorts 1 and 3a). Extended follow-up data from the dose escalation portion and dose expansion cohort 1 of the study were recently presented at the 2021 American Society of Clinical Oncology (ASCO) annual meeting and published in Cancer Discovery. This is the first BTD for patritumab deruxtecan and the seventh BTD across Daiichi Sankyo’s oncology portfolio. 2 “The Breakthrough Therapy Designation for patritumab deruxtecan acknowledges the need for new treatment approaches to overcome resistance and improve survival in patients with metastatic TKI-resistant, EGFR-mutated non-small cell lung cancer,” said Ken Takeshita, MD, Global Head, R&D, Daiichi Sankyo. “We are proud that the FDA has once again recognized our innovative science and technology and we look forward to bringing this potential first-in-class HER3 directed antibody drug conjugate to patients with this specific type of lung cancer as quickly as possible.”
The primary objective of the dose expansion part of the study is to assess efficacy of patritumab deruxtecan as measured by confirmed objective response rate (ORR) assessed by blinded independent central review. Secondary study endpoints include investigator-assessed ORR, safety and pharmacokinetics. The study enrolled patients at multiple sites in Asia, Europe and North America. For more information, visit ClinicalTrials.gov. About Patritumab Deruxtecan Patritumab deruxtecan (HER3-DXd) is one of three lead DXd ADCsin the oncology pipeline of Daiichi Sankyo. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, patritumab deruxtecan is comprised of a fully human anti-HER3 IgG1 monoclonal antibody attached to a topoisomerase I inhibitor payload (an exatecan derivative, DXd) via a stable tetrapeptide-based cleavable linker. Patritumab deruxtecan is currently being evaluated in a comprehensive development program across multiple cancers as both a monotherapy and in combination with other anticancer treatments. The development program includes HERTHENA-Lung01, a pivotal phase 2 study in patients with locally advanced or metastatic EGFR-mutated NSCLC previously treated with a TKI and platinum-based chemotherapy; a phase 1/2 study in HER3 expressing metastatic breast cancer; a phase 1 study in combination with osimertinib in locally advanced/metastatic EGFR-mutated NSCLC; and, a phase 1 study in previously treated patients with metastatic or unresectable NSCLC. 4 Patritumab deruxtecan is an investigational medicine that has not been approved for any indication in any country. Safety and efficacy have not been established.
For more information, please visit www.daiichisankyo.com.
DESTINY-Lung04 Phase 3 Trial of ENHERTU® Initiated in Patients with Previously Untreated HER2 Mutant Metastatic Non-Small Cell Lung Cancer Tokyo, Munich and Basking Ridge, NJ – (December 23, 2021) – Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced that the first patient was dosed in the global DESTINY-Lung04 phase 3 trial evaluating the efficacy and safety of ENHERTU® (trastuzumab deruxtecan), a HER2 directed antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN), as a first-line treatment in patients with HER2 mutant unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC). DESTINY-Lung04 is the first head-to-head trial in NSCLC evaluating ENHERTU as a first-line treatment compared to the standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation. Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths globally, with 80% to 85% classified as NSCLC. 1,2,3 There are currently no medicines approved specifically for the treatment of HER2 mutant NSCLC, which affects approximately 2% to 4% of patients with non-squamous NSCLC.4,5 Current standard of care in the first-line metastatic setting of patients with HER2 mutant NSCLC is PD-1 or PD-L1 immunotherapy with or without platinum-based chemotherapy.6 While these treatment regimens can improve survival in NSCLC, approximately 40% to 60% of tumors do not respond to initial treatment and disease progression occurs, underscoring the need for additional treatment approaches. 7,8,9,10,11 “The results seen in the DESTINY-Lung01 trial showed a robust and durable tumor response in previouslytreated patients with HER2 mutant metastatic non-small cell lung cancer,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Based on these promising findings, we are conducting DESTINY-Lung04 to evaluate the potential of ENHERTU as an earlier line of therapy in this patient population.” 2 About DESTINY-Lung04 DESTINY-Lung04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, nonsquamous NSCLC harboring a HER2 exon 19 or 20 mutation. Patients will be randomized 1:1 to receive either ENHERTU or standard of care. The primary endpoint of DESTINY-Lung04 is progression-free survival (PFS) as assessed by blinded independent central review (BICR). Secondary endpoints include overall survival, investigator-assessed PFS, overall response rate and duration of response as assessed by BICR and investigator, pharmacokinetics, patient-reported tolerability, immunogenicity and safety. DESTINY-Lung04 will enroll approximately 264 patients at multiple sites across Asia, Europe, and North America. For more information about the trial, visit ClinicalTrials.gov.
About ENHERTU ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed antibody drug conjugate (ADC). Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker. ENHERTU (5.4 mg/kg) is approved in more than 30 countries for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received two or more prior anti-HER2- based regimens based on the results from the DESTINY-Breast01 trial. A supplemental New Drug Application is under review in Japan for the treatment of adult patients with HER2 positive unresectable or recurrent breast cancer previously treated with trastuzumab and a taxane, based on the results from the DESTINY-Breast03 trial. ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial. A Type II Variation is currently under review by the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen. ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
Indications ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with: • Unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2- based regimens in the metastatic setting. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. • Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
For more information, please visit www.daiichisankyo.com.
Dec. 23, 2021 8:21 AM ET
By: Mamta Mayani, SA News Editor
Dec 22, 2021
– Leqvio® Becomes Fourth RNAi Therapeutic Approved by U.S. FDA and First and Only for Lowering LDL-C in Atherosclerotic Cardiovascular Disease (ASCVD) Which Can Affect Up to 30 Million Americans –
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 22, 2021-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today highlighted the significance of the U.S. Food and Drug Administration’s (FDA) approval of Leqvio® (inclisiran), the fourth small interfering RNA (siRNA) therapy (or RNAi therapeutic) approved in the U.S., and the first and only to lower low-density lipoprotein cholesterol (also known as “bad cholesterol” or LDL-C). Leqvio is indicated in the U.S. as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of LDL-C. Alnylam scientists discovered inclisiran and published the first clinical data. Alnylam also supported early clinical development. As of January 2020, Novartis has obtained global rights to develop, manufacture and commercialize inclisiran under a license and collaboration agreement. Novartis AG continues to develop inclisiran and commercialize Leqvio worldwide, with Alnylam eligible to receive tiered royalties between 10 and 20 percent on global sales.
Leqvio is the fourth Alnylam-discovered medicine using its RNAi therapeutic platform to be approved to date. The Leqvio approval marks the first U.S. approval of an RNAi therapeutic indicated to treat a major risk factor for a highly prevalent disease. Alnylam launched its first RNAi therapeutic in 2018 with the FDA approval of ONPATTRO® (patisiran) for treatment of the polyneuropathy caused by hATTR amyloidosis, a progressive and life-threatening, rare, genetic disease. Leqvio was approved to lower LDL cholesterol and has the potential to benefit millions of people with ASCVD and also those with HeFH around the world.
“The approval of Leqvio, a potentially transformational medicine for lowering LDL-C is a historic event for Alnylam and its RNAi therapeutics platform. The demonstrated ability of Leqvio to lower LDL cholesterol up to 52% versus placebo on top of maximally tolerated statins with just two doses per year after an initial dose and another at three months represents a breakthrough that carries the potential to treat millions of people with ASCVD who are struggling to control elevated LDL cholesterol,” said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. “More broadly, we believe the approval of Leqvio validates the future potential of RNAi therapeutics in large population diseases, and facilitates Alnylam’s advancement toward its bold Alnylam P5x25 strategy and goals. We are proud to share in the significance of this milestone with Novartis who made this approval a reality.”
History of Leqvio (inclisiran)
Inclisiran was discovered by Alnylam and, in collaboration with The Medicines Company, advanced into clinical development in 2014. Upon successful completion of Phase 1 clinical studies, the ORION clinical program was launched in 2015. The FDA approval was based on results from the comprehensive Phase III ORION-9, -10 and -11 clinical trials, where all of the 3,457 participants with ASCVD or HeFH had elevated LDL-C while being on a maximally tolerated dose of statin therapy. This comprehensive Phase 3 program represents the largest clinical program conducted to date for an investigational RNAi therapeutic program. Two complementary Phase 3 cardiovascular outcomes trials, ORION-4 and the Novartis initiated VICTORION-2-PREVENT are currently ongoing.
“We believe that the creation of Leqvio was made possible by the development of our ESC-GalNAc conjugate delivery platform,” said Kevin Fitzgerald, Ph.D., Chief Scientific Officer of Alnylam, and scientist who led the initial development of Leqvio at Alnylam. “The U.S. approval of Leqvio will bring RNAi therapeutics to even more patients with elevated or inadequately controlled LDL-C. Moreover, this approval highlights the potential for additional Alnylam RNAi therapeutic programs in prevalent disease indications.”
In the U.S., Leqvio is indicated as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia HeFH or clinical ASCVD, who require additional lowering of LDL-C. The effect of Leqvio on cardiovascular morbidity and mortality has not been determined.
The European Medicines Agency (EMA) granted inclisiran marketing authorization in December 2020 for adults with primary hypercholesterolaemia (heterozygous familial and non‑familial) or mixed dyslipidaemia, as an adjunct to diet in combination with a statin or statin with other lipid‑lowering therapies in patients unable to reach LDL‑C goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid‑lowering therapies in patients who are statin‑intolerant, or for whom a statin is contraindicated. Leqvio has now been approved in more than 50 countries.
As part of Alnylam’s strategic financing agreement with Blackstone, a leading private equity firm, 50 percent of Leqvio-related Alnylam royalties will flow to Blackstone.
For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211221005519/en/
Alnylam Pharmaceuticals, Inc.
Source: Alnylam Pharmaceuticals, Inc.
Dec. 22, 2021 4:47 PM ET
By: Dulan Lokuwithana, SA News Editor
WALTHAM, Mass., Dec. 22, 2021 /PRNewswire/ -- Syndax Pharmaceuticals, Inc. ("Syndax," the "Company" or "we") (Nasdaq: SNDX), a clinical stage biopharmaceutical company developing an innovative pipeline of cancer therapies, today announced that the European Commission has granted Orphan Drug Designation to SNDX-5613, the Company's highly selective oral menin inhibitor, for the treatment of acute myeloid leukemia (AML).
"Supported by a growing body of clinical data, we firmly believe that SNDX-5613 is ideally positioned to serve as a best-in-class, meaningful intervention for patients with NPM1 and MLLr acute leukemias," said Briggs W. Morrison, M.D., Chief Executive Officer of Syndax. "Receipt of Orphan Drug Designation from the European Commission further validates the important role that SNDX-5613 could play in the treatment of this highly underserved patient population, and we are fully committed to ensuring that it is able to reach as many of these patients as possible."
The European Commission grants Orphan Drug Designation for medicinal products intended to treat life-threatening or chronically debilitating conditions that affect fewer than five in 10,000 people in the European Union (EU) and when no satisfactory method of diagnosis, prevention, or treatment of the condition can be authorized. The designation provides certain benefits and incentives in the EU, including protocol assistance, fee reductions, and ten years of market exclusivity once the medicine is on the market.
SNDX-5613 was previously granted Orphan Drug Designation for the treatment of adult and pediatric AML by the U.S. Food and Drug Administration.
SNDX-5613 is a potent, selective, small molecule inhibitor of the menin-MLL binding interaction that is being developed for the treatment of mixed lineage leukemia rearranged (MLLr) acute leukemias including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), and NPM1 mutant AML. In preclinical models of MLLr acute leukemias, SNDX-5613 demonstrated robust, dose-dependent inhibition of tumor growth, resulting in a marked survival benefit. Menin-MLL interaction inhibitors have also demonstrated robust treatment benefit in multiple preclinical models of NPM1 mutant AML, which represents the most frequent genetic abnormality in adult AML. SNDX-5613 is currently being evaluated in the Company's AUGMENT-101 Phase 1/2 open-label clinical trial for the treatment of relapsed/refractory (R/R) acute leukemias. SNDX-5613 was granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) and European Commission for the treatment of patients with AML, and Fast Track designation by the U.S. FDA for the treatment of adult and pediatric patients with R/R acute leukemias harboring a mixed lineage leukemia rearranged MLLr or NPM1 mutation.
For more information, please visit www.syndax.com or follow the Company on Twitter and LinkedIn.
View original content:https://www.prnewswire.com/news-releases/syndax-announces-orphan-drug-designation-granted-to-sndx-5613-by-european-commission-for-the-treatment-of-acute-myeloid-leukemia-301449487.html
SOURCE Syndax Pharmaceuticals, Inc.
Dec. 22, 2021 7:35 AM ET
By: Mamta Mayani, SA News Editor
December 21, 2021 8:56am EST
FDA also allows integrated or meta-analysis of the previous trial results in CD20 final analysis
CD20 is allowed to have four dosages of leronlimab in the first four weeks via IV infusion
VANCOUVER, Wash.--(BUSINESS WIRE)-- CytoDyn Inc. (OTCQB: CYDY) (“CytoDyn” or the “Company”), a late-stage biotechnology company developing leronlimab, a CCR5 antagonist with the potential for multiple therapeutic indications, today announced that it has received a positive response from the U.S. Food and Drug Administration (“FDA”) to conduct a Phase 3, randomized, double blind, placebo controlled trial to evaluate the efficacy and safety of leronlimab in combination with standard of care for critically ill patients with COVID-19 pneumonia with need for Invasive Mechanical Ventilation ("IMV”) or Extracorporeal Membrane Oxygenation (“ECMO”).
The submission of this protocol was previously announced on December 9th. Patients in this trial will be randomized in a 1:1 ratio to receive up to four doses of 700 mg leronlimab with standard of care or placebo with standard of care administered via IV infusion weekly over a four-week treatment period (dosage on days 0, 7, 14, and 21).
Nader Pourhassan, Ph.D., CytoDyn’s President and Chief Executive Officer, commented, “As COVID-19 cases continue to surge in the U.S., we are grateful for the opportunity to move forward with the Phase 3 trial of leronlimab as a treatment option for critically ill COVID-19 patients. There continues to be an immense need for therapeutic options to support this population, and we are optimistic that Phase 3 will show promising results. In previous trials we had issues with our CRO that we now have overcome, and are very excited that the FDA in their recent communication with CytoDyn have stated, ‘As there are now several completed, ongoing, or planned randomized trials of PRO140 (leronlimab) that include severe or critical hospitalized COVID-19 patients, any integrated or meta-analysis would be strengthened if you prespecified analysis details and submitted these for review before results of ongoing or planned trials are Unblinded.’ Since the beginning of the current pandemic, leronlimab has received about 100 eINDs approved for leronlimab by the FDA for use in critically ill COVID-19 patients in the U.S., as a result of these FDA approved eINDs and strong results from most of them, physicians have published four papers in peer review journals. Meanwhile leronlimab was also used in Philippines, under compassionate Special Permit for a fee by over 240 patients with very high rate of success. All these accomplishments along with our current trials in Brazil, we are very hopeful that we will be part of the solution to the current pandemic in U.S. and abroad especially in the critically ill population. We look forward to working with the FDA to expand the access to leronlimab as the fight against COVID-19 continues.”
The U.S. Food and Drug Administration (FDA) granted CytoDyn Fast Track designation to explore two potential indications using leronlimab to treat Human Immunodeficiency Virus (HIV) and metastatic cancer. The first indication is combination therapy with HAART for HIV-infected patients, and the second is for metastatic triple-negative breast cancer (mTNBC). Leronlimab is an investigational humanized IgG4 mAb that binds to CCR5, a cellular receptor important in HIV infection, tumor metastases, and other diseases, including nonalcoholic steatohepatitis (NASH). Leronlimab has been studied in 16 clinical trials involving more than 1,200 people and met its primary endpoints in a pivotal Phase 3 trial (leronlimab combined with HIV standard care in patients with multi-drug resistance to current available classes of HIV drugs).
Leronlimab, among various potential applications, is a viral-entry inhibitor in HIV/AIDS. It binds to CCR5, thus protecting healthy T cells from viral infection by blocking the predominant HIV (R5) subtype from entering those cells. Leronlimab does not work on other strains of HIV (for example X4), however, R5 is the most dominant strain of HIV. Five clinical trials have demonstrated leronlimab could significantly reduce or control HIV viral load in humans. The leronlimab antibody appears to be a powerful antiviral agent with fewer side effects and less frequent dosing requirements than currently used daily drug therapies. Cancer research has shown CCR5 may play a role in tumor invasion, metastases, and tumor microenvironment control (for example, through angiogenesis). Published studies have shown that blocking CCR5 can reduce tumor metastases in laboratory and animal models of aggressive breast and prostate cancer. Leronlimab reduced human breast cancer metastasis by more than 97% in a murine xenograft model. As a result, CytoDyn is conducting two clinical trials, one, a Phase 2 in mTNBC, which was granted Fast Track designation by the FDA in 2019, and a second, a Phase 2, basket trial which encompasses 22 different solid tumor cancers.
The CCR5 receptor plays a central role in modulating immune cell trafficking to sites of inflammation. After completing two clinical trials with COVID-19 patients (a Phase 2 and a Phase 3), CytoDyn initiated a Phase 2 investigative trial for post-acute sequelae of SARS COV-2 (PASC), also known as COVID-19 Long-Haulers. This trial evaluated the effect of leronlimab on clinical symptoms and laboratory biomarkers to further understand the pathophysiology of PASC. It is currently estimated that between 10-30% of those infected with COVID-19 develop long-term sequelae. Common symptoms include fatigue, cognitive impairment, sleep disorders, and shortness of breath. CytoDyn plans to pursue clinical trials to evaluate leronlimab’s effect on immunological dysregulation in other post-viral syndromes, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
CytoDyn is also conducting a Phase 2 clinical trial for NASH to evaluate the effect of leronlimab on liver steatosis and fibrosis. Pre-clinical studies revealed a significant reduction in NAFLD and a reduction in liver fibrosis using leronlimab. There are currently no FDA approved treatments for NASH, which is a leading cause of liver transplant. About 30 to 40 percent of adults in the U.S. live with NAFLD, and 3 to 12 percent of adults in the U.S. live with NASH. There have been no strong safety signals identified in patients administered leronlimab in multiple disease spectrums, including patients with HIV, COVID-19, and oncology.
More information is at www.cytodyn.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211221005432/en/
Source: CytoDyn Inc.
Released December 21, 2021
Dec. 21, 2021 9:28 AM ET
Dec. 20, 2021 12:18 PM ETBy: Jonathan Block, SA News Editor
adeno-associated virus serotype 5 (AAV5) vector containing the hSERPING cDNA sequence encoding human C1-esterase inhibitor (C1-INH)
bluebird bio Announces FDA Priority Review of Biologics License Application for eli-cel Gene Therapy for Cerebral Adrenoleukodystrophy (CALD) in Patients Without a Matched Sibling Donor
If approved, eli-cel will be the first and only gene therapy for the treatment of CALD, a rare neurodegenerative disease primarily affecting young children that can lead to progressive, irreversible loss of neurologic function and death
FDA set PDUFA date of June 17, 2022
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 17, 2021--
bluebird bio, Inc. (Nasdaq: BLUE) today announced that the U.S. Food and Drug Administration (FDA) has accepted for priority review the Biologics License Application (BLA) for elivaldogene autotemcel (eli-cel, Lenti-D®), the company’s gene therapy for cerebral adrenoleukodystrophy (CALD) in patients less than 18 years of age. Eli-cel is an investigational one-time gene therapy, custom-designed to treat the underlying cause of this irreversible neurodegenerative disease and to stabilize neurologic function. The agency set a Prescription Drug User Fee Act (PDUFA) goal date of June 17, 2022.
“Eli-cel is an important potential therapeutic option for patients with CALD—a devastating neurodegenerative disease—and we are encouraged to be moving forward given the urgent unmet need for these children and their families,” said Andrew Obenshain, chief executive officer, bluebird bio. “As the second BLA acceptance for bluebird bio this year, this is a meaningful milestone in our work to deliver one-time treatments for severe genetic diseases.”
If approved, eli-cel will be the first approved treatment to address the underlying genetic cause of disease for patients living with CALD in the U.S. – offering appropriate patients an alternative to allogeneic hematopoietic stem cell transplant (allo-HSCT), which is associated with serious potential complications and mortality that increase in patients without a matched sibling donor. It is estimated that more than 70% of patients diagnosed with CALD do not have a matched sibling donor.
The BLA for eli-cel is supported by efficacy and safety data from the completed Phase 2/3 Starbeam study (ALD-102) (N=32). Additionally, the BLA contains data for 23 subjects dosed in the Phase 3 ALD-104 study. Study ALD-104 has subsequently completed enrollment and follow-up is ongoing. All patients who completed ALD-102, as well as those who will complete ALD-104, are invited to participate in a long-term follow-up study (LTF-304).
In ALD-102, 90.6% (29/32) of patients met the primary endpoint of Major Functional Disabilities (MFD)-free survival at 24 months. As previously reported, two patients withdrew from study ALD-102 at investigator discretion, and one additional subject experienced rapid disease progression early in the study, resulting in MFDs and subsequent death. All patients who completed ALD-102 enrolled in follow-up study LTF-304. The median duration of follow-up is 3.5 years (42.3 months; 13.4, 83.7).
Adverse reactions attributed to eli-cel observed in clinical trials include myelodysplastic syndrome, cystitis viral, pancytopenia, and vomiting. There have been no reports of graft-versus-host-disease, graft failure or rejection, transplant-related mortality, or replication competent lentivirus in the 55 patients who received eli-cel in clinical studies (ALD-102/LTF-304 and ALD-104).
On August 9, bluebird bio announced that the eli-cel clinical program was placed on a clinical hold, following a Suspected Unexpected Serious Adverse Reaction (SUSAR) of myelodysplastic syndrome (MDS). Available evidence suggests that the event was likely mediated by Lenti‑D lentiviral vector (LVV) insertion. Consistent with this known risk, two additional cases of MDS have subsequently been reported and details have been shared with the FDA and study investigators. The FDA clinical hold for eli-cel is ongoing and all patients who received eli-cel in the clinical program continue to be closely monitored, per study protocols. Given the devastating and fatal nature of CALD and lack of other treatment options for patients without a matched sibling donor, bluebird bio continues to assess the overall benefit/risk profile of the product as favorable for patients with CALD who do not have a matched sibling donor.
The FDA’s Priority Review designation is granted to therapies that have the potential to provide significant improvements in the treatment, diagnosis or prevention of serious conditions, and targets a review timeline of six months after the 60-day FDA BLA filing decision, compared to a standard review timeline of 10 months after the 60-day FDA filing decision.
The FDA previously granted eli-cel Orphan Drug status, Rare Pediatric Disease designation, and Breakthrough Therapy designation.
Adrenoleukodystrophy (ALD) is a rare, X-linked metabolic disorder that primarily affects males; worldwide, an estimated one in 21,000 male newborns are diagnosed with ALD. The disorder is caused by mutations in the ABCD1 gene that affect the production of adrenoleukodystrophy protein (ALDP) and subsequently leads to toxic accumulation of very long-chain fatty acids (VLCFAs), primarily in the adrenal gland and white matter of the brain and spinal cord. Approximately 40% of boys with ALD will develop CALD, the most severe form of ALD. CALD is a progressive and irreversible neurodegenerative disease that involves the breakdown of myelin, the protective sheath that nerve cells need to function effectively, especially for thinking and muscle control. The onset of symptoms of CALD typically occurs in childhood (median age 7). Early diagnosis and treatment of CALD is essential, as nearly half of patients who do not receive treatment die within five years of symptom onset.
About elivaldogene autotemcel (eli-cel, Lenti-D®) gene therapy
eli-cel uses ex vivo transduction with the Lenti-D lentiviral vector (LVV) to add functional copies of the ABCD1 gene into a patient’s own hematopoietic stem cells (HSCs). The addition of the functional ABCD1 gene allows patients to produce the ALD protein (ALDP), which is thought to facilitate the breakdown of very long-chain fatty acids (VLCFAs). The expression of ALDP and effect of eli-cel is expected to be life-long. The goal of treatment with eli-cel is to stop the progression of CALD and, consequently, preserve as much neurological function as possible, including the preservation of motor function and communication ability. Importantly, with eli-cel, there is no need for donor HSCs from another person.
bluebird bio’s clinical development program for eli-cel includes the completed pivotal Phase 2/3 Starbeam study (ALD-102) and the ongoing Phase 3 ALD-104 study, which has completed enrollment. Additionally, bluebird bio is conducting a long-term safety and efficacy follow-up study (LTF-304) for patients who have received eli-cel for CALD and completed two years of follow-up in ALD-102 or ALD-104. Clinical studies of eli-cel are currently on hold with the FDA.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211217005659/en/
Source: bluebird bio, Inc.
New and Updated Data Demonstrating Sustained Treatment Response in Patients Treated in Largest Sickle Cell Gene Therapy Program To-Date Presented at ASH21 and Published in NEJM
Updated data from the pivotal cohort of HGB-206 reinforce that optimized manufacturing and treatment processes are associated with improved biologic and clinical outcomes, including stable production of gene therapy-derived anti-sickling hemoglobin and continued complete resolution of severe VOEs up to 36 months follow-up (n=2)
Patient-reported data on health-related quality of life (HRQoL) complement clinical findings and the strongest HRQoL improvements in any sickle cell gene therapy program
CAMBRIDGE, Mass.--(BUSINESS WIRE)--Dec. 12, 2021-- bluebird bio, Inc. (NASDAQ: BLUE) today announced updated results from its Phase 1/2 HGB-206 study of lovotibeglogene autotemcel (lovo-cel; formerly LentiGlobin® for SCD, bb1111) gene therapy for sickle cell disease, including further analyses from its pivotal cohort, HGB-206 Group C, following enhancements to the manufacturing protocols and treatment process. In addition to continued complete resolution of severe vaso-occlusive events (VOEs), patients in Group C achieved near normal levels of key hemolysis markers and experienced sustained improvements in patient-reported quality of life following treatment. Data were presented in two oral sessions at the 63rd American Society of Hematology (ASH) Annual Meeting and Exposition, taking place December 11-14, 2021, at the Georgia World Congress Center in Atlanta and virtually; select data from the Group C cohort of the HGB-206 study were simultaneously published in The New England Journal of Medicine (NEJM).
“Data presented at ASH and published today in The New England Journal of Medicine affirm that this lentiviral gene transfer for sickle cell disease has the potential to improve the day-to-day reality of people living with sickle cell disease by eliminating the disruptive, painful crises that can occur multiple times per month,” said John F. Tisdale, MD, Chief, Cellular and Molecular Therapeutics Branch, NHLBI, Bethesda, Md. “Sickle cell is a complex and often misunderstood disease that is associated with more symptoms and long-term effects than pain alone. It is encouraging to see that the treatment fundamentally impacted the pathophysiology of patients’ disease through the sustained production of vector-derived anti-sickling hemoglobin to substantially reduce sickling and hemolysis.”
Clinical studies evaluating lovo-cel in sickle cell disease represent the largest sickle cell disease gene therapy data set to date. As of February 17, 2021, 49 patients have been treated with lovo-cel with up to six years of patient follow-up (median: 24 months) across the HGB-205 (n=3), HGB-206 (n=44) and HGB-210 (n=2) clinical studies, representing more than 109 total patient-years of data. The Phase 1/2 HGB-206 trial includes Groups A (n=7), B (n=2) and C (n=35), reflecting progressive adaptations to the treatment and manufacturing processes.
Sickle cell disease is a serious, progressive and debilitating genetic disease caused by a single mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin (HbS). HbS causes red blood cells (RBCs) to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and unpredictable, painful VOEs requiring frequent hospitalization. In the U.S., the median age of death for someone with sickle cell disease is 43-46 years. Additionally, one in four people living with sickle cell disease experience a stroke by age 45.
In the HGB-206 study, VOEs are defined as episodes of acute pain with no medically determined cause other than a vaso-occlusion, lasting more than two hours and severe enough to require care at a medical facility. This includes acute episodes of pain, acute chest syndrome (ACS), acute hepatic sequestration and acute splenic sequestration. A severe VOE requires a 24-hour hospital stay or emergency room visit or at least two visits to a hospital or emergency room over a 72-hour period, with both visits requiring intravenous treatment.
lovo-cel adds functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their RBCs can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, thereby reducing sickled RBCs, hemolysis and other complications.
“The remarkable depth and breadth of data presented at ASH and published in The New England Journal of Medicine distinctively demonstrates the impact of lovo-cel on biologic and clinical outcomes, as well as to patient-reported outcomes that indicate a meaningful difference in the daily lives of people with sickle cell disease,” said Richard Colvin, MD, PhD, Chief Medical Officer, bluebird bio. “The ability to trace how lovo-cel integrates on a genetic level is a distinguishing characteristic of LVV gene therapy and confers a unique understanding of how the proposed mechanism of action of the drug product is correlated to safety and clinical outcomes.”
Data published in The New England Journal of Medicine is titled Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease Gene Therapy.
Updated HGB-206 Group C Efficacy & Safety Data
As of February 2021, the 35 Group C patients had up to 37.6 months of follow-up (median of 17.3; min-max: 3.7-37.6 months), for a total of 54.8 patient-years of experience.
Following engraftment, median total hemoglobin increased from 8.5 g/dL at baseline to ≥11 g/dL from six through up to 36 months post-infusion in all patients; notably, sickle hemoglobin (HbS) in all patients was less than 60% of total hemoglobin, and gene therapy-derived anti-sickling hemoglobin, HbAT87Q, contributed at least 40% of total hemoglobin.
These decreased levels of sickle hemoglobin (HbS) after lovo-cel infusion were comparable to individuals living with sickle trait (βS/βA), not in the study—in general, people with sickle cell trait enjoy normal life spans with no medical problems related to sickle cell trait.
All evaluable patients (n=25) continued to experience complete resolution of severe VOEs through up to 36 months of follow-up, compared with a median of 3.5 per year (min-max: 2.0-13.5) in the 24 months before enrollment.
HGB-206 is an ongoing, Phase 1/2 open-label study designed to evaluate the efficacy and safety of lovo-cel gene therapy for sickle cell disease that includes three treatment cohorts: Groups A (n=7), B (n=2) and C (n=35). A refined manufacturing process designed to increase vector copy number (VCN) and further protocol refinements made to improve engraftment potential of gene-modified stem cells were used for Group C. Group C patients also received lovo-cel made from HSCs collected from peripheral blood after mobilization with plerixafor, rather than via bone marrow harvest, which was used in Groups A and B of HGB-206.
Under a Cooperative Research and Development Agreement (CRADA), the National Heart, Lung, and Blood Institute, part of the National Institutes of Health, assisted bluebird in conducting clinical trials of its investigational LentiGlobin® gene therapy.
About lovotibeglogene autotemcel (lovo-cel; formerly LentiGlobin® for SCD, bb1111)
lovotibeglogene autotemcel (lovo-cel) gene therapy is an investigational one-time treatment being studied for sickle cell disease (SCD), that is designed to add functional copies of a modified form of the β-globin gene (βA-T87Q-globin gene) into a patient’s own hematopoietic (blood) stem cells (HSCs). Once patients have the βA-T87Q-globin gene, their red blood cells (RBCs) can produce anti-sickling hemoglobin (HbAT87Q) that decreases the proportion of HbS, with the goal of reducing sickled RBCs, hemolysis, and other complications. bluebird bio’s clinical development program for lovo-cel includes the completed Phase 1/2 HGB-205 and ongoing Phase 1/2 HGB-206 and Phase 3 HGB-210 studies. bluebird bio is also conducting a long-term safety and efficacy follow-up study (LTF-307) for people who have participated in bluebird bio sponsored clinical studies of lovo-cel.
As of February 17, 2021, a total of 49 patients have been treated with lovo-cel, with up to six years of patient follow-up, in the HGB-205 (n=3), HGB-206 (n=44), and HGB-210 (n=2) clinical studies. The HGB-206 total includes: Group A (n=7), B (n=2), and C (n=35), representing progressive adaptations to the manufacturing and treatment and processes. In the Group C cohort of the Phase 1/2 HGB-206 study, no severe vaso-occlusive events (VOEs) were reported with up to 24 months of follow-up in patients with a history of at least four severe VOEs and at least six months of follow-up.
The safety data profile remains generally consistent with the risks of autologous stem cell transplantation and myeloablative single-agent busulfan conditioning, as well as underlying SCD. One non-serious, Grade 2 adverse event (AE) of febrile neutropenia was considered related to lovo-cel. There were no serious AEs related to lovo-cel.
In the Group C cohort of the HGB-206 study, one patient with underlying cardiopulmonary disease and SCD-related complications died 20 months post-treatment; the treating physician and an independent monitoring committee agreed his death was unlikely related to lovo-cel.
In the initial cohort (Group A) of the HGB-206 study, two patients treated with lovo-cel developed acute myeloid leukemia (AML). After thorough investigations into the cases, bluebird bio determined that these were unlikely related to the insertion of bluebird’s lentiviral vector (LVV) gene therapy for SCD.
For more information on lovo-cel studies, visit: https://www.bluebirdbio.com/our-science/clinical-trials or clinicaltrials.gov.
The FDA has granted orphan drug designation, fast track designation, regenerative medicine advanced therapy (RMAT) designation, and rare pediatric disease designation for lovo-cel.
lovo-cel is investigational and has not been approved in any geography.
LentiGlobin and bluebird bio are trademarks of bluebird bio, Inc.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211212005093/en/
Source: bluebird bio, Inc.
Dec. 13, 2021 8:41 AM ET
By: Mamta Mayani, SA News Editor
December 12, 2021Download PDF
INDIANAPOLIS, Dec. 12, 2021 /PRNewswire/ -- Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company (NYSE: LLY), today announced updated clinical data from the pirtobrutinib global Phase 1/2 BRUIN clinical trial in patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) and mantle cell lymphoma (MCL). Pirtobrutinib is an investigational, highly selective, non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor. These data are being presented in oral presentations at the 2021 American Society of Hematology (ASH) Annual Meeting (abstracts 391 and 381).
"BRUIN is now the largest clinical trial conducted to date that has enrolled CLL/SLL patients previously treated with modern standards of care including BTK and BCL2 inhibitors. In this real-world population of relapsed/refractory patients, pirtobrutinib continues to demonstrate robust activity with a safety profile amenable to chronic administration. Now with the longer follow-up that this analysis affords, we are encouraged by evidence of durable disease control in this very heavily pretreated CLL/SLL population," said Anthony Mato, M.D., MSCE, director of the CLL Program at Memorial Sloan Kettering Cancer Center and a presenting author. "As recently detailed by a global panel of experts in Clinical Cancer Research, there are currently no evidence-based treatment options for patients following covalent BTK and BCL2 inhibitor therapy. Pirtobrutinib has the potential to offer a meaningful new approach for these CLL/SLL patients, as well as those patients who are less heavily pretreated."
"I'm pleased to share the pirtobrutinib data in MCL patients with the hematology community at ASH", said Michael Wang, M.D., Puddin Clarke Endowed Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center and a presenting author. "Since our last analysis of these data, we have doubled the number of evaluable BTK pretreated patients and observed a nearly-identical response rate. New treatment options following covalent BTK therapy represent an area of urgent unmet need and the durable response rate observed with pirtobrutinib demonstrates its potential to provide a significant clinical advancement for patients with MCL following covalent BTK therapy."
Key Data Presented at ASH
As of July 16, 2021, 618 patients were enrolled in the study, including 296 with CLL/SLL, 134 with MCL, and 188 with other B-cell malignancies. The efficacy data presented at ASH are based on investigator response assessments. Patients were considered efficacy-evaluable if they had at least one post-baseline response assessment or if they discontinued treatment prior to their first post-baseline response assessment.
Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL)
Among the 296 CLL/SLL patients enrolled, 261 were previously treated with a BTK inhibitor and are the subject of this analysis. The median number of prior lines of therapy was three with 100% receiving a prior BTK inhibitor, 88% an anti-CD20 antibody, 79% chemotherapy, 41% venetoclax, 20% a PI3K inhibitor, 6% CAR-T therapy and 2% stem cell transplant.
In 252 efficacy-evaluable patients (an additional nine patients ongoing prior to first restaging), 171 responded including two complete responses (CR), 137 partial responses (PR), 32 partial responses with ongoing lymphocytosis (PR-L), and 62 stable disease (SD), resulting in an overall response rate (ORR) of 68% (95% CI: 62-74). Responses continue to deepen over time, with the ORR rising to 73% (88/119) for those followed 12 months or more, and ORR remains consistent regardless of reason for prior BTK discontinuation, type or number of prior therapies or BTK C481 or PCLG2 mutational status.
Pirtobrutinib demonstrated evidence of durable activity with a median progression-free survival (PFS) not reached in patients who had received at least a prior BTK inhibitor (lower limit of 95% confidence interval of 17.0 months, median of three prior lines of therapy). In patients who had received at least a BTK inhibitor and BCL2 inhibitor (median of five lines of prior therapy), the estimated median PFS was 18 months, although these data remain immature and unstable due to the small percentage of patients with progression. As of the data cut-off, 74% (194/261) of BTK pre-treated patients remained on pirtobrutinib. Median follow-up for all BTK pre-treated patients was 9.4 months (range 0.3-27.4 months).
In an exploratory analysis in patients with prior progression on a BTK inhibitor, the PFS with pirtobrutinib was similar in patients with BTK C481-mutated and BTK C481-wildtype CLL and SLL.
Loxo Oncology at Lilly is studying pirtobrutinib in multiple Phase 3 studies. Details on the trials can be found in Trials in Progress posters (abstracts 2422, 3732, 3736 and 3742) and on lillyloxooncologypipeline.com.
About Pirtobrutinib (LOXO-305)
Pirtobrutinib is an investigational, highly selective, non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, and marginal zone lymphoma. Currently available covalent BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies can be limited by acquired resistance, most commonly through BTK C481 mutations. In rapidly growing tumors with inherently high rates of BTK turnover, resistance to covalent BTK therapies may be the result of incomplete target inhibition. Pirtobrutinib was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors. Interested patients and physicians can contact the Loxo Oncology at Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email email@example.com.
About the BRUIN Phase 1/2 Trial
This first-in-human, global, multi-center Phase 1/2 trial evaluates pirtobrutinib as a single agent in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin's lymphomas (NHL). The trial includes a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The Phase 1 dose escalation enrolls patients with CLL/SLL or NHL who have received at least two prior lines of therapy and have progressed or are intolerant to standard of care. The dose escalation phase followed a "3+3" design with pirtobrutinib dosed orally in 28-day cycles. As dose cohorts were cleared, additional patients could enroll in cleared cohorts and intra-patient dose escalation was permitted. The primary objective of the Phase 1 portion of the trial is to determine the maximum tolerated dose and recommended Phase 2 dose. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Overall Response Rate (ORR) and Duration of Response, as determined by appropriate histology-specific response criteria). In the Phase 2 dose expansion, patients are enrolled across various cohorts, depending on disease type and prior therapy. The primary endpoint for Phase 2 is ORR. Secondary endpoints include duration of response (DOR), overall survival (OS), safety, and pharmacokinetics (PK).
About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom. P-LLY
Disclosure: Dr. Mato has provided consulting and advisory services to Loxo Oncology at Lilly and Eli Lilly and Company.
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SOURCE Eli Lilly and Company
December 12, 2021 at 9:00 AM ESTPDF Version
- No adverse events related to investigational SAR445136 were reported
- All four treated patients experienced increases in total hemoglobin, fetal hemoglobin and percent F cells; none required blood transfusions post engraftment
BRISBANE, Calif.--(BUSINESS WIRE)--Dec. 12, 2021-- Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicine company, today announced updated preliminary proof-of-concept clinical data from the Phase 1/2 PRECIZN-1 study of SAR445136, a zinc finger nuclease gene-edited cell therapy candidate in development with Sanofi for the treatment of sickle cell disease (SCD). These data are being presented today at the 63rd American Society for Hematology Annual Meeting and Exposition taking place from December 11-14 virtually and in Atlanta, GA. The poster presentation, which includes follow-up data up to 91 weeks for the longest-treated patient, is available on Sangamo’s website in the Investors and Media section under Events and Presentations.
“We are very pleased with these updated preliminary proof-of-concept efficacy and safety results, which we believe illustrate the therapeutic potential of zinc finger nuclease engineered cell therapy to address the current unmet needs of patients with sickle cell disease,” said Rob Schott, M.D., M.P.H, F.A.C.C, Head of Development at Sangamo. “We believe this is an important demonstration of our versatile zinc finger platform translating meaningfully into the clinic.”
As of the September 22, 2021 cutoff date, the most recently treated patient in the PRECIZN-1 Phase 1/2 study had been followed for 26 weeks and the longest-treated patient had been followed for 91 weeks. None of the four treated patients required blood transfusions post engraftment. Total hemoglobin stabilized by Week 26 after treatment with SAR445136 in all four patients. Fetal hemoglobin level increased from 0.1-11% at screening to 14-39% by Week 26 in all four patients and was 38% in the longest-treated patient at 91 weeks. Percent F cells increased to 64-96% by 39 weeks of follow-up in all four patients, persisting at 99% in the patient with 91 weeks of follow-up. The SAR445136 investigational drug product had on-target BCL11A gene modification (61-78%) in all four patients.
“These preliminary proof of concept efficacy and safety results support the potential therapeutic value of the zinc finger nuclease-mediated modification of the BCL11ESE region,” said Karin Knobe, Head of Development, Rare Diseases and Rare Blood Disorders at Sanofi.
As of the cutoff date, there were no adverse events (AEs) assessed as related to SAR445136. Most AEs reported in the screening, mobilization, apheresis and conditioning periods were SCD-related events. One serious adverse event of sickle cell anemia with crisis (vaso-occlusive crisis or VOC) was reported approximately nine months after treatment with SAR445136 in one patient, and no other SCD-related events were reported in the four patients post-infusion.
Additional data from this study are expected to be presented at a medical meeting in 2022.
About the PRECIZN-1 study
PRECIZN-1 is an ongoing first-in-human, open label, single arm, multi-site Phase 1/2 study in up to eight patients with SCD evaluating the safety and tolerability of cell therapy candidate SAR445136. The therapeutic product is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology targeting the BCL11a gene erythroid-specific enhancer (ESE) to increase endogenous fetal hemoglobin (HbF) production. SAR445136 has received Fast Track Designation from the FDA and Orphan Medicinal Product from the EMA. The safety and efficacy of SAR445136 has not been reviewed by any regulatory authority worldwide.
For more information about Sangamo, visit www.sangamo.com.
View source version on businesswire.com: https://www.businesswire.com/news/home/20211212005050/en/
Source: Sangamo Therapeutics, Inc.
Dec. 13, 2021 3:06 AM ET
By: Mamta Mayani, SA News Editor
December 12, 2021 at 4:30 PM ESTPDF Version
NEW YORK & BRISBANE, Calif.--(BUSINESS WIRE)--Dec. 12, 2021-- Pfizer Inc. (NYSE: PFE) and Sangamo Therapeutics, Inc. (Nasdaq: SGMO), a genomic medicines company, today announced updated follow-up data from the Phase 1/2 Alta study of giroctocogene fitelparvovec, an investigational gene therapy for patients with moderately severe to severe hemophilia A. The Alta study data, in patients with severe hemophilia A, are being presented today at the 63rd American Society for Hematology Annual Meeting and Exposition taking place from December 11-14 virtually and in Atlanta, GA. The oral presentation slides, which include follow-up data up to 195 weeks for the longest-treated patient, are available on Sangamo’s website in the Investors and Media section under Events and Presentations.
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At 104 weeks, the five patients in the highest dose 3e13 vg/kg cohort had mean factor VIII (FVIII) activity of 25.4% via chromogenic clotting assay. In this cohort, mean annualized bleeding rate (ABR) was 0.0 in the first year post-infusion and was 1.4 throughout the total duration of follow-up as of the October 1, 2021 cutoff date. All bleeding events occurred after week 69 post-infusion. Two patients experienced bleeding events necessitating treatment with exogenous FVIII. No participants in the highest dose cohort have resumed prophylaxis.
“These latest results further suggest the potential of this investigational therapy to bring transformational benefit to eligible patients living with severe hemophilia A, if confirmed in ongoing clinical trials,” said Seng H. Cheng, Senior Vice President and Chief Scientific Officer, Pfizer Rare Disease.
“We continue to be encouraged by findings from the Phase 1/2 Alta study in patients with severe hemophilia A,” said Rob Schott, M.D., M.P.H, F.A.C.C, Head of Development at Sangamo. “We believe these two-year results demonstrate the potential of this gene therapy candidate to minimize significant symptoms associated with hemophilia A and become an alternative to the current burden of disease management.”
Giroctocogene fitelparvovec was generally well-tolerated in this Phase 1/2 study. Among the five patients in the highest dose cohort, four received corticosteroids for liver enzyme (ALT/AST) elevations. All elevations fully resolved with oral corticosteroids. As previously reported, one patient in the highest dose cohort had a treatment-related serious adverse event of hypotension (grade 3) and fever (grade 2), with symptoms of headache and tachycardia, which occurred six hours post-infusion with giroctocogene fitelparvovec and resolved approximately 12 hours post-infusion. Across all four cohorts, 26 treatment-related adverse events occurred in six patients as of the October 1, 2021 cutoff date. No other treatment-related serious adverse events were reported as of the cutoff date. Additionally, no confirmed FVIII inhibitor development occurred, and no thrombotic events were reported.
The Phase 3 AFFINE clinical trial of giroctocogene fitelparvovec in patients with hemophilia A has started and is over 50% enrolled. Following the observation of FVIII levels greater than 150% in some treated patients, Pfizer voluntarily paused screening and dosing of additional patients in the trial to implement a protocol amendment to provide clinical management guidance for elevated FVIII levels. Subsequently, on November 3, 2021, the U.S. Food and Drug Administration (FDA) informed Pfizer that this trial has been placed on clinical hold while the protocol amendment and associated documents are reviewed.
About the Alta Study
The Phase 1/2 Alta study is an open-label, dose-ranging, multicenter clinical trial designed to assess the safety and tolerability of giroctocogene fitelparvovec in patients with severe hemophilia A. The mean age of the 11 male patients assessed across four dose cohorts (9e11 vg/kg - 2 patients, 2e12 vg/kg - 2 patients, 1 e13 vg/kg - 2 patients and 3e13 vg/kg - 5 patients) is 30 years (range 18-47 years). Patients in this study will be assessed every six months until they enroll in a long-term follow-up study.
About the AFFINE study
The Phase 3 AFFINE (NCT04370054) study is an open-label, multicenter, single arm study to evaluate the efficacy and safety of a single infusion of giroctocogene fitelparvovec in more than 60 adult (ages 18-64 years) male participants with moderately severe to severe hemophilia A. Eligible study participants will have completed at least six months of routine FVIII prophylaxis therapy during the lead-in Phase 3 study (NCT03587116) in order to collect pretreatment data for efficacy and selected safety parameters.
The primary endpoint is impact on annualized bleeding rate (ABR) through 12 months following treatment with giroctocogene fitelparvovec. This will be compared to ABR on prior FVIII prophylaxis replacement therapy. The secondary endpoints include FVIII activity level after the onset of steady state and through 12 months following infusion of giroctocogene fitelparvovec.
About giroctocogene fitelparvovec
The U.S. Food and Drug Administration has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to giroctocogene fitelparvovec, which also received Orphan Medicinal Product designation from the European Medicines Agency. Giroctocogene fitelparvovec is being developed as part of a collaboration agreement for the global development and commercialization of gene therapies for hemophilia A between Sangamo and Pfizer. In late 2019, Sangamo transferred the manufacturing technology and the Investigational New Drug (IND) application to Pfizer. Giroctocogene fitelparvovec is currently being studied in the Phase 3 AFFINE study.
For more information about Sangamo, visit www.sangamo.com.
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Source: Sangamo Therapeutics, Inc.
Dec. 13, 2021 2:39 AM ET
By: Mamta Mayani, SA News Editor