FUS

Neoadjuvant treatment with pepinemab appears to induce abundant, mature lymphoid structures that correlate with durable clinical benefit of immunotherapy in patients with metastatic melanoma. Pepinemab, Semaphorin 4D blocking immunotherapy, also appears to induce the formation of efficient lymphoid structures in “cold” tumors of patients with recurrent and metastatic head and neck cancer. April 21, 2025 -- Vaccinex, Inc. (Nasdaq: VCNX), a clinical-stage biotechnology company pioneering a differentiated approach to treating cancer and Alzheimer’s disease (AD) through the inhibition of Semaphorin 4D (SEMA4D), today announced that it will present exciting new data characterizing the unique mechanism of pepinemab to enhance immune responses to checkpoint therapies, corresponding with improved survival benefit in patients with melanoma and head and neck cancer at the 2025 Annual Meeting of American Association for Cancer Research (AACR) in Chicago on April 29, 2025. Elizabeth Evans, PhD, Senior VP Discovery and Translational Medicine, will present results of these studies in two presentations. AACR Conference Information: Date:Tuesday, April 29, 2025 Presentation title:Regulating dendritic cells to promote mature tertiary lymphoid structures and enhance anti-tumor immunity. Presentation #3975 Time:9-12 AM CDT/10 AM – 1 PM EDT. Session Title:The Tumor Immune Interplay as a Driver of Progression Presentation title:Neoadjuvant pepinemab enhances DC function associated with mature tertiary lymphoid structures and activity of immune checkpoint blockade in patients with metastatic melanoma. Presentation #6007 Time:2-5 PM CDT/ 3-6 PM EDT. Session Title:Therapeutic Antibodies, Including Engineered Antibodies 2 Access:Posters will be presented in-person on Tuesday, April 29 at McCormick Place Convention Center, Chicago, Illinois, and on AACR 2025 virtual meeting platform at 1:00 PM ET on Friday, April 25, 2025. Previously reported data from these two clinical studies suggest a crucial role of pepinemab to facilitate immune cell interactions within highly organized and robust centers of immunity, called tertiary lymphoid structures, or TLS. By blocking the SEMA4D inhibitory signal to Dendritic Cells (DC), pepinemab allows productive, coordinated interactions between SEMA4D+ T cells, key effector cells capable of eradicating tumors, and DC, regulatory cells that promote immune cell interactions within TLS so as to amplify mature T cell responses. New data will characterize clinical outcomes, biomarkers, and mechanisms of these interactions in patients treated with pepinemab in combination with immune checkpoint therapy. Boosting TLS within tumors is an area of growing excitement because the presence of TLS has been shown to correlate with clinical benefit and positive response to immune checkpoint therapy. A limitation in the field has been identification of safe and effective therapies that can induce formation and harness the potential of TLS to enable durable benefit to patients. Pepinemab may represent a solution to this problem, as our data demonstrate the potential of pepinemab to turn immunologically cold tumors, such as HPV-negative and PD-L1-low head and neck cancer, into hot immune centers by inducing robust and mature TLS. Neoadjuvant immunotherapy has emerged as a promising approach in the treatment of various cancers, showing improved immune and clinical benefit in the preoperative setting compared to standard post surgery adjuvant treatments. Despite these advances, many patients who initially benefit from antibodies that block inhibitory checkpoint molecules (e.g. PD-1, CTLA 4) will progress. More effective combination therapies are needed. Neoadjuvant treatment with pepinemab enhanced TLS maturity and correlated with longer recurrence-free survival when combined with immune checkpoint inhibitors in patients with metastatic melanoma. Evaluation of pepinemab in the neoadjuvant setting for patients with head and neck cancer is ongoing and will be reported at upcoming scientific meeting this Spring. Pepinemab is a humanized IgG4 monoclonal antibody designed to block SEMA4D, which can otherwise bind to plexin-B1 receptors to trigger collapse of the actin cytoskeleton in cells and lead to loss of homeostatic functions of dendritic cells in immune tissue and of astrocytes and other glial cells in the brain. Pepinemab appears to be well-tolerated with a favorable safety profile in multiple clinical trials in different cancer and neurological indications. Vaccinex, Inc. is pioneering a differentiated approach to treating slowly progressive neurodegenerative diseases and cancer through the inhibition of semaphorin 4D (SEMA4D). The Company’s lead drug candidate, pepinemab, blocks SEMA4D, a potent biological effector that it believes prevents infiltration and activation of immune cells in tumors and triggers damaging inflammation in neurodegenerative diseases. In oncology, pepinemab is being evaluated in combination with KEYTRUDA® in the Phase 1b/2 KEYNOTE-B84 study in recurrent or metastatic head and neck cancer (HNSCC) and in combination with BAVENCIO® in a Phase 1b/2 study in patients with metastatic pancreatic adenocarcinoma (PDAC). The oncology clinical program also includes several investigator-sponsored studies in solid tumors including breast cancer and melanoma. We believe pepinemab has also given promising results as a monotherapy in the Phase 1b/2 SIGNAL-AD study in Alzheimer’s Disease, and the Company has previously published promising Phase 2 data suggesting a slowing of cognitive decline in Huntington’s disease. Vaccinex has global commercial and development rights to pepinemab and is the 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. KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. BAVENCIO®/avelumab is provided by Merck KGaA, Darmstadt, Germany, previously as part of an alliance between the healthcare business of Merck KGaA, Darmstadt, Germany and Pfizer. The content above comes from the network. if any infringement, please contact us to modify.

RSS Share Otsuka Pharmaceutical Co., Ltd. (Otsuka) is pleased to announce our entry into an exclusive worldwide licensing agreement with Ionis Pharmaceuticals, Inc. (Ionis) for rights to manufacture and market Ionis' ulefnersen (generic name; development code is ION363), a drug candidate under development for the treatment of patients with amyotrophic lateral sclerosis (ALS) caused by mutation of the fused in sarcoma (FUS) gene. This agreement marks Otsuka's second introduction of an antisense oligonucleotide (ASO) medicine from Ionis, following our acquisition of development and sales rights in Europe and Asia, including Japan, for the hereditary angioedema attack suppressant drug donidalorsen (generic name). ALS is a serious neurodegenerative disease that causes rapid muscle weakness in the limbs and respiratory muscle paralysis. Once the disease has manifested, it generally continues to progress, and in a few years it can become difficult to breathe spontaneously. The number of ALS patients worldwide is on the rise, and it is estimated that by 2040 there will be over 300,000 people with the disease.*1. FUS-ALS is caused by mutations in the FUS gene. It is the second most common causative gene for ALS in Japan and the third or fourth most common in Europe and the United States. Unlike typical ALS, FUS-ALS is more common in younger people, with the average age of onset being around 40, and is characterized by extremely rapid progression of the disease.*1,2 This drug candidate, discovered and developed by Ionis, aims to treat FUS-ALS, a neurodegenerative condition caused by the accumulation of abnormal FUS protein in neurons due to a genetic mutation, by inhibiting production of the mutated FUS protein. Delivery is by intrathecal administration every 12 weeks. Ionis is conducting the ongoing phase 3 trial for ulefnersen in multiple countries, including Japan, subject to cost reimbursement by Otsuka starting in 2025. If development and then regulatory reviews proceed successfully, ulefnersen could become the first treatment for FUS-ALS. Under the terms of the agreement, Otsuka will pay Ionis an upfront payment of U.S. $10 million, plus milestone payments based on achievement of regulatory approvals and sales targets. Ionis is also eligible to earn royalties on product sales. Otsuka will apply for regulatory approvals and exclusively carry out manufacturing and sales of the product worldwide. Makoto Inoue, president and representative director of Otsuka Pharmaceutical Co., Ltd. commented, "Otsuka Pharmaceutical is committed to the global development of treatments for rare diseases such as autosomal dominant polycystic kidney disease (ADPKD), IgA nephropathy, lupus nephritis, hereditary angioedema (HAE) and phenylketonuria (PKU) in order to respond to underaddressed medical needs. Through our expanded collaboration with Ionis Pharmaceuticals, we will strive to contribute to the treatment of patients worldwide with ALS accompanied by FUS mutations." *1 Nature Communications （https://www.nature.com/articles/ncomms12408） *2 Journal of Human Genetics (https://www.nature.com/articles/s10038-022-01055-8)

SOUTH SAN FRANCISCO, Calif.--( BUSINESS WIRE )--Trace Neuroscience, Inc., a biopharmaceutical company expanding the promise of genomic medicine for people living with neurodegenerative diseases, today announced its launch with a $101 million Series A financing led by Third Rock Ventures, with participation from Atlas Venture, GV and RA Capital Management. The company is developing novel genomic therapies that restore UNC13A protein to re-establish healthy communication between nerves and muscle cells impacted by neurodegenerative disease. Trace Neuroscience’s lead program is an antisense oligonucleotide (ASO) designed to preserve and potentially improve muscle function in people living with amyotrophic lateral sclerosis (ALS), including those with the sporadic form that affects nine out of 10 people with the disease. “UNC13A is a highly compelling genetic target directly linked to ALS disease progression and survival. Insights from the human genome have led to transformative medicines for many diseases, and with what we now know about the role of UNC13A, we believe the time is right to apply this approach to ALS,” said Eric Green, M.D., Ph.D., co-founder and CEO of Trace Neuroscience. “We envision a world where UNC13A restoration improves outcomes across a range of neurodegenerative diseases, including for the approximately 30,000 people in the U.S. living with ALS.” The formation of Trace Neuroscience is based on simultaneous convergent discoveries from the company’s co-founders linking abnormal function of TDP-43 protein with the loss of UNC13A protein, an essential component for neuronal communication in the brain and spinal cord. In almost all people with ALS, this relationship progressively breaks down and leads to decreased mobility, paralysis and difficulty breathing. “Genomic-based therapies have begun to transform the lives of people living with ALS. But so far, they have only been effective for those rare forms of the disease caused by SOD1 or FUS mutations, which account for only 3% of all ALS cases. The remaining people, including those with sporadic disease, the most common form that occurs randomly without a clear cause, need new treatments grounded in human genetics with defined mechanisms of action,” said co-founder Aaron Gitler, Ph.D., Professor of Genetics at Stanford University. “Our insights into UNC13A biology may be the key to slowing disease progression, preserving or restoring muscle function and extending survival for people living with ALS.” Targeted Approach, Broad Impact Approximately 97% of people with ALS produce insufficient amounts of UNC13A, which is directly regulated by the TDP-43 protein that controls RNA splicing. When TDP-43 stops functioning normally, as occurs in nearly all people with ALS, the UNC13A messenger RNA (mRNA) is improperly spliced, which hinders adequate UNC13A production. Trace Neuroscience’s ASO development candidate is designed to deliver a targeted intervention by binding directly to UNC13A mRNA to regulate its processing and ensure proper splicing, thereby correcting synaptic dysfunction and preserving neuronal signaling. “UNC13A is critical for neurons to communicate amongst each other and with muscles through synaptic function, which is lost in ALS. Being able to re-establish this is groundbreaking. Our focus is now on rapidly translating this science into a life-changing medicine by advancing our lead program toward the clinic,” said co-founder Pietro Fratta, M.D., Ph.D., Professor of Cellular and Molecular Neuroscience at University College London, Francis Crick Institute. “This is an exciting time in brain disease innovation, and we also see potential for treating frontotemporal dementia and over half of Alzheimer’s disease patients where TDP-43 pathology occurs and UNC13A is lost.” Leaders in Genomic Medicine Innovation Trace Neuroscience leadership includes clinicians at the forefront of neurodegenerative research, renowned neuroscience drug developers and proven company builders: Co-founders Pietro Fratta, M.D., Ph.D., Professor of Cellular and Molecular Neuroscience, University College London, Francis Crick Institute Aaron Gitler, Ph.D., Professor of Genetics, Stanford University Eric Green, M.D., Ph.D., CEO, Trace Neuroscience Michael Ward, M.D., Ph.D., Senior Investigator, National Institute of Neurological Disorders and Stroke, National Institutes of Health Management team Irina Antonijevic, M.D., Ph.D., Chief Medical Officer Megan Baierlein, Chief Operating Officer Eric Green, M.D., Ph.D., CEO Marjie Hard, Ph.D., SVP, Development Sciences Nick Mordwinkin, Pharm.D., Ph.D., Chief Business Officer and Chief Strategy Officer Precillia Redmond, Chief People Officer Board of directors Jeffrey Tong, Ph.D., Chairman; Partner, Third Rock Ventures David Grayzel, M.D., Partner, Atlas Venture Eric Green, M.D., Ph.D., CEO, Trace Neuroscience Douglas Kerr, M.D., Ph.D., Chief Medical Officer, Dyne Therapeutics Anthony Philippakis, M.D., Ph.D., General Partner, GV Richard Scheller, Ph.D., Chairman of R&D, BridgeBio Dodzie Sogah, Ph.D., Venture Partner, Third Rock Ventures “The Trace Neuroscience team is strongly positioned with the right leadership, the right scientific approach and the right molecules to disrupt the treatment paradigm in ALS and beyond,” said Chairman Jeffrey Tong, Ph.D., Partner at Third Rock Ventures. “People living with neurodegenerative diseases are waiting for more effective new treatments, and UNC13A restoration has the potential to deliver meaningful innovation that will improve their quality of life and overall health outcomes.” About Trace Neuroscience Trace Neuroscience is a biopharmaceutical company on a mission to expand the promise of genomic medicine for people living with neurodegenerative diseases. With an initial focus on ALS, the company is developing novel therapies to restore UNC13A protein function to re-establish healthy communication between nerves and muscle cells. Trace Neuroscience launched in 2024 with funding from Third Rock Ventures and other leading life sciences investors, and is headquartered in South San Francisco, CA. For more information, please visit us at www.traceneuro.com and follow us on LinkedIn and X .