TIM1

LAPIX Therapeutics, Inc. (“LAPIX”), a biopharmaceutical company focused on developing novel, orally bioavailable immune system restoration therapies for autoimmune diseases, today announced that it has received clearance of its Investigational New Drug (IND) application from the U.S. Food and Drug Administration (FDA) to initiate a Phase 1 clinical trial for its first-in-class, immune tolerance restoration small molecule, LPX-TI641, for the treatment of multiple sclerosis (MS). The clinical trial is expected to begin dosing in 4Q 2023. “We believe in empowering and restoring the immune system to fight disease and the FDA clearance of our IND application for LPX-TI641 represents momentum in our technology and scientific approach,” said Anas M. Fathallah, Ph.D., Chief Executive Officer and co-founder of LAPIX. “We are excited to begin our first-in-human clinical study evaluating LPX-TI641 and its potential to be a first of its kind non-immune suppressive therapeutic option for autoimmune diseases.” The Phase 1 trial is designed to evaluate the safety, tolerability, and pharmacokinetics of LPX-TI641 in healthy subjects after a single ascending dose. Data from the Phase 1 study along with LPX-TI641’s antigen-agnostic versatility could allow for the rapid pivot to other autoimmune indications such as rheumatoid arthritis. “We aspire to transform how the medical field treats patients diagnosed with serious and complex immune diseases and we are deeply committed to helping as many people as possible,” added Dr. Fathallah. “Our antigen-agnostic immune tolerance restoration approach centered on developing Tim (T-cell immunoglobulin and mucin domain) agonists, along with our in-depth knowledge of immunology and immune tolerance are the keys to unlocking transformative therapies for patients with additional consideration for their quality of life.” About LPX-TI641 LPX-TI641 is an investigational, novel, and proprietary orally bioavailable small molecule T cell immunoglobulin and mucin domain-containing protein (TIM) 3/4 receptor agonist. The TIM family of receptors play an important role in autoimmunity. LPX-TI641’s primary pharmacology is the upregulation of Foxp3+/DC4+ T-cells (T-regs) and of Tim1+/CD25+/CD19+ (B-regs) and inhibition/downregulation of Th17. The combined effects of LPX-TI641’s pharmacology is to allow the adaptive immune system to re-establish self-tolerance (T-reg/Th17 balance and B-regs) without affecting the innate immune system. The efficacy of LPX-TI641 versus standards of care has been evaluated in several animal models of MS and those models have shown favorable efficacy of LPX-TI641 in treatment escalation and treatment induction/maintenance paradigms mimicking current clinical management paradigms of MS without inducing neutropenia or lymphocytopenia. It is currently under development for neuro-autoimmune indications such as MS, with the intent to expand into rheumatoid arthritis amongst other autoimmune conditions. About LAPIX Therapeutics LAPIX Therapeutics Inc. is a Boston, MA-based company in the biopharma sector, focused on developing novel, orally bioavailable immune system restoration therapies, including immune tolerance restoration therapy for autoimmune diseases, immune tolerance induction therapies for gene therapy, and immune function restoration therapies for oncology. To learn more, visit www.lapix.com or follow us on LinkedIn and Twitter. The content above comes from the network. if any infringement, please contact us to modify.

Research foundational to Larkspur’s newly disclosed TIM-1 program published by founder Vijay K. Kuchroo in Nature WATERTOWN, Mass., June 26, 2023 (GLOBE NEWSWIRE) -- Larkspur Biosciences revealed today that one of their lead programs is a first-in-class B cell checkpoint, TIM-1. This announcement follows the publication by Larkspur co-founder Vijay K. Kuchroo, DVM, PhD (Samuel L. Wasserstrom Professor, Neurology, Harvard Medical School; Senior Scientist, Neurology, Brigham and Women’s Hospital) in the journal Nature of TIM-1 as a targetable checkpoint protein central to B-cell anti-tumor activity. Immunotherapies targeting T cells have transformed the treatment of many types of cancers. Recent discoveries have highlighted that the presence of tertiary lymphoid structures in tumors – areas of B cell and T cell activation – are associated with positive responses to checkpoint blockade. Larkspur’s approach addresses the unique ways that tumors hijack the immune system, targeting bottlenecks that tumors use to subvert the immune system in order to develop precision immunotherapies for molecularly defined patient populations. This newly disclosed program adds a unique way to use B cells to drive anti-tumor responses. "The discovery of this novel B cell checkpoint protein, outlined in the Nature publication, unlocks the potential of targeting B cells to enhance immunotherapy responses,” said Dr. Kuchroo. “These findings support broadening the application of immune checkpoint blockade in cancer immunotherapy and provide a clear path to translation, which Larkspur is advancing within its pipeline.” Dr. Kuchroo, along with lead author Lloyd Bod, PhD (Mass General Cancer Center), and colleagues, discovered a type of B cell expressing TIM-1 expanded as tumors grew in melanoma. Using an antibody to TIM-1, they discovered that targeting TIM-1 and PD-1 in the melanoma model led to a better anti-tumor response, underscoring the potential of targeting both B cells and T cells in cancer. “It has recently been shown that the presence of B cells at the tumor is associated with positive responses to checkpoint blockade for cancer patients,” said Catherine Sabatos-Peyton, PhD, CEO of Larkspur Biosciences. “TIM-1 offers a novel way to harness the power of B cells at the tumor and potentially drive more meaningful anti-tumor responses for more patients. We look forward to continuing to progress our TIM-1 program as part of our mission to create the next precision immunotherapies to outsmart cancer.” The Nature article titled “B-cell-specific checkpoint molecules that regulate anti-tumour immunity” was published on June 21, 2023. The research briefing “Uncovering a role for B cells in antitumour immunity” provides a summary of the article. About Larkspur BiosciencesLarkspur Biosciences is building the next precision immunotherapies to outsmart cancer. Larkspur’s approach targets the unique ways that tumors hijack the immune system by developing precision immunotherapies for molecularly defined patient populations in order to overcome these bottlenecks. The company is advancing its first-in-class programs to outsmart the tumor and enable robust and sustained immune responses in colorectal cancer (CRC) and beyond. LarkX, the company’s target discovery platform, leverages tumor genetics and immune phenotypes from patient-derived data to fuel its pipeline and offers the opportunities to address multiple types of cancer. Visit us at www.larkspur.bio and follow us on LinkedIn and Twitter. CONTACT:Adam SilversteinScient PRadam@scientpr.com

B cells are thought to play a critical role in innate and adaptive immunity, but their exact role in anti-tumor immunity remains unknown. Researchers with expertise in immunology collaborated with experts in dermatology to further understand the role of B cells and identify a subset of cells that may play a critical role. B cells are thought to play a critical role in innate and adaptive immunity, but their exact role in anti-tumor immunity remains unknown. Researchers at Brigham and Women's Hospital with expertise in immunology collaborated with experts in dermatology from Massachusetts General Hospital to further understand the role of B cells and identify a subset of cells that may play a critical role. In collaboration with the Broad Institute they used a technique called single-cell profiling, which allows them to look at all the genes in the cell to study these B cells in mouse and human cancers. They found a cell surface receptor called TIM-1 expressed on these B cells during melanoma growth. They also characterized multiple accompanying cell surface proteins that were involved in the B cell's immune function. Interestingly, they found that deleting a molecule TIM-1, but not any of the other accompanying proteins, dramatically decreased tumor growth. The researchers concluded that TIM-1 controls B cell activation and immune response that combats cancer, including activating another type of the killer tumor-specific T cells for inhibiting tumor growth. "The collaboration across institutions was extremely fruitful as we combined our immunology expertise at the Brigham with work at David Fisher's MGH laboratory where seminal discoveries in skin malignancies have been made," said lead author Lloyd Bod, PhD, of the Department of Neurology at the Brigham, who conducted this work while completing his postdoctoral fellowship at the Brigham. Bod is now an Assistant Professor and an independent investigator at the Mass General Cancer Center. "The collaboration allowed us to test and demonstrate the therapeutic potential of targeting TIM-1 in melanoma models."