Siglec-10

REDWOOD CITY, CA, USA I April 14, 2025 I Pheast Therapeutics , a private biotechnology company developing novel therapies to unleash the power of macrophages on aggressive, difficult-to-treat cancers, today announced that the first patient has been treated in its Phase 1 clinical trial evaluating PHST001, an anti-CD24 macrophage checkpoint inhibitor, in patients with advanced solid tumors. “The start of this Phase 1 trial is an important milestone for Pheast and for the advancement of next generation macrophage checkpoint therapies,” said Roy Maute, Ph.D., Cofounder and CEO, Pheast Therapeutics. “We believe PHST001 has the potential to provide new treatment options for patients, particularly in cancers where other immunotherapies have not been effective.” The multicenter, open-label Phase 1 study will enroll up to 80 patients with advanced relapsed and/or refractory solid tumors (ClinicalTrials.gov Identifier: NCT06840886 ). The study’s primary objectives include evaluating safety and tolerability of PHST001 and establishing the recommended Phase 2 dose, with secondary endpoints assessing pharmacokinetics and early signs of anti-tumor activity. Raphaël Rousseau, M.D., Ph.D., Chief Medical Officer, Pheast Therapeutics, said, “PHST001 has demonstrated robust activity across tumor types and a favorable safety profile in preclinical studies. Furthermore, these data suggest that PHST001 may overcome tumor immune evasion through a differentiated approach to macrophage activation. We are pleased to have initiated this study as a first step in understanding the clinical potential of PHST001 to improve patient outcomes across multiple cancer types.” Irving Weissman, M.D., scientific co-founder of Pheast Therapeutics added, “CD24 is a key mechanism that tumors use to evade macrophage-mediated immune responses. PHST001 was developed based on foundational research into this pathway, and I’m encouraged to see this science progressing into the clinic. It’s a meaningful step toward harnessing the full potential of the innate immune system in cancer.” Preclinical data presented at SITC 2024 highlight PHST001’s potential across multiple cancer types, and its differentiation as a novel macrophage checkpoint inhibitor uniquely designed to target all glyco-variants of CD24. By binding CD24 with high affinity and specificity, PHST001 promotes macrophage-induced phagocytosis in a variety of cancer cell types and significantly shrinks tumors in in vivo models. Additionally, PHST001 has a favorable pharmacokinetic profile in non-human primates and does not induce immune-mediated toxicity in in vitro studies. About CD24 CD24 is a cell surface protein that plays a key role in tumor immune evasion by engaging Siglec-10, an inhibitory receptor on macrophages. This interaction suppresses macrophage-mediated clearance of cancer cells, allowing tumors to escape destruction by the innate immune system. CD24 was identified as a novel macrophage checkpoint through foundational work by Dr. Amira Barkal, principal founder of Pheast. Along with other co-founders, Drs. Irving Weissman, Ravi Majeti, and Roy Maute, Pheast’s research opened the door to therapeutic strategies targeting CD24 to drive innate immune responses against cancer. About PHST001 PHST001 is an anti-CD24 macrophage checkpoint inhibitor designed to overcome immune suppression in the tumor microenvironment. CD24 is highly expressed by many human cancers, including ovarian and triple negative breast cancer (TNBC), and high expression of CD24 is a negative prognostic factor in multiple cancer indications. Pheast has engineered PHST001 to be a best in class antibody designed to induce macrophages to phagocytose cancer cells and initiate a powerful immune response. About Pheast Therapeutics Pheast is a clinical-stage immuno-oncology company focused on activating the innate immune system in the fight against cancer. Founded as a spinout from Stanford University and led by scientific experts in innate immunity and cancer immunotherapy, Pheast is developing novel therapies for some of the most difficult-to-treat and aggressive cancers. Pheast is backed by leading life sciences investors, Catalio Capital Management and ARCH Venture Partners. For more info, visit Pheast.com and connect on LinkedIn . SOURCE: Pheast Therapeutics

PALO ALTO, Calif.--( BUSINESS WIRE )-- Pheast Therapeutics (“Pheast”), a biotech developing novel macrophage checkpoint therapies to defy cancer, today announced the presentation of new preclinical data for PHST001, an anti-CD24 antibody drug candidate that is designed to block a key macrophage "don't eat me" signal on cancer cells. The data were presented at the 39th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) taking place both virtually and at the George R. Brown Convention Center in Houston from November 6-10, 2024. The presented data show that PHST001, through potent CD24 binding, promotes macrophage-induced phagocytosis in a number of cancer cells and significantly shrinks tumors in vivo. In addition, PHST001 has a favorable PK profile in non-human primates and does not induce immune-mediated toxicity in vitro. “These data build on the results we presented earlier this year at PEGS showing that PHST001 can powerfully induce an anti-cancer immune response and drive therapeutic efficacy in challenging mouse model systems,” said Roy Maute, Ph.D., Cofounder and CEO, Pheast Therapeutics. “Macrophage checkpoint therapies such as PHST001 have the potential to expand clinical options for patients in high unmet need oncology indications where other immunotherapies have not yet been successful.” CD24 is highly expressed by many human cancers, including ovarian and triple negative breast cancer (TNBC), and high expression of CD24 is a negative prognostic factor in multiple cancer indications. CD24 interacts with the macrophage receptor Siglec-10, and shields cancer cells from attack by macrophages. Pheast has engineered PHST001 to bind CD24 on the surface of cancer cells with high affinity and specificity and to block Siglec-10 binding. “The preclinical data demonstrate the potential of PHST001 to address multiple cancer types, and its differentiation as a novel macrophage checkpoint inhibitor with potent inhibition of CD24," said Suzana Kahn, Ph.D., Senior Director, Biology at Pheast Therapeutics. "PHST001 does not have a toxic preclinical profile, which, combined with its superior efficacy in our preclinical models, supports the initiation of first-in-human clinical trials.” Dr. Kahn presented these data in a poster presentation entitled, “PHST001, a humanized anti-CD24 antibody, induces phagocytosis of human tumor cells in vitro and tumor clearance in vivo.” About Pheast Therapeutics Pheast is a preclinical stage immuno-oncology company focused on targeting immune evasion pathways to activate the innate immune system to defy cancer and help patients thrive. Founded and led by scientific experts in innate immunity and cancer immunotherapy, Pheast is developing novel immunotherapies for some of the most difficult-to-treat and aggressive cancers, including ovarian cancer and triple negative breast cancer. For more info, visit www.pheast.com .

ONC-841 is a potential first-in-class SIGLEC10 antibody with broad application in oncology Designed to break tumor evasion of the immune system, ONC-841 can rejuvenate anti-tumor T cells, NK cells and macrophages within the tumor microenvironment Initial Phase 1 safety, pharmacokinetics, and clinical activity data for ONC-841 monotherapy are expected in 2025 ROCKVILLE, Md., Sept. 04, 2024 (GLOBE NEWSWIRE) -- OncoC4, Inc. (“OncoC4”), a late-stage biopharmaceutical company developing novel medicines for cancer and immunological diseases, today announced the first patient has been dosed in the first-in-human Phase 1 ONC-841-002 trial (NCT06352359) evaluating ONC-841, a potential first-in-class SIGLEC10 blocking antibody for the treatment of solid tumors. “Dosing the first patient in this first-in-human trial for ONC-841 marks an important step for our SIGLEC program which holds promise to treat a range of malignancies,” said Yang Liu, PhD, Co-Founder, CEO and CSO of OncoC4. “Targeting a novel SIGLEC10 immune checkpoint, ONC-841 is designed to block tumor evasion of the immune system by activating anti-tumor immunity within the tumor microenvironment. We are very excited at the broad therapeutic potential of ONC-841 and look forward to initial Phase 1 data in 2025.” ONC-841-002 is a Phase 1 open label, dose-escalation trial evaluating the safety, efficacy and pharmacokinetics of ONC-841 as a single agent in patients with advanced and or metastatic solid tumors. The study will assess seven dose levels of intravenous ONC-841 once every 4 weeks at multiple clinical centers throughout the United States. The trial principal investigator is Dr. Tianhong Li of the University of California, Davis Comprehensive Cancer Center. OncoC4 enrolled its first patient under the care of site investigator Dr. John Hamm, of Norton Cancer Institute in Louisville, Kentucky. Initial data on the safety, pharmacokinetics, and clinical activity of ONC-841 monotherapy are expected in 2025. Dr. Hamm added, “It is very exciting to be part of this journey. As oncologists we know we need better answers and through clinical trials like this, especially in the past 5 years, we have seen rapid improvements in cancer care and treatment.” Discovered in house, ONC-841 is a humanized antagonist anti-SIGLEC10 monoclonal antibody. To our knowledge, it is the first SIGLEC10 antagonist to enter clinical development. Siglec10 is an inhibitory receptor gene broadly expressed in tumor-infiltrating immune cells that plays an important role in tumor evasion of the immune system through its interaction with CD24 present on tumor cells. ONC-841 blocks this interaction, enabling anti-tumor activation of immune cells including NK cells, macrophages and T cells. SIGLEC10 has an authentic immunoreceptor tyrosine-based inhibitory motif, which is distinct from other siglecs such as SIGLEC15. In preclinical studies ONC-841 has been shown increased phagocytosis of cancer cells and improved function of tumor-infiltrating T cells and innate cells, as well as enhanced antibody-dependent CD16a signalling, a surrogate for antibody-dependent cell mediated cytotoxicity (ADCC). About OncoC4Based in Rockville, Maryland, OncoC4 is a privately held, late clinical-stage biopharmaceutical company that is actively engaged in the discovery and development of novel biologics for the treatment of cancer and immunological diseases. Its most advanced program is BNT316/ONC392 (gotistobart), a Phase 3, next generation anti-CTLA-4 antibody that is designed to allow CTLA-4 to recycle and maintain its protective function against autoimmune diseases while enhancing anti-tumor activity at the same time. In addition, OncoC4 is targeting CD24-Siglec pathway, an innate immune checkpoint discovered by its cofounders. OncoC4 has two first-in-class clinical stage SIGLEC programs, including AI-071, a Phase 2 ready SIGLEC agonist designed for difficult to treat immune related adverse events, and ONC-841, a Phase 1 SIGLEC10 antagonist for the treatment of solid tumors. OncoC4’s portfolio also includes preclinical programs targeting the CD24 cancer immune evasion pathway. More information: www.oncoc4.com. CONTACTS OncoC4Investor Contact:Alexandra FoliasLifeSci Advisorsafolias@lifesciadvisors.comMedia Contact:Kristin PolitiLifeSci Advisorskpoliti@lifescicomms.com About Norton Cancer InstituteAs the leading provider of cancer care in Louisville and Southern Indiana, Norton Cancer Institute’s mission is to blend comprehensive treatment and services with compassion, hope and healing for patients and their families. Through a multidisciplinary approach, its team offers patients the latest in treatments and technology focused on cancer prevention, diagnosis, care and survivorship. The institute’s specialists cover a broad range of oncology subspecialties, including behavioral, breast medical and radiation, gastrointestinal medical and radiation, genitourinary medical and radiation, gynecologic, head and neck medical and surgical, neurologic, orthopedic, sarcoma and connective tissue medical, and thoracic medical and radiation oncology, as well as cancer genetics, hematology and oncologic dermatology. Norton Cancer Institute offers state-of-the-art medical, surgical and radiation therapies, including minimally invasive robotic surgery, stereotactic radiosurgery (Novalis Tx and TrueBeam STx) and advanced brachytherapy. Patients have access to groundbreaking research through its participation in dozens of innovative National Cancer Institute and industry-sponsored clinical trials. Extensive educational, physical and emotional support services, including support groups, seminars, art and music therapy, massage therapy, yoga and nutritional counseling are available through five Norton Cancer Institute Resource Centers. Norton Cancer Institute is designated by the American College of Surgeons Commission on Cancer as the only accredited Integrated Network Cancer Program in Kentucky. More information is available at NortonCancerInstitute.com. CONTACTS Norton Cancer InstituteLynne ChoatePublic Relations managerLynne.choate@nortonhealthcare.org