The clinical-stage biotechnology company Pheast Therapeutics has announced the treatment of the first patient in its Phase 1 clinical trial evaluating PHST001, a novel anti-CD24 macrophage checkpoint inhibitor, in patients with advanced solid tumors. This milestone marks a significant advancement in the development of next-generation immunotherapies targeting the innate immune system.
"The start of this Phase 1 trial is an important milestone for Pheast and for the advancement of next generation macrophage checkpoint therapies," said Dr. Roy Maute, Cofounder and CEO of 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."
Trial Design and Objectives
The multicenter, open-label Phase 1 study (ClinicalTrials.gov Identifier: NCT06840886) will enroll up to 80 patients with advanced relapsed and/or refractory solid tumors. The trial's primary objectives include evaluating the safety and tolerability of PHST001 and establishing the recommended Phase 2 dose. Secondary endpoints will assess pharmacokinetics and early signs of anti-tumor activity.
Dr. Raphaël Rousseau, Chief Medical Officer at Pheast Therapeutics, highlighted the agent's promising preclinical profile: "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."
The Science Behind PHST001
PHST001 represents a novel approach to cancer immunotherapy by targeting CD24, a cell surface protein that plays a critical role in tumor immune evasion. CD24 engages Siglec-10, an inhibitory receptor on macrophages, suppressing their ability to clear cancer cells and allowing tumors to escape destruction by the innate immune system.
Dr. Irving Weissman, scientific co-founder of Pheast Therapeutics, explained: "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."
The therapeutic approach emerged from groundbreaking research led by Dr. Amira Barkal, principal founder of Pheast, along with co-founders Drs. Irving Weissman, Ravi Majeti, and Roy Maute. Their work identified CD24 as a novel macrophage checkpoint and opened new possibilities for therapeutic intervention.
Promising Preclinical Data
Preclinical data presented at the Society for Immunotherapy of Cancer (SITC) 2024 meeting highlighted PHST001's potential across multiple cancer types. The antibody is uniquely designed to target all glyco-variants of CD24, binding with high affinity and specificity to promote macrophage-induced phagocytosis in various cancer cell types.
In preclinical models, PHST001 demonstrated significant tumor shrinkage and a favorable pharmacokinetic profile in non-human primates without inducing immune-mediated toxicity in in vitro studies. These results suggest potential efficacy across a range of solid tumors, including those with historically poor responses to existing immunotherapies.
Clinical Significance and Unmet Need
CD24 is highly expressed in many human cancers, including ovarian cancer and triple-negative breast cancer (TNBC), with high expression correlating with negative prognosis in multiple cancer indications. By targeting CD24, PHST001 aims to overcome immune suppression in the tumor microenvironment and induce macrophages to phagocytose cancer cells, potentially initiating a powerful immune response.
This approach could be particularly valuable for patients with solid tumors that have proven resistant to current immunotherapies. Solid tumors, which account for the majority of cancer diagnoses, represent abnormal masses of tissue that typically do not contain cysts or liquid areas and can be classified as sarcomas, carcinomas, or lymphomas based on the cell types involved.
About Pheast Therapeutics
Pheast Therapeutics is a clinical-stage immuno-oncology company focused on activating the innate immune system against cancer. Founded as a spinout from Stanford University and led by scientific experts in innate immunity and cancer immunotherapy, the company is developing novel therapies for difficult-to-treat and aggressive cancers.
The company is backed by leading life sciences investors, including Catalio Capital Management and ARCH Venture Partners, and is headquartered in Redwood City, California. With PHST001 now in clinical development, Pheast is advancing its mission to harness macrophage biology for more effective cancer treatments.
