First Patient Treated in Trial of PHST001 for Advanced Solid Tumors

The First patients has been dosed in a phase 1 trial of PHST001, a novel macrophage checkpoint inhibitor for advanced solid tumors.

Pheast Therapeutics announced that the first patient has been treated in a phase 1 clinical trial evaluating PHST001 in patients with advanced solid tumors, according to a news release from the company.

“The start of this phase 1 trial is an important milestone for Pheast and for the advancement of next generation macrophage checkpoint therapies,” Dr. Roy Maute, Cofounder and CEO of Pheast Therapeutics,” said in the news release. “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 or refractory solid tumors. The trial's primary goals are to evaluate the safety and tolerability of PHST001 and determine the recommended phase 2 dose. Secondary endpoints include assessing pharmacokinetics and early signs of anti-tumor activity.

“PHST001 has demonstrated robust activity across tumor types and a favorable safety profile in preclinical studies,” Dr. Raphaël Rousseau, Chief Medical Officer, Pheast Therapeutics, said in the news release, “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.”

Preclinical data presented at the 39^th Annual Meeting of the Society for Immunotherapy of Cancer 2024 highlighted the potential of PHST001 across several cancer types and its distinction as a novel macrophage checkpoint inhibitor designed to target all glyco-variants of CD24. The agent binds CD24 with high affinity and specificity, promoting macrophage-induced phagocytosis in various cancer cell types and significantly reducing tumor size in in vivo models. PHST001 also demonstrated a favorable pharmacokinetic profile in non-human primates and did not induce immune-mediated toxicity in in vitro studies.

“CD24 is a key mechanism that tumors use to evade macrophage-mediated immune responses,” Dr. Irving Weissman, scientific co-founder of Pheast Therapeutics, said in the news release. “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.”

About CD24, PHST001 and Solid Tumors

CD24, a cell surface protein, helps tumors evade the immune system by binding to Siglec-10, an inhibitory receptor on macrophages. This interaction suppresses macrophage activity, allowing cancer cells to avoid destruction by the innate immune system. Dr. Amira Barkal, principal founder of Pheast, led foundational work identifying CD24 as a novel macrophage checkpoint. Alongside co-founders Drs. Irving Weissman, Ravi Majeti and Roy Maute, the team’s research laid the groundwork for targeting CD24 to boost innate immune responses against cancer.

PHST001, developed by Pheast, targets CD24 to help reverse immune suppression in the tumor microenvironment. The investigational macrophage checkpoint inhibitor is designed to stimulate the immune system by encouraging macrophages to engulf cancer cells. CD24 is overexpressed in several cancers, including ovarian and triple-negative breast cancer, and is associated with worse outcomes across tumor types.

According to the National Cancer Institute, a solid tumor is an abnormal mass of tissue that typically does not contain cysts or liquid areas. These tumors may be benign, meaning not cancerous, or malignant, meaning cancerous. They are classified based on the type of cells that form them. Examples include sarcomas, carcinomas and lymphomas. Leukemias or blood cancers generally do not form solid tumors.

(ClinicalTrials.gov Identifier: NCT06840886)

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