The First sufferers has been dosed in a part 1 trial of PHST001, a novel macrophage checkpoint inhibitor for superior strong tumors.
Pheast Therapeutics introduced that the primary affected person has been handled in a part 1 scientific trial evaluating PHST001 in sufferers with superior strong tumors, in response to a information launch from the corporate.
“The beginning of this part 1 trial is a vital milestone for Pheast and for the development of subsequent era macrophage checkpoint therapies,” Dr. Roy Maute, Cofounder and CEO of Pheast Therapeutics,” stated within the information launch. “We consider PHST001 has the potential to offer new therapy choices for sufferers, notably in cancers the place different immunotherapies haven’t been efficient.”
The multicenter, open-label part 1 examine will enroll as much as 80 sufferers with superior relapsed or refractory strong tumors. The trial’s main objectives are to judge the protection and tolerability of PHST001 and decide the really useful part 2 dose. Secondary endpoints embody assessing pharmacokinetics and early indicators of anti-tumor exercise.
“PHST001 has demonstrated strong exercise throughout tumor sorts and a positive security profile in preclinical research,” Dr. Raphaël Rousseau, Chief Medical Officer, Pheast Therapeutics, stated within the information launch, “Moreover, these knowledge recommend that PHST001 could overcome tumor immune evasion by a differentiated strategy to macrophage activation. We’re happy to have initiated this examine as a primary step in understanding the scientific potential of PHST001 to enhance affected person outcomes throughout a number of most cancers sorts.”
Preclinical knowledge offered on the 39th Annual Assembly of the Society for Immunotherapy of Most cancers 2024 highlighted the potential of PHST001 throughout a number of most cancers sorts and its distinction as a novel macrophage checkpoint inhibitor designed to focus on all glyco-variants of CD24. The agent binds CD24 with excessive affinity and specificity, selling macrophage-induced phagocytosis in numerous most cancers cell sorts and considerably decreasing tumor dimension in in vivo fashions. PHST001 additionally demonstrated a positive pharmacokinetic profile in non-human primates and didn’t induce immune-mediated toxicity in in vitro research.
“CD24 is a key mechanism that tumors use to evade macrophage-mediated immune responses,” Dr. Irving Weissman, scientific co-founder of Pheast Therapeutics, stated within the information launch. “PHST001 was developed based mostly on foundational analysis into this pathway, and I’m inspired to see this science progressing into the clinic. It’s a significant step towards harnessing the complete potential of the innate immune system in most cancers.”
About CD24, PHST001 and Strong Tumors
CD24, a cell floor protein, helps tumors evade the immune system by binding to Siglec-10, an inhibitory receptor on macrophages. This interplay suppresses macrophage exercise, permitting most cancers cells to keep away from destruction by the innate immune system. Dr. Amira Barkal, principal founding father of Pheast, led foundational work figuring out CD24 as a novel macrophage checkpoint. Alongside co-founders Drs. Irving Weissman, Ravi Majeti and Roy Maute, the group’s analysis laid the groundwork for focusing on CD24 to spice up innate immune responses in opposition to most cancers.
PHST001, developed by Pheast, targets CD24 to assist reverse immune suppression within the tumor microenvironment. The investigational macrophage checkpoint inhibitor is designed to stimulate the immune system by encouraging macrophages to engulf most cancers cells. CD24 is overexpressed in a number of cancers, together with ovarian and triple-negative breast most cancers, and is related to worse outcomes throughout tumor sorts.
In line with the Nationwide Most cancers Institute, a strong tumor is an irregular mass of tissue that sometimes doesn’t comprise cysts or liquid areas. These tumors could also be benign, that means not cancerous, or malignant, that means cancerous. They’re labeled based mostly on the kind of cells that type them. Examples embody sarcomas, carcinomas and lymphomas. Leukemias or blood cancers typically don’t type strong tumors.
(ClinicalTrials.gov Identifier: NCT06840886)
For extra information on most cancers updates, analysis and schooling, don’t overlook to subscribe to CURE®’s newsletters right here.
