Pheast's PHST001 Shows Broad Preclinical Activity in Peer-Reviewed CD24 Publication

Pheast Therapeutics announced a peer-reviewed publication in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR), detailing the preclinical foundation for PHST001, its high-affinity IgG4 anti-CD24 monoclonal antibody currently in phase 1 clinical development.¹ The published findings show that PHST001 binds CD24 with high affinity, blocks CD24-Siglec-10 signaling, and drives macrophage phagocytosis of tumor cells.¹ PHST001 demonstrated anti-tumor activity across six solid tumor models, ovarian, breast, endometrial, pancreatic, lung, and cholangiocarcinoma, and enhanced the effects of chemotherapy, radiotherapy, and antibody-drug conjugates, including in treatment-resistant tumor models.¹ The findings also revealed crosstalk between the adaptive immune system and macrophages activated by PHST001.¹

Irving Weissman, MD, co-founder of Pheast Therapeutics, said, "Cancer cells survive in part by expressing cell surface 'don't eat me' signals that suppress critical immune surveillance functions of the immune system's macrophages. CD24 is one of the most important of these signals expressed on several types of human cancer cells; this publication shows that blocking it with PHST001 can mobilize macrophages against a broad range of solid tumors. This is a significant advance for the field of innate immune therapy against cancer and is critical for the next stages to determine the potential of PHST001 to become an important new cancer treatment."²

How does PHST001 work?

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.² CD24 was identified as a novel macrophage checkpoint through foundational work by Amira Barkal, PhD, principal founder of Pheast, alongside co-founders Irving Weissman, MD, Ravi Majeti, MD, and Roy Maute, PhD.² That original discovery, published in Nature in 2019, first demonstrated that CD24 functions as a dominant innate immune checkpoint in ovarian cancer and breast cancer, working through its interaction with the inhibitory receptor Siglec-10 on tumor-associated macrophages, and showed that genetic ablation or antibody blockade of CD24 robustly increased phagocytosis of CD24-expressing tumors and extended survival in vivo.³ PHST001 is designed as a potential best-in-class antibody engineered to induce macrophages to phagocytose cancer cells and initiate a broader immune response.²

Roy Maute, PhD, co-founder and chief executive officer of Pheast, said, "The combination benefit outlined in this publication is exactly what we are now testing in patients, where PHST001 has already shown promising early signs of activity. These peer-reviewed data underpin our conviction in CD24 as a critical target and Pheast's leadership in macrophage checkpoint immunotherapy."²

What is the current clinical status of PHST001?

PHST001 is being evaluated in the ongoing Phase 1 PHST001-101 trial (NCT06840886) in patients with relapsed or refractory solid tumors.² Monotherapy dose-escalation is nearly complete, and chemotherapy combination cohorts are now underway across multiple solid tumor types, including ovarian cancer.² Pheast expects to present initial clinical data at an upcoming medical meeting.² PHST001 received FDA Fast Track Designation for the treatment of ovarian cancer in June 2025.²

What happens next?

With the preclinical mechanistic and combination data now published in a peer-reviewed journal, Pheast's near-term focus shifts to completing monotherapy dose-escalation and advancing its chemotherapy combination cohorts, ahead of presenting initial clinical data at a future medical meeting.²

References

1. Faget DV, Brewer RE, Sampaio J, et al. (2026 Jul 22). Targeting CD24 Activates Macrophages to Reduce Tumor Burden in Preclinical Models of Solid Tumors. Clin Cancer Res. doi:10.1158/1078-0432.CCR-26-0481. https://aacrjournals.org/clincancerres/article/doi/10.1158/1078-0432.CCR-26-0481/786982/Targeting-CD24-Activates-Macrophages-to-Reduce
2. Pheast Therapeutics Announces Publication in Clinical Cancer Research Demonstrating Robust Anti-Tumor Activity of PHST001. (2026 Jul 22). BusinessWire. https://www.businesswire.com/news/home/20260720055417/en/Pheast-Therapeutics-Announces-Publication-in-Clinical-Cancer-Research-Demonstrating-Robust-Anti-Tumor-Activity-of-PHST001
3. Barkal AA, Weiskopf K, Kao KS, et al. (2019 Aug). CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019;572(7769):392-396. https://pubmed.ncbi.nlm.nih.gov/31367043/