Pheast Therapeutics is a biotechnology company focused on novel approaches to cancer treatment within immuno-oncology. Its mission is to develop therapies that activate the body’s innate immune system to combat aggressive cancers. By targeting specific pathways that cancer cells use to evade detection, Pheast aims to enable the immune system to recognize and eliminate cancerous cells.
Targeting the CD24 Don’t Eat Me Signal
Macrophages are a type of white blood cell. These cells act as first responders, capable of detecting, engulfing, and ultimately destroying abnormal or foreign cells through a process called phagocytosis. Macrophages commonly infiltrate solid tumors and are abundant within the tumor microenvironment.
Despite their presence, cancer cells devise sophisticated methods to escape this immune surveillance. They achieve this by displaying specific cell surface signals, known as “don’t eat me” signals. This interaction suppresses the macrophage-mediated clearance of cancerous cells, allowing tumors to persist and grow.
Pheast Therapeutics identified CD24 as a “don’t eat me” signal that cancer cells exploit. CD24 is a cell surface protein highly expressed by many human cancers, and its presence often correlates with a poorer prognosis in various cancer indications. This protein interacts with Siglec-10, an inhibitory receptor found on macrophages.
Pheast’s strategy involves blocking this CD24 signal. By disrupting the interaction between CD24 on cancer cells and Siglec-10 on macrophages, the company aims to “unmask” the cancer cells. This unmasking allows macrophages to recognize and engulf the cancer cells, initiating an immune response against the tumor.
A Novel Checkpoint Inhibitor
Other “don’t eat me” signals have been explored as therapeutic targets. CD47, for instance, is a macrophage checkpoint protein that transmits an inhibitory signal to immune cells. However, CD47 is ubiquitously expressed on most healthy cells, including red blood cells.
This widespread expression of CD47 can lead to safety challenges, as blocking it might inadvertently affect healthy cells and cause side effects like anemia. In contrast, CD24 exhibits a more restricted expression pattern. CD24 is not found on blood cell types, such as red blood cells or platelets.
The differentiated expression profile of CD24 presents an advantage, suggesting a more targeted therapy with reduced risk of off-target effects. CD24 is highly expressed on certain aggressive cancer types, including ovarian cancer and triple-negative breast cancer. This makes CD24 a promising target for immunotherapies.
Pheast’s Therapeutic Programs
Pheast Therapeutics is developing therapeutic candidates to target the CD24 “don’t eat me” signal. The company’s lead therapeutic candidate is PHST001, an anti-CD24 monoclonal antibody. This antibody binds to CD24 on cancer cells, blocking its interaction with Siglec-10 on macrophages.
PHST001 is designed to overcome immune suppression within the tumor microenvironment, enabling macrophages to phagocytose cancer cells and trigger an anti-tumor immune response. Pheast is focusing its initial efforts on treating aggressive cancers, including ovarian and triple-negative breast cancer, and exploring its potential in colorectal cancer and cholangiocarcinoma.
The company initiated a Phase 1 clinical trial (NCT06840886) to evaluate PHST001 in patients with advanced relapsed or refractory solid tumors. This study aims to enroll up to 80 patients to assess safety, tolerability, pharmacokinetics, and early anti-tumor activity. The U.S. Food and Drug Administration (FDA) granted Fast Track Designation to PHST001 for advanced platinum-resistant ovarian cancer, both as a monotherapy and in combination with chemotherapy for platinum-sensitive disease.
Company Origins and Strategic Alliances
Pheast Therapeutics emerged from foundational research conducted at Dr. Irv Weissman’s laboratory at Stanford University. Scientific insights into CD24’s role as a novel macrophage checkpoint were uncovered by Dr. Amira Barkal, a principal founder of Pheast.
Dr. Weissman, an expert in stem cell biology and macrophage immune checkpoints, along with Dr. Barkal, Dr. Ravi Majeti, and Dr. Roy Maute, are scientific founders of the company. Dr. Weissman and Dr. Majeti also co-founded Forty Seven Inc., a CD47-targeting company acquired by Gilead Sciences in 2020. Pheast secured $76 million in Series A funding in April 2022, with Catalio Capital Management and ARCH Venture Partners leading the investment round. Additional investors include Alexandria Venture Investments, Risk and Reward (R2), and Stanford University’s Presidential Venture Fund, providing resources to advance its pipeline toward clinical development.