FDA fast tracks PHST001 as treatment for ovarian cancer
Pheast therapy targets CD24 protein
Pheast Therapeutics has received fast track designation from the U.S. Food and Drug Administration (FDA) for PHST001, its candidate treatment for ovarian cancer, a type of gynecological cancer.
The FDA designation covers the therapy on its own for advanced platinum-resistant ovarian cancer or combined with chemotherapy for platinum-sensitive ovarian cancer. The designation, designed to speed the development of medications for serious and life-threatening conditions, makes Pheast eligible for increased interactions with the FDA and, potentially, expedited review.
“We are committed to advancing PHST001 through the clinic and accelerating its development for cancer patients in urgent need of more effective treatments,” Raphaël Rousseau, MD, PhD, Pheast’s chief medical officer, said in a company press release.
Pheast is running a Phase 1 clinical trial (NCT06840886) testing the therapy for people with relapsed or refractory solid tumors. The trial is currently recruiting at sites across the U.S., with an estimated enrollment of up to 80 participants, including some with ovarian cancer.
Ovarian cancer is the second most common type of gynecological cancer. It begins in the ovaries, the female reproductive organs that produce eggs and hormones.
Treatment approaches for ovarian cancer
Different forms of the disease begin in different types of ovarian cells. Most frequently, the epithelial cells lining the outside of the ovaries are the ones first affected. These tumors often grow slowly, then become more aggressive. It is common for the cancer to spread outside the ovaries by the time of diagnosis. Treatment approaches may include chemotherapy, radiotherapy, or surgery.
One important factor in treatment planning is platinum sensitivity, which refers to how well the cancer responds to platinum-based chemotherapy drugs. If the cancer shrinks or disappears for six months or more after treatment, it is considered platinum-sensitive. If it returns sooner, it is platinum-resistant.
CD24 is a protein found on the surface of cells. Tumors, including those related to ovarian and breast cancers, express CD24 at high rates. Higher levels of CD24 predict poorer clinical outcomes in ovarian and other cancers.
The protein engages the Siglec10 receptor on macrophages, a type of white blood cell that surrounds and kills cells and disposes of them. This acts as a signal for the macrophages not to destroy the CD24-expressing cells, allowing cancer cells to survive.
Pheast designed PHST001 to interrupt this process by targeting CD24. It disrupts the interaction between CD24 and Siglec10. This allows macrophages to kill the cancer cells, curbing tumor growth, according to Pheast.
In testing with cells derived from ovarian and other tumors, PHST001 bound to CD24 with high affinity. These petri dish experiments showed that macrophages then attacked and killed cancerous cells. The therapy also led to significant inhibition of tumor growth in mouse models of difficult to treat breast cancers.
With these positive results, Pheast began its Phase 1 trial this year. The first portion of the trial is testing escalating doses of PHST001 delivered via into-the-vein infusions every three weeks. As data become available from this part of the study, the company will plan a second portion, trying selected doses in larger groups of participants.
The trial’s primary goals are to evaluate the safety and tolerability of the therapy, with assessments planned 21 days after the first dose and 90 days after the last dose. Secondary endpoints include describing pharmacokinetics, or how the therapy moves through the body, and preliminary anti-tumor activity.
“Receiving Fast Track designation from the FDA reinforces the promise of CD24 as a next-generation immuno-oncology target and highlights the potential of PHST001 to address a critical unmet need in the treatment of ovarian cancer,” Rousseau said.
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