Tempest Therapeutics has received a "Study May Proceed" letter from the U.S. Food and Drug Administration (FDA) for a Phase 2 clinical trial of TPST-1495 in patients with Familial Adenomatous Polyposis (FAP), marking a significant advancement in developing new treatment options for this high-risk genetic condition.
TPST-1495, the company's novel dual receptor inhibitor of prostaglandin (PGE2) signaling, represents Tempest's second clinical program to enter Phase 2 development. The trial will be conducted by the Cancer Prevention Clinical Trials Network with financial support from the National Cancer Institute's Division of Cancer Prevention.
"Receiving the FDA's clearance to proceed with our Phase 2 clinical trial for TPST-1495 in FAP marks an important step forward in developing new treatment options for patients suffering from this high-risk disease that significantly increases the risk of multiple GI cancers," said Sam Whiting, M.D., Ph.D., chief medical officer and head of R&D of Tempest.
Understanding Familial Adenomatous Polyposis
FAP is a rare genetic disorder characterized by the development of numerous polyps in the colon and rectum. If left untreated, these polyps almost inevitably progress to colorectal cancer. Patients with FAP typically undergo colectomy as a preventive measure, but remain at risk for polyp development in other parts of the gastrointestinal tract, particularly the duodenum.
The condition significantly increases patients' risk of developing multiple gastrointestinal cancers, underscoring the urgent need for innovative therapeutic approaches beyond surgical intervention.
Phase 2 Trial Design and Objectives
The planned Phase 2 study will specifically target FAP patients who have previously undergone colectomy. The primary efficacy objective is to assess TPST-1495's ability to reduce duodenal polyp burden by comparing baseline endoscopy to endoscopy results after 6 months of treatment.
Additional objectives include evaluating the reduction of polyp burden in retained rectum or ileal pouch-anal anastomosis (IPAA) and assessing the overall safety profile of TPST-1495. The study is expected to begin this year, with data anticipated in 2026.
Mechanism of Action and Potential Impact
TPST-1495 works by inhibiting prostaglandin (PGE2) signaling through a dual receptor mechanism. PGE2 has been implicated in promoting inflammation and cancer progression, making it a promising target for both cancer treatment and prevention.
Dr. Whiting emphasized the significance of this collaboration, stating, "This collaboration with the Cancer Prevention Clinical Trials Network, financially supported by the National Cancer Institute's Division of Cancer Prevention, underscores the urgent need for innovative approaches in cancer prevention, and we look forward to advancing this potential promising therapy to help patients facing this difficult disease."
About Tempest Therapeutics
Tempest Therapeutics, headquartered in Brisbane, California, is a clinical-stage biotechnology company developing first-in-class targeted and immune-mediated therapeutics to fight cancer. The company's portfolio includes small molecule product candidates with tumor-targeted and/or immune-mediated mechanisms designed to treat a wide range of tumors.
The advancement of TPST-1495 into Phase 2 trials represents an important milestone for Tempest as it continues to expand its clinical pipeline. The company's programs range from early research to later-stage investigation in randomized global studies in first-line cancer patients.
Future Outlook
If successful, TPST-1495 could provide a much-needed non-surgical option for FAP patients who currently have limited treatment alternatives. The focus on reducing duodenal polyp burden addresses a critical unmet need, as duodenal cancer is a leading cause of death in FAP patients who have undergone colectomy.
The collaboration between Tempest Therapeutics, the Cancer Prevention Clinical Trials Network, and the National Cancer Institute highlights a growing emphasis on developing preventive strategies for high-risk cancer populations, potentially establishing a new paradigm in cancer prevention.
