TPST-1495 receives FDA orphan drug designation for the treatment of FAP hereditary intestinal polyposis syndrome

2025year4month, American biopharmaceutical companyTempest Therapeuticsofficially announced that its innovative drug TPST-1495 has been granted orphan drug status (Orphan Drug) by the U.S. Food and Drug Administration (FDA) Designation), the drug is intended to treat a rare but high-risk genetic disease - familial adenomatous polyposis (Familial Adenomatous Polyposis, FAP). This recognition marks that TPST-1495 has made critical progress in the treatment of FAP and is expected to provide new treatment hope for FAP patients who currently lack effective treatments.

FAPis an autosomal dominant disease derived from mutations in the APC tumor suppressor gene. It usually begins in adolescence and is characterized by the repeated formation of hundreds to thousands of adenomatous polyps in the colon and other parts of the gastrointestinal tract. Without timely intervention, these polyps can easily become cancerous, leading to various malignant tumors of the digestive system such as colorectal cancer, gastric cancer, and duodenal cancer. Therefore, FAP is considered to be one of the high-risk pre-cancer states. Currently, the standard treatment is usually colectomy to prevent the occurrence of cancer. However, surgery cannot completely eliminate the risk of cancer. Regular lifelong examinations are still required after surgery to detect possible new lesions in other parts of the body.

To address this clinical gap, Tempest developed TPST-1495 as a highly selective dual EP2/EP4 prostaglandin receptor antagonist with a clear mechanistic target. By inhibiting the key cancer-promoting receptors EP2 and EP4 in the PGE2 signaling pathway, it disrupts the multiple effects of prostaglandins in tumor formation, including stimulating tumor cell proliferation, promoting angiogenesis, and weakening the immune system's ability to recognize and eliminate tumors. It is worth noting that TPST-1495 retains EP1 andEP3 also shows good specificity in receptor activity, which helps reduce potential side effects and improve efficacy and safety.

To further validate the potential of TPST-1495 in the treatment of FAP, a study was conducted by the National Cancer Institute (NCI ) funded by the Cancer Prevention Clinical Trials Network (CCRTN) will be launched in 2025. This clinical trial is expected to complete key data collection in the next year and a half, and the relevant results are expected to be officially announced in 2026. If the trial goes well, TPST-1495 is expected to become the first targeted drug that can be used to delay or prevent FAP related cancers.

In general, the development of TPST-1495 not only brings new hope to FAP patients, but also explores new directions for other prostaglandin-mediated cancer treatments. Obtaining orphan drug status will give the drug more policy and research and development support, including clinical trial fee reductions and extension of the market exclusivity period, which will help it accelerate its entry into the market. With the accumulation of trial data in the future, TPST-1495 may become an important disease intervention tool in clinical practice, providing unprecedented treatment options for people at high risk of hereditary bowel cancer.

References:Tempest Receives Orphan Drug Designation from the FDA for TPST-1495 to Treat Patients with FAP