The FDA has cleared Sapience Therapeutics to begin clinical development of ST316 in familial adenomatous polyposis, with a Phase 1b study planned for 2027.

ST316 moves into FAP development

Sapience Therapeutics has received US Food and Drug Administration (FDA) clearance for its Investigational New Drug (IND) application for ST316 in familial adenomatous polyposis (FAP).

ST316 is an investigational peptide designed to block the interaction between β-catenin and BCL9, components of the Wnt/β-catenin signalling pathway. Sapience is developing the treatment for FAP, a rare inherited condition in which patients develop large numbers of adenomatous polyps in the colon and rectum and have a high lifetime risk of colorectal cancer.

The FDA has previously granted ST316 Orphan Drug designation for FAP. The regulatory agency’s orphan designation database lists the indication as designated but confirms that ST316 is not FDA approved for FAP.

The company plans to evaluate ST316 in a Phase 1b study in adults with FAP who have undergone colectomy and subsequently developed recurrent polyps. The planned study is designed to assess safety, tolerability, pharmacokinetics and pharmacodynamics, as well as preliminary evidence of whether ST316 can reduce polyp recurrence. The trial is currently listed as not yet recruiting, with an estimated start in January 2027.

Barry Kappel, chief executive officer of Sapience Therapeutics, said: “We are pleased to reach this important regulatory milestone for ST316.”

He added that the company’s approach is intended to selectively inhibit oncogenic β-catenin activity while avoiding some of the toxicities associated with broader inhibition of the Wnt pathway. Sapience said this is particularly relevant to FAP, where treatment could require long-term administration.

Targeting β-catenin in FAP

FAP is generally associated with mutations in the APC gene and abnormal activation of the Wnt/β-catenin pathway. Patients can develop hundreds or thousands of colorectal polyps, and management commonly involves regular surveillance and surgery.

There are currently no FDA-approved medicines specifically for FAP, according to Sapience. The company is therefore investigating whether targeting β-catenin could provide a medical approach to reducing the burden of recurrent polyps.

ST316 has already been studied in patients with advanced solid tumours. In the Phase 1 portion of the company’s ST316-101 study, 23 patients received ST316 as monotherapy. The study subsequently expanded into Phase 2 testing in colorectal cancer, where the drug is being investigated alongside standard-of-care treatment.

At the April 2026 data cut-off presented at the American Association for Cancer Research (AACR) Annual Meeting, 15 patients with second-line metastatic colorectal cancer had received ST316 in combination with FOLFIRI and bevacizumab. Sapience reported a confirmed objective response rate of 47%, with seven confirmed partial responses, and a disease control rate of 93%. These results are from a small, ongoing study and are separate from the planned FAP programme.

The company has said the colorectal cancer findings, together with preclinical FAP data, support investigation of ST316 in diseases in which β-catenin signalling is implicated.

A new clinical programme for FAP

The planned FAP study will provide the first clinical assessment of ST316 specifically in people with familial adenomatous polyposis.

Sapience’s approach is intended to interfere with oncogenic β-catenin activity by blocking its interaction with BCL9 rather than broadly suppressing the Wnt pathway. The company has argued that this selectivity could avoid effects on normal Wnt-dependent processes, including intestinal stem cell renewal and bone homeostasis.

However, the FAP programme remains at an early clinical stage. The FDA IND clearance allows the company to proceed with the clinical investigation; it does not establish the safety or efficacy of ST316 in FAP.

If the planned Phase 1b study begins as expected, its findings should provide the first clinical evidence of whether the β-catenin/BCL9 approach can affect recurrent polyps in people living with FAP.