Sapience Therapeutics, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted the company an Investigational New Drug (IND) application for ST316 (IND 184073) for the treatment of familial adenomatous polyposis (FAP), a rare inherited disorder associated with the development of hundreds to thousands of precancerous colorectal polyps and a significantly increased risk of colorectal cancer.
FAP typically results from mutations in the APC gene. Without intervention, individuals with FAP face a near-certain lifetime risk of developing colorectal cancer. Current management strategies rely heavily on intensive surveillance and prophylactic surgery, underscoring the need for effective medical therapies that can reduce disease burden and delay or prevent surgical intervention.
FAP affects an estimated 1 in 5,000 to 10,000 individuals in the US, according to the National Organization for Rare Disorders, and there are currently no FDA-approved medical therapies for the condition.
ST316 has previously received Orphan Drug designation from the FDA for the treatment of FAP.
“We are pleased to reach this important regulatory milestone for ST316,” said Barry Kappel, chief executive officer of Sapience Therapeutics.
“ST316’s unique mechanism of action is designed to selectively inhibit oncogenic β-catenin activity while avoiding the toxicities associated with broader Wnt pathway inhibition. The favourable safety and tolerability profile observed with ST316 monotherapy in the phase 1 clinical study strengthens the potential of this differentiated approach, particularly in FAP, where long-term treatment requires a high bar for safety and tolerability. Together with supportive preclinical activity in FAP models of disease, we believe ST316 has the potential to become an important new therapeutic option for patients with this serious inherited condition.”
ST316 has already demonstrated encouraging clinical activity in an ongoing phase 2 expansion study in second-line metastatic colorectal cancer (2L mCRC). As presented at AACR 2026, and based on an April 13, 2026 data cutoff, 15 patients had been enrolled and treated with ST316 in combination with standard of care (FOLFIRI and bevacizumab), with a confirmed objective response rate (ORR) of 47%, including seven confirmed partial responses, and a disease control rate (DCR) of 93%. These results compare favourably to historical outcomes for FOLFIRI and bevacizumab in 2L mCRC patients, which have demonstrated an 11% ORR.
Responses were observed across multiple patient subgroups, including those with RAS-mutated and RAS wild-type tumours, liver metastases, and prior bevacizumab exposure. In the 23-patient phase 1 monotherapy portion of the study, ST316 demonstrated a favourable safety and tolerability profile, as previously disclosed at AACR 2026. These results provide clinical validation of β-catenin/BCL9 pathway antagonism in humans and support the rationale for evaluating ST316 in other β-catenin-driven diseases, including FAP, where the pathway is uniformly activated.