Highly encouraging initial clinical results in second-line colorectal cancer (2L CRC): 47% objective response rate, disease control in 93% of patients
TARRYTOWN, N.Y., April 20, 2026 /PRNewswire/ -- Sapience Therapeutics, Inc., a clinical-stage biotechnology company focused on the discovery and development of peptide therapeutics to address oncogenic and immune dysregulation that drive cancer, today announced the presentation of new data on its clinical and pipeline programs at the American Association for Cancer Research (AACR) Annual Meeting 2026, taking place April 17-22, 2026, in San Diego, California. The posters will include the first public disclosure of clinical data from the Phase 2 dose expansion study of ST316, the company's first in class β-catenin antagonist, in metastatic colorectal cancer (mCRC).
Colorectal cancer is the third most commonly diagnosed cancer in both men and women and the second leading cause of cancer-related death in the United States.1 The Wnt/β-catenin pathway drives more than 80% of these cases,2 making it one of the highest-value targets in oncology. Despite decades of industry investment, no Wnt-targeted therapy has reached approval, as prior approaches were consistently constrained by systemic toxicity.
In Sapience's ongoing Phase 2 expansion study of ST316, 15 patients with 2L CRC have been enrolled and treated with a combination of ST316 and standard-of-care, FOLFIRI + bevacizumab. As of an April 13, 2026 cutoff date:
The confirmed objective response rate (ORR) per RECIST 1.1 was 47%, with 7 of 15 patients having a confirmed Partial Response (PR). This ORR compares favorably to historical studies evaluating the combination of anti-VEGF and chemotherapy in 2L CRC (ORR range: 5 - 23%).3
The disease control rate (DCR) was 93%, with 14 patients classified as having Stable Disease (SD) or PR.
Responses were seen in RAS-mutated and RAS-wild type patients, patients with liver metastases, and patients treated with prior bevacizumab.
In the ST316 Phase 1 monotherapy dose escalation study, trial objectives were achieved, which demonstrated:
Potent on-target pharmacodynamic effects, including significant and consistent knock down of Wnt-related signatures in tumor cells but not in adjacent normal cell types, recapitulation of a β-catenin/BCL9 genetic knock-out signature, reduced expression of Wnt target genes, and loss of cancer stem cell features.
Dose-proportional pharmacokinetics that achieve predicted efficacious exposures.
A well-tolerated safety profile, with no dose-limiting toxicities (DLTs) or related serious adverse events (SAEs) observed.
"We are extremely encouraged by the ST316 data we are presenting at AACR 2026. Metastatic colorectal cancer patients continue to face poor survival outcomes with currently available therapies, and our results highlight ST316's potential to address a wide segment of this underserved population," said Barry Kappel, Ph.D., Sapience's Chief Executive Officer. "The efficacy observed in combination with standard-of-care provides a strong foundation for advancing ST316 both within and beyond CRC, and we look forward to initiating additional clinical studies to unlock these opportunities. We are preparing a monotherapy Phase 1b study in familial adenomatous polyposis (FAP), a precancerous Wnt-driven syndrome marked by the development of hundreds of intestinal polyps that typically develops into CRC. With no approved treatments for FAP, ST316 presents a compelling opportunity to meet this critical unmet need."
In addition to the ST316 clinical data, Sapience will also present non-clinical data at AACR demonstrating that ST316 suppresses and reprograms immunosuppressive myeloid cells that are driven by β-catenin, and on its FraAP program, a first-in-class antagonist of the activator protein 1 (AP-1) complex, showing potent anti-tumor activity in head and neck squamous cell carcinoma (HNSCC) models.
Details of the presentations are as follows:
Title: "ST316, a first in class β-catenin antagonist, demonstrates safety and efficacy in metastatic colorectal cancer (mCRC)"
Session Title: Phase II and Phase III Clinical Trials
Location: Poster Section 52, Poster Board Number 20
Abstract Number: CT156
Date and Time: Monday, April 20, 2026, 2:00PM – 5:00PM PST
Title: "Antagonism of β-catenin/BCL9 interaction suppresses polymorphonuclear myeloid-derived suppressor cell generation and maintenance"
Session Title: Oncogenic Pathways and Cancer Immunity
Location: Poster Section 7, Poster Board Number 5
Abstract Number: 5562
Date and Time: Tuesday, April 21, 2026, 2:00PM – 5:00PM PST
Title: "Targeted antagonism of the activator protein 1 transcription factor complex results in potent anti-tumor activity in HNSCC models"
Session Title: Oncogenic Transcription Factors and Cancer Programs
Location: Poster Section 24, Poster Board Number 17
Abstract Number: 4767
Date and Time: Tuesday, April 21, 2026, 9:00AM – 12:00PM PST
More information can be found on the AACR Annual Meeting 2026 website.
About the Phase 1/2 Trial of ST316
ST316-101 (NCT05848739) is a first-in-human, open-label, Phase 1/2 dose escalation and expansion study designed to determine the safety, tolerability, PK, PD and early efficacy of ST316. The Phase 1 dose escalation portion of the study tested various dose levels of ST316 in patients with selected advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway, including colorectal cancer (CRC). ST316 is currently being evaluated in the Phase 2 dose expansion portion of the study in CRC patients in combination with relevant standards of care and in multiple lines of treatment. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to ST316 for the treatment of familial adenomatous polyposis (FAP).
About ST316
ST316 is a first-in-class antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex responsible for driving oncogene expression and immune exclusion in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. Aberrant activation of the Wnt/β-catenin pathway is a critical driver of tumor progression and immune evasion in tumors including colorectal cancer (CRC). Targeting this pathway is challenging for multiple reasons including its role in normal tissue physiology. BCL9 is a co-activator essential for oncogenic β-catenin activity, but not its physiologic functions, highlighting the β-catenin/BCL9 interaction as a therapeutic target. ST316 was designed to selectively disrupt the β-catenin and BCL9/9L interaction, resulting in disruption of oncogenic Wnt/β-catenin transcriptional activity and potent antitumor activity, with no negative impact on intestinal or bone physiology.
About Sapience Therapeutics
Sapience Therapeutics, Inc. is a privately held, clinical-stage biotechnology company focused on discovering and developing peptide therapeutics to address oncogenic and immune dysregulation that drive cancer. With in-house discovery capabilities, Sapience has built a pipeline of therapeutic candidates called SPEARs™ (Stabilized Peptides Engineered Against Regulation) that disrupt intracellular protein-protein interactions, enabling targeting of transcription factors which have traditionally been considered undruggable. Sapience can also direct cargo to cell surface targets with their new class of molecule called SPARCs™ (Stabilized Peptides Against Receptors on Cancer), enabling delivery of radioisotope payloads such as α-particles to cancer cells. Sapience is advancing its lead programs, ST316, a first-in-class antagonist of β-catenin, and lucicebtide (formerly known as ST101), a first-in-class antagonist of C/EBPβ, through Phase 2 clinical trials.
For more information on Sapience Therapeutics, please visit and engage with us on LinkedIn.
_____________________________________________________________
1 Siegel RL, Kratzer TB, Wagle NS, Sung H, Jemal A. Cancer statistics, 2026. CA Cancer J Clin. 2026; e70043. doi: 10.3322/caac.70043
2 Yaeger et al., Clinical Sequencing Defines the Genomic Landscape of Metastatic Colorectal Cancer, 2018, Cancer Cell 33, 125–136.
3 Iwamoto et al, Ann Oncol 2015 (EAGLE Study); Van Cutsem et al, JCO 2012 (VELOUR Study); Tabernero et al, Lancet Oncol 2015 (RAISE Study); Bennouna et al, Lancet Oncol 2013 (ML18147 Study); Masi et al, Ann Oncol 2015 (BEBYP Study); Giantonio et al, JCO 2007 (E3200 Study)
SOURCE Sapience Therapeutics, Inc.
21%
more press release views with
Request a Demo
