β-catenin peptide inhibitors(FogPharma)

TARRYTOWN, NY, USA I June 13, 2023 I 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, announced today that the first patient has commenced treatment in its Phase 1-2 study evaluating the Company's first-in-class antagonist of β-catenin, ST316. Though a principal driver of many cancers, β-catenin has evaded drug discovery efforts for more than 30 years. ST316 is designed to selectively target oncogenic activation of the Wnt/β-catenin signaling pathway, without impacting its activity in normal cells. 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 will test various dose levels of ST316 in patients with select advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. With its first patient dosed on June 5, 2023, the Company expects to complete the Phase 1 portion of the study in the second half of 2024. Following completion of the study's Phase 1 portion, the recommended dose will advance to the Phase 2 portion of the study, in which ST316 will be tested in four advanced solid tumor types that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. Sapience is conducting the Phase 1 study across several sites in the United States. "Dosing our first patient with ST316 is a significant accomplishment for our team, which has remained undaunted by the challenge of drugging one of the most challenging cancer targets, the Wnt/β-catenin pathway," said Dr. Abi Vainstein-Haras, Sapience's Chief Medical Officer. "We are thrilled to advance our second molecule from the bench to the clinic. Given the relevance of Wnt/β-catenin in the development of multiple cancers, we are excited about ST316's potential to make a meaningful difference for the many patients suffering from cancers driven by abnormalities in this pathway." In March 2023, Sapience announced that it received IND clearance from the U.S. Food and Drug Administration (FDA) to proceed with a Phase 1-2 clinical trial of ST316 for the treatment of solid tumors. At the American Association for Cancer Research (AACR) Annual Meeting 2023, Sapience presented late-breaking data on ST316 highlighting its immunotherapeutic potential. In May 2023, Sapience was awarded a $2 million SBIR grant from the National Cancer Institute (NCI) of the National Institutes of Health (NIH) to support non-clinical studies for ST316. About the Wnt/ β -catenin Pathway β-catenin is a critical member of the canonical Wnt signaling pathway, a well-known pathway that is critically involved in embryonic development and adult tissue homeostasis. Wnt pathway hyperactivity is known to play a role in greater than 50% of solid tumors, in which it is a driver of oncogenesis and immune suppression. Because of the importance of the Wnt pathway in normal functioning adult cells, development of β-catenin-targeted therapies that block the Wnt pathway has been hampered by toxicity and off-target effects. There are currently no approved drugs that target the Wnt/β-catenin pathway. About ST316 ST316 is a first-in-class peptide antagonist of the interaction between β-catenin and its co-activator, BCL9, a complex that drives oncogene expression in multiple cancers where aberrant Wnt/β-catenin pathway signaling is observed. ST316 exposure in cancer cells prevents BCL9-driven nuclear localization of β-catenin and inhibits formation of the Wnt enhanceosome protein complex. Disruption of this interaction selectively suppresses the transcription of oncogenic Wnt target genes that regulate proliferation, migration, invasion and the metastatic potential of tumor cells, as well as genes that regulate the immunosuppression of the tumor microenvironment. ST316 creates a pro-immune tumor microenvironment and in preclinical models has shown to be synergistic with checkpoint inhibition. Due to its selectivity and downstream modulation of the Wnt/β-catenin pathway, ST316 presents an opportunity to safely and effectively target Wnt/β-catenin driven cancers without the toxicities previously seen with other Wnt pathway agents. The Phase 1 dose-escalation portion of the Phase 1-2 study has begun enrolling and dosing patients with select advanced solid tumors that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. The Phase 2 dose-expansion portion will utilize the recommended ST316 dose to assess its safety and early efficacy in four specific tumor types that are known to harbor abnormalities of the Wnt/β-catenin signaling pathway. 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. Sapience's in-house discovery platform, PADS™ Peptide Antagonist Discovery System), enables the rational design of novel peptides with optimized properties for clinical development. Leveraging PADS™, 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 is advancing its lead programs, ST316, a first-in-class antagonist of β-catenin, and ST101, a first-in-class antagonist of C/EBPβ, through Phase 1-2 clinical trials. For more information on Sapience Therapeutics, please visit www.sapiencetherapeutics.com and engage with us on LinkedIn . SOURCE: Sapience Therapeutics

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- FogPharma®, a biopharmaceutical company committed to transforming the lives of patients through a new precision medicine approach widely applicable to important and challenging intracellular targets, today announced the first patient has been dosed in a first-in-human Phase 1/2 clinical trial of, FOG-001, the company’s first-in-class TCF-blocking β-catenin inhibitor. FOG-001 represents the first development candidate arising from FogPharma’s pioneering Helicon™ therapeutics, a new class of drugs capable of modulating protein-protein interactions that may otherwise be challenging to drug. “The Wnt/β-catenin signaling pathway is one of the most frequently activated oncogenic pathways and a well-described driver of many cancers, but this target had been frustratingly beyond therapeutic reach until the discovery of FOG-001,” said Gregory Verdine, Ph.D., founder and chief executive officer of FogPharma. “I am proud of our team’s inventiveness, hard work and dedication towards advancing our exceptional science to this very important milestone and look forward to FogPharma’s next chapter as a clinical-stage company.” “FOG-001 has the potential to become a significant new treatment option for the large number of cancer patients whose disease is driven by derangement of the Wnt/β-catenin pathway, including those with colorectal cancer,” said Mathai Mammen, M.D., Ph.D., who will become chairman, president and chief executive officer of FogPharma on June 12, 2023. “Metastatic colorectal cancer is a devastating malignancy with increasing prevalence and few approved therapies directly targeting oncogenic driver mutations. These patients are in need of novel therapeutic options. We look forward to characterizing the safety, tolerability and anti-tumor activity of FOG-001 in this Phase 1/2 trial.” The first-in-human, multicenter, open-label, non-randomized dose escalation and dose expansion Phase 1/2 trial will aim to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of FOG-001 in up to 200 patients with Wnt/β-catenin signaling pathway activated advanced or metastatic solid tumors, with an initial focus on colorectal cancer (CRC). The Phase 1 portion aims to enroll 60 patients and will assess the safety and tolerability of FOG-001 across a range of dose levels to determine the best doses to progress to the Phase 2 portion. The Phase 2 portion will aim to enroll up to 140 patients to further characterize the safety, tolerability and anti-tumor activity of single-agent FOG-001 at the recommended Phase 2 dose. About Fog-001 FOG-001 is a first-in-class TCF-blocking β-catenin inhibitor. FOG-001 represents the first of FogPharma’s proprietary, conformationally stabilized α-helical polypeptide (Helicon™) therapeutics, a new class of drugs that combine the cell-penetration of small molecules with the broad target engagement of protein therapeutics. Helicons are uniquely capable of modulating disease-relevant interactions that have otherwise proven challenging to drug. FOG-001 combines key features that distinguish it from previously reported Wnt/β-catenin pathway modulators: FOG-001 acts inside the cell where it binds directly to the key oncogenic driver β-catenin; and FOG-001 blocks the Wnt pathway at the most downstream node, disrupting the interaction between β-catenin and the transcription factor TCF, thereby abrogating the signal transmission by which Wnt pathway mutations are believed to drive oncogenesis. In biochemical and cellular studies, FOG-001 has been shown to potently and selectively disrupt the interaction of β-catenin with TCF. Preclinical studies have demonstrated the ability of FOG-001 to cause tumor growth inhibition and complete regression by disrupting β-catenin-dependent signaling. FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients in participants with Wnt/β-catenin signaling pathway activated advanced or metastatic solid tumors. About FogPharma® FogPharma is a biopharmaceutical company pioneering the discovery and development of the Helicon™ therapeutics, which are small proteins capable of efficient cell-entry and modulating protein-protein interactions that may otherwise be challenging to drug. Through this novel modality, FogPharma aims to address the limitations of existing drug classes and achieve universal druggability – a world where no targets are off-limits to new medicines. Spun out of Harvard University by pioneering academic scientist and successful biotech company builder Dr. Gregory Verdine, FogPharma is advancing a broad pipeline of Helicon therapeutics against important and biologically validated cancer targets that have remained elusive to other approaches, with the goal of providing new targeted treatment options for significant cancer patient populations. In November 2022, FogPharma completed a $178 million Series D financing and has raised more than $360 million to date from leading life sciences investors. FogPharma is headquartered in Cambridge, Mass. For more information, please visit . ©2023 Fog Pharmaceutical, Inc. FOGPHARMA is a registered trademark of Fog Pharmaceuticals, Inc.