APC

BRISBANE, Calif., April 21, 2025 (GLOBE NEWSWIRE) -- Tempest Therapeutics, Inc. (Nasdaq: TPST), a clinical-stage biotechnology company developing first-in-class1 targeted and immune-mediated therapeutics to fight cancer, today announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to TPST-1495, the company’s novel dual receptor inhibitor of prostaglandin (PGE2) signaling, for the treatment of patients with Familial Adenomatous Polyposis (FAP). “Receiving orphan drug designation for TPST-1495, our second clinical program, is a significant milestone in our mission to bring innovative therapies to patients with unmet medical need,” said Stephen Brady, President and CEO of Tempest. “This designation for the treatment of FAP underscores Tempest’s mission to make a meaningful difference in the lives of patients and builds on the momentum from prior designations received for amezalpat in hepatocellular carcinoma.” A Phase 2 study evaluating TPST-1495 in patients with FAP is set to begin this year, conducted by the Cancer Prevention Clinical Trials Network and funded by the National Cancer Institute (NCI) Division of Cancer Prevention. Data from this study are expected in 2026. About Familial Adenomatous Polyposis FAP is a high-risk inherited syndrome associated with the development of cancer in affected patients and has no approved medical therapies. In the US, the disease affects approximately one in 5,000 to 10,000 individuals2. FAP is caused by autosomal dominant inactivating mutations in the tumor suppressor gene APC. Patients with FAP develop large numbers of adenomatous polyps throughout the gastrointestinal tract, often starting in their teenage years. These growths have a high risk of malignant transformation and can give rise to invasive cancers of the colon, stomach, duodenum, rectum, and other tissues. Standard of care treatment for patients with FAP is surgical removal of the colon (colectomy) early in life to reduce the likelihood of cancer development. Even after colectomy, patients must receive careful surveillance for development of cancer elsewhere in the GI tract throughout their lifetime. While surgical management and surveillance have improved the prognosis for patients with FAP, cancer remains a major cause of death for patients with FAP. About Orphan Drug Designation The FDA's Orphan Drug Designation program provides orphan status to therapies intended for the treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the United States. This designation provides certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved. About Tempest Therapeutics Tempest Therapeutics is a clinical-stage biotechnology company advancing a diverse portfolio of small molecule product candidates containing tumor-targeted and/or immune-mediated mechanisms with the potential to treat a wide range of tumors. The company’s novel programs range from early research to later-stage investigation in a randomized global study in first-line cancer patients. Tempest is headquartered in Brisbane, California. More information about Tempest can be found on the company’s website at www.tempesttx.com. Forward-Looking Statements This press release contains forward-looking statements, as that term is defined under the federal securities laws, that are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking terminology such as “may,” “will,” “should,” “would,” “could”, “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions. Forward-looking statements contained in this press release include but are not limited to statements relating to: the initiation, timing and results of the Phase 2 study for TPST-1495; and the ability of TPST-1495 to benefit from the ODD designation, including potential tax credits and market exclusivity. Any forward-looking statements in this press release are based on Tempest Therapeutics’ current expectations, estimates and projections about its industry as well as management’s current beliefs and expectations of future events only as of today and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks relating to: changes in the regulatory environment resulting in potentials delays in the clinical development and regulatory approval of our product candidates, including TPST-1495; the volatility and uncertainty in the capital markets for biotechnology companies; and our ability to raise additional capital or other pursue our plan to identify and complete a strategic transaction on attractive terms or at all. These and other factors that may cause actual results to differ from those expressed or implied are discussed in greater detail in the “Risk Factors” section of the company’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission (SEC) on March 27, 2025, as well as in other filings the company may make with the SEC in the future. Except as required by applicable law, Tempest Therapeutics undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise. These forward-looking statements should not be relied upon as representing Tempest Therapeutics’ views as of any date subsequent to the date of this press release and should not be relied upon as prediction of future events. In light of the foregoing, investors are urged not to rely on any forward-looking statement in reaching any conclusion or making any investment decision about any securities of Tempest Therapeutics. Investor & Media Contacts: Sylvia Wheeler Wheelhouse Life Science Advisors swheeler@wheelhouselsa.com Aljanae Reynolds Wheelhouse Life Science Advisors areynolds@wheelhouselsa.com

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer, today announced the presentation of a trial-in-progress poster on the Company’s first-in-human clinical trial evaluating FOG-001, the first and only direct inhibitor of β-catenin TCF4 , at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium taking place in San Francisco from January 23-25, 2025. FOG-001 is being evaluated in a Phase 1/2 clinical trial ( NCT05919264 ). The multicenter, open-label, non-randomized trial aims to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of FOG-001 in patients with microsatellite stable colorectal cancer (MSS CRC) and other solid tumors with Wnt pathway activating mutations (WPAM+). The trial plans to enroll patients in multiple third-line MSS CRC cohorts as both a monotherapy and in combination with FOLFOX+bevacizumab, anti-PD-1/PD-L1, or trifluridine/tipiracil+bevacizumab. At the 2025 J.P. Morgan Healthcare Conference, Parabilis provided an update on the trial’s progress. The Company disclosed that more than 60 patients with locally advanced or metastatic solid tumors have been dosed with FOG-001 to date, and that early clinical data demonstrate monotherapy antitumor activity and in-tumor target engagement. Preliminary Phase 1/2 data are expected to be shared publicly in 2025. Full details of the poster are as follows: Title: “A Phase 1/2 study of FOG-001, a first-in-class direct β-catenin:TCF inhibitor, in patients with colorectal cancer, hepatocellular carcinoma, and other locally advanced or metastatic solid tumors” Abstract Number: TPS322 Presentation Date and Time: January 25, 2025, 7:00-7:55 a.m. PST Session Information: Trials in Progress Poster Session C Location: Level 1, West Hall, Moscone West About FOG-001 FOG-001 is an investigational first-in-class competitive inhibitor of β-catenin interactions with the T-cell factor (TCF) family of transcription factors, and is currently in clinical development. By directly targeting the β-catenin TCF4 protein-protein interaction, FOG-001 is intended to block the Wnt signaling pathway irrespective of the various APC and beta-catenin mutations that typically drive disease. 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. FOG-001 is currently being evaluated in a first-in-human Phase 1/2 clinical trial in patients with locally advanced or metastatic solid tumors. About Parabilis Medicines (Formerly Fog Pharmaceuticals) Parabilis Medicines is a clinical-stage biopharmaceutical company dedicated to creating extraordinary medicines for people living with cancer. Through its Helicon discovery platform, Parabilis is engineering precisely tuned, stabilized helical peptide therapeutics that have the potential to unlock a large number of traditionally undruggable targets. This versatile platform enables applications for Helicons across three main areas: functional inhibitors of intracellular protein-protein interactions, targeted protein degraders, and targeted radiopharmaceuticals. Parabilis is advancing a pipeline of first-in-class programs across these three domains, led by FOG-001, its clinical-stage β-catenin TCF4 inhibitor. Parabilis is headquartered in Cambridge, Mass., and is well-capitalized, with more than $500 million raised to date from leading life sciences investors. For more information, please visit: www.parabilismed.com

BEIJING, Jan. 8, 2025 /PRNewswire/ -- In a recent achievement, DP Technology's hit discovery platform RiDYMO® has successfully designed a cyclic peptide targeting β-catenin, a historically "undruggable" protein, in just two months. This innovative AI-driven approach combines advanced algorithms, physics simulations, and high-throughput experimentation to rapidly develop potential drug candidates for challenging targets. The platform's success with β-catenin, a key player in cancer development, demonstrates its potential to revolutionize drug discovery for previously intractable targets. Continue Reading Fig. 1 RiDYMO® : an AI for Science-Driven Hit Discovery and Optimizaton Platform Fig. 2 The workflow of the Cyclic Peptide Screening Process Based on the RiDYMO® Platform Fig. 3 Experimental Results of 29 Cyclic Peptide Molecules The Wnt/β-catenin pathway plays a crucial role in various biological functions and is implicated in multiple cancers[1-3]. Despite its importance as a therapeutic target[4-7], β-catenin has long been considered "undruggable" due to its flat protein surface[8-10]. The RiDYMO® platform overcomes this challenge by leveraging a vast library of over 10^12 cyclic peptides and macrocyclic molecules, incorporating both natural and non-natural amino acids. Using the RiDYMO® platform, researchers rapidly designed and screened cyclic peptide molecules for β-catenin binding. The process involved: Optimizing the β-catenin protein structure to improve the binding interface. High-throughput screening and design of cyclic peptides using the platform's extensive library. Synthesis and testing of 29 candidate molecules. The results were impressive, with 12 compounds showing strong inhibition of protein-protein interactions (IC50≤10 μM), a success rate of over 40%. One standout compound, designated as compound 24, effectively bound to β-catenin, disrupted its interaction with BCL9, and inhibited the Wnt/β-catenin signaling pathway. Dr. Dongdong Wang, Co-President of DP Technology's Drug Discovery Unit, emphasized the platform's ability to tackle undruggable targets and rapidly design high-quality compounds. The RiDYMO® platform's success with β-catenin demonstrates its potential to accelerate the development of orally available cyclic peptide drugs, potentially transforming the pharmaceutical industry's approach to challenging targets. This breakthrough in cyclic peptide design for β-catenin showcases the power of AI-driven drug discovery platforms in addressing previously intractable targets, potentially opening new avenues for cancer treatment and other therapeutic areas. About the RiDYMO® Hit Discovery and Optimization Platform RiDYMO® is a state-of-the-art hit discovery and optimization platform developed by DP Technology, leveraging the principles of AI for Science. It employs the proprietary Hermite® computational drug design software to elucidate the dynamics of "undruggable" targets and explores a broader chemical space encompassing small molecules, macrocycles, and cyclic peptides. By integrating advanced artificial intelligence, physics-based algorithms, and high-throughput experimentation, the platform excels in designing oral macrocyclic compounds and rapidly delivers innovative drug candidates. As one of its core algorithms, Reinforced Dynamics (RiD)[4] has a significant advantage in the sampling efficiency of molecular dynamics simulation. By fully leveraging the high-dimensional representation capabilities of neural networks, RiD can efficiently capture dynamic conformational changes in complicated biomolecular systems. Previously, the core RiD algorithm of the platform was published in Nature Computational Science [11]. The study demonstrated that RiD could achieve a more comprehensive free energy surface within 1.86 μs, compared to 100 μs required by traditional MD methods, representing nearly a hundredfold increase in efficiency. RiDYMO® has been successfully employed in various drug discovery programs, including the development of small molecule compounds for crucial targets such as c-Myc and GPX4, as well as other modalities such as cyclic peptides and ADCs. For more information, please visit our website. (). About Hermite Hermite® is a next-generation computational drug design platform developed by DP Technology, powered by AI for Science, to provide a comprehensive solution for drug design. Hermite® integrates industry-leading tools such as the Free Energy Perturbation module ("Uni-FEP"), and the ultra-high-throughput virtual screening tool ("Uni-VSW"). The platform supports key stages of drug discovery from protein structure prediction and target validation to hit discovery and lead optimization. In addition, the platform offers an interactive, web-based molecular visualization experience, with detailed management of projects, teams, and data. It features full compliance certification, multi-tier security measures. Users have the flexibility to choose between cloud-based or private deployment options. Hermite® is rapidly gaining traction in the pharmaceutical industry, with over 60% of leading companies in China utilizing the platform across more than 50 drug pipelines. This growing trust is reflected in the impressive number of calculations performed—over 200,000 Uni-FEP calculations to date—demonstrating Hermite®'s reliability and effectiveness as a powerful tool for drug discovery and development. For more information, please visit: References: Salik B, et al. Targeting RSPO3-LGR4 signaling for leukemia stem cell eradication in acute myeloid leukemia. Cancer Cell. 2020;38(2):263–78.e6. Liu J, et al. Wnt/β-catenin signal ling: function, biological mechanisms, and therapeutic opportunities. Signal Transduct Target Ther. 2022 Jan 3;7(1):3. Choi BR, Cave C, Na CH, Sockanathan S. GDE2-dependent activation of canonical wnt signaling in neurons regulates oligodendrocyte maturation. Cell Rep. 2020;31(5):107540. Zhang L, Shay JW. Multiple roles of APC and its therapeutic implications in colorectal cancer. J. Natl. Cancer Inst. 2017;109(8). Belenguer G, et al. RNF43/ZNRF3 loss predisposes to hepatocellular-carcinoma by impair ing liver regeneration and altering the liver lipid metabolic ground-state. Nat. Commun. 2022;13(1):334. Cao L, et al. Helicobacter pylori-induced RASAL2 Through Activation of Nuclear Factor-κB Promotes Gastric Tumorigenesis via β-catenin Signaling Axis. Gastroenterology. 2022 May;162(6):1716-1731.e17. Hashemi M, et al., Biological functions and molecular interactions of Wnt/β-catenin in breast cancer: Revisiting signaling networks. Int. J. Biol. Macromol. 2023 Mar 31:232:123377. Hwang et al., Direct Targeting of b-Catenin by a Small Molecule Stimulates Proteasomal Degradation and suppresses Oncogenic Wnt/β-Catenin Signaling. 2016, Cell Rep. 16, 28–36. Tanton et al., A novel β-catenin/BCL9 complex inhibitor blocks oncogenic Wnt signaling and disrupts cholesterol homeostasis in colorectal cancer. 2022, Sci. Adv. 8, eabm3108. Scuoppo C. et al., "ST316, a Clinical Peptide Antagonist of β-catenin, Induces Anti-Tumor Immune Responses by Multiple Mechanisms of Action." AACR 2024. Wang D, et al. Efficient sampling of high-dimensional free energy landscapes using adaptive reinforced dynamics. 2022, Nat. Comp. Sci. 2, 20. SOURCE DP Technology WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED