Pan-RAS (Fog Pharma)

SHANGHAI and SAN DIEGO, April 9, 2024 /PRNewswire/ -- GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies in oncology and immunology, today announced the latest findings of GFH547, an oral panRAS (ON) inhibitor, in a late-breaking research abstract at the 2024 American Association for Cancer Research (AACR) Annual Meeting. GFH547 is developed with novel mechanism of action by reshaping and repurposing intracellular cyclophilin A (CypA) protein to target active RAS proteins across most wild/mutant subtypes. Preclinical data demonstrated profound panRAS inhibitory activity of GFH547 and it holds the potential to overcome adaptive and acquired resistance against SIIP (switch II pocket)-based KRAS inhibitors. "Secondary mutations detected among subjects in clinical studies of KRAS inhibitors have paved the way for the development of future therapies, and GFH547 is anticipated as a new-generation inhibitor to combat the drug resistance. GenFleet's KRAS G12C inhibitor (GFH925) has had its New Drug Application accepted with Priority Review Designation in China. From the first-generation KRAS inhibitor to a new-generation pan-RAS inhibitor, the continuous achievements underscore GenFleet's insight into the development of RAS pathway targeted therapies. The top-tier development also showcases the depth of GenFleet's cutting-edge pipeline and its value potential." stated Fusheng Zhou, Ph.D., Vice President of GenFleet's Drug Discovery Department. Abstract Title: GFH547: An orally bioavailable, cyclophilin A-hijacking panRAS (ON) inhibitor with broad spectrum anti-tumor activities Abstract No.: LB165/11 The GFH547-Cyp A-RAS tripartite complex inhibits most wild/mutant subtypes of active, GTP-bound RAS proteins GFH547 has demonstrated preliminary efficacy to inhibit RAS proteins across most subtypes including the KRAS mutant proteins commonly found in human tumors (especially harboring G12C, G12D and G12V mutations). Compared with targeting RAS proteins or the RAS-RAF complex alone, the recruitment of CypA into the tripartite complex induces more profound inhibition of RAS pathway (including the RAS proteins and their downstream interaction with RAF). The deep inhibition of KRAS pathway was observed following a single oral administration of GFH547 in KRAS mutant CDX tumors. GFH547 also demonstrates dose-dependent anti-tumor activity and drives tumor regression in KRAS mutant tumor models. GFH547 is superior to the mainstream SIIP-based KRAS inhibitors in overcoming adaptive and acquired resistance GFH547 is resistant to RTK activation by EGF stimulation which attenuates potency of current mainstream SIIP-based KRAS inhibitors. It is also effective to cells carrying secondary KRAS mutations causing acquired resistance to SIIP-based KRAS inhibitors. Overall, GFH547 demonstrates promising bioavailability, kinase selectivity and safety in the preclinical research. About RAS and GFH457 RAS proteins, in active GTP-bound or inactive GDP-bound form, are binary molecular switches controlling cellular responses in signaling pathways including RAS-RAF-MEK-ERK、PI3K/AKT/mTOR. Three RAS genes encode for protein isoforms, namely Kirsten Ras (KRAS), Harvey Ras (HRAS) and Neuroblastoma Ras (NRAS), and KRAS is the most frequently mutated oncogene in humans. GFH547 is a novel small-molecule panRAS (ON) inhibitor hijacking Cyp A to target active, GTP bound RAS proteins of most wild/mutant subtypes, including most commonly found KRAS mutant (G12C, G12D, G12V, etc.) proteins. Preclinical research of GFH547 demonstrates dose-dependent anti-tumor activity and drives tumor regression in multiple KRAS mutant tumor models. GFH547 is also superior to the mainstream SIIP (switch II pocket)-based KRAS inhibitors in overcoming adaptive and acquired resistance. About GenFleet Therapeutics GenFleet Therapeutics, a clinical-stage biotechnology company focusing on cutting-edge therapies, is dedicated to serving significant global unmet medical needs in oncology and immunology. Based on the deep understanding of disease biology and translational medicine, GenFleet's proprietary and fully integrated R&D platform highlights multiple cutting-edge products with novel mechanisms and global IP. Since its inception in 2017, GenFleet has built up industry-leading capabilities and expertise in developing novel drug candidates - both small molecules and biologics. Its pipeline includes over 10 programs, many of which have entered multi-regional clinical trials across China (including Taiwan), the United States, Europe and Australia. To date, GenFleet has over 5 clinical studies encompassing IND stage to phase II studies and completed co-development partnerships with numerous publicly listed companies worldwide. GenFleet is expected to progress additional programs into the clinic, as well as transition from a clinical stage biotech company into a commercial stage biopharmaceutical company in the next 3-5 years. SOURCE GenFleet Therapeutics

Poster Includes Preclinical Data on Pan-RAS Compounds Demonstrating Inhibition in Breast Cancer Models CARLSBAD, Calif., Oct. 23, 2023 (GLOBE NEWSWIRE) -- Qualigen Therapeutics, Inc. (Nasdaq: QLGN), a clinical-stage therapeutics company focused on developing treatments for adult and pediatric cancers with potential for Orphan Drug Designation, today announces a poster presentation on the Company’s Pan-RAS platform at the American Association for Cancer Research (AACR) Special Conference in Breast Cancer Research, held October 19th to 22nd at the Westin San Diego Bayview. “The RAS pathway continues to be an area of immense interest within the scientific community and biopharmaceutical industry. Due to the prevalence and severity of RAS-driven tumors, there is a high unmet need to discover and develop more broadly acting RAS-targeted compounds. We believe a pan-RAS approach may potentially overcome KRAS G12C resistance that affects depth and duration of responses of emerging therapies,” commented Michael Poirier, Qualigen’s Chairman and CEO. “We are grateful for our partnership with Dr. Geoff Clark and his team at the University of Louisville, who have demonstrated the therapeutic potential of our approach to RAS.” RAS is seldom mutated in breast cancer, but it is often hyperactivated by upregulation of positive regulator activity (such as Her-2) or down-regulation of negative regulator activity (such as NF1 or DAB2IP). These effects are particularly common in Luminal B breast cancer. As a result, we have developed a series of novel direct Pan-RAS inhibitors that exhibit a distinct binding mechanism to other currently described RAS inhibitors. Poster highlights included: Our RAS inhibitors suppressed the interaction of RAS with its downstream mitogenic effectors and suppressed RAS signaling pathways (MAPK and RAL pathways) in Luminal B breast cell model systems. Our Pan-RAS compounds inhibited 3D growth at doses that have little effect on normal 2D growth and are active against in vivo xenograft breast tumors and can be orally available. Abstract #: B020 Title: “Pan-RAS Inhibitors to Treat Luminal B Breast Cancer” Author/s: Geoff Clark, Ph.D., et. al. Presentation Date: October 21, 2023 5:00 to 7:00pm PT Location Westin San Diego Bayview VIEW POSTER RAS is the most common cancer oncogene. Activating mutations in one of the three human RAS gene isoforms (KRAS, HRAS, or NRAS) are present in about one-fourth of all cancers. For example, mutant KRAS is found in 98% of pancreatic ductal adenocarcinomas, 52% of colon cancers, and 32% of lung adenocarcinomas. According to the National Cancer Institute, mutant KRAS subsets of these three cancers alone are diagnosed in more than 170,000 people each year in the United States, resulting in more than 120,000 deaths annually.1 Substantial scientific and pharmaceutical industry interest is evident by the compounds either approved or in development to treat devastating RAS-driven advanced solid tumors, such as pancreatic cancer. About Pan-RAS Qualigen Therapeutics is collaborating with Dr. Geoff Clark and Dr. Joe Burlison at the University of Louisville, Kentucky to develop a series of potentially highly potent compounds to take forward into preclinical development. Lead compounds are believed to suppress or block the interaction of endogenous RAS with c-RAF, and thereby influence the KRAS, HRAS, and NRAS effector pathways. RAS acts as a “hub” that activates multiple effector pathways, hence blocking any single pathway may be ineffective for many RAS-driven tumor types, including pancreatic, lung, and colorectal cancers. This approach could potentially enable a differentiated, pan-RAS strategy for inhibiting the MAPK, PI3K, and RAL pathways implicated in cancer cell proliferation, survival, and differentiation. About Qualigen Therapeutics, Inc. Qualigen Therapeutics, Inc. is a clinical-stage therapeutics company focused on developing treatments for adult and pediatric cancer. Our investigational QN-302 compound is a small molecule selective transcription inhibitor with strong binding affinity to G4s prevalent in cancer cells; such binding could, by stabilizing the G4s against “unwinding,” help inhibit cancer cell proliferation. The investigational compounds within Qualigen’s family of Pan-RAS oncogene protein-protein interaction inhibitor small molecules are believed to block the binding of mutated RAS proteins to their effector proteins, thereby leaving the mutated RAS unable to cause further harm. In theory, such mechanism of action may be effective in the treatment of about one quarter of all cancers, including certain forms of pancreatic, colorectal, and lung cancers. Forward-Looking Statements This news release contains forward-looking statements by Qualigen that involve risks and uncertainties and reflect the Company's judgment as of the date of this release. These statements include those related to the Company's prospects and strategy for development of its therapeutic drug candidates, including the anticipated timeline for initiating the Company’s Phase 1 clinical trial and enrolling and dosing of patients and the identification of a late in vivo candidate. Actual events or results may differ from the Company's expectations. There can be no assurance that the Company will be able to successfully develop any drugs (including QN-302, Pan-RAS and QN-247); that preclinical development of the Company's drugs (including Pan-RAS and QN-247) will be completed on any projected timeline or will be successful; that any clinical trials will be approved to begin by or will proceed as contemplated by any projected timeline, or at all; that any future clinical trial data will be favorable or that such trials will confirm any improvements over other products or lack negative impacts; that preclinical study results the Company observed in animals will be borne out in human patients; that any drugs will receive required regulatory approvals (or Fast Track designation or Orphan Drug status) or that they will be commercially successful; that patents will issue on the Company's owned and in-licensed patent applications; that such patents, if any, and the Company's currently owned and in-licensed patents would prevent competition; or that the Company will be able to procure or earn sufficient working capital to complete the development, testing and launch of the Company's prospective therapeutic products (including QN-302, Pan-RAS and QN-247). The Company's stock price could be harmed if any of the events or trends contemplated by the forward-looking statements fail to occur or is delayed or if any actual future event otherwise differs from expectations. Additional information concerning these and other risk factors affecting the Company's business can be found in the Company's prior filings with the Securities and Exchange Commission, including its most recent annual report on Form 10-K, all of which are available at . The Company disclaims any intent or obligation to update these forward-looking statements beyond the date of this news release, except as required by law. This caution is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. For more information about Qualigen Therapeutics, Inc., please visit . Contact: Investor Relations ir@qlgntx.com Source: Qualigen Therapeutics, Inc.