KRAS G12D x KRAS G12V

April 23, 2025 -- Silexion Therapeutics Corp. (NASDAQ: SLXN) (“Silexion” or the “Company”), a clinical-stage biotechnology company pioneering RNA interference (RNAi) therapies for KRAS-driven cancers, today announced a strategic collaboration with Catalent, a global leader in advanced delivery technologies, clinical development, and manufacturing solutions for therapeutics. Under the agreement, Catalent will conduct formulation development and clinical manufacturing activities for Silexion's next-generation siRNA candidate, SIL204, at its state-of-the-art facility in Limoges, France. The collaboration will focus on optimizing both the systemic and intratumoral delivery formulations of SIL204, supporting Silexion's recently announced dual-route development strategy designed to target both primary tumors and metastases in KRAS-driven cancers. This collaboration builds upon Silexion's recently reported breakthrough preclinical data demonstrating SIL204's significant efficacy in reducing both primary tumor growth and metastatic spread in clinically relevant orthotopic pancreatic cancer models. SIL204 targets a broad spectrum of KRAS mutations (including G12D, G12V, G12R, Q61H, and G13D), which are critical drivers in pancreatic, colorectal, and lung cancers. "Our collaboration with Catalent represents a significant advancement in our SIL204 development program," said Ilan Hadar, Chairman and CEO of Silexion Therapeutics. "Following our recent promising preclinical results and the unveiling of our expanded development plan, we look forward to this partnership advancing the optimization of SIL204's formulation for both systemic and intratumoral delivery routes. Catalent's expertise in complex formulation development will be instrumental as we work toward our goal of initiating human clinical trials in the first half of 2026." Catalent's Limoges facility is its European center of excellence for clinical biologics formulation development and drug product manufacturing, specializing in complex injectable formulations. The collaboration will leverage Catalent's extensive experience in developing sustained-release technologies to enhance SIL204's therapeutic potential through improved stability, bioavailability, and delivery precision. This collaboration is part of Silexion's comprehensive strategy to advance SIL204 through preclinical development and into clinical trials, with plans to conduct additional toxicology and pharmacodynamic studies throughout 2025, followed by potential regulatory submissions to the Israel Ministry of Health in the second half of 2025 and to the European Union in the first half of 2026. Silexion Therapeutics is a pioneering clinical-stage, oncology-focused biotechnology company developing innovative RNA interference (RNAi) therapies to treat solid tumors driven by KRAS mutations, the most common oncogenic driver in human cancers. The Company's first-generation product, LODER™, has shown promising results in a Phase 2 trial for non-resectable pancreatic cancer. Silexion is also advancing its next-generation siRNA candidate, SIL204, designed to target a broader range of KRAS mutations and showing significant potential in preclinical studies. The Company remains committed to pushing the boundaries of therapeutic innovation in oncology, with a focus on improving outcomes for patients with difficult-to-treat cancers. The content above comes from the network. if any infringement, please contact us to modify.

Study results of two investigational drugs that target KRAS-driven cancers co-developed by RAS Initiative investigators at the Frederick National Laboratory for Cancer Research (FNL) and now being tested in patients will be presented at the American Association for Cancer Research Annual Meeting April 25-30 at McCormick Place in Chicago.  Both compounds, BBO-8520 and BBO-11818, were developed in partnership via Cooperative Research and Development Agreement (CRADA) with BridgeBio Oncology Therapeutics (BBOT) and Lawrence Livermore National Laboratory.  Representatives of BBOT, sponsor of the clinical trials for both agents, will present the data during the AACR meeting.  James P. Stice, an associate director at BBOT, will discuss results of pre-clinical studies on BBO-8520 in a mini symposium on novel antitumor agents, Monday, April 28 in room S103. BBO-8520 targets KRAS G12C, the most common KRAS variant in lung cancer.   On Tuesday, April 29, BBOT Associate Director Carlos Stahlhut will present a poster on preclinical studies of BBO-11818, which shows activity against multiple KRAS mutants, and falls into the category of a pan-KRAS inhibitor.  The poster is in section 21 from 9 a.m. to noon.  Laboratory tests show BBO-8520 blocks the active “ON” and inactive “OFF” states of KRAS G12C, resulting in rapid KRAS inhibition. While existing treatments for KRAS G12C-driven cancer have shown promising clinical efficacy, they block the KRAS G12C “OFF” state only, and patients develop resistance to the drug. The collaborators published results of pre-clinical assays in Cancer Discovery.   There are no approved targeted therapies against other KRAS variants, which drive several major cancer types including pancreatic, colorectal and non-small cell lung cancer. BBO-11818 has shown activity against multiple KRAS mutants including KRAS G12D and KRAS G12V in their active and inactive states. The National Cancer Institute established the RAS Initiative in 2013 to explore and target RAS, the most frequently mutated oncogene in cancer, which at the time had no viable treatments. FNL is at the center of the hub-and-spoke model of a worldwide collaboration to investigate the complexity of RAS biology and therapy through the RAS Initiative.   Mary Ellen Hackett Manager, Communications Office 301-401-8670

BridgeBio Oncology Therapeutics, a company working to advance the field of therapies addressing a validated but elusive group of cancer targets, has reached a deal to go public in a SPAC merger that brings more than $450 million to support clinical testing of three drug candidates. The merger agreement announced Friday is with Helix Acquisition Corp. II, a SPAC sponsored by affiliates of Cormorant Asset Management. When the deal closes, the combined company will take the BridgeBio Oncology Therapeutics name and is expected to trade on the Nasdaq under the stock symbol “BBOT.” BridgeBio Oncology spun out of BridgeBio Pharma last year, backed by $200 million in financing led by Cormorant. The biotech aims to improve on current approaches to RAS, a family of proteins that act like an on/off switch to regulate cell growth. Mutated versions of these signaling proteins drive cancer proliferation. Amgen’s Lumakras and Bristol Myers Squibb’s Krazati (from Mirati Therapeutics), which address a specific mutation called KRAS G12C, have FDA approvals in colorectal and non-small cell lung cancer. Both small molecule drugs work by targeting KRAS G12C when it is in the “off” state, locking the mutated protein in this inactive form. Health IT Reducing Clinical and Staff Burnout with AI Automation As technology advances, AI-powered tools will increasingly reduce the administrative burdens on healthcare providers. By Dr. Michael Blackman, Chief Medical Officer at Greenway Health BridgeBio Oncology aims to drug KRAS G12C in both the “on” and “off” states with a drug codenamed BBO-8520. A Phase 1 study is testing this drug in patients with non-small cell lung cancer. Preliminary data for BBO-8520, as a monotherapy and in combination with Merck immunotherapy Keytruda, are expected in the second half of 2025. A second drug candidate, BBO-10203, blocks the interaction between RAS and PI3K alpha, a family of enzymes involved in cellular growth and proliferation. While PI3K alpha inhibitors have reached the market, BridgeBio Oncology aims to offer a better safety profile. A Phase 1 test is underway evaluating BBO-10203 in advanced cases of breast cancer, colorectal cancer, and non-small cell lung cancer. The third drug, BBO-11818, is a pan-KRAS inhibitor targeting mutant versions KRAS proteins in both the “on” and “off” states. BridgeBio Oncology says this molecule is designed to offer potency against KRAS G12D and KRAS G12V mutations; dosing of the first patient is expected in the first half of this year. In an investor presentation, Helix said the ability to target many types of KRAS G12mutation-driven cancers creates opportunities for drug combinations, treatment across the various stages of cancer, and revenue from multiple drugs. BridgeBio Oncology has a large market opportunity with about 250,000 patients diagnosed annually in the U.S. across the target indications of breast, lung, colorectal, and pancreatic cancers, according to the presentation. “The company’s pipeline has the potential for paradigm-shifting impact on the treatment of some of the highest prevalence malignancies and we look forward to seeing patient impact further materialize as the clinical trials move forward,” Bihua Chen, founder and CEO of Cormorant and CEO of Helix, said in a prepared statement. presented by Artificial Intelligence What Keeps Healthcare CIOs Up at Night: Balancing Technology Investments with Consumer Expectations When it comes to managing inbound phone calls, underperformance has devastating cost implications. By Stephanie Baum BridgeBio Oncology faces competition from other companies trying to develop next-generation KRAS inhibitors. Revolution Medicines expects data readouts this year for the KRAS G12D inhibitor zodronrasib and the KRAS G12C inhibitor elironrasib. Both drugs are in early clinical development as monotherapies and as part of combination treatments for solid tumors. Frontier Medicines’ lead program, FMC-376, inhibits KRAS G12C in both its active and inactive states. A Phase 1/2 test is ongoing. As for Bristol Myers Squibb, the Mirati acquisition that brought Krazati included another drug candidate in early clinical development for KRAS G12D-mutated solid tumors. Meanwhile, Astellas Pharma’s approach to KRAS G12D degrades the target protein. BridgeBio Oncology brings to the Helix merger about $100 million in cash. That money will be combined with $196 million of Helix’s own funds. The newly public company will raise additional capital from a group of institutional investors, led by Cormorant, who have committed to purchase BridgeBio Oncology shares priced at $10.36 each to raise another $260 million. The cash is expected to provide enough runway to last into 2027, according to the investor presentation. The boards of directors of BridgeBio Oncology and Helix have approved the proposed merger, which is expected to be completed in the third quarter of this year. The transaction still needs shareholder approvals. Illustration: Getty Images