On January 12, 2026 Leapfrog Bio, a clinical-stage precision oncology company dedicated to discovering and developing novel targeted therapies for cancers caused by loss-of-function (LOF) mutations, reported the publication of a peer‑reviewed study in npj Systems Biology and Applications, a Nature Portfolio journal, titled "Challenges and opportunities for oncology drug repurposing informed by synthetic lethality." The paper provides a practical framework for drug retargeting in oncology and highlights core discoveries that helped guide the optimization of Leapfrog Bio’s OncoSLX Platform.
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"This paper validates two fundamental realities in targeted cancer drug discovery: genetic targeting opportunities discovered in cell lines are more likely to hold up in the clinic when caused by a driver mutation, and drugs behave very differently from genetic knockouts, so screening them against the causal biology is essential," said Tomas Babak, Ph.D., Founder and Chief Scientific Officer of Leapfrog Bio and co-author on the publication. "Our OncoSLX platform is built on these principles and allows us to run thousands of these drug-mutation tests against all cancer driver mutations simultaneously, quickly identifying potent, genetically targeted treatments for LOF cancers."
Dr. Babak continued, "By screening clinically safe drugs, we can restart development in Phase 2 in genetically selected patients where the probability of efficacy is higher. We expect this approach to be significantly accelerating and derisking as we advance through development."
"Leapfrog Bio was founded to bring the transformative benefit of precision medicines to the many patients with cancers caused by LOF mutations, for whom targeted options are limited," said Greg Vontz, Chief Executive Officer of Leapfrog Bio. "Among our most promising discoveries to date is the vulnerability of EP300 LOF cancers to BET inhibitors, like our lead candidate, LFB190. Leveraging learnings from our OncoSLX platform, we are positioned to advance LFB190 directly into mid-stage development. We look forward to initiating our planned Phase 1b/2a trial in mid-2026."
LFB190 is an oral, small-molecule, potentially best-in-class BETi in development for the more than 60,000 U.S. patients annually who are diagnosed with EP300-mutated solid tumors, including non-small cell lung, bladder, colon, pancreatic, head and neck, and bile duct cancers. While BET inhibitors have been widely studied across cancer indications, they have shown limited efficacy in genetically unselected populations. Extensive preclinical studies have shown that BET inhibitors can be highly effective when used to treat EP300-driven cancers, and previous clinical development of LFB190 as an untargeted therapy has shown favorable safety and tolerability for the drug.
About OncoSLX Platform
OncoSLX Platform is Leapfrog Bio’s proprietary pharmacogenetic platform that screens clinically characterized small molecules against isogenic models of cancer driver mutations, focusing on loss‑of‑function biology. Unlike traditional synthetic‑lethality approaches based on gene knockouts, OncoSLX captures the full spectrum of drug biology and then integrates real‑world outcomes data to prioritize indications likely to deliver survival benefit, compressing timelines and reducing translational risk. This approach identifies novel treatments for loss-of-function-driven cancers that cannot be discovered by conventional methods.
About LFB190 and EP300-Mutated Cancers
LFB190 is a novel, oral BET inhibitor for the treatment of solid tumors driven by EP300 loss-of-function (LOF) mutations. Leapfrog Bio’s OncoSLX Platform has identified a novel synthetic lethality relationship between BET inhibitors and EP300 LOF mutations, which are a known and frequent cancer driver with no targeted therapy available. LFB190 has shown strong preclinical efficacy in patient-derived xenograft (PDX) models of EP300-mutated cancers. EP300 is a tumor suppressor gene involved in chromatin remodeling and transcriptional regulation. When mutated, its loss contributes to tumor progression across multiple cancer types, including approximately 6 percent of non-small cell lung cancers (NSCLC), approximately 15 percent of bladder cancers, and similar frequencies in colon, pancreatic, and head and neck cancers. While BET inhibitors have historically shown limited efficacy in unselected populations, Leapfrog Bio’s platform revealed a compelling effect in EP300-mutated tumors.
(Press release, Leapfrog Bio, JAN 12, 2026, View Source [SID1234661957])