On September 28, 2026 BlossomHill Therapeutics, Inc. (Nasdaq: BLSM), a clinical-stage biopharmaceutical company applying an intentional, chemistry-based approach to design and develop innovative small molecule medicines for the treatment of cancer, reported the presentation of preclinical data on BH-501284 at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development, taking place September 25-28, 2026, in San Diego, CA. BH-501284 is a novel, orally bioavailable, non-covalent, pseudo-irreversible pan-KRAS inhibitor designed to overcome limitations of current KRAS-targeted therapies.

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"KRAS mutation has historically been one of the most challenging oncogenic drivers to target, and while recent advances have validated its therapeutic potential, we believe there remains an opportunity to develop a pan-KRAS inhibitor capable of delivering potent and durable target inhibition across a broad range of KRAS mutations," said Jean Cui, Ph.D., Founder and Chief Executive Officer of BlossomHill Therapeutics. "We designed BH-501284 with a novel Switch-II chemical scaffold and pseudo-irreversible binding characteristics intended to achieve prolonged, potent and selective inhibition of KRAS mutations, which we believe may result in improved efficacy and tolerability. These preclinical data demonstrate sustained KRAS pathway suppression, and deep and durable antitumor activity across multiple KRAS-mutant tumor models, further supporting the advancement of BH-501284 toward an IND submission in Q12027."

Presentation highlights:

BH-501284 exhibited potent and prolonged activity across a broad range of KRAS mutations. BH-501284 showed a target residence time of more than 54 hours in a SPR study using GDP- state KRAS G12D protein, extended KRAS signaling inhibition in KRAS-mutant cell lines, and potent cellular activity across multiple KRAS mutations, while sparing HRAS and NRAS.
BH-501284 showed deep and durable antitumor activity across multiple preclinical KRAS-mutant tumor models. Treatment resulted in tumor regression across pancreatic, lung and colorectal cancer models with KRAS G12V, D or C mutation at relatively low doses. In a KRAS G12C lung cancer model, pseudo-irreversible BH-501284 achieved tumor regression comparable to covalent, irreversible KRAS G12C inhibitors.
BH-501284 demonstrated deeper and more durable tumor regression than tricomplex RAS inhibitors. In a KRAS G12D pancreatic cancer model, BH-501284 achieved deeper and more durable tumor regression than tricomplex inhibitors when administered at similar doses.
BH-501284 also demonstrated the potential to combine with an anti-PD-1 treatment. In a KRAS G12D colorectal cancer model, the combination demonstrated prolonged survival compared with either treatment alone.
About BH-501284
BH-501284 is an investigational, orally bioavailable pan-KRAS inhibitor, which utilizes a novel Switch-II chemical scaffold to achieve prolonged, potent and selective inhibition of KRAS mutations. We believe this molecule, which uses a non-covalent scaffold, is unique in its potential to achieve tight and durable binding, a feature described as "pseudo-irreversible" binding. In preclinical studies, BH-501284 demonstrated sustained blocking of KRAS signaling leading to deeper and more durable antitumor activities in KRAS mutant cells and tumor models at low dose levels.

(Press release, BlossomHill Therapeutics, SEP 28, 2026, View Source [SID1234671135])