Bristol-Myers, H3 Biomedicine explore RNA splicing drugs for cancer

BMS and H3 will conduct research together, after which the former will take responsibility for the development and commercialization of selected compounds. (Pixabay/rawpixel)

Bristol-Myers Squibb is tapping Eisai spinoff H3 Biomedicine and its RNA-splicing technology for a multiyear research partnership. The pair will investigate whether new treatments based on H3’s platform can elicit a stronger response against cancer. 

Under the deal, Bristol-Myers and H3 will work on research aimed at developing immune therapies for cancer using the latter’s RNA-splicing platform. Beyond that, BMS will take care of development and commercialization of selected compounds. H3 will stand to pick up undisclosed amounts in an upfront payment, development, regulatory and sales milestones, and certain royalties, the pair said in a statement. Eisai will hold onto the option to co-develop and co-commercialize “certain compounds” that come out of the partnership. 

“Bristol-Myers Squibb is looking forward to collaborating with H3 to advance the science and research around RNA splicing,” said Percy Carter, head of discovery chemistry and molecular technologies at Bristol-Myers Squibb, in the statement. “H3 has deep expertise in defining the role of changes in RNA homeostasis that contribute to cancer. This collaboration will allow both companies to gain a deeper understanding about alterations in RNA splicing and an opportunity to discover new medicines that can potentially improve outcomes for patients.”  


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RELATED: H3 Biomedicine boosts its cancer collab with Foundation Medicine

RNA splicing is a step in the process by which genes make proteins from DNA. Instructions from DNA are transcribed to mRNA, which then translates these instructions into proteins. RNA splicing happens between these two steps, when pre-mRNA turns into RNA. 

RELATED: Genomic analysis uncovers prevalence of RNA splicing mutations in 33 tumor types

Earlier this year, H3 published research showing that RNA splicing mutations are more common and appear in more cancers than previously thought, opening up new indications for H3’s own work and spotlighting RNA splicing factors as a target for others developing cancer treatments. The company used whole exome and RNA sequencing to analyze 10,000 patient samples across 33 tumor types. The analysis studied more than 400 splicing factors, finding 199 genes with putative driver mutations, including loss-of-function mutations and hot spot, or oncogenelike, mutations. They also found splicing factor mutations in all 33 tumor types, with mutations occurring in as many as 60% of samples in some tumor types.  

H3 has three molecules in its pipeline: H3B-6527, an inhibitor of fibroblast growth factor receptor 4 (FGFR4) for liver cancer; H3B-6545, a modulator of wild-type and mutant estrogen receptor (ERα); and H3B-8800 inhibitor of wild-type and mutant SF3b complex, a splicing factor gene. H3B-8800 is in a phase 1 study evaluating its safety and efficacy in patients with myelodysplastic syndromes, acute myeloid leukemia and chronic myelomonocytic leukemia who carry mutations in splicing factor genes.

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