Black Diamond Therapeutics (BDTX) Announces Publication of New Computational and Functional Analyzes of HER2 Mutations Based on its Proprietary MAP Discovery Engine
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Black Diamond Therapeutics, Inc. (Nasdaq:BDTX) today announced the publication of data identifying novel oncogenic allosteric mutations of HER2 that support the capabilities of the Mutation-Allostery-Pharmacology (MAP) discovery engine and further suggest the need new inhibitors to treat mutant HER2 cancers. The article, titled “Computational and functional analyzes of HER2 mutations revealing allosteric activation mechanisms and altered pharmacological effects” by Ishiyama et al. was published online by the Cancer Research Journal of the American Association for Cancer Research (AACR) on May 3, 2022.
“At the heart of our precision medicine approach to cancer treatment is the ability to identify novel full-spectrum oncogenic mutations. This study provides strong justification for the power of our MAP discovery engine, as we have identified novel oncogenic allosteric HER2 mutations that further suggest the need for new treatment options. These results support our comprehensive approach to cancer treatment by demonstrating the value and importance of oncogenicity prediction, biological validation, protein conformation-based drug design, and MasterKey inhibitor development against mutation families,” said Elizabeth Buck, Chief Scientific Officer of Black Diamond Therapeutics. “In this study, Black Diamond’s proprietary MAP scoring and functional validation analyzes were able to provide new insights into the oncogenic activity and therapeutic targeting of HER2 mutations in cancer, in addition to identifying 22 novel oncogenic HER2 mutations. . As the number of unique mutations in cancers is expected to increase over time, there remains a need for an efficient means of identifying oncogenic mutations. We believe that our MAP technology has the potential to fill this gap and provide essential information for the use of precision medicine to treat cancers caused by rare oncogenic mutations.
The peer-reviewed article describes computational and functional analyzes of HER2 mutations showing that Black Diamond’s MAP discovery engine has the ability to identify and experimentally validate 22 novel oncogenic HER2 mutations. By applying his computational approach to 820 single-nucleotide variants, a list of 222 known mutations and potential driver mutations was produced. Of these 222 mutations, 37 HER2 mutations were determined experimentally to be driver mutations, consisting of 15 previously characterized oncogenic mutations and 22 newly identified oncogenic mutations. Black Diamond researchers found that these oncogenic mutations primarily affect allosteric sites in the extracellular domain (ECD), transmembrane domain (TMD), and kinase domain (KD) of HER2. Additionally, Black Diamond was able to describe the unique pharmacological characteristics of these novel HER2 driver mutations that make them susceptible to a unique drug discovery screening strategy.