On May 12, 2022 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, reported the publication of data identifying new oncogenic HER2 allosteric mutations that support the Mutation-Allostery-Pharmacology (MAP) discovery engine’s capabilities and further suggest the need for novel inhibitors to treat HER2-mutant cancers (Press release, Black Diamond Therapeutics, MAY 12, 2022, View Source [SID1234614359]). The paper, titled "Computational and Functional Analyses of HER2 Mutations Revealing Allosteric Activation Mechanisms and Altered Pharmacologic Effects" by Ishiyama et al. was published online by the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Cancer Research Journal on May 3, 2022.

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"At the core of our precision medicine approach to cancer treatment is the ability to identify new, full spectrum oncogenic mutations. This study provides strong rationale for the power of our MAP discovery engine as we identified new oncogenic HER2 allosteric mutations that further suggest the need for novel treatment options. These findings support our overall 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 analyses were able to provide new insights into the oncogenic activity and therapeutic targeting of HER2 mutations in cancer in addition to identifying 22 new oncogenic HER2 mutations. As the number of unique mutations across cancers is expected to rise over time, there remains a need for an effective means of identification of oncogenic mutations. We believe that our MAP technology has the potential to fill this gap and provide critical insights for the use of precision medicine to treat cancers driven by rare oncogenic mutations."

The peer-reviewed paper describes computational and functional analyses of HER2 mutations showing that Black Diamond’s MAP discovery engine has the ability to identify and experimentally validate 22 new oncogenic HER2 driver mutations. By applying its 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 experimentally determined to be driver mutations, comprised of 15 previously characterized and 22 newly identified oncogenic mutations. Black Diamond researchers found that these oncogenic mutations mostly affected allosteric sites in the extracellular domain (ECD), transmembrane domain (TMD), and kinase domain (KD) of HER2. In addition, Black Diamond was able to describe the unique pharmacological characteristics of these new HER2 driver mutations that render them susceptible to unique drug discovery screening strategy.