Benzinga | Oct 8, 2021 04:06PM EDT

Black Diamond Therapeutics Highlights Presentation Of Preclinical Data On BDTX-1535, B-Raf, Fibroblast Growth Factor Receptor Programs At AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics

Black Diamond Therapeutics, Inc. (NASDAQ:BDTX), a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, today announced the presentation of preclinical data for three early-stage pipeline programs in oral and poster sessions at the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics.

"Despite clinical advances in precision medicines for patients with non-small cell lung cancer (NSCLC) harboring an epidermal growth factor receptor (EGFR) mutation, multiple areas of unmet need persist, which include patients whose tumors have developed resistance to current-generation therapies, express non-canonical (or uncommon) mutations, and have metastasized to the brain," said Elizabeth Buck, Ph.D., Chief Scientific Officer of Black Diamond Therapeutics. "BDTX-1535 has demonstrated a breadth of coverage of oncogenic EGFR mutations expressed in NSCLC, which coupled with a brain-penetrant pharmacokinetic (PK) profile, supports the potential of BDTX-1535 as an optimal therapeutic candidate for these NSCLC patient populations."

Dr. Buck continued: "Additionally, B-Raf (BRAF) and fibroblast growth factor receptor (FGFR) are validated therapeutic targets, yet current standards of care are associated with meaningful limitations, yielding persistent unmet needs for these cancer patients. Our BRAF program compounds are designed to selectively target a full spectrum of Class II/III BRAF oncogenic mutations without inducing paradoxical activation, which can lead to secondary malignancies. Our FGFR compounds are designed to target a full spectrum of oncogenic FGFR2 and FGFR3 mutations, including known resistance mutations, while sparing FGFR1, the inhibition of which is associated with toxicities, including hyperphosphatemia."

The presentations describe the following data:

BDTX-1535 Program:

The presentation describes preclinical data for BDTX-1535, which is designed as a potent, selective, and brain-penetrant inhibitor of a spectrum of EGFR mutations expressed in glioblastoma multiforme (GBM) and NSCLC.

* In cell-based assays, BDTX-1535 achieved potent and selective inhibition of EGFR mutations expressed in NSCLC, including the EGFR- C797S mutation that can arise following treatment with osimertinib.

* BDTX-1535 demonstrated a favorable brain-penetrant PK profile in mouse, rat, and dog models.

* In an EGFR Exon19+C797S mouse allograft efficacy model, BDTX-1535 showed dose-dependent tumor growth inhibition and achieved complete regression without notable impact on body weight.

* Black Diamond expects to file an Investigational New Drug (IND) application for BDTX-1535 in the first half of 2022.

BRAF Program:

The presentation describes preclinical data for a lead compound from Black Diamond's BRAF program, which is designed for potency and selectivity against a spectrum of non-canonical Class II/III (non-V600) mutations, as well as to avoid induction of paradoxical activation.

* In cell-based assays, the lead compound demonstrated potent inhibition of a spectrum of Class II/III BRAF mutations.

* In contrast to current-generation BRAF inhibitors, such as encorafenib and vemurafenib, treatment of cells harboring wild type BRAF (WT-BRAF) with the Black Diamond compound was not observed to lead to an increase in protein kinase RNA-like endoplasmic reticulum kinase (pERK), a signal of paradoxical activation.

* In a BRAF-KIAA1549 fusion allograft tumor model, the lead compound exhibited dose-dependent inhibition of pERK and anti-tumor efficacy.

* Black Diamond anticipates an IND filing in 2022.

FGFR Program:

The presentation illustrates the Black Diamond approach, which centers on a four-pronged optimization strategy designed to deliver an inhibitor with broad coverage of FGFR2 and FGFR3 oncogenes, while sparing inhibition of FGFR1 and retaining activity against resistance mutations.

* In cell-based assays, FGFR program compounds demonstrated potent and selective inhibition of a spectrum of FGFR2/3 oncogenic mutations, while sparing FGFR1.

* Additionally, in cell-based assays, FGFR program compounds demonstrated improved potency against resistance mutations.

* In an in vivo study conducted in a UM-UC-14 (FGFR3-S249C) mouse model, FGFR program compounds demonstrated anti-tumor activity. Additionally, in mouse and rat models, FGFR program compounds did not promote hyperphosphatemia.

* Black Diamond anticipates an IND filing in 2022.

"Our BDTX-1535, BRAF, and FGFR programs exemplify Black Diamond's MasterKey approach to drug discovery in which we are able to harness the power of our proprietary MAP drug discovery engine to design spectrum-selective candidates engineered to overcome the limitations of current therapies in each target area," said David M. Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "These programs underscore the productivity of our MAP engine, and we look forward to providing updates across our pipeline as we advance toward our goal of delivering product candidates that can expand the reach of precision medicine and, in turn, address areas of true unmet need."

The presentations from the AACR-NCI-EORTC meeting are available on the "Scientific Presentations and Publications" section of the Black Diamond Therapeutics website.