On May 7, 2021 Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a precision oncology medicine company pioneering the discovery and development of small molecule, MasterKey therapies, reported financial results for the first quarter ended March 31, 2021 and provided a corporate update (Press release, Black Diamond Therapeutics, MAY 7, 2021, View Source [SID1234579434]).
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"The first quarter of 2021 has been marked by meaningful progress across Black Diamond’s pipeline of MasterKey inhibitor therapies, each of which is designed by leveraging our proprietary MAP platform to address an unmet need for patients with a range of genetically defined cancers," said David M. Epstein, Ph.D., President and Chief Executive Officer of Black Diamond Therapeutics. "We look forward to presenting initial clinical data for our lead program, BDTX-189, at the ASCO (Free ASCO Whitepaper) Annual Meeting later this quarter, as well as to continuing to report on progress across the pipeline throughout the year."
Recent Developments
BDTX-189:
Black Diamond continued to enroll and dose patients in the MasterKey-01 study, a Phase 1/2 clinical trial of BDTX-189. More than 50 patients have been dosed with BDTX-189 to date. Eligibility included all solid tumors harboring any of the more than 50 pre-defined genomic alterations in EGFR and human epidermal growth factor receptor 2 (HER2). The Company is on track to complete the dose-escalation portion of the Phase 1 clinical trial in the first half of 2021.
Initial Phase 1 clinical PK, safety, and preliminary efficacy data will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting.
The Company is working toward selection of the recommended Phase 2 dose for BDTX-189 and plans to initiate the safety expansion cohort in the second quarter of 2021. The Phase 2 portion of the MasterKey-01 study is on track to begin in the second half of 2021.
In April 2021, the Company presented pre-clinical data on BDTX-189 at the AACR (Free AACR Whitepaper) Annual Meeting:
Black Diamond employed a novel physiologically based pharmacokinetic (PBPK) modeling strategy, accounting for compound-specific determinants of BDTX-189 metabolism and disposition, to prospectively predict the clinical PK profile and active dose range of BDTX-189.
Preclinical PBPK modeling indicated that BDTX-189 would be readily orally absorbed with a short elimination half-life (approximately two hours) while maintaining suppression of ErbB pathway biomarkers over the dosing interval, consistent with the irreversible mechanism of action and the desired PK/pharmacodynamic (PD) profile.
Active dose levels in humans were projected to be in the 400–800 mg QD range based on the exposure-tumor growth inhibition relationship in multiple mouse patient-derived xenograft (PDX) models harboring ErbB allosteric mutations.
BDTX-1535:
In April 2021, the Company presented pre-clinical data on BDTX-1535 at the AACR (Free AACR Whitepaper) Annual Meeting:
In cell-based assays, BDTX-1535 achieved potent and selective inhibition of all members of the family of oncogenic EGFR variants expressed in GBM.
BDTX-1535 demonstrated a favorable brain-penetrant PK profile in mouse, rat, and dog models.
Tumor growth inhibition in mouse models bearing intracranial GBM6 patient-derived tumors expressing allosteric EGFR mutants was achieved.
BDTX-1535 demonstrated potent and selective inhibition of rare Exon 18 mutations and the C797S mutation, supporting the potential for utility beyond GBM, such as in non-small cell lung cancer (NSCLC).
Black Diamond expects to file an Investigational New Drug (IND) application for BDTX-1535 in the first half of 2022.
Early-Stage Pipeline:
In March 2021, Black Diamond presented pre-clinical data for its B-Raf Proto-Oncogene (BRAF) and fibroblast growth factor receptor (FGFR) programs at European Society for Medical Oncology Targeted Anticancer Therapies Congress:
Black Diamond’s BRAF program candidates have been designed for potency against a spectrum of non-canonical Class II/III (non-V600), as well as to avoid induction of paradoxical activation. Tumor regression in mouse models has been observed.
Black Diamond’s FGFR program candidates are inhibitors with broad coverage of FGFR2 and FGFR3 oncogenes, while sparing inhibition of FGFR1 and retaining activity against gatekeeper mutations. Tumor regression in mouse models has been observed.
The Company anticipates IND filings for both programs in 2022.
Corporate:
In January 2021, Black Diamond appointed oncology clinical development veteran Kapil Dhingra, M.B.B.S., to its Board of Directors.
Financial Highlights
Black Diamond ended the first quarter of 2021 with $290.1 million in cash, cash equivalents, and investments compared to $357.2 million as of March 31, 2020. Net cash used in operations was $24.5 million for the first quarter of 2021 compared to $11.3 million for the first quarter of 2020.
Research and development (R&D) expenses were $22.8 million for the first quarter of 2021 compared to $7.4 million for the first quarter of 2020. The increase in R&D expenses was primarily related to an increase in headcount, and increased spend across preclinical and clinical development.
General and administrative (G&A) expenses were $7.9 million for the first quarter of 2021 compared to $5.5 million for the first quarter of 2020. The increase in G&A expenses was primarily due to an increase in personnel and other corporate-related costs.
Upcoming Events
Initial PK, safety, and preliminary efficacy data from the Phase 1 dose-escalation portion of the MasterKey-01 clinical trial of BDTX-189 in advanced solid tumors will be presented as poster presentations at the ASCO (Free ASCO Whitepaper) Annual Meeting. Presentation details are as follows:
Title: Safety and Preliminary Efficacy from the Phase 1 Portion of MasterKey-01: A First-in-Human Dose-Escalation Study to Determine the Recommended Phase 2 Dose (RP2D), Pharmacokinetics (PK), and Preliminary Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB mutations, in Patients with Advanced Solid Malignancies
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 9:00 AM ET
Abstract ID: 3086
Title: Clinical pharmacokinetics of BDTX-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study
Session Type: Poster Session
Session: Developmental Therapeutics – Molecularly Targeted Agents and Tumor Biology
Date and Time: Friday, June 4, 9:00 AM ET
Abstract ID: 3097
About BDTX-189
BDTX-189 is an orally available, irreversible, and ATP competitive small molecule inhibitor that is designed to block the function of a family of oncogenic epidermal growth factor receptor (EGFR) and ErbB-2 (epidermal growth factor receptor 2 [HER2]) proteins across a range of tumor types. BDTX-189 is designed as a MasterKey inhibitor targeting a family of previously undrugged and functionally similar oncogenic mutations in a tumor-agnostic manner. These mutations include extracellular domain allosteric mutations of HER2, as well as EGFR and HER2 kinase domain Exon 20 insertions, and additional activating oncogenic drivers of ErbB. The ErbB receptors are a group of receptor tyrosine kinases involved in key cellular functions, including cell growth and survival. BDTX-189 is also designed to spare normal, or wild-type, EGFR, which we believe has the potential to improve upon the toxicity profiles of current ErbB kinase inhibitors. Currently, there are no medicines approved by the U.S. Food and Drug Administration (FDA) to target all of these oncogenic mutations with a single therapy.
BDTX-189 is currently being evaluated in a Phase 1/2 clinical trial (MasterKey-01) in adult patients with advanced solid tumors expressing a range of alterations of ErbB receptors, including oncogenic MasterKey mutations, HER2-WT amplification, HER3 mutation, EGFR exon 19 deletion, and L858R mutation who have no standard therapy available or for whom standard therapy is considered unsuitable or intolerable. In July 2020, the FDA granted Fast Track designation to BDTX-189 for the treatment of adult patients with solid tumors harboring an allosteric HER2 mutation or an EGFR or HER2 Exon 20 insertion mutation who have progressed following prior treatment and who have no satisfactory treatment options.