Black Diamond Therapeutics Presents Trial in Progress Poster for BDTX-1535 and Preclinical Data on BDTX-1535 and BDTX-4933 at the 2023 American Association of Cancer Research Annual Meeting
April 17 2023 - 3:01PM
Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage
precision oncology medicine company developing MasterKey therapies
designed to overcome limitations of existing therapies by targeting
families of oncogenic driver mutations in patients with genetically
defined cancers, today announced the presentation of three posters
highlighting the design of the phase 1 clinical study of BDTX-1535
and new preclinical data on BDTX-1535 and BDTX-4933 at the 2023
American Association of Cancer Research (AACR) Annual Meeting being
held in Orlando, Florida.
“Black Diamond’s MasterKey approach to precision
oncology medicines is grounded in our deep understanding of the
characterization of oncogenic mutations, and these presentations
highlight the depth of our work to expand the addressable patient
population for precision oncology. With an everchanging treatment
landscape for genetically defined cancers, we believe that our
approach to grouping our targets into druggable oncogene families
presents a truly differentiated opportunity to address the
continuing unmet need of patients,” said Elizabeth Buck, Ph.D.,
Chief Scientific Officer of Black Diamond. “Our MAP Drug Discovery
Engine has enabled us to intricately design MasterKey inhibitors
based on extensive preclinical and real-world data, elucidating
what we believe to be the necessary attributes for effectively
targeting shared, activated conformations used by oncogenic drivers
for tumor growth. Our fourth-generation irreversible brain
penetrant EGFR MasterKey inhibitor, BDTX-1535, has demonstrated its
ability to achieve potent anti-tumor activity against EGFR
alterations and amplifications in a broad range of preclinical
NSCLC and GBM models and we look forward to continuing to advance
its development in the clinic and providing a first clinical update
in the second half of this year. Our next most advanced program,
BDTX-4933 was designed to be brain penetrant and selectively
inhibits aberrant RAF signaling as result of BRAF class I, II, III
and RAS oncogenic mutations without inducing paradoxical
activation. We are encouraged by the results shared today, which
support its potentially best-in-class profile.”
BDTX-1535 Program:
Black Diamond presented two posters highlighting
BDTX-1535’s preclinical development as well as the ongoing Phase 1
study.
In a poster titled, “Discovery of BDTX-1535, a
novel brain penetrant, irreversible, potent, wild type sparing EGFR
MasterKey inhibitor that targets oncogenic kinase domain mutations
as well as extracellular domain alterations for the treatment of
NSCLC and GBM,” Black Diamond outlined the unmet need for next
generation EGFR inhibitors that target classical driver mutations
as well as acquired and intrinsic resistance mutations expressed in
the context of EGFR driver mutations in non-small cell lung cancer
(NSCLC), and EGFR alterations expressed in glioblastoma multiforme
(GBM). Additional highlights include:
- While EGFR C797S substitution is a frequently reported
post-osimertinib resistance mutation, real world evidence indicates
the emergence of other EGFR alterations that lead to resistance to
osimertinib including EGFR kinase domain mutations (e.g., S768I),
extracellular domain alterations (e.g., EGFRvIII, A289X), and EGFR
amplification.
- A family of extracellular domain EGFR alterations occurs in
nearly 50% of GBM patients and these alterations are clinically
resistant to all current generation inhibitors.
- Real world data in GBM demonstrates EGFR alterations often
co-occur and persist throughout treatment with current standard of
care therapy. Black Diamond observed that the oncogenic isoform of
EGFR in GBM is a covalent homo-dimer which can be formed and
paradoxically activated by the binding of reversible EGFR
inhibitors.
- Black Diamond concluded that an effective EGFR inhibitor should
meet four design principles and be: 1) potent and selective against
a broad family of intracellular, extracellular EGFR oncogenic
alterations and amplification, 2) wild type EGFR sparing, 3)
irreversible to avoid paradoxical activation, and 4) central
nervous system (CNS) penetrant.
In a poster titled, “A Phase 1 Study to Assess
BDTX-1535, an Oral EGFR Inhibitor, in Patients with Glioblastoma or
Non-Small Cell Lung Cancer,” Black Diamond outlined its ongoing
Phase 1, open-label, multicenter study to assess the safety,
tolerability, pharmacokinetics, CNS penetrance and preliminary
antitumor activity of BDTX-1535 in recurrent GBM (rGBM) or locally
advanced or metastatic NSCLC with or without CNS disease. Key
highlights include:
- The monotherapy dose escalation portion will evaluate BDTX-1535
in patients with either rGBM expressing EGFR alterations or locally
advanced/metastatic NSCLC harboring sensitizing EGFR mutations with
or without CNS disease.
- Patients with rGBM must have previously received available
standard therapy of surgical resection followed by
chemoradiotherapy and/or temozolomide (TMZ). Eligible NSCLC
patients must have EGFR mutated NSCLC that has progressed following
standard of care EGFR inhibitor therapy.
- Following the establishment of a provisional recommended Phase
2 dose, BDTX-1535 monotherapy will be explored in the following
dose expansion cohorts to further evaluate safety, pharmacokinetics
(PK), and preliminary assessment of efficacy: 1) rGBM with
confirmed EGFR alterations, 2) NSCLC with uncommon EGFR mutations
following EGFR inhibitor therapy, and 3) NSCLC with acquired EGFR
resistance mutation(s) following a 3rd generation EGFR inhibitor in
the first-line setting. NSCLC patients may enroll with or without
CNS metastases and must not be known to express excluded resistance
mutations such as EGFR T790M or MET.
- BDTX-1535 will also be studied in combination with TMZ to
assess safety, tolerability, and a recommended combination dose for
the treatment of patients with rGBM harboring EGFR mutations or
variants.
- Enrollment was initiated in 2022 and dose escalation is
ongoing. Dose Expansion cohorts are expected to open in 2023.
Black Diamond remains on track to provide a
clinical update on BDTX-1535 in the second half of 2023.
BDTX-4933 Program:
In a poster titled, “Preclinical
characterization of a brain penetrant RAF inhibitor, BDTX-4933,
targeting oncogenic BRAF Class I/II/III and RAS mutation,” Black
Diamond outlined its approach to characterizing BRAF, RAS and MAPK
pathway in addition to the design and preclinical development of
BDTX-4933:
- Mutations in BRAF and RAS are often oncogenic and lead to a
constitutively active MAPK pathway that promotes aberrant cell
proliferation and tumor growth.
- BDTX-4933 is a potent, reversible, CNS penetrant RAF MasterKey
inhibitor designed to target a large family of oncogenic BRAF class
I, II, III and RAS mutants.
- In a panel of cancer cell lines that endogenously express BRAF
or RAS mutations, BDTX-4933 demonstrated inhibition of the MAPK
pathway signaling without paradoxical activation, resulting in
potent inhibition of cellular proliferation.
- In tumor models in vivo, BDTX-4933 showed target engagement,
inhibiting ERK phosphorylation, achieving strong anti-tumor
activity and tumor regression across tumor models driven by either
BRAF or RAS mutations.
- BDTX-4933 exhibits high CNS exposure leading to dose-dependent
tumor growth inhibition, and survival benefit in an intracranial
tumor model harboring oncogenic BRAF mutation.
- Based on preclinical data, BDTX-4933 has a potential
best-in-class profile to treat cancer patients harboring oncogenic
BRAF Class I, II, III and RAS mutations, with or without brain
disease.
Black Diamond expects to initiate a Phase 1
clinical trial of BDTX-4933 in patients with tumors harboring
all-class BRAF or RAS mutations in the second quarter of 2023.
The posters from the AACR Annual Meeting are
available on the “Scientific Presentations and Publications”
section of the Black Diamond Therapeutics website.
About Black Diamond Therapeutics
Black Diamond Therapeutics is a clinical-stage
precision oncology medicine company focused on the development of
MasterKey therapies that target families of oncogenic mutations in
clinically validated targets. Black Diamond leverages a deep
understanding of cancer genetics and onco-protein structure and
function, to discover and develop innovative MasterKey therapies.
The Company’s MasterKey therapies are designed to overcome
resistance, minimize on-target, wild-type mediated toxicities, and
be brain-penetrant to address significant unmet medical needs of
patients with genetically defined cancers. The Company is advancing
a robust pipeline with lead clinical-stage program BDTX-1535,
targeting MasterKey mutations in both EGFR mutant-positive
non-small cell lung cancer (NSCLC) and in glioblastoma multiforme
(GBM), and BDTX-4933, a program targeting RAF MasterKey mutations
in solid tumors, as well as discovery-stage research programs. The
Company’s proprietary Mutation-Allostery-Pharmacology, or MAP drug
discovery engine, is designed to allow Black Diamond to analyze
population-level genetic sequencing tumor data and validate
MasterKey mutations. For more information, please visit
www.blackdiamondtherapeutics.com.
Forward-Looking Statements
Statements contained in this press release
regarding matters that are not historical facts are
“forward-looking statements” within the meaning of the Private
Securities Litigation Reform Act of 1995. Because such statements
are subject to risks and uncertainties, actual results may differ
materially from those expressed or implied by such forward-looking
statements. Such statements include, but are not limited to,
statements regarding: the continued development and advancement of
BDTX-1535 and BDTX-4933, including the ongoing Phase 1 clinical
trial and the expected timing for data updates for BDTX-1535 and
the timing for initiating a Phase I clinical trial of BDTX-4933.
Any forward-looking statements in this statement are based on
management’s current expectations of future events and are subject
to a number of risks and uncertainties that could cause actual
results to differ materially and adversely from those set forth in
or implied by such forward-looking statements. Risks that
contribute to the uncertain nature of the forward-looking
statements include those risks and uncertainties set forth in its
Annual Report on Form 10-K for the year ended December 31, 2022,
filed with the United States Securities and Exchange Commission and
in its subsequent filings filed with the United States Securities
and Exchange Commission. All forward-looking statements contained
in this press release speak only as of the date on which they were
made. The Company undertakes no obligation to update such
statements to reflect events that occur or circumstances that exist
after the date on which they were made.
Contact:
Julie Seidel, Stern Investor Relations
(212) 362-1200
investors@bdtx.com
media@bdtx.com
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