Black Diamond Therapeutics, Inc.

NEW YORK, Oct. 22, 2024 /PRNewswire/ -- For some proteins, a single mutation, or change in its DNA instructions, is all it takes to tip the balance between functioning normally and causing cancer. But despite causing major disease, these slightly mutated proteins can resemble their normal versions so closely that treatments designed to target mutants could also harm healthy cells. Led by researchers at NYU Langone Health and its Perlmutter Cancer Center, a new study describes the development of a biologic, a drug derived from natural biological systems, that targets a mutant cancer protein called HER2 (human epidermal growth factor receptor 2) without attacking its nearly identical normal counterpart on healthy cells. While still in the early stages, this technique could lead to new therapies to treat cancer patients with HER2 mutations with minimal side effects, the researchers say. "We set out to make an antibody that can recognize a single change in the 600 amino acid building blocks that make up the exposed part of the HER2 protein, which conventional wisdom says is very difficult, said lead study author Shohei Koide, PhD, a professor in the Department of Biochemistry and Molecular Pharmacology at NYU Grossman School of Medicine and member of Perlmutter Cancer Center. "The fact that we were able to detect the difference of a single amino acid so cleanly was a surprise." The new findings revolve around HER2, a protein that occurs on the surfaces of many cell types and that turns on signaling pathways that control cell growth. It can cause cancer when a single amino acid s the protein into "always-active" mode, which in turn causes cells to divide and multiply uncontrollably. Cancer can also result when cells accidentally make extra copies of the DNA instructions that code for the normal version of HER2 and express higher levels of the protein on their surfaces. There are a few FDA-approved therapies, including trastuzumab and pertuzumab, that can treat this kind of cancer, but these therapies all work at the level of HER2 on the cell surface, where only low levels of the mutated version of HER2 occur. "That means we cannot mark cancer cells just by looking at HER2 levels," said Dr. Koide, who also serves as director of cancer biologics at NYU Langone. In addition, since some approved therapies cannot tell the difference between mutant and normal HER2, they are more likely to harm healthy cells expressing normal HER2. Publishing in the journal Nature Chemical Biology online Oct. 22, the study shows how the researchers harnessed their new protein-engineering technique to develop antibodies that recognize only mutant HER2. Antibodies are large, Y-shaped proteins that bind to specific targets and flag down immune cells to destroy those targets. In a process that mimics natural antibody development, the researchers subjected antibodies to multiple rounds of mutation and selection, looking for variants that recognized mutant HER2 but not the normal version. By taking atomic images with a cryo-electron microscope, the team saw how their new antibodies interacted with HER2 spatially (kept two HER2 molecules from interacting to signal), which let the team continually refine their antibody designs. But selectively recognizing mutant HER2 was only part of developing an effective cancer treatment, since antibodies need to work with the immune system to kill cancer cells. A particular challenge is the case in which cancer cells have only small numbers of mutant HER2 on their surfaces to which an antibody can attach. To address this challenge, the researchers converted their antibody into a bispecific T cell engager, a molecule in which the antibody targeting the mutant protein is fused to another antibody that binds to and activates immune cells called T cells. One end of the antibody sticks to the mutant HER2 on a cancer cell, while the other triggers T cells to kill the cancer cell. Further testing showed this method killed mutant HER2 cancer cells in dishes but spared normal ones. When the researchers tested their T-cell engagers in mice with mutant HER2 tumors, the treatment significantly reduced tumor growth. It did so without causing weight loss or visible sickness in the mice, which suggested the treatment had few side effects in the animals. However, Dr. Koide noted that because there are differences between mouse and human proteins, it is possible the lack of obvious side effects stemmed from the antibody binding even less to mouse wild-type HER2 than to the human version. Future studies will tell. Moving forward, Dr. Koide said the researchers will continue fine-tuning their antibody with the goal of developing a treatment. While the T cell engager molecule was the most potent of the things they tried, he said, there could be better options they have not tested yet. In addition, they plan to apply their antibody engineering technique to develop highly specific antibodies that may treat other mutant proteins causing cancers. In addition to Dr. Koide, other NYU Langone researchers involved in this study are lead author Injin Bang, as well as Takamitsu Hattori, Nadia Leloup, Alexis Corrado, Atekana Nyamaa, and Akiko Koide. Other study co-investigators include Ken Geles and Elizabeth Buck, at Black Diamond Therapeutics in New York City. This work was supported by National Institutes of Health grant P30CA01608. Dr. Bang, Dr. Hattori, Dr. Leloup, Dr. A. Koide, Dr. Geles, Dr. Buck, and Dr. S. Koide are listed as inventors of a patent application for the therapy described in this study, from which they may benefit financially. Dr. S. Koide is a co-founder and holds equity in Aethon Therapeutics, and Revalia Bio, and receives consulting fees from Aethon Therapeutics. He has received research funding from Aethon Therapeutics, argenx BVBA, Black Diamond Therapeutics, and PureTech Health. Dr. Geles and Dr. Buck hold equity in Black Diamond Therapeutics. These relationships are managed in keeping with the policies of NYU Langone. Media Inquiries David March 212-404-3528 [email protected] STUDY DOI 10.1038/s41589-024-01751-w STUDY LINK WILL BECOME ACTIVE AFTER EMBARGO LIFTS SOURCE NYU Langone Health System WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Black Diamond Therapeutics is cutting an unspecified number of workers, including several executives, and making changes to its pipeline in an effort to extend its cash runway. As part of the restructuring, CBO/CFO Fang Ni and chief people officer Elizabeth Montgomery are leaving Black Diamond. As of Feb. 15, Black Diamond had 54 full-time employees. It had laid off 30% of its workforce in 2022. Black Diamond said it is also looking for partnerships as it deprioritizes its program in RAF/RAS-mutant solid tumors. The company now plans to focus on advancing its lead program, dubbed BDTX-1535, into pivotal development. The changes are expected to extend the cash runway into the second quarter of 2026. Last month, Black Diamond read out a small batch of Phase 2 data for BDTX-1535, a tyrosine kinase inhibitor, in patients with relapsed/refractory EGFR-mutant non-small cell lung cancer (NSCLC). Of the 19 evaluable patients who were on the 200 mg dose and expressed mutations showing resistance to AstraZeneca’s Tagrisso, five achieved a confirmed partial response, one of whom later progressed to an unconfirmed complete response, and another three achieved an unconfirmed partial response. In a note on Monday, TD Cowen analysts described the drug as having “a Tagrisso-like safety profile” and they anticipate an accelerated approval in second-line or higher EGFRm NSCLC if “this data holds.” They also wrote that while they are “disappointed that the other programs will not be advanced internally, we think the move is prudent given the capital position of the company and the strength of data BDTX-1535 has generated to date.” More data are expected in the first quarter, when Black Diamond plans to share initial Phase 2 data for the drug in the frontline setting for patients with EGFRm NSCLC. The company may also have updated Phase 2 data in patients with recurrent EGFRm NSCLC early next year, along with a potential registration path based on FDA feedback.

Company advancing BDTX-1535 in EGFRm NSCLC towards key inflection points in Q1 2025 Will deprioritize BDTX-4933 and seek potential partners Anticipated cost savings expected to extend cash runway into Q2 2026 CAMBRIDGE, Mass., Oct. 07, 2024 (GLOBE NEWSWIRE) -- Black Diamond Therapeutics, Inc. (Nasdaq: BDTX), a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer, announced today a corporate restructuring to focus resources on advancing lead program BDTX-1535 into pivotal development, and to extend the Company’s expected cash runway into Q2 2026. BDTX-1535 has demonstrated robust Phase 2 clinical activity across a broad spectrum of epidermal growth factor receptor mutations (EGFRm) in patients with recurrent non-small cell lung cancer (NSCLC). In Q1 2025, Black Diamond anticipates sharing initial Phase 2 data for BDTX-1535 in the frontline setting for patients with EGFRm NSCLC. Also in Q1 2025, the Company plans to present updated Phase 2 results for BDTX-1535 in patients with recurrent EGFRm NSCLC and a potential registration path in the recurrent setting based on feedback from the FDA. Black Diamond is actively seeking partnerships as it deprioritizes its BDTX-4933 program in RAF/RAS-mutant solid tumors. To enable focused investment in BDTX-1535, Black Diamond has also taken steps to optimize operations, including a reduction in force, while retaining core drug development and management expertise. As part of the restructuring, Chief Business Officer and Chief Financial Officer Fang Ni and Chief People Officer Elizabeth Montgomery are departing the Company. Erika Jones, Senior Vice President of Finance and Principal Accounting Officer, has been appointed Principal Financial Officer of the Company. Cost savings from the restructuring and other actions described above are expected to be sufficient to fund operations into Q2 2026. “BDTX-1535 is a well-tolerated oral TKI with the potential to benefit patients with EGFRm NSCLC across multiple lines of therapy,” said Mark Velleca, M.D., Ph.D., Chief Executive Officer of Black Diamond Therapeutics. “We remain focused on advancing BDTX-1535 and presenting additional Phase 2 data in Q1 2025. I am deeply grateful to each member of the Black Diamond team, whose hard work and valuable contributions have brought us to the threshold of pivotal development for our lead program.” About BDTX-1535 BDTX-1535 is an oral, brain-penetrant MasterKey inhibitor of oncogenic EGFR mutations in NSCLC, including classical mutations, non-classical mutations, and the C797S resistance mutation. BDTX-1535 is a fourth-generation tyrosine kinase inhibitor (TKI) that potently inhibits, based on preclinical data, more than 50 EGFR mutations expressed across a diverse group of patients with NSCLC in multiple lines of therapy. Based on preclinical data, BDTX-1535 also inhibits EGFR extracellular domain mutations and alterations commonly expressed in glioblastoma (GBM) and avoids paradoxical activation observed with earlier generation reversible TKIs. A “window of opportunity” trial of BDTX-1535 in patients with GBM is ongoing (NCT06072586) and a Phase 2 trial is ongoing in patients with NSCLC (NCT05256290). About Black Diamond Therapeutics Black Diamond Therapeutics is a clinical-stage oncology company developing MasterKey therapies that target families of oncogenic mutations in patients with cancer. The Company’s MasterKey therapies are designed to address a broad spectrum of genetically defined tumors, overcome resistance, minimize wild-type mediated toxicities, and be brain penetrant to treat central nervous system disease. The Company is advancing a Phase 2 NSCLC trial of BDTX-1535, a brain-penetrant fourth-generation EGFR MasterKey inhibitor targeting EGFR-mutant NSCLC and GBM. 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 potential of BDTX-1535 to address the unmet medical need for patients with recurrent NSCLC and for newly diagnosed NSCLC patients with non-classical EGFR mutations and benefit patients with NSCLC across multiple lines of therapy, the continued development and advancement of BDTX-1535, including the ongoing clinical trials and the timing of clinical updates for BDTX-1535 in patients with NSCLC; the expected timing for regulatory feedback and the disclosure of potential registrational pathways for BDTX-1535 in NSCLC; potential partnership opportunities for BDTX-4933; the expected cost savings from the restructuring; and expected cash runway. Any forward-looking statements in this press release 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, 2023, 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. Contacts For Investors:investors@bdtx.com For Media:media@bdtx.com