Pursuing Next Generation Solutions for Defeating Cancer

In the bustling corridors of Yale New Haven Hospital, where the hum of urgency meets the rhythm of healing, Mark Velleca, MD, PhD, began his residency journey in 1995. As he witnessed the anguish and discomfort patients faced when considering limited, toxic treatment options such as chemotherapy, he realized his desire to actualize the Hippocratic Oath from a new angle and decided to parlay his experience as a healthcare professional into oncology drug development. Building on his successful track record in biotech, Dr. Velleca’s path led to Black Diamond Therapeutics (BDTX) (BDTX), a clinical-stage oncology company developing investigational MasterKey therapies targeting families of oncogenic mutations, where he now serves as CEO.

Similarly driven by a deep commitment to improving patient lives, Elizabeth Buck, PhD, Co-Founder and CSO of BDTX, has dedicated more than two decades to groundbreaking research in oncology. Her journey began with a clear purpose: to make a meaningful difference for people battling cancer. With a background in discovery and translational research, Dr. Buck’s early endeavors supported the development of the first generation of oral epidermal growth factor receptor (EGFR) inhibitors for lung cancer treatment. Since 2015, she has pioneered the advancement of BDTX’s understanding of EGFR structure and function, and how to effectively drug groups of oncogenic and drug-resistant mutations affecting this receptor. Dr. Buck spearheaded the development of BDTX’s innovative MAP drug discovery engine, unlocking the potential of its MasterKey investigational therapies to reach a larger patient population beyond the narrow subset of cancer-driving mutations that were targeted with earlier generation treatments.

Drs. Velleca and Buck, along with BDTX’s team of seasoned drug developers and biotech industry veterans, are committed to bringing hope to cancer patients by developing transformative breakthroughs. Drawing from their rich experiences in both clinical settings and laboratories, they anchor the company’s mission to provide people living with cancer the opportunity to experience longer, healthier lives.

Unique Approach

Scientists are now beginning to grasp more fully the landscape of oncogenic mutations that fuel tumor growth, given the increasing adoption of liquid biopsies and advances in genetic sequencing methods uncovering a range of mutations that drive cancer. Yet current targeted therapies only act against a limited subset of mutations. BDTX is determined to deliver treatments to patients whose tumor mutational profiles are actively changing throughout their journey─with the goal of ultimately defeating cancer resistance. The idea behind BDTX’s strategy is developing potential MasterKey-based treatments, which could offer one solution for many mutations affecting a given target, such as EGFR or BRAF. Importantly, BDTX believes that designing a drug to specifically address the broad range of mutations is a better strategy than taking drugs designed for individual mutations and trying to retrofit them to patients with these evolving sets of mutations.

Dedication to Patients in an Evolving NSCLC Mutational Landscape

Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases worldwide. Up to 20% of people with NSCLC in North America and Europe, and up to 50% of those in Asia, harbor mutations in EGFR. Through its unique approach, BDTX discovered and is advancing its investigational agents BDTX-1535 and BDTX-4933, two MasterKey therapies that target entire families of broad, genetically defined oncogenic mutations.

BDTX-1535, an orally administered fourth-generation EGFR inhibitor that is being studied in NSCLC and glioblastoma (GBM), was designed to address the broad spectrum of EGFR mutations that can drive NSCLC, including both classical and non-classical EGFR oncogenic driver mutations. It also targets the C797S acquired resistance mutation, which can arise in patients with NSCLC who have progressed following a previous EGFR inhibitor therapy such as osimertinib. This is especially relevant given today’s evolving treatment landscape and the resulting mechanisms of resistance that change the prevalence of these mutations.

Due to its brain penetrance, BDTX-1535 has the potential to treat patients with NSCLC that has spread to the brain and those with GBM, a difficult-to-treat, aggressive cancer that can occur in the brain or spinal cord.

BDTX is currently advancing BDTX-1535 in a Phase 2 trial for patients with EGFR-positive NSCLC across multiple lines of therapy. This open-label Phase 2 multi-cohort study evaluates the safety and antitumor activity of BDTX-1535 in first-, second-, and third-line patients with EGFR-positive NSCLC. Patients are being enrolled both in a first-line setting for those expressing EGFR non-classical mutations and in second- and third-line settings following prior treatment with an EGFR inhibitor.

Other clinical trials of BDTX programs include:

• Study of BDTX-1535 in Recurrent High-Grade Glioma (HGG) Participants with EGFR Alterations or Fusions
• BDTX-4933-101: Phase 1 Trial in BRAF and Select RAS/MAPK Mutation-Positive Cancers

BDTX Impact

At BDTX, we’re driven by a simple goal: to improve patients’ lives. We’re dedicated to listening to patients, working with caregivers, healthcare professionals, and advocacy groups, and to developing innovative treatments that offer hope and empowerment. Together, we’re fighting for a better future.

For more information about our clinical trials, visit clinicaltrials.gov or reach out to blackdiamondtx@careboxhealth.com.

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