STIFEL 2026 HEALTHCARE CONFERENCE - BLACK DIAMOND THERAPEUTICS INC

Financial Performance:

• No specific revenue, earnings, or cash flow figures provided as the company is in the clinical development phase (Phase 2/3).
• Management confirmed the need for additional capital to complete lung cancer Phase 3 and glioblastoma (GBM) trials, with plans to secure funding via dilutive or non-dilutive sources.
• Phase 2 trial data matured with 16-month median follow-up for the frontline non-classical EGFR population (43 patients) and 24 patients in the no-brain-mets cohort.

Guidance and Future Outlook:

• Phase 3 Initiation: Expected to begin in the second quarter of 2025; trial design confirmed by FDA as a 300-patient randomized global trial (1:1).
• Timeline to Approval: Accelerated approval via CNS-ORR data anticipated by 2029; full approval contingent on PFS data.
• GBM Trial: Interim PFS data expected in H1 2028; potential conversion to Phase 3 if positive.
• Data Milestones: Updated safety data at the 150mg dose to be disclosed at First Patient In (FPI) and at a medical meeting in H2 2025.

Business Segments and Product Lines:

• Silivertinib (Lead Asset): Positioning as a best-in-class, fourth-generation EGFR TKI with superior brain penetrance compared to Osimertinib.
• Indication Scope: Targets non-classical EGFR mutations (including Exon 20 insertions and >50 other "atypical" mutations), covering ~50% of the EGFR mutant NSCLC population.
• Trial Design: Includes a randomized arm for patients with brain metastases (primary endpoint: CNS-ORR per RANO-BM criteria) and a single-arm cohort (80 patients) for patients without brain metastases.
• GBM Program: Phase 2 randomized trial combining Silivertinib with Temozolomide vs. Temozolomide alone; dose confirmed at 150mg.
• Manufacturing: Drug supply, registration batches, stability studies, and ADME (radio-labeled) studies completed; deemed "Big Pharma" ready.

Market and Competitive Landscape:

• Target Population: Addresses the ~25% of EGFR-mutant NSCLC patients with non-classical mutations who currently lack potent oral treatment options.
• Competitive Advantage: Silivertinib demonstrated a CNS-ORR of 86% (vs. ~35% for Afatinib/Osimertinib) in treatment-naïve patients without prior radiation.
• Efficacy Benchmarks: Median PFS of 12.2 months in the Phase 2 cohort vs. 5.1 months for Osimertinib and 6.1 months for Afatinib (data from Memorial Sloan Kettering and others).
• Market Dynamics: FDA agreed to a global trial control arm utilizing both Osimertinib and Afatinib to reflect global prescribing standards; competitors often focus on narrower mutation subsets (e.g., PACT mutations).

Risks and Challenges:

• Safety Management: Original 200mg dose required high rates of dose reduction due to EGFR-mediated AEs (rash, diarrhea); mitigated by moving to 150mg starting dose.
• Regulatory Path: While CNS-ORR supports accelerated approval, full approval relies on PFS; FDA requires "no detriment" on Overall Survival (OS) rather than statistical non-inferiority.
• Trial Enrollment: Potential physician preference for radiation in symptomatic brain lesions, though trial design allows irradiation of specific symptomatic lesions while counting other lesions for analysis.
• Capital Requirements: Need to secure significant funding to advance two late-stage trials and reach approval endpoints.

Management Commentary and Tone:

• Confidence: Highly confident and optimistic regarding the FDA partnership, describing the path to approval as "clear" and the drug as a "home run" for the target population.
• Strategic Clarity: Emphasized the simplification of patient selection (classical vs. non-classical) to ease trial enrollment and future prescribing.
• Safety: Reassured investors that the 150mg dose maintains efficacy (no loss of response depth) while improving tolerability compared to the 200mg dose.
• Global Ambition: Confirmed readiness for global operations with trials expanding into China, Taiwan, Europe, South America, and Japan.

Analyst Questions and Answers:

• Control Arm: FDA agreed to a mix of Osimertinib and Afatinib for the global control arm to reflect real-world usage patterns.
• Powering: Trial is adequately powered to detect a ~35-point difference in CNS-ORR; even if control improves, Silivertinib is expected to exceed 70%.
• Radiation Use: Patients with symptomatic lesions can undergo radiation and remain on the trial; the primary goal is sparing patients from unnecessary radiation if the drug controls disease.
• Dose Formulation: The 150mg dose uses existing pill strengths (two 75mg tablets), requiring no new formulation.
• Leptomeningeal Disease: FDA specifically requested inclusion of a small cohort for this high-unmet-need population.

Other Key Points:

• Brain Activity: The drug showed 23.5-month median PFS in patients without baseline brain mets over 16-month follow-up, with zero observed brain metastases despite rigorous 6-week MRI surveillance.
• GBM TAM: Approximately 50,000 patients globally with EGFR alterations in Glioblastoma; Silivertinib is the only EGFR TKI to potently inhibit EGFR amplification.
• Paradoxical Activation: Unlike other EGFR TKIs, Silivertinib does not cause paradoxical activation, addressing a historical failure point for the drug class in GBM.
• Partnerships: Management is open to international partnerships for ex-US rights to support global development.