Q4 2026 Silevertinib Program Update Webcast - BLACK DIAMOND THERAPEUTICS INC

Financial Performance:

• No specific financial metrics (revenue, earnings, cash flow, or debt) were disclosed as Black Diamond Therapeutics is a clinical-stage company; the call focused entirely on clinical trial results, regulatory milestones, and operational timelines.
• The company confirmed ongoing enrollment in Phase II Cohort 4 at the 150 mg dose since August, with no new safety signals reported and a median dose intensity of 126 mg/day.

Guidance and Future Outlook:

• Phase III Initiation: The pivotal Phase III trial for non-small cell lung cancer (NSCLC) is scheduled to initiate in the second quarter of 2027.
• Data Catalysts: Cohort 4 safety data (required for Phase III launch) to be submitted prior to Q2 2027; preliminary data from Phase III open-label cohorts expected in 2028; CNS-ORR data (accelerated approval endpoint) expected in 2029.
• Glioblastoma (GBM): Interim Progression-Free Survival (PFS) data expected in the first half of 2028, with potential conversion to a registrational Phase III trial if positive.
• Market Timing: Management estimates 18 months for Phase III enrollment, targeting data readiness in 2029 to compete with current competitors.

Business Segments and Product Lines:

• Silvvertinib (NSCLC): Focused on non-classical EGFR mutations (NCMs); updated Phase II data shows 86% CNS-ORR in patients with untreated brain metastases (vs. ~35-36% historical controls) and 23.5 months median PFS in patients without baseline brain metastases (vs. 9.8 months historically).
• Silvvertinib (GBM): Phase II trial in EGFR variant 3 and MGMT unmethylated patients is enrolling in the randomized phase at 150 mg; the drug targets high brain penetrance to address aggressive glioblastoma.
• Patient Population: FDA agreed to define the target population as all oncogenic EGFR mutations excluding exon 19 del, L858R, and exon 20 insertions (covering ~50 mutations), significantly broader than PAM-restricted competitors.
• New Product Opportunities: Potential expansion into adjuvant settings and leptomeningeal disease cohorts suggested by the FDA.

Market and Competitive Landscape:

• Differentiation: Silvvertinib demonstrates the strongest brain penetrance of any EGFR TKI, with unbound drug levels in brain tumors >5x IC50.
• Competitive Gap: Current standard-of-care options (Afatinib, Osimertinib) show CNS-ORR of ~35% and median PFS of 5-6 months in brain metastasis patients; Silvvertinib doubles these metrics.
• Market Size: NCMs represent ~25% of EGFR-mutated lung cancer cases; the potential addressable market is noted as three times the size of the Exon 20 insertion market and double the size of the PAM mutation market.
• Competitor Risk: Competitors pursuing approval via systemic ORR face higher regulatory hurdles (66% ORR required) compared to Silvvertinib's CNS-ORR focus.

Risks and Challenges:

• Enrollment: While confidence is high, Phase III enrollment must accommodate varying standard-of-care practices (Afatinib vs. Osimertinib) across US, Asia, and South America.
• Regulatory Path: Accelerated approval relies on CNS-ORR durability; failure to maintain CNS response over time could impact final approval or label negotiation.
• Safety Monitoring: Requirement to submit specific safety data regarding dose reductions from the 150 mg dose before Phase III launch.

Management Commentary and Tone:

• Tone: Management expressed high confidence and optimism, describing the FDA End-of-Phase II meeting as a "home run" and "highly collaborative."
• Key Sentiment: Leadership emphasized that controlling brain metastases is the "key driver" of durable survival benefit and that the FDA recognizes CNS activity as a superior surrogate endpoint for approval in this setting.
• Strategic Clarity: Management articulated a clear, differentiated path to approval that competitors cannot replicate due to their lack of robust CNS data.

Analyst Questions and Answers:

• Global Enrollment: Confirmed that an "investigator's choice" control arm (Afatinib vs. Osimertinib) will accommodate regional standard-of-care differences, ensuring broad trial representativeness.
• Competitor Comparison: Analysts noted competitors' systemic ORR requirements; Management agreed this presents a risk for competitors if they cannot meet high systemic response thresholds.
• Dose Selection: FDA required only a minimal follow-up (approx. 6 weeks) to demonstrate tolerability at the 150 mg dose before Phase III starts; no large safety cohort is mandated.
• Trial Powering: The trial is well-powered to detect the difference between 86% and 35% CNS-ORR; even if the drug's performance drops, the statistical power remains sufficient.
• Market Uptake: Management expressed confidence that even NCCN guideline inclusion (without full FDA approval initially) would drive adoption given the high rate of brain progression with current therapies (75% in NSCLC patients).

Other Key Points:

• Methodology: The Phase II trial enrolled a real-world global population (US/Canada) with over 33 unique non-classical mutations, avoiding the bias of Asia-centric trials.
• Surveillance Rigor: Patients received brain MRIs every six weeks, with no new brain metastases observed in the 24 patients without baseline brain mets over 16 months of follow-up.
• Radiation Avoidance: A key market driver is the ability to offer a systemic pill alternative to intracranial radiation, which patients prefer due to side effects.
• Label Strategy: Management aims to position the drug as the standard of care for all frontline NCM patients, leveraging the single-arm cohort data for label negotiation.