ORIC® Enozertinib Program Update Call - ORIC PHARMACEUTICALS INC

Explicit Guidance:

• No financial guidance (revenue, earnings, margins, capex, opex, cash flow, tax rate, share count, dividends, or buybacks) is provided, as the company is pre-revenue and in clinical development.
• Cash Runway: Cash on hand is sufficient to fund operations through the second half of 2028. This guidance assumes the initiation of Redwood 1 (Enozertinib Phase 3), Himalayas 1 (RINDSY Metastat Phase 3), and the maintenance of current burn rates.
• Upcoming Milestones: Expect top-line data readouts for ORR (accelerated approval) and PFS (full approval) post-trial initiation; specific dates for data readouts are not yet provided.

Business-Segment Outlook:

• Enozertinib (EGFR Atypicals): Management plans to initiate Redwood 1, a global Phase 3 trial in the first half of 2027. The trial will target treatment-naive patients with EGFR atypical mutations (exon 19 deletions and L861Q).
• Enozertinib (EGFR Exon 20): Three development cohorts are under evaluation: monotherapy, combination with chemotherapy, and combination with amivantamab. Maturity data for all three cohorts is expected in mid-2027. If data supports a preferred regimen, initiation of Redwood 2 (Exon 20 Phase 3) is targeted for 2027 (following the mid-2027 data release).
• RINDSY Metastat (RIN2): Phase 3 trial (Himalayas 1) is ongoing; expected to provide top-line data prior to the 2028 cash runway conclusion.
• Commercial Target: Aims to capture a substantial share of the $3.5 billion U.S. market for first-line EGFR atypical and Exon 20 NSCLC (projected $2.5B for atypicals, >$1B for Exon 20) and a comparable global opportunity ($5B+ total).

Market and Competitive Outlook:

• Competitive Landscape: Management identifies a "best-in-class" opportunity in EGFR atypicals where no current approved or late-stage therapy combines systemic efficacy, robust CNS activity, and favorable tolerability.
• Benchmarking: Competitors highlighted include Afatinib (limited CNS activity), Osimertinib (low potency in atypicals despite CNS penetration), Amivantamab + Lazertinib (complex regimen), Firminertinib (safety concerns/negative Phase 3 in Exon 20), and Sunvozertinib (poor CNS HR in metastatic patients).
• Market Share Projection: Based on blinded market research with 75 U.S. oncologists, a therapy with the projected profile of Enozertinib (high CNS efficacy, low off-target toxicity) is expected to capture approximately 60% share of the EGFR atypical market.
• Historical Precedent: Cites Osimertinib (4th to market), Alectinib (3rd), and Lorlatinib (5th) in classical ALK/EGFR markets as examples where "best-in-class" CNS activity rapidly drove market leadership despite late entry.

Macro / Industry Outlook:

• Regulatory Strategy: Alignment received from the FDA on Phase 3 design (Redwood 1), including dose (80mg QD), patient population, and dual endpoints (ORR for accelerated approval; PFS for full approval) under the "Project BRR" framework.
• Global Expansion: Planning for "ex-U.S." regulatory interactions to support a global trial execution in 10+ countries (North America, Europe, Asia Pacific).
• Patient Stratification: No caps placed on the control arm (Osimertinib vs. Afatinib) selection to reflect real-world practice; stratification will be implemented to account for geographical and physician preferences.

Strategic Initiatives:

• Redwood 1 (EGFR Atypical Phase 3): A randomized, global trial comparing Enozertinib (80mg QD) vs. physician's choice of Osimertinib or Afatinib. Primary endpoints: ORR (BICR) for accelerated approval and PFS (BICR) for full approval. Key secondary endpoints: OS and Intracranial ORR.
• Enrollment Criteria: Trial will allow patients with treated/stable brain metastases and untreated but asymptomatic brain metastases. Management advises enrolling "wide open" with active intracranial disease to maximize relevance.
• Exon 20 Strategy: Pending mid-2027 data from Phase 1b cohorts to determine the optimal path (monotherapy vs. combinations) for Phase 3 initiation (Redwood 2).
• Operational Readiness: Completing selection of global CROs and finalizing country/site lists and ethical/regulatory submissions to support H1 2027 trial start.

Risks and Headwinds to Outlook:

• Clinical Trial Risks: Phase 3 outcomes (ORR, PFS, OS) may not meet statistical significance or regulatory expectations; median PFS and duration of response remain immature in current Phase 1b data.
• Competitor Dynamics: Potential negative developments in late-stage competitor programs (e.g., Firminertinib, Verubinertinib) or new data from competitors like Sunvozertinib could alter the perceived unmet need or comparative advantage.
• Regulatory Uncertainty: While FDA alignment is achieved, additional data requirements or changes in regulatory pathways (e.g., acceptance of CNS endpoints) could impact timing.
• Safety: While current Phase 1b data shows no treatment-related discontinuations, long-term tolerability and potential off-target toxicities (cardiac, hepatic, hematologic) remain monitoring points, particularly as dose reductions (39% of patients) have occurred in the broader safety set.
• Pricing and Reimbursement: Viability dependent on maintaining current pricing levels and market access in a competitive oncology landscape.

Management Tone on the Future:

• Confidence Level: Highly confident and urgent ("imperative to move as rapidly as possible").
• Differentiation Narrative: Strong emphasis on "best-in-class" potential driven by the ability to treat untreated brain metastases effectively, a capability they assert is missing in current standard-of-care and late-stage competitors.
• Caveats: Management repeatedly notes that PFS is immature but "tracking favorably" and "out-distancing" historical benchmarks, while urging investors to contextualize current response rates against a significantly more challenging patient population (65% baseline CNS disease vs. ~30% in competitors).
• Strategic Alignment: Reiterated commitment to the Phase 3 roadmap and cash runway, stating that the new Enozertinib plan is already factored into the 2028 cash outlook, indicating no need for additional near-term financing.

Miscellaneous:

• Data Cutoff: Clinical data presented is as of September 4, 2026.
• Trial Enrichment: No active enrichment strategy was used for CNS-positive patients; enrollment was physician-driven due to the lack of alternative therapies for untreated CNS disease.
• Phase 3 Design Specifics: The control arm allows physician choice between Osimertinib and Afatinib, with stratification by this choice and geography.
• Safety Profile: 88% 6-month landmark PFS, 84% systemic confirmed ORR, 70% intracranial confirmed ORR in the Phase 1b atypical cohort; no grade 4/5 events or treatment-related discontinuations observed.