GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - ORIC PHARMACEUTICALS INC

Explicit Guidance:

• No explicit financial guidance (revenue, earnings, margins, capex, opex, or cash flow targets) provided; cash runway of $388 million (Q2 2026 end) extends into the second half of 2028, contingent on the initiation of the REDWOOD ONE Phase 3 trial in H1 2027.

Business-Segment Outlook:

• Oncology Programs:
  • RINC-Z (Metastatic Prostate Cancer): Phase 3 "Himalayas 1" study initiated H1 2026; enrollment expected to take ~16 months; top-line data expected H1 2028.
  • RINC-Z (Future Trials): Potential Phase 3 "Himalayas 2" initiation next year (H1 2027) in either the post-ARi metastatic CRPC setting (where Pfizer has no Phase 3) or the metastatic CSPC setting (to capture a 5-year therapy duration vs. 14-month duration in CRPC).
  • INOZERTINIB (EGFR TKI - Atypical Mutations): Phase 3 "REDWOOD 1" trial design finalized; trial initiation planned H1 2027; study will be single-agent vs. physician's choice (Osimeritinib/Afatinib); accelerated approval path via Project FrontRunner possible based on ORR/DOR interim analysis.
  • INOZERTINIB (EGFR TKI - Exon 20 Insertions): Data update expected mid-2027 to determine strategy (monotherapy, chemo combo, or combination with Imevitamab) for potential Phase 3 entry.
• Pipeline Expansion: No new late-stage asset launches anticipated before 2027; focus remains on existing clinical programs.

Market and Competitive Outlook:

• Prostate Cancer: Anticipated validation of PRC2 inhibition mechanism following Pfizer's MEVPRO1 readout in February 2027; expects market to support multiple players due to substantial unmet need and durable clinical benefits (14+ months PFS observed in Phase 2); envisions future as combination-heavy regimens.
• Lung Cancer (EGFR Atypical): Viewed as a "low bar" success environment compared to existing standards (Afatinib/Osimertinib) due to poor tolerability and lack of CNS activity in competitors; expects high response rates (84%) and CNS activity (70%) to drive adoption.
• Lung Cancer (Exon 20): Highly crowded; success requires matching or exceeding monotherapy benchmarks (~60% ORR) or higher efficacy in combinations while maintaining safety (<20% Grade 3 AEs).

Macro / Industry Outlook:

• Regulatory Pathway: Confidence in obtaining accelerated approval for Inozertinib in Atypical EGFR mutations via Project FrontRunner based on interim ORR/DOR data.
• Clinical Trial Design: Anticipates standard-of-care control arms will likely be split between Afatinib (higher response, poor tolerability, low CNS activity) and Osimertinib (better tolerated, moderate CNS activity), creating a favorable differentiation point for a highly brain-penetrant agent.
• Pricing/Dosing: Regulatory acceptance of 400mg once-daily dosing for RINC-Z (vs. 1,250mg BID or 875mg BID for competitors) anticipated due to favorable PK profile (24-hour half-life).

Strategic Initiatives:

• Trial Initiation: Commencement of REDWOOD 1 Phase 3 trial in H1 2027.
• Partnerships: Existing clinical supply agreement with J&J for Imevitamab combination studies in Exon 20 space.
• Milestones: Planned program update in H2 2026 covering Himalayas 1 enrollment status and potential Phase 3 pathway decisions; Inozertinib Exon 20 update scheduled for mid-2027.

Risks and Headwinds to Outlook:

• Competitor Readout: Pfizer's MEVPRO1 data (Feb 2027) remains a critical inflection point; scenarios range from "big miss" (unlikely per management view) to "small miss" or "near miss" where safety/tolerability issues could still favor RINC-Z.
• Enrollment Uncertainty: Himalayas 1 enrollment started H1 2026; specific tracking data not yet available, though 16-month duration is projected.
• Study Design Ambiguity: The choice of the next Phase 3 setting for RINC-Z (CSPC vs. Post-ARi) and the specific cohort selection for Inozertinib Exon 20 (monotherapy vs. combo) are "TBD" pending late 2026/2027 data maturity.
• Safety/Tolerability: While current data suggests better safety profiles for RINC-Z and Inozertinib vs. competitors, late-stage failure due to unexpected AEs remains a risk.

Management Tone on the Future:

• Confidence: High confidence in the PRC2 mechanism and the superiority of the "allosteric EED inhibition" pharmacology over EZH2 inhibitors regarding drug properties (solubility, bioavailability) and safety.
• Differentiation: Strong emphasis on CNS penetrance as the primary differentiator for Inozertinib, citing 70% CNS ORR in a heavily pre-treated population (65% baseline brain mets).
• Optimism: Describes the prostate cancer future as "bright" with room for multiple modalities; views the upcoming competitor readout as validation rather than a threat, given their safety differentiation.
• Hedging: Repeated use of "TBD" and "expecting" regarding Phase 3 timing and specific study designs pending further data maturation.

Miscellaneous:

• Combination Partners: Darolutamide selected as the preferred AR inhibitor partner for RINC-Z (vs. Pfizer's Enzalutamide) to avoid CYP3A4 drug-drug interaction (DDI) issues requiring dose increases.
• Inclusion Criteria: REDWOOD 1 trial will include patients with active brain metastases and PAC mutations, broadening the pool beyond classical Atypical EGFR mutations.