STIFEL 2026 HEALTHCARE CONFERENCE - ORIC PHARMACEUTICALS INC

Financial Performance:

• No specific financial metrics (revenue, earnings, margins, cash flow, debt) disclosed as Oric Pharmaceuticals is a clinical-stage company currently in late-stage development.
• Funding status or burn rate not explicitly detailed in this transcript segment.

Guidance and Future Outlook:

• Confirmed a second-half program update for 2026, which may include data on the "Himalayas I" Phase III trial, a potential second Phase III study in prostate cancer, or incremental data from existing cohorts; guidance remains valid despite Pfizer's MEVPRO-1 delays.
• PRC-2 (Rinco-Metastat): Top-line data expected from the "Himalayas I" Phase III trial (post-abiraterone mCRPC) in H1 2028.
• EGFR (Inozertinib): Planned initiation of a Phase III trial for "atypical" mutations in H1 2027; additional data for "Exon 20" mutations expected mid-2027.
• Management expresses high confidence in the biological mechanism based on robust preclinical and clinical data, maintaining a positive outlook despite external delays.

Business Segments and Product Lines:

• Rinco-Metastat (PRC-2 Inhibitor):
  • Mechanism: Allosteric PRC-2 inhibitor reversing resistance by increasing AR signaling and KLK3 (PSA) expression; designed to overcome resistance to AR inhibitors.
  • Differentiation: Focus on differentiated safety profile (fewer drug-drug interactions, better tolerability) compared to market leaders like Darolutamide, which is crucial for long-term treatment in elderly populations.
  • Status: Phase III "Himalayas I" ongoing; potential to advance to Castration-Sensitive Prostate Cancer (CSPC) or earlier lines depending on future results.
• Inozertinib (EGFR TKI):
  • Mechanism: Highly brain-penetrant EGFR TKI designed to treat patients with brain metastases.
  • Key Data (ESMO): 84% Investigator-reported ORR (80% BIRC); CNS objective response of 70% in patients with untreated brain mets; 67% CNS disease control rate.
  • Trial Design: Randomized Phase III for "atypical" mutations (80mg QD) vs. physician's choice (Osimertinib/Afatinib); enrollment allows both treated and untreated brain mets.
  • Pipeline: Monotherapy, chemo-combination, and amivantamib combination being evaluated for Exon 20 mutations with data expected mid-2027.

Market and Competitive Landscape:

• PRC-2 Landscape: Pfizer's MEVPRO-1 delayed primary completion to Q1 2027 (February), but Oric views the delay as likely driven by lower event rates due to treatment efficacy rather than safety issues.
  • Pfizer's Phase II randomized data showed 14.3-month PFS vs. ~6.75 months control, validating the mechanism.
  • J&J's RIPTAC data (new mechanism) noted as exciting but early; Oric maintains PRC-2 inhibitors have a strong, validated rationale for combination with standard AR inhibitors.
• EGFR Landscape: Addresses a significant unmet need in "atypical" mutations (~3% of lung cancer), a larger population than ROS1 or RET.
  • Current standard options (Afatinib, Osimertinib) show limited efficacy in atypicals, lack brain penetration, or have poor tolerability.
  • Inozertinib differentiates via superior brain penetration and efficacy in untreated brain mets, similar to how newer ALK inhibitors differentiated via CNS activity.
• Market Opportunity: Prostate cancer is identified as underserved; safety differentiation is a key commercial driver (e.g., Darolutamide's success) due to long treatment duration (4-5 years).

Risks and Challenges:

• External Delays: Dependence on Pfizer's timeline for MEVPRO-1 to provide final de-risking validation for the PRC-2 mechanism.
• Safety Profile: Potential on-target toxicities (e.g., fatigue, diarrhea) associated with PRC-2 inhibitors, though Oric claims a better profile than Pfizer's regimen.
• Endpoint Challenges: PSA levels may not correlate with clinical benefit for PRC-2 inhibitors (mechanism-driven PSA increase possible); regulatory success relies on RPFS rather than PSA responses.
• Control Arm Variability: Uncertainty regarding the exact split of control arm therapies (ARPI switch vs. docetaxel) which impacts the benchmark for PFS.
• Competitive Evolution: Need to navigate future combination data from competitors (e.g., J&J, T-cell engagers) and potential new entrants.

Management Commentary and Tone:

• Tone: Highly confident and optimistic, characterizing the PRC-2 mechanism as "highly validated" and expressing strong conviction in the totality of their data.
• Strategy: Management emphasizes that initiating Phase III ahead of Pfizer's top-line readout was a calculated decision based on consistent preclinical and early clinical data, safety differentials, and the "totality of the evidence" from multiple PRC-2 programs.
• Market Dynamics: Explicitly highlighted the commercial viability of safety differentiation in prostate cancer, citing market research where >70% of physicians would prescribe based on safety alone if efficacy is comparable.
• Clarity on PSA: Management clarified that PSA surges can occur due to the mechanism (increased KLK3) but do not negate the clinical benefit or RPFS data.

Analyst Questions and Answers:

• Q: Interpretation of Pfizer's MEVPRO-1 delay?
  • A: Likely due to fewer events occurring (higher efficacy in treatment arm) rather than safety failures; "Big Miss" scenario is deemed low probability given biological validation.
• Q: Impact of PSA blinding in Phase III vs. Phase I?
  • A: Early discontinuation due to lack of PSA response is a Phase I/II issue; Phase III blinding removes this risk, expected to improve trial retention.
• Q: Pfizer's single-agent monotherapy ESMO data (9-month PFS, no PSA response)?
  • A: Mechanism explains the lack of PSA drop (increased KLK3); 9-month PFS as monotherapy validates the potential for synergy in combination, which is Oric's focus.
• Q: Phase III powering and potential adjustments based on Pfizer data?
  • A: Protocol similar to Pfizer's (HR 0.66 target). Oric plans to enroll assuming a Feb 2027 readout; adjustments may be made if Pfizer provides detailed color on safety/regimen issues post-readout.
• Q: Future Phase III settings (CSPC vs. mCRPC)?
  • A: Post-ARi mCRPC is the current focus; CSPC is a strong candidate for the next study due to larger population and longer treatment duration, contingent on future data.
• Q: EGFR Phase III design and CNS enrichment?
  • A: Trial allows both treated and untreated brain mets; enrichment may happen naturally due to drug efficacy, but will not be prospectively forced.

Other Key Points:

• PSA Mechanism Confounder: PRC-2 inhibitors uniquely increase PSA expression (KLK3) while still providing clinical benefit, a nuance that distinguishes them from traditional AR inhibitors and explains early-phase data anomalies.
• Control Arm Benchmarks: Management estimates the control arm PFS will range from 5-8 months (ARPI ~5-6 months, Docetaxel ~7-8 months), making Pfizer's expected 14.3-month treatment arm data highly significant.
• EGFR Exon 20 Strategy: Oric is pioneering the combination of Inozertinib with Amivantamib, a approach not currently pursued by competitors.
• Market Validation: Oric notes that the "atypical" EGFR mutation population is larger than many other targeted therapy indications, presenting a substantial commercial opportunity.