GUGGENHEIM 3RD ANNUAL HEALTHCARE INNOVATION CONFERENCE - ORIC PHARMACEUTICALS INC

Financial Performance:

• Ended Q2 with $388 million in cash and investments, providing a runway extending into the second half of 2028.
• As a clinical-stage oncology company, the firm has no reported revenue; financial focus is strictly on capital management to support late-stage trials.
• Runway assumptions include the initiation of the Phase 3 "Himalayas 1" study in prostate cancer and the potential Phase 3 "Redwood 1" study for EGFR atypicals in the first half of next year.

Guidance and Future Outlook:

• Prostate Cancer: Expect top-line data for the Phase 3 "Himalayas 1" trial (RINZ-Metastat + Darolutamide) in the first half of 2028, approximately 18 months behind Pfizer's expected timeline.
• EGFR Atypicals: Plan to initiate Phase 3 "Redwood 1" trial (Inozertinib) in the first half of next year.
• EGFR Exon 20: Aiming for a strategic update in mid-2027 to determine the optimal development path (monotherapy vs. combinations) for Inozertinib.
• Program Updates: Scheduled for a mid-2026 program update on RINZ (covering enrollment, next-phase strategy, and incremental data) and a mid-2027 update on Inozertinib Exon 20 data.
• Pfizer Catalyst: Monitoring Pfizer's Phase 2 "MEVPRO1" readout, expected in February 2027, as a critical validation point for the PRC2 inhibitor class.

Business Segments and Product Lines:

• RINZ (Inzometastat): An allosteric PRC2 inhibitor targeting the EED subunit (vs. EZH2 of competitors) for prostate cancer in combination with AR inhibitors (Darolutamide chosen over Enzalutamide due to fewer drug-drug interactions).
  • Phase 3 "Himalayas 1" enrolled ~600 patients (post-abiraterone metastatic CRPC), capping control arm usage of AR inhibitors/docetaxel at 60%.
  • Dose: 400mg once daily; exhibits improved pharmacokinetics (24-hour half-life) compared to competitors (3-4 hour half-life), suggesting better tolerability.
• Inozertinib: An EGFR Tyrosine Kinase Inhibitor (TKI) with two primary indications:
  • Atypicals: Presented ESMO data showing an 80-84% objective response rate (ORR) and 70% CNS ORR in a cohort with 65% baseline brain metastases. 0% treatment discontinuation rate observed.
  • Exon 20 Insertions: Pursuing a three-prong approach: monotherapy, combination with chemotherapy, and combination with Imvanimab (via J&J supply agreement).

Market and Competitive Landscape:

• Prostate Cancer: Views the market as large enough to support multiple players; sees PRC2 inhibitors as enabling long-term, durable benefits (similar to Pfizer's 14-month PFS data).
• Differentiation: Highlights RINZ's sustained drug profile vs. the high-frequency, high-dose regimens required by competitors (e.g., Pfizer's Mevrometastat) to manage short half-lives and Cmax-driven toxicity.
• EGFR Atypicals: Positions Inozertinib against standard of care (Afatinib and off-label Osimertinib), arguing superiority in CNS penetration and response rates for a heavily pre-treated population with brain metastases.
• Competition: Acknowledges J&J's new mechanism in prostate cancer and Pfizer's imminent readout as competitive milestones but maintains a bullish view on the PRC2 class.

Risks and Challenges:

• Clinical Trial Timing: Dependence on Pfizer's MEVPRO1 data readout (Feb 2027) to validate the mechanism; a "near miss" or failure by Pfizer could impact investor sentiment, though a total failure is deemed unlikely given the robust biological rationale.
• Exon 20 Uncertainty: No Phase 3 commitment yet; future strategy depends on whether monotherapy or combination data meets benchmarks (monotherapy ~60% ORR, combinations higher).
• Regulatory Path: While "Redwood 1" has potential for accelerated approval via Project FrontRunner, final approval is tied to PFS endpoints following interim analysis.
• Control Arm Composition: In "Redwood 1," the choice of control (Afatinib vs. Osimertinib) may vary by physician preference due to Afatinib's lack of CNS activity and Osimertinib's lack of specific approval for atypicals.

Management Commentary and Tone:

• Tone: Highly confident and optimistic regarding clinical data, particularly the CNS efficacy and safety profile of Inozertinib and the tolerability advantages of RINZ.
• Strategic Focus: Emphasizes "overcoming resistance" in cancer; management is proactive in design (e.g., enrolling patients with brain mets, specific control arm caps) to maximize differentiation.
• Flexibility: Willing to pivot based on competitor data (e.g., waiting for Pfizer readout) but remains aggressive on timeline for their own Phase 3 initiation.

Analyst Questions and Answers:

• Mechanism Comparison: Clarified that RINZ binds EED (allosteric) rather than EZH2 (catalytic), offering similar potency but superior drug properties (solubility, half-life).
• Safety vs. Efficacy: Addressed concerns about safety by citing the "Darolutamide" analog advantage; noted that higher doses of competitors are driven by short half-lives, whereas RINZ's 24-hour half-life supports once-daily dosing with lower toxicity.
• Phase 2 Data Interpretation: Confirmed that the 14.3-month PFS seen in Pfizer's Phase 2 is a strong validation point, though noting that RINZ's safety profile could allow for longer patient retention.
• Exon 20 Strategy: Explained the decision to test three distinct arms (mono, chemo, Imvanimab) to identify the best risk/reward profile before committing to Phase 3.

Other Key Points:

• Darolutamide Partnership: Selected as the preferred AR inhibitor partner for RINZ due to its superior safety profile compared to Enzalutamide and Apalutamide, which also suffer from drug-drug interaction (DDI) issues requiring dose adjustments.
• Brain Metastasis Focus: Inozertinib's 70% CNS response rate is a key differentiator, validated in a study where 65% of patients had untreated baseline brain metastases, a significantly higher rate than typical industry trials (12-30%).
• Regulatory Strategy: The "Redwood 1" design includes an opportunity for interim analysis based on Objective Response Rate (ORR) and Duration of Response (DOR) to seek accelerated approval before confirming Progression-Free Survival (PFS).