Oric Pharmaceuticals (ORIC) Jefferies 2024 Global Healthcare Conference summary

Pipeline and program updates

• Focus on small molecule drug development for solid tumors, especially lung, prostate, and breast cancers, with three programs recently completing phase 1 studies; two advancing to later-stage development.

• ORIC-944, a PRC2 EED inhibitor for prostate cancer, shows superior drug properties over competitors, including a 20-hour half-life and no CYP autoinduction.

• ORIC-944 demonstrates at least equivalent or better preclinical and translational efficacy compared to Pfizer's compound, with strong synergy in combination with AR modulators.

• Combination studies with AR inhibitors are starting in the first half of the year, with a general program update expected mid-year.

• No preference among AR inhibitors for combination; phase 2 study design allows flexibility, with a decision on preferred AR inhibitor expected in the second half of next year.

Competitive landscape and strategy

• Pfizer's PRC2 inhibitor has shown strong efficacy in combination with enzalutamide, with phase 2 results anticipated to be positive based on phase 1 data and strategic moves.

• Pfizer is launching two phase 3 studies in metastatic CRPC, targeting both post-abiraterone and treatment-naive populations, representing a $10 billion market.

• Accelerated approval in prostate cancer is less likely, but all regulatory paths will be considered if clinical signals are strong.

• For ORIC-114, a brain-penetrant TKI for EGFR and HER2 exon 20 mutations, the main differentiator is CNS activity, addressing a significant unmet need.

• ORIC-114 has shown CNS responses in heavily pretreated patients, including those with untreated brain metastases, and is enrolling three expansion cohorts for further evaluation.

Clinical development and future plans

• ORIC-114's expansion cohorts include EGFR exon 20 inhibitor-naive, HER2 exon 20, and EGFR atypical mutations, with strong investigator interest in the frontline setting.

• CNS activity is a key differentiator, as current standard treatments lack this property; small molecule therapy is preferred over radiation for brain metastases.

• Phase 1b data updates for ORIC-114 are expected in the first half of 2025, with pivotal studies potentially starting in the second half of 2025 and NDA filings targeted for the second half of 2027.

• Success benchmarks for ORIC-114 cohorts are 35%-45% ORR and demonstration of CNS activity, with a wide therapeutic index supporting dose selection.

• First-line confirmatory studies for ORIC-114 are planned for 2026, with potential strategies including head-to-head versus chemo or combination approaches.