Oric Pharmaceuticals (ORIC) investor relations material

Clinical program highlights

• Achieved high systemic and CNS response rates in EGFR-mutated NSCLC, including 67% ORR and 100% intracranial ORR in first-line patients with EGFR exon 20 mutations and active brain metastases.

• 80 mg once daily was selected as the preferred dose for future development, balancing efficacy and safety with lower rates of dose reductions and interruptions compared to 120 mg.

• No significant off-target toxicities were reported at 80 mg, with a favorable safety profile and mostly Grade 1 or 2 adverse events.

• Profound CNS activity was observed, including 100% intracranial response rates in first-line patients with measurable brain metastases and confirmed complete responses in non-measurable CNS disease.

• Next program update is planned for mid-2026, ahead of potential Phase 3 registrational trials.

Differentiation and competitive positioning

• Highly selective for EGFR, sparing other kinases and minimizing off-target toxicities such as cardiac, hepatic, and hematological events.

• Demonstrated robust brain penetrance, with therapeutic levels confirmed in cerebrospinal fluid and strong anti-tumor activity in preclinical and clinical settings.

• Response rates and CNS activity exceed or match best competitor datasets, even with a higher proportion of patients with baseline brain metastases.

• Tolerability at 80 mg is similar or superior to competitor compounds, with low discontinuation rates and manageable adverse events.

• Oral, once-daily regimen and manageable safety profile enhance commercial appeal.

Clinical data and patient outcomes

• In second-line EGFR exon 20 patients, 80 mg dose achieved a 45% confirmed objective response rate and 100% disease control rate, with deep and durable responses.

• First-line EGFR exon 20 and PACC cohorts showed high response rates (up to 80% ORR in PACC), with rapid onset of responses, often by the first four-week scan.

• CNS responses were observed in both measurable and non-measurable brain metastases, including complete responses in untreated, active CNS disease.

• Most responders remained on treatment at median follow-ups of 30–33 weeks, indicating promising durability.

• Responses were consistent across a broad spectrum of EGFR mutations, including near loop, far loop, and complex PACC mutations.