Arvinas (ARVN) Jefferies London Healthcare Conference 2024 summary

Pipeline and clinical development updates

• Two lead candidates are in phase 3, partnered with Pfizer and Novartis, with additional wholly owned programs in immuno-oncology, neuroscience, and immunology.

• LRRK2 degrader will have first-in-human data in April; phase 2 for BCL6 started earlier this year.

• Transition of 766 to Novartis is underway, with milestones and royalties expected.

• Data-rich 12 months ahead, with vepdegestrant combination data at San Antonio in December and updated guidance for VERITAC-2 phase 3 data in Q1, likely February.

• Plans to start a second-line combination study with vepdegestrant and CDK4/6 inhibitors next year, and considering a first-line study with atirmociclib or palbociclib.

Study design, endpoints, and regulatory considerations

• VERITAC-2 phase 3 is event-driven, with a two-month delay in primary completion due to event accrual, not enrollment.

• ESR1 mutation rate in the study is expected to be 40%-50%, consistent with recent data from similar studies.

• Strongest efficacy anticipated in ESR1 mutant patients, but activity also expected in wild type; regulatory base case is a restricted label for ESR1 mutants, with potential for broader approval if data support.

• Median PFS for fulvestrant in the control arm is expected to be 3-4 months, lower than some recent studies due to more heavily pretreated patients.

• Emphasis on hazard ratio and placebo-adjusted delta over absolute PFS for evaluating efficacy.

Competitive landscape and future strategy

• Cross-study comparisons are discouraged due to differences in patient populations and prior treatments.

• Combination strategies are prioritized, especially for first-line and adjuvant settings, as most patients in second line will receive combination therapy.

• Ongoing and planned studies include combinations with current and next-generation CDK4/6 inhibitors, with a focus on future market leaders like atirmociclib.

• Clinical benefit rate and response rate are key metrics for upcoming data presentations, with last year’s Palbo-Vepdeg combo showing a 60% clinical benefit rate.

• Strategic decisions on first-line and adjuvant studies will be informed by upcoming efficacy and safety data.