Chimerix (CMRX) Jefferies 2024 Global Healthcare Conference summary

Program overview and study design

• Lead program dordaviprone is in a global phase III trial for H3 K27M-mutant high-grade glioma, an ultra-rare and aggressive brain cancer with high unmet need.

• The study is active at about 140 sites across 13 countries, enrolling newly diagnosed patients with good performance status post-radiation.

• Two dosing regimens are tested: standard and double dose, both compared to control, with endpoints including overall survival (OS) and progression-free survival (PFS).

• Interim OS analyses are planned at 50% and 75% of events, with final OS expected in late 2025.

• Success criteria include hazard ratios of 0.52 (first interim), 0.64 (second interim), and 0.73 (final OS).

Regulatory and approval pathways

• Success at either interim or final OS analysis could support regulatory approval; PFS is not currently a surrogate endpoint for FDA but may be discussed for accelerated approval.

• Provisional approval filing in Australia is planned by end of 2024, following a three-step process, with expanded access already ongoing.

• Other ex-US accelerated approval opportunities are being explored.

Differentiation and clinical context

• The study targets a population with very limited treatment options and poor prognosis, where standard therapies offer minimal benefit.

• High awareness and anticipation among neuro-oncologists due to the lack of alternatives and promising early data.

• The trial is designed as a controlled, definitive study with survival as the gold standard endpoint.

• Recent advances in neuro-oncology for genetically defined populations set a precedent, but this study addresses a uniquely aggressive tumor.