AtaiBeckley (ATAI) TD Cowen 46th Annual Health Care Conference summary

Phase III trial design and regulatory feedback

• Two pivotal Phase III trials for BPL-003 in TRD: one with 350 patients testing 8 mg (effective dose), 4 mg (psychedelic but lower), and placebo, with a four-week primary endpoint and 12 weeks of blinded data, plus open-label extension allowing redosing as early as eight weeks.

• Second trial (ReConnection 2) uses a two-dose induction (8 mg, two weeks apart), focusing on dose response and safety, with FDA comfortable with placebo as comparator for both trials.

• Placebo chosen for cleanest analysis and robust safety database, aligning with recent regulatory trends and comparators in other psychedelic trials.

• FDA's focus includes ensuring a large safety database due to chronic condition and intermittent dosing, with open-label extensions to monitor long-term safety.

• Monitoring protocols refined for Phase III, including readiness for discharge and cardiovascular monitoring, but no major changes from Phase IIb.

Phase IIb data insights and dose selection

• Phase IIb used three arms: 12 mg, 8 mg, and 0.3 mg (sub-perceptual), with a four-week primary endpoint; 8 mg showed better efficacy and tolerability than 12 mg.

• 12 mg dose had higher anxiety-related adverse events (14% vs. 4% for placebo and 8 mg), with events occurring during or within two weeks of dosing.

• One case of suicidal ideation linked to anxiety in a patient with prior history, resolved after hospitalization.

• 85% of Phase IIb subjects met discharge criteria within two hours post-dose, supporting scalability in clinical settings.

• Dose-ranging approach informed selection of 8 mg as optimal for efficacy and safety in Phase III.

Industry context and trial design rationale

• Comparator doses in other psychedelic trials (e.g., Compass, MindMed/Definium) informed design; FDA now prefers perceptual, not sub-perceptual, comparators to address functional unblinding.

• Four-week primary endpoint chosen for consistency with Phase IIb and regulatory comfort, differing from six-week endpoints in other programs.

• Placebo control arms provide broader safety data and clearer efficacy separation.

• FDA did not require a double 4 mg dose arm, focusing instead on overall dose response.