COMPASS Pathways (CMPS) Study update summary

Study background and unmet need

• Over 4 million adults in the U.S. suffer from treatment-resistant depression (TRD), a chronic and burdensome condition with high patient burden, increased suicide risk, and economic impact.

• TRD patients have failed at least two prior antidepressant treatments and experience longer, more severe episodes than typical MDD patients.

• Only two medicines are approved for TRD, with limited use, highlighting a significant unmet need.

Study design and methodology

• Two pivotal Phase 3 trials (COMP005 and COMP006) evaluated COMP360 in TRD, enrolling over 1,000 participants.

• COMP005: U.S.-based, randomized, double-blind, placebo-controlled, single 25 mg dose vs placebo, 258 participants, three study parts (up to 52 weeks).

• COMP006: International, randomized, double-blind, 581 participants, two 25 mg doses vs 10 mg and 1 mg, three study parts (up to 52 weeks), with primary endpoint at six weeks.

• Both studies required discontinuation of existing antidepressants and included highly symptomatic, chronic TRD patients; baseline demographics matched TRD epidemiology.

• Blinded remote raters and active low-dose comparators were used to minimize expectancy and unblinding effects.

Efficacy results

• Both trials met primary endpoints, showing highly statistically significant and clinically meaningful reductions in MADRS scores at Week 6 for COMP360 25 mg versus control arms.

• Rapid onset of effect observed from the day after administration, sustained through Week 6, with durable effects lasting at least 26 weeks for responders.

• Clinically meaningful MADRS reduction (≥25%) was achieved by 25% of participants in COMP005 and 39% in COMP006 at Week 6 in the 25 mg arm.

• Over 40% of COMP005 participants who had not remitted by 6 weeks entered remission after a second dose.

• Dose response observed, with 25 mg outperforming lower doses and placebo at all time points.