Cybin (HELP) Study Update summary

Key findings from 12-month phase 2 data

• 100% of patients remained responsive to CYB003 at 12 months after just two doses, with nearly all in remission; only two missed the remission cutoff by one point, which was not clinically relevant.

• The average improvement in MADRS score was 23 points, far exceeding the 2–3 points considered clinically meaningful.

• The durability of effect suggests infrequent dosing, potentially just a couple of times per year, offering significant advantages for patients, providers, and payers.

• The safety profile was highly favorable, with no long-term adverse events or suicidality observed over a year.

• Two doses proved more effective than one, validating the study's dosing strategy.

Study presentations and program updates

• Presented 12-month efficacy results from Phase 2 CYB003 study in MDD at ACNP 2024, showing durable response and remission rates.

• Shared results from a completed Phase 1b study on drug-drug interactions between DMT and SSRIs in MDD patients.

• Initiated Phase 3 PARADIGM program evaluating CYB003 in MDD.

• Advanced CYB004, a deuterated DMT program, currently in Phase 2 for generalized anxiety disorder.

Phase 3 program (PARADIGM) design and objectives

• The PARADIGM program includes three pivotal studies: APPROACH (two-arm), EMBRACE (three-arm, dose-response), and EXTEND (long-term extension).

• APPROACH and EMBRACE will each enroll about 110 patients per arm, with primary endpoints at six weeks and secondary at 12 weeks.

• EXTEND will assess durability of response and allow for additional dosing if relapse occurs, with a maximum of five doses per year.

• Studies are being conducted at 36 sites across the US and Europe, with careful site selection to ensure high-quality data.

• The program is designed to provide comprehensive data on acute efficacy, speed of response, and durability for regulatory submission.