Cybin (HELP) Status Update summary

Key clinical results and program updates

• 12-month Phase 2 data for CYB003 showed 100% response and 71% remission rates at the 16mg dose, with a mean 23-point reduction in MADRS scores, and no adverse events reported at 12 months.

• CYB003 is administered as an adjunctive therapy, allowing patients to remain on their existing antidepressants, and demonstrated durable efficacy with just two doses given three weeks apart.

• CYB003 received FDA breakthrough therapy designation, expediting its development and review, and Phase 3 Paradigm program has been initiated with two pivotal trials (Approach and Embrace) and a long-term extension (Extend).

• The Phase 3 program is designed in alignment with FDA guidance, including measures to address functional unblinding and expectancy bias, and will enroll a similar patient population as Phase 2.

• CYB004, a deuterated DMT for generalized anxiety disorder, is in Phase 2 with top-line data expected in Q1 2025.

Market need and healthcare impact

• Major depressive disorder (MDD) and generalized anxiety disorder (GAD) represent large, underserved markets, with over 300 million people affected by depression globally and high rates of inadequate response to current treatments.

• CYB003's rapid and durable effects could reduce the burden on psychiatric care infrastructure, offering a less frequent dosing regimen compared to existing intermittent treatments like TMS and esketamine.

• Surveyed healthcare providers show strong interest in integrating this class of treatments, with 94% open to adoption if approved.

• Clinics and payers are supportive, with the two-dose-per-year model seen as attractive for both efficiency and cost containment.

• Results may represent a shift from symptomatic relief to potentially changing the course of MDD.

Safety, trial design, and commercialization

• CYB003 demonstrated a favorable safety profile, with only mild, transient adverse events such as headache and nausea, and no suicidality or long-term sequelae.

• Psychological support is provided as good medical practice during dosing, but not as structured psychotherapy; FDA is expected to require some form of support if approved.

• The company is well-capitalized with CAD 154 million in cash as of September 30, 2024, sufficient to fund Phase 3 trials through top-line data.

• Commercialization groundwork is underway, including engagement with clinics, payers, and preparation for REMS and care delivery models.

• NDA submission is targeted for 2027, following expected Phase 3 readouts in 2026.