atai Life Sciences Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Clinical Pipeline Highlights

“With multiple clinical-stage programs aimed at addressing significant unmet patient needs in mental health and the capital to fund us into the first half of 2026, we believe we are in a strong position to advance our clinical candidates towards proof of concept in patients. Recently we announced dosing the first patient in our Phase 2 study of RL-007 in CIAS and the modification of the GRX-917 clinical development plan to advance directly into a proof-of-concept study in patients with anxiety.”

Florian Brand, CEO and Co-Founder of atai

• The first patient was recently dosed in the phase 2b study of RL-007 in patients with CIAS and topline results from this study are expected in the 2^nd half of 2024.
• The phase 2b US-based study is a randomized, placebo-controlled, double-blind, 3-arm study evaluating 20mg and 40mg of RL-007 vs placebo in approximately 230 patients with CIAS. The primary endpoint of the study is the change from baseline in the MATRICS Consensus Cognitive Battery (MCCB) neurocognitive composite score, a well-established regulatory endpoint, at week 6.
• RL-007 is an orally available compound that modulates cholinergic, glutamatergic and GABA-B receptors, thereby putatively altering the excitatory/inhibitory balance in the brain to produce pro-cognitive effects. It has previously been evaluated in 10 clinical studies with over 500 unique participants dosed to-date and in which it was well tolerated at all doses tested.
• Notably, in four clinical studies that assessed cognition, including one in patients with CIAS, the compound consistently demonstrated pro-cognitive effects. In atai’s previous Phase 2a proof-of-mechanism study in CIAS of RL-007, the compound showed a large effect size on Symbol Coding, a sub-component of the MCCB that correlates with the overall composite.

• The clinical development plan was modified to proceed with a phase 2 study in patients, which is intended to generate the robust clinical data needed to best inform a future registrational program. More details of the phase 2 clinical development plan will be provided upon initiation of the study.
• In January 2022, positive results were announced from the phase 1 single and multiple ascending dose study of GRX-917. In this study, GRX-917 was well-tolerated. Additionally, GRX-917 had an improved pharmacokinetic profile relative to etifoxine and provided pharmacodynamic evidence of GABA receptor target engagement through qEEG.
• GRX-917 is a deuterated version of etifoxine, a drug used for anxiety and first approved in France in 1979. Etifoxine has a rapid onset and efficacy comparable to benzodiazepines, which are currently considered standard of care. In contrast to benzodiazepines, etifoxine appears to be non-addictive, less sedating, and better tolerated. It is believed that etifoxine achieves its anxiolytic activity by increasing the endogenous production of brain neurosteroids like allopregnanolone.

• COMPASS Pathways (“COMPASS”) recently announced an acceleration of the Pivotal Trial 1 (COMP 005) part of the phase 3 program in TRD, with top line data from Pivotal Trial 1 now expected in the summer 2024.
• The on-going phase 3 program is composed of two pivotal trials, each of which will have a long-term follow-up component. The primary endpoint in both pivotal trials is the change from baseline in MADRS total score at week 6.
• COMP360 is a proprietary formulation of synthetic psilocybin that is administered in conjunction with psychological support. Previously, COMPASS completed a phase 2b study with top line data showing a statistically significant (p<0.001) and clinically relevant improvement in depressive symptom severity after three weeks for patients who received a single high dose of COMP360 psilocybin with psychological support.

• In the fourth quarter of 2022, the first subject was dosed in a Phase 1 study of VLS-01. Initial results from the study are expected in the 1st half of 2023.
• The phase 1 study is a two-part single-ascending dose study designed to evaluate the safety, tolerability and relative bioavailability of oral transmucosal film (OTF) versus intravenous (IV) formulations of VLS-01.
• The study includes atai’s IDEA-1 companion digital therapeutic for psychological support to be used in combination with VLS-01. The app-based support comprises “(mind)set-and-setting” prior to dosing and limited post-dose integration appropriate for healthy volunteers.
• VLS-01 is an OTF formulation of DMT. DMT is a partial agonist of the 5-HT 1A/2A/2C receptors, characterized by an intrinsically short duration of psychedelic effect, with a serum half-life estimated at less than 10 minutes. DMT results in rapid-acting antidepressant effects when administered via IV infusion in patients with major depressive disorder (MDD). VLS-01 is formulated for oral delivery, potentially eliminating the need for IV infusion.

• In the third quarter of 2022, the first subject was dosed in a phase 1/2 study of Ibogaine. Initial results from the Phase 1 portion of the study are expected in the 1^st half of 2023.

• In the third quarter of 2022, a phase 1 study of EMP-01 was initiated. Initial results from this study are expected in the 2^nd half of 2023.