It’s been a volatile few months for atai Life Sciences. The psychedelic juggernaut had a less-than-ideal start to 2023 as the much-anticipated Phase 2 results for its most advanced program — PCN-101 (R-ketamine) — did not meet expected trial endpoints. The stock took a beating as investors tried to re-assess expectations.

The future of PCN-101 has been the primary lingering question, as well as which program might take the lead for the potentially stalled ketamine program.

Today we got some clarity, as atai released a pipeline update. Here some highlights:

• Florian Brand, CEO and Co-Founder of atai. “… we are excited to announce the updated clinical strategy for GRX-917. The compound will progress directly into a phase 2 study in patients living with an anxiety disorder to accelerate development and generate the robust clinical data needed to inform a potential future registration.”

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• RL-007: First patient dosed in the on-going phase 2b study in cognitive impairment associated with schizophrenia
• PCN-101 (R-Ketamine for Treatment-Resistant Depression): atai will continue to support Perception’s development of PCN-101 through an additional IV-to-subcutaneous bridging study, which is currently on-track to be completed in the middle of 2023. In parallel, atai continues to work with Perception Neuroscience to explore strategic partnership options.
• atai is implementing some corporate restructuring, giving it an extended its cash runway into 1H 2026.

atai’s stock was up several percent pre-market on the news. See the full press release below.

• RL-007: First patient dosed in the on-going phase 2b study in cognitive impairment associated with schizophrenia
• GRX-917: Intention to progress GRX-917 into a phase 2 study in an anxiety disorder as the next step in clinical development
• COMP360: Recently announced acceleration of the Pivotal Trial 1 (COMP 005) part of the phase 3 program, with top line data now expected in the summer of 2024
• Corporate: As a result of our recent restructuring and pipeline updates, the company has extended its cash runway, which is now expected into 1H 2026

NEW YORK and BERLIN, March 06, 2023 (GLOBE NEWSWIRE) — atai Life Sciences (NASDAQ: ATAI) (“atai”), a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders, provided key clinical pipeline and corporate updates.

“The dosing of the first patient in the phase 2b study of RL-007 in CIAS earlier this quarter exemplifies the execution capabilities of our team as we advance our programs into later-stage clinical studies,” said Florian Brand, CEO and Co-Founder of atai. “Along these lines, we are excited to announce the updated clinical strategy for GRX-917. The compound will progress directly into a phase 2 study in patients living with an anxiety disorder to accelerate development and generate the robust clinical data needed to inform a potential future registration.”

Mr. Brand continued, “As part of our efforts to further focus our capital allocation towards generating meaningful clinical readouts in the near-term and to optimize our operational efficiency, we reduced our team by approximately 30%. I am grateful for the dedication of the team members impacted by this decision and their contributions towards our mission.”

Pipeline Updates

RL-007 (Pro-Cognitive Neuromodulator for Cognitive Impairment Associated with Schizophrenia (CIAS))

• The first patient was recently dosed in the phase 2b study of RL-007 in patients with CIAS. Initial results from this study are expected in the 2^nd half of 2024.
• The phase 2b 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 US-based study is the MATRICS Consensus Cognitive Battery neurocognitive composite score at 6-weeks.
• 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.
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• Notably, in four clinical studies that assessed cognition, including one in patients with CIAS, the compound consistently demonstrated pro-cognitive effects.

GRX-917 (Deuterated Etifoxine for Anxiety Disorders)

• The clinical development plan has been updated to now proceed with a phase 2 study in patients. The updated plan is anticipated to generate the robust clinical data needed to best support potential registration. More details on the clinical development plan will be provided upon initiation of the study.
• The updated plan follows the positive results from the phase 1 single and multiple ascending dose study of GRX-917. In this trial, 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 leading benzodiazepines, like alprazolam and lorazepam, which are currently considered standard of care. In contrast to these benzodiazepines, however, and based on more than 40 years of the use of etifoxine in clinical practice, etifoxine appears to be non-addictive and does not seem to have the same sedation and other common adverse events. It is believed that etifoxine achieves its anxiolytic activity by increasing endogenous production of brain neurosteroids like allopregnanolone.

PCN-101 (R-Ketamine for Treatment-Resistant Depression)

• In January 2023, in conjunction with the phase 2a study results of PCN-101, atai announced it would further evaluate the data and work with its subsidiary Perception Neuroscience (“Perception”) to determine next steps for the program.
• atai will continue to support Perception’s development of PCN-101 through the IV-to-subcutaneous bridging study, which is currently on-track to be completed in the middle of 2023. In parallel, atai continues to work with Perception Neuroscience to explore strategic partnership options.
• PCN-101 is a single isomer of ketamine and belongs to a new generation of glutamate receptor modulators with the potential for rapid-acting antidepressant activity and anti-suicidal effects. Pharmacologically, PCN-101 is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist. Both depression model studies in rodents and clinical data suggest that R-ketamine could possess more durable effects than S-ketamine despite a lower affinity to the NMDA receptor and potentially a more favorable safety and tolerability profile.

COMP360 (Psilocybin Therapy for Treatment-Resistant Depression)

• On February 28^th, COMPASS Pathways (“COMPASS”) announced an acceleration of the Pivotal Trial 1 (COMP 005) part of the phase 3 program in treatment-resistant depression, with top line data now expected in the summer 2024.
• 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.

Corporate Updates

• As part of a strategic review of its pipeline and to enhance operational efficiency and focus, the Company has reduced its workforce by approximately 30%.
• The majority of the cost savings will result from a workforce reduction in general and administration and non-clinical development.
• The Company has extended its cash runway, which is now expected into 1H 2026.

About atai Life Sciences

atai Life Sciences is a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders. Founded in 2018 as a response to the significant unmet need and lack of innovation in the mental health treatment landscape, atai is dedicated to acquiring, incubating, and efficiently developing innovative therapeutics to treat depression, anxiety, addiction, and other mental health disorders.

By pooling resources and best practices, atai aims to responsibly accelerate the development of new medicines across its companies to achieve clinically meaningful and sustained behavioral change in mental health patients.

atai’s vision is to heal mental health disorders so that everyone, everywhere can live a more fulfilled life. For more information, please visit www.atai.life