Affective Disorders, Psychotic

The phase 2b proof-of-concept trial will evaluate the novel compound, RL-007, for pro-cognitive effects in patients with Cognitive Impairment Associated with Schizophrenia (CIAS). The trial was initiated and has begun patient screening this month with first-patient-in anticipated by end-of-year. There are currently no FDA-approved medications for CIAS, a major cause of disability in 80% of patients with schizophrenia1. Topline results are expected in the first half of 2024. NEW YORK and BERLIN, Dec. 19, 2022 (GLOBE NEWSWIRE) -- Today, atai Life Sciences N.V. (Nasdaq: ATAI) (“atai”), a clinical-stage biopharmaceutical company aiming to transform the treatment of mental health disorders, announced the initiation of its Phase 2b proof-of-concept clinical trial for RL-007 for Cognitive Impairment Associated with Schizophrenia (CIAS), a condition for which there are currently no FDA-approved treatments. The Phase 2b trial is a randomized, placebo-controlled, double-blind, 3-arm study evaluating 2 doses of RL-007 and a placebo among 234 patients. The trial includes a 6-week treatment period with the MATRICS Consensus Cognitive Battery (MCCB) as the primary endpoint. The MCCB has been supported by the FDA as an approvable endpoint for CIAS. The trial will be conducted in the US, and patient screening is currently underway. 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 ten clinical studies, including one in the CIAS indication, with over 500 unique participants dosed to-date. In December 2021, atai announced positive biomarker data from a Phase 2a proof-of-mechanism study designed to evaluate the effects of RL-007 on safety, tolerability, electroencephalogram-based biomarkers, and cognition. RL-007 was well tolerated and demonstrated a clinically meaningful pro-cognitive pro with previous Phase 1 and Phase 2 trials of this compound. These results supported the progression of an RL-007 Phase 2b proof-of-concept trial with the goal of demonstrating the pro-cognitive effect of RL-007 in CIAS. Schizophrenia affects approximately 24 million people worldwide. The disease is frequently associated with significant distress and impairment in personal, family, social, educational, occupational, and other important areas of life. For example, cross-sectionally, only 10% of patients with schizophrenia are employed in a competitive role2. Furthermore, they are 2 to 3 times more likely to die early compared to the general population3. 80% of people with schizophrenia suffer from cognitive impairments, which include poor learning and retention of verbal information, as well as the most consistent findings of executive functioning deficits and an impaired ability to encode and retain verbally presented information4. “Schizophrenia is a debilitating neurological disease that can reduce life expectancy by almost 20 years. What’s worse is only about 30% of people with psychosis receive specialist mental health care,” commented atai Co-Founder and CEO Florian Brand. “The safety pro positive pro-cognitive efficacy of RL-007 show promise for the significant unmet needs of people suffering from schizophrenia.” “RL-007’s unique pharmacology as a GABA/nicotinic modulator, acute onset of action, and excellent tolerability pro it from competitor pipeline options,” stated Srinivas Rao, atai Co-Founder and Chief Scientific Officer. “It has the potential for complimentary use with antipsychotics. We look forward to the Phase 2b results anticipated H1 2024.” 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. atai Life Sciences’ subsidiary, Recognify Life Sciences, is conducting this study. 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 Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. The words “believe,” “may,” “will,” “estimate,” “continue,” “anticipate,” “intend,” “expect,” “initiate,” “could,” “would,” “project,” “plan,” “potentially,” “preliminary,” “likely,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements include express or implied statements relating to, among other things: statements regarding the trials by Recognify Life Sciences and future activities thereunder; the potential of RL-007; the success, cost, and timing of development of our product candidates, including the progress of preclinical and clinical trials and related milestones; our business strategy and plans; potential acquisitions; available funding under the Hercules Capital, Inc. loan facility; and the plans and objectives of management for future operations and capital expenditures. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond our control and which could cause actual results, levels of activity, performance, or achievements to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements. These forward-looking statements are subject to a number of risks, uncertainties, and assumptions that could cause actual results to differ materially from those expressed or implied by the forward-looking statements, including without limitation: we are a clinical-stage biopharmaceutical company and have incurred significant losses since our inception, and we anticipate that we will continue to incur significant losses for the foreseeable future; we will require substantial additional funding to achieve our business goals, and if we are unable to obtain this funding when needed and on acceptable terms, we could be forced to delay, limit or terminate our product development efforts; our limited operating history may make it difficult to evaluate the success of our business and to assess our future viability; we have never generated revenue and may never be profitable; clinical and preclinical development is uncertain, and our preclinical programs may experience delays or may never advance to clinical trials; we rely on third parties to assist in conducting our clinical trials and some aspects of our research and preclinical testing, and those clinical trials, including progress and related milestones, may be impacted by several factors including the failure by such third parties to meet deadlines for the completion of such trials, research, or testing, changes to trial sites and other circumstances; we cannot give any assurance that any of our product candidates will receive regulatory approval, which is necessary before they can be commercialized; third parties may claim that we are infringing, misappropriating or otherwise violating their intellectual property rights, the outcome of which would be uncertain and may prevent or delay our development and commercialization efforts; and a pandemic, epidemic, or outbreak of an infectious disease, such as the COVID-19 pandemic, may materially and adversely affect our business, including our preclinical studies, clinical trials, third parties on whom we rely, our supply chain, our ability to raise capital, our ability to conduct regular business, and our financial results. These and other important factors described in the section titled “Risk Factors” in our Annual Report on Form 10-K for the fiscal year ended December 31, 2021 filed with the Securities and Exchange Commission (“SEC”), our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K, as updated by our subsequent filings with the SEC, may cause our actual results, performance, or achievements to differ materially and adversely from those expressed or implied by the forward-looking statements. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change. Contact Information Investor Contact: Stephen Bardin Chief Financial Officer IR@atai.life Media Contact: Allan Malievsky Senior Director, External Affairs PR@atai.life ______________________ 1 Bora E., et al, Cognitive Impairment in Schizophrenia and Affective Psychoses: Implications for DSM -V Criteria and Beyond. Schizophr Bull. 2010 Jan;36(1):36-42. doi: 10.1093/schbul/sbp094. Epub 2009 Sep 23. 2 Marwaha S, Johnson S, Bebbington P, et al. Rates and Correlates of Employment in People with Schizophrenia in the UK, France and Germany. Br J Psychiatry. 2007;191(1):30-37. 3 World Health Organization, 10 January 2022 4 Bowie CR, Harvey PD. Cognitive Deficits and Functional Outcome in Schizophrenia. Neuropsychiatr Dis Treat. 2006 Dec;2(4):531-6. doi: 10.2147/nedt.2006.2.4.531. PMID: 19412501; PMCID: PMC2671937.

—Company adds leading neuroscience experts with decades of experience in industry, at the National Institute of Mental Health, and in clinical practice— —Board to advise on company’s R&D of genetically engineered neuroactive therapeutics derived from fungi and plants— NEW YORK & CAMBRIDGE, England--(BUSINESS WIRE)-- Empyrean Neuroscience, Inc., a genetic engineering company dedicated to developing neuroactive compounds to treat neuropsychiatric and neurologic disorders, today announced its scientific advisory board. The board is composed of neuroscience experts with decades of experience developing therapies at some of the world’s largest pharmaceutical companies, in leadership positions at the National Institute of Mental Health (NIMH), and at leading academic institutions and hospitals. Their deep expertise will help guide Empyrean as the first company with a genetic engineering platform for developing small molecule therapeutics from fungi and plants. "We are proud to be joined by three physician-scientists who have led decades of important research and development across academia, industry, government, and clinical practice in neuroscience,” said Fred Grossman, D.O., FAPA, Empyrean’s chief medical officer. “Our SAB understands the potential of Empyrean’s first-in-class genetic engineering approach to developing therapeutics in areas of severe unmet medical need. I am honored to have the opportunity to collaborate with them as we contribute to scientific and clinical understanding of neurologic and neuropsychiatric disorders and advance our programs.” The founding members of Empyrean’s scientific advisory board are: William Z. Potter, M.D., Ph.D., is emeritus co-chair of the neuroscience steering committee at the Foundation for the National Institutes of Health. He was previously senior advisor at NIMH and vice president, franchise integrator in neuroscience at Merck Research Laboratories. Before joining Merck, he was executive director and Lilly clinical research fellow of the neuroscience therapeutic area at Lilly Research Laboratories. Before Lilly, he held the position of chief, section on clinical pharmacology, intramural research program, at NIMH. Dr. Potter has authored more than 300 publications in the field of preclinical and clinical pharmacology, mostly focused on drugs used in affective illnesses and methods for evaluating drug effects in humans. He has received many honors during his career, including the 1975–1977 Falk Fellowship from the American Psychiatric Association, the 1986 Meritorious Service Medal from the U.S. Public Health Service, the 1990 St. Elizabeth’s Residency Program Alumnus of the Year Award, and the 2018 Andrew C. Leon Distinguished Career Award of the International Society for CNS Clinical Trials and Methodology. Dr. Potter received his medical degree and doctorate in pharmacology from Indiana University and board certification in psychiatry in 1978. Husseini K. Manji, M.D., was most recently global head of science for minds at Johnson & Johnson and was previously global therapeutic head of neuroscience at Janssen Research & Development, where he led the neuroscience therapeutic area and oversaw the development of Spravato (esketamine), which was granted fast track and breakthrough therapy designations by the U.S. Food & Drug Administration and was approved for treatment-resistant depression. Dr. Manji spent more than a decade at the National Institutes of Health and the NIMH, where he helped develop the mood and anxiety disorders program and served as its director. He is a visiting professor at the University of Oxford and a visiting professor in the department of psychiatry at Duke University School of Medicine. Dr. Manji received his medical degree from the University of British Columbia, is a fellow of the Royal College of Physicians and Surgeons of Canada, is an elected member of the National Academy of Medicine and sits on the board of trustees of McLean Hospital. Francis S. Lee, M.D., Ph.D., is the chairman of the department of psychiatry at Weill Cornell Medicine and psychiatrist-in-chief at NewYork-Presbyterian Hospital, where he oversees one of the largest academic psychiatric programs in the United States. At Weill Cornell, Dr. Lee runs a lab that focuses on connecting molecular neuroscience with psychiatry through studies of how factors such as brain-derived neurotropic factor and endocannabinoids contribute to the pathophysiology and treatment of neuropsychiatric disorders. He received his medical degree and doctorate from the University of Michigan, followed by psychiatry residency training at the Payne Whitney Clinic at NewYork-Presbyterian/Weill Cornell Medical Center. He completed postdoctoral training in molecular neuroscience at the Skirball Institute at New York University and the University of California, San Francisco. About Empyrean Neuroscience Empyrean Neuroscience is a genetic engineering company developing a pipeline of neuroactive therapeutics to treat a range of neuropsychiatric and neurologic disorders. Through precision genetic modification, transformation, and regeneration of fungi and plants, the company’s platform allows for the creation of small molecule therapeutics. In addition, the platform enables the discovery of novel small molecules that may exhibit therapeutic properties. The company is based in New York City and Cambridge, UK.

Pear Therapeutics, a Boston and San Francisco-based developer of digital strategies to address a broad range of mental health conditions, has released results of a study showing promising engagement with its program Thrive, which uses a smartphone app along with medication to treat patients with schizophrenia, schizoaffective disorder and bipolar disorder. Thrive offers 24/7 patient monitoring and support to patients, and provides real-time interventions targeting symptoms of schizophrenia including hallucinations and delusions. It also offers support for schizophrenia-related mood disorders. The study, published in the Journal of Medical Internet Research, followed 342 patients between the age of 18 and 60 with schizophrenia-spectrum disorders. The patients had been diagnosed with a disorder, admitted to a psychiatric hospital and subsequently discharged. Patients were given a research version of Thrive to see whether they would engage with it, and found that 74 percent of the patients were successfully able to use the digital therapy three to six months after discharge, and, on average, using the therapy for 82 percent of the weeks they had the mobile phone. The researchers also found that patients engaged with the app every other day, and when engaged, they used the on-demand features more than once per day. Those who used the app for the entirety of the study used it an average of 4.3 days per week. "Patients with schizophrenia are traditionally considered a high risk patient population and the period immediately following hospitalization is of particularly high risk. This study debunks the concern that patients who are not clinically stable are not capable of using mobile interventions," Dr. Dror Ben-Zeev, PhD, Director of the mHealth for Mental Health Program at Dartmouth College, who led the study, said in a statement. The study was led by Ben-Zeev, and was supported by a grant from the Department of Health and Human Services and the Center for Medicare and Medicaid Services. It builds on previous studies – the research version of Thrive has been evaluated across seven clinical studies in 504 patients. In one of those studies, Thrive showed efficacy in treating schizophrenia across a 33-patient longitudinal study. Patients demonstrated an 8 percent improvement in the Positive and Negative Syndrome Scale, which is the primary endpoint in clinical trials for schizophrenia treatments. Participants, who were already taking antipsychotics at study start, were offered Thrive and followed for a month, and were found to be using the app an average of 5.2 times per day for 86.5 percent of the days they had the device. "Coupled with prior results demonstrating enhanced outcomes in patients with schizophrenia-spectrum disorders, this study suggests that Thrive could be an efficacious, long-lived therapeutic intervention,” Corey McCann, president and CEO of Pear said in a statement. We are particularly excited to have the opportunity to bring Thrive through regulatory approval and payor reimbursement. We are committed to making this product part of the standard of care for treating serious mental illness.”