About Atai Life Sciences N.V.

ATAI Life Sciences N.V. (atai) operates as a clinical-stage biopharmaceutical company. Programs The company has built a diversified pipeline of drug and discovery development programs, including psychedelic and nonpsychedelic compounds. Psychedelics are emerging as novel breakthrough therapies for mental health disorders, such as depression and, with growing scientific support, recent regulatory advancements and increasing patient and physician acceptance. There is a growing body of clinical evidence that supports the potential efficacy and safety profile of psychedelics, which may have potential therapeutic benefits, such as a rapid onset of effect and sustained efficacy after a short-course of administration. The company’s pipeline also includes nonpsychedelic compounds. These programs, which include new molecular entities, as well as variants of known compounds with unique pharmacology, have the potential to address unmet needs in mental health disorders. These programs vary across stage of development, indication and mechanism of action, which will improve the commercial potential and risk profile of the company’s pipeline in the aggregate. The company also prioritizes the development of compounds and compound classes that have shown potential for efficacy and safety in prior clinical trials or observational studies. Enabling Technologies and Drug Discovery Platforms The company is developing enabling technologies that have the potential to support the programs in the company’s pipeline. The company has enabling technologies housed at atai companies, including Introspect Digital Therapeutics, as well as IntelGenx Technologies, a strategic investment of the company. While many of these technologies remain in early stage development, the company is investigating the IntelGenx Technologies’ oral thin film (‘OTF’) drug delivery system in a Phase 1 clinical trial as a novel formulation of Viridia's VLS-01. In addition, the company conducts early-stage drug discovery through the company’s discovery platform companies. Expanding intellectual property has been essential to the company’s strategy since inception, with key investments made to unlock NCEs. The company has made substantial progress in the company’s drug discovery efforts as of December 31, 2022, synthesizing and screening approximately 700 compounds and identifying novel scaffolds that display potential in targeting mental health disorders. Ownership in COMPASS COMPASS Pathways plc (‘COMPASS’) is developing its investigational COMP360 psilocybin therapy, which comprises the administration of COMP360 with psychological support from specially trained therapists, with an initial focus on treatment-resistant depression (‘TRD’). COMPASS is conducting a Phase 3 pivotal program composed of two pivotal trials, each of which will have a long-term follow-up component. Topline pivotal data for the first and second trials are expected in the summer of 2024 and mid-2025, respectively. As of December 31, 2022, the company beneficially owned a 22.4% equity interest in COMPASS. Key Clinical Programs The company’s pipeline consists of therapeutic candidates across multiple neuropsychiatric indications including depression, cognitive impairment associated with schizophrenia (‘CIAS’), anxiety, opioid use disorders (‘OUD’), and post-traumatic stress disorder (‘PTSD’). There may be additional indications with potential for treatment using psychedelic therapeutics, including obsessive-compulsive disorder, attention deficit hyperactivity disorder and eating disorders, each of which represent areas of unmet medical need. The following details the company’s lead clinical programs, including related prior evidence in humans based on third-party clinical trials or studies, recent advancements, and upcoming milestones, as applicable. RL-007 (Recognify Life Sciences) Product Concept: RL-007 is an orally bioavailable compound that has exhibited neuroplasticity enhancing effects in vitro and ex vivo, as well as pro-cognitive, anxiolytic, and antinociceptive effects in non-clinical studies. Although the precise molecular target and mechanism of action for RL-007 has not yet been fully elucidated, RL-007 has been demonstrated to modulate the cholinergic, glutamatergic and GABA neurotransmitter systems. Overall, RL-007 putatively alters the excitatory/inhibitory balance in the brain. The compound has been assessed in ten Phase 1 and Phase 2 clinical trials. In four clinical studies in which cognition was assessed, including two Phase 1 and two Phase 2 clinical studies, the compound has demonstrated pro-cognitive effects. As of December 31, 2022, over 500 participants had been dosed with no evidence of safety issues. The company is initially developing this compound for the treatment of CIAS. Prior Evidence - Non-Clinical & Clinical Data Non-Clinical RL-007 has been shown to be active in a broad range of non-clinical models, consistently exhibiting pro-cognitive, anxiolytic, antinociceptive and anticonvulsant effects. Although the precise molecular target and mechanism of action for RL-007 has not been elucidated, studies with co-delivered antagonists suggest that RL-007 modulates both inhibitory and excitatory neuronal signaling through the gamma-aminobutyric acid GABAB and alpha4beta2 nicotinic receptor complexes. In addition, a microdialysis study has demonstrated that the oral administration of an intermediate (10 mg/kg) but not high (100 mg/kg) dose of RL-007 to rats results in increased extracellular concentrations of GABA in the ventral hippocampus (a brain structure understood to play an important role in memory). In contrast to other compounds that increase extracellular concentrations of GABA or that are agonists of GABAB receptors, RL-007 does not appear to induce the classic GABA side effects such as sedation (in animal models), suggesting the involvement of additional pharmacological mechanisms. Studies in several species have demonstrated that RL-007 can reverse the effects of scopolamine, a muscarinic antagonist that induces temporary cognitive impairment, and can also improve performance in complex memory tasks in aged animals, bringing their performance to a comparable level as young animals. For example, in an in vivo model in normal and scopolamine challenged dogs, RL-007 demonstrated enhanced effects on cognition. In the figure below, investigators observed enhanced learning and memory with an inverted U-shaped dose response. Phase 1 Scopolamine Challenge A third-party Phase 1 study enrolled 23 healthy volunteers to evaluate the effect of RL-007 on the scopolamine cognition model in healthy volunteers. RL-007 was administered ter in die, or three times a day (‘TID’) for one day and then co-administration with scopolamine on Day 2 to induce a temporary cognitive impairment. RL-007 was well tolerated. A statistically and clinically significant reversal of the scopolamine-induced cognitive impairment was observed with the 30 mg TID dose. Additionally, marked changes in quantitative encephalogram (qEEG) were found at all doses tested. Notably, and consistent with non-clinical evidence, the dose response was inverted U-shaped, with the most significant changes observed at the 30mg dose-level. Phase 2 Study in Diabetic Peripheral Neuropathic Pain (DPNP) A third-party conducted a Phase 2 study that enrolled 181 patients with DPNP in a double-blind, randomized, placebo-controlled study. While unsuccessful in demonstrating a clinically meaningful effect on pain scores with RL-007, as part of this trial, cognitive function was assessed using a standard computerized cognitive test battery, Cogstate, which assessed cognitive abilities, such as attention, concentration, verbal learning and memory, working memory and global cognitive functioning. In the cohort receiving RL-007 at the lower dose (40 mg TID for one week, then 80 mg TID for three weeks), significant improvement in immediate and delayed word recall was observed compared with placebo, suggesting that RL-007 may be associated with cognitive enhancement. In addition, investigators observed subjects in the lowest dose cohort (40/80 mg) exhibited an improvement in verbal learning (Cohen’s d = 0.31) and memory (Cohen’s d = 0.36), underscoring the effects on cognition and inverted-U dose response observed in prior clinical and non-clinical studies. Phase 2a Study in CIAS Recognify initiated a Phase 2a proof-of-mechanism study in the United States for RL-007 in 32 CIAS patients. The study was designed to evaluate the safety and tolerability of RL-007, as well as effects on clinical activity endpoints, including a subset of the MATRICS Consensus Cognitive Battery (MCCB) to assess cognition. In December 2021, the company announced positive clinical data from the Phase 2a study of RL-007 in CIAS patients. RL-007 was well tolerated and demonstrated a clinically meaningful pro-cognitive profile consistent with previous Phase 1 and Phase 2 trials of this compound. The totality of the results observed in this Phase 2a study supported the progression of RL-007 in clinical development to further demonstrate the pro-cognitive benefit of RL-007 in CIAS. Recent Advancements: In the first quarter of 2023, the company announced the dosing of the first patient in the Phase 2b proof-of-concept clinical trial for RL-007 in CIAS. The Phase 2b trial is a randomized, placebo-controlled, double-blind, three arm study evaluating 20mg and 40mg of RL-007 compared to placebo in approximately 230 patients. The primary endpoint of the study is the MCCB neurocognitive composite score at 6-weeks. The company anticipates reporting top-line results from this study in the second half of 2024. GRX-917 (deuterated Etifoxine -GABA Therapeutics) Product Concept: GRX-917 is a novel compound that potentiates neurosteroidogenesis, that is being developed as a treatment for Generalized Anxiety Disorder (GAD). GRX-917 is a deuterated form of etifoxine (Stresam), an anxiolytic drug approved in France and other countries. Etifoxine has demonstrated rapidity of onset and magnitude of efficacy comparable to benzodiazepines in the treatment of anxiety-related disorders. Additionally, etifoxine’s safety profile has been reported to be superior to benzodiazepines, with less sedation, cognitive impairment, amnesia or ataxia, and minimal human abuse liability. In contrast to benzodiazepines, etifoxine and GRX-917 appear to produce their anxiolytic effects by enhancing neurosteroidogenesis and thus increasing the concentration of endogenous brain neurosteroids, including allopregnanolone. Allopregnanolone is a potent positive allosteric modulator of the GABAA receptor which, in the presence of GABA, results in further attenuation of neuronal activity. GRX-917 does not activate the GABAA receptor at clinically efficacious concentrations. The pharmacological profile of GRX-917 has been evaluated and compared to etifoxine in a series of pre-clinical studies, which have demonstrated that GRX-917 has similar efficacy and pharmacology to etifoxine. GRX-917 has been observed to have improved metabolic stability conferred by deuteration compared to etifoxine. Prior Evidence – Non-Clinical & Clinical Data Etifoxine & GRX-917 Non-Clinical Etifoxine and GRX-917 have shown anxiolytic effects in the elevate plus maze (EPM) mouse model. Finasteride, an inhibitor of neurosteroid biosynthesis, was able to fully inhibit the anxiolytic activity of GRX-917 and etifoxine in the EPM model, suggesting that both compounds work via modulation of neurosteroidogenic activity. In humans, the anxiolytic activity of etifoxine hydrochloride is not inhibited in the presence of the benzodiazepine antagonist flumazenil (Schlichter et al, 2000), supporting the notion that etifoxine’s anxiolytic effects are not driven by the direct activation of the benzodiazepine site of the GABAA receptor. GRX-917’s half-life in human and rat liver microsomes is increased by 82% compared to etifoxine. In rats, this enhanced in-vitro metabolic stability translated in-vivo to a 1.7-fold increase in maximum concentration (i.e. Cmax) and a 2.5 fold increase in exposure (i.e. AUC) for the GRX-917 compared to etifoxine. Terminal half-life was also increased by 20%. The effect of deuterium substitution on enhancing microsome stability is identical (+82%) in rats and humans, pointing to a similar metabolic pathway. Therefore, GRX-917’s superior rat pharmacokinetic profile is expected to translate to humans. Phase 1 Safety, Tolerability and PK Study of Etifoxine In 2020, GABA Therapeutics completed a Phase 1 study of etifoxine to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics (via qEEG) of single (100 mg) and multiple doses (100 mg, twice a day (‘BID’) for seven days) of oral etifoxine in normal healthy volunteers. The results quantified the PK of etifoxine and served as a benchmark for the single and multiple ascending dose study GRX-917. Phase 1 Single and Multiple Ascending Dose Study In June 2021, GABA initiated a Phase 1 single and multiple ascending dose trial of GRX-917. The Phase 1 trial was a randomized, double-blind, placebo-controlled study of the safety, tolerability and pharmacokinetics of single and multiple-ascending doses of GRX-917 up to 500mg as single doses and 300mg given every twelve hours for seven days, respectively. In January 2023, the company announced positive final results from the Phase 1 study. GRX-917 was well-tolerated in the single ascending dose and multiple ascending dose cohorts. Additionally, the data confirmed an improved pharmacokinetic profile, including longer half-life and increased bioavailability compared to etifoxine. Quantitative electroencephalography (qEEG) data showed dose-dependent increases in frontal beta power, providing evidence of target engagement. Regulatory Authorities Pharmacovigilance assessments of Etifoxine An analysis of the safety profile of etifoxine (2000-2012) was completed by the French National Agency for the Safety of Medicines and Health Products (‘ANSM’) France showed that the profile of Adverse Drug Reaction (ADR) is globally similar to that expected and there were no new safety data regarding the risks identified in the spontaneous reporting data. In over 14 million prescriptions of Stresam between 2000 and 2012, there was a low ADR rate of ~ 21 per million treatments. There were only sporadic reports of ADRs relating to abuse, misuse or dependence. Data from this pharmacovigilance study were reviewed by the ANSM and this resulted a confirmation of the favorable risk-benefit assessment subject to the conduct of additional studies. As risk mitigation measures, revisions were made to the label information and a letter was sent to healthcare professionals in 2014. Further to the ANSM’s study, in 2021 the ANSM initiated a referral towards the European Medicines Agency (‘EMA’) leading to a review of Stresam’s (etifoxine) benefit-risk based on additional available data, including the results of a new study. The review was carried out by the EMA’s Committee for Medicinal Products for Human Use (‘CHMP’) which concluded that Stresam can continue to be used for the treatment of anxiety disorders, but it must not be used in patients who previously had severe skin reactions or severe liver problems after taking etifoxine. Third-Party Non-Inferiority Study of Etifoxine vs. Lorazepam A third-party conducted a study to compare the efficacies of etifoxine (50mg TID) and lorazepam (.5 – 1mg BID) monotherapies in the treatment of adjustment disorder with anxiety over a period of 28 days. The study demonstrated that etifoxine works as rapidly as lorazepam, with etifoxine continuing its effects beyond the treatment period, while lorazepam shows rebound post-treatment. Recent Advancements: In March 2023, the company updated the GRX-917 development plan to proceed with a Phase 2 study in patients with an anxiety disorder. The updated plan is anticipated to generate the robust clinical data needed to inform potential registrational studies. The company expects to provide more details on the clinical development plan upon initiation of the study. Viridia Life Sciences: VLS-01 (N,N-Dimethyltryptamine; (‘DMT’)) for TRD Product Concept: VLS-01 is an OTF formulation of DMT. Pharmacologically, 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. Intravenous (IV) DMT administration results in rapid-acting antidepressant effects in patients with major depressive disorder (MDD). VLS-01’s OTF formulation may eliminate the need for IV infusion. The company is initially focused on a subtype of MDD, referred to as TRD. TRD is a severe form of MDD, comprising patients who do not respond adequately to two or more pharmacological treatments. Approximately one third of patients with MDD are diagnosed with TRD. Prior Evidence – Non-Clinical and Clinical Data VLS-01 Non-Clinical Neural plasticity is considered to be a critical mechanism by which serotonergic psychedelics exert antidepressant effects. DMT acts as a partial agonist of the 5-HT 1A/2A/2C receptors, primarily in cortical neurons and the limbic system, where it is believed to increase neuroplasticity and decrease functional connectivity. In vitro and in vivo assays for neuritogenesis and synaptogenesis in the prefrontal cortex of adult rats demonstrated DMT’s potential to significantly increase dendritic arbor complexity along with functionality (assessed by ex-vivo slice recordings of excitatory postsynaptic currents [EPSCs]), suggesting the potential to restore prefrontal cortex deficits observed in the pathophysiology of depression. In a series of behavioral experiments conducted in male rats, a single intraperitoneal injection of 10 mg/kg DMT, a hallucinogenic dose based on rodent drug discrimination data, demonstrated an antidepressant-like effect in the forced swim test, as indicated by a significant reduction in immobility and increase in swimming. DMT has limited oral bioavailability, and current clinical studies conducted by third parties typically involve either IV or inhaled routes of administration. Given the challenges—both commercial and safety—with these routes, the company is developing VLS-01 as an OTF formulation, which is expected to provide a more convenient and acceptable route of administration. The company’s proprietary formulation has demonstrated good mucosal penetration of DMT when tested in vitro in a standard model involving pig mucosal tissue. Phase 2a Study of IV DMT fumarate in Major Depressive Disorder The third-party Phase 2a study investigated the safety and efficacy of DMT fumarate with supportive therapy compared to placebo with supportive therapy, in 34 patients with moderate/severe MDD. Patients were administered a short IV infusion of 21.5mg of DMT fumarate, resulting in a 20 to 30-minute psychedelic experience. The study met the primary and key secondary endpoints, demonstrating a placebo-adjusted reduction of -10.8 (p=0.002) and -7.4 (p=0.02) in MADRS scores at one- and two-weeks post-dose, respectively. DMT fumarate was well tolerated with no drug-related serious adverse events reported, including no reports of suicidal ideation or behavior. There were no clinically significant safety concerns in any treatment group, including with vital signs, electrocardiogram (ECG) or clinical laboratory findings. This study provides strong proof of concept data for DMT as a potential treatment for depression and supports the development of the OTF formulation of DMT, VLS-01, which may simplify in-clinic administration relative to an IV formulation. Recent Advancements: A Phase 1 open-label, single ascending dose, two-part trial of VLS-01 was initiated in October of 2022. The study compares the safety, tolerability, and pharmacokinetics of VLS-01 administered via IV infusion and oral routes, as well as the pharmacodynamics of DMT using qEEG and other measures. The company expects topline results for the Phase 1 study during the first half of 2023. DemeRx IB: DMX-1002 (ibogaine) for OUD Product Concept: DMX-1002 is an oral formulation of ibogaine, a cholinergic, glutamatergic and monoaminergic receptor modulator that is a naturally occurring psychedelic product isolated from a West African shrub, which the company is developing for the treatment of OUD. The company is initially focused on OUD, a form of SUD characterized by uncontrolled and persistent self-administration of opioids, resulting in significant impairment, distress, and mortality. Prior Evidence – Clinical Data: A single dose of another formulation of ibogaine has been shown in several case series to be an effective treatment for acute opioid withdrawal, from both the physiological and psychological perspectives. A 2018 publication authored by the founder of DemeRx IB describes the results of clinical use of ibogaine to treat SUD in over 180 patients. In this clinical study, treatment of 75 opioid-dependent and 81 cocaine-dependent patients with single doses of 8 mg/kg to 12 mg/kg ibogaine led to significant and durable reductions in ratings of craving at discharge on day 12 and at one-month post-treatment. In addition, both opioid- and cocaine-dependent patients reported improved mood from as early as five days after dosing up to at least one-month follow-up. Ibogaine was generally well tolerated when administered in a highly controlled clinical setting. All patients experienced a hallucinatory, dream-like state which typically resolved between six and 12 hours after dosing, though subjective effects were observed up to 24 hours after dosing in some subjects. There were no serious adverse events or deaths that occurred from administration of ibogaine to drug dependent patients in the dose range used in this trial. Recent Advancements: DMX-1002 is being tested in an ongoing Phase 1/2 trial to evaluate its safety, tolerability, pharmacokinetics, and efficacy in recreational drug users and healthy volunteers, to help inform future studies in patients with OUD. The company expects initial data from the Phase 1 study in the first half of 2023. EmpathBio: EMP-01 (MDMA derivative) for PTSD Product Concept: EMP-01 is an oral formulation of an MDMA derivative being developed for the treatment of PTSD. The company is developing EMP-01 as a better tolerated alternative to racemic MDMA for this indication. Prior Evidence - Clinical Data: In a meta-analysis of 21 third-party trials of other formulations of MDMA combined with psychotherapy for the treatment of PTSD, the benefits of such treatment were statistically significant versus placebo or active placebo-assisted therapy alone. In addition, a recent third-party randomized, double-blind, placebo-controlled phase 3 study of 90 patients with severe PTSD showed a statistically significant reduction in PTSD symptoms in the MDMA-assisted psychotherapy group versus placebo. Recent Advancements: In September 2022, after having received approvals from Medsafe, the New Zealand Medicines and Medical Devices Safety Authority and the Health and Disability Ethics Committees, the company initiated its Phase 1 single ascending dose trial to assess the safety and tolerability of orally administered EMP-01 in up to 32 healthy volunteers. This trial will also incorporate the company’s digital therapeutics technology, with the technology used to prepare subjects prior to dosing. The company expects initial results for the Phase 1 study in the second half of 2023. Other Clinical Programs Perception Neuroscience: PCN-101(R-Ketamine) for TRD Product Concept: PCN-101, a subcutaneous formulation of R-ketamine, as a therapy for psychiatric indications, initially focused on TRD. PCN-101 is being evaluated as a rapid-acting antidepressant therapy with potential benefits over S-ketamine, including a non-dissociative profile that has the potential to allow for at-home-use. Prior Clinical Evidence: In a third-party, open label clinical trial, another formulation of R-ketamine was observed to produce a rapid and durable response with limited dissociative side effects in a small number of patients with TRD. In January 2023, results from the Phase 2a proof-of-concept study were announced. The objective of this study was to assess the efficacy of PCN-101 for the two doses, 30 mg and 60 mg, which were sub-dissociative and non-sedating based upon Phase 1 results. To achieve a sufficiently differentiated and commercially viable treatment in TRD in line with the company’s internal target product profile, the company sets the following targets for the single dose Phase 2a study. On efficacy, the company targeted a placebo adjusted change from baseline of 5 or more points on the MADRS at 24 hours, the primary endpoint. On safety/tolerability, the company targeted sedation and dissociation comparable to placebo, operationalized as a risk ratio of less than 2. The observed mean change from baseline on the MADRS at 24 hours was -15.3 for PCN-101 60 mg and -13.7 for placebo (placebo adjusted change of -1.6; p-value 0.5). The magnitude of both the placebo effect and the drug effect were comparable to that seen in several other acute antidepressant trials incorporating inpatient overnight stays. The efficacy of the 60 mg dose was greater when considering only U.S. sites at the 24-hour time point, though the placebo effect was similar to that observed in the full sample set (-19.2 MADRS mean change from baseline on 60mg PCN-101 vs. -14.4 on placebo; p-value 0.32). However, it should be noted that the number of patients in the U.S.-only subset was small (9 on PCN-101 and 8 on placebo). The single 60 mg dose of PCN-101 showed an efficacy signal at each timepoint over the 2-week timeframe of the study, potentially indicating a sustained duration of effect. The results did reach statistical significance (p-value 0.04) at the 15-day endpoint in the U.S.-only subset in an exploratory analysis. PCN-101 was generally well-tolerated with rates of sedation and dissociation comparable to placebo. Recent Advancements: In conjunction with the Phase 2a study results of PCN-101, the company would further evaluate the data and work to determine next steps for the program. The company will continue to support Perception’s development of PCN-101 through an IV-to-subcutaneous bridging study, which is on-track to be completed in the middle of 2023. In parallel, the company is continuing to work with Perception Neuroscience to explore strategic partnership options. Kures: KUR-101(deuterated mitragynine) for OUD Product Concept: KUR-101 is a formulation of deuterated mitragynine that is being developed for the treatment of OUD. Mitragynine is the active component of the leaves of the kratom tree (Mitragnyna speciosa). Prior Evidence: Kratom has a long history of traditional medicine use as an analgesic in parts of Southeast Asia, and its use in the United States has increased in recent years, particularly amongst individuals seeking to reduce prescription opioid consumption or manage opioid withdrawal symptoms. Published third-party human data involving isolated mitragynine are limited, but recent mechanistic insights suggest that this compound may be well-suited for the medically assisted therapy of OUD. Recent Advancements: In December 2022, the company announced results from the Phase 1 study of KUR-101 in healthy volunteers. This two-part trial was designed to assess the safety, tolerability, pharmacokinetics, and analgesic activity of KUR-101. Overall, KUR-101 failed to show a greater therapeutic index—the ratio of analgesic activity to respiratory depression—compared to oxycodone. Considering the totality of data generated as of December 31, 2022, the company is working with Kures Therapeutics to explore external funding and strategic partnership options. Intellectual Property As of December 31, 2022, the company’s intellectual property portfolio included 32 issued U.S. patents, 273 issued non-U.S. patents, 37 pending U.S. patent applications, 65 pending non-U.S. patent applications, 26 pending U.S. provisional applications, and 27 PCT applications. Perception Neuroscience (PCN-101) Perception Neuroscience in-licenses three issued U.S. patents, three foreign issued patents in Japan and 2 foreign issued patents in Europe and Canada, four U.S. pending patent applications and 15 foreign pending patent applications in Brazil, Canada, China, Europe, Hong Kong, and Japan covering the composition of and methods of using R-ketamine (PCN-101) for the treatment of depressive symptoms in mental disorders, neurological disorders and substance abuse. Perception Neuroscience also in-licenses one U.S. pending patent application and one foreign issued patent in Australia and seven foreign pending patent applications in Brazil, Canada, China, Europe, Hong Kong, Israel and Japan covering the composition of matter of S-Norketamine for the treatment of depressive symptoms. Perception Neuroscience also owns one issued U.S. patent, one U.S. pending patent application and seven foreign pending patent applications in Australia, Canada, China, Europe, Hong Kong, Japan and Mexico covering the method of using R-ketamine (PCN-101) for the treatment of depressive symptoms in mental disorders and substance abuse, as well as two pending PCT application directed to R-Ketamine salts and pharmaceutical compositions and one U.S. provisional patent application directed to methods of administering R-Ketamine. Perception Neuroscience’s owned and in-licensed issued patents and any patents issuing from the owned or in-licensed pending patent applications, if granted, are expected to expire between 2034 and 2043, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Recognify (RL-007) Recognify in-licenses ten issued U.S. patents and 39 foreign issued patents in Europe, Australia, Brazil, Canada, China, Hong Kong, Israel, South Africa, India, Japan, Republic of Korea, Mexico, New Zealand and Russia, covering RL-007, including the pharmaceutical composition of and methods of using RL-007. The patents licensed to Recognify are expected to expire between 2026 and 2034, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. DemeRx IB (DMX-1002) DemeRx IB owns five issued U.S. patents and two foreign issued patents in Europe and Australia, four U.S. pending patent applications, and four foreign pending patent applications in Australia, Europe, Hong Kong and Canada covering methods of treatment using ibogaine (DMX-1002). DemeRx IB’s issued patents and any patents issuing from the pending applications, if granted, are expected to expire in 2035, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Atai Life Sciences AG owns one pending U.S. patent application and one pending PCT patent application, covering methods of improving the therapeutic effectiveness and safety profile of ibogaine. Any patents issuing from these pending patent applications, if granted, are expected to expire in 2042, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. GABA Therapeutics (GRX-917) GABA Therapeutics owns two issued U.S. patents, one U.S. pending patent application, eleven issued foreign patents in Australia, Brazil, Canada, China, Europe, Mexico, Israel, Japan, Republic of Korea and Mexico and three foreign pending patent applications in India and Japan, covering the pharmaceutical composition and corresponding methods of use of the deuterated analogs of etifoxine (GRX-917). GABA Therapeutics owns one U.S. provisional patent application, covering methods of administering GRX-917. GABA Therapeutics’ issued patents and any patents issuing from the pending patent applications, if granted, are expected to expire between 2036 and 2044, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Viridia Life Sciences (VLS-01) Atai Life Sciences AG owns one issued U.S. patent, three U.S. pending patent applications and two PCT patent applications, covering DMT compositions exhibiting unique PK profiles following administration and new DMT salts and polymorphic forms, including DMT succinate (VLS-01). Any patents issuing from these pending patent applications, if granted, are expected to expire in 2042, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Atai Life Sciences AG owns four U.S. pending patent applications, three PCT patent applications and two U.S. provisional patent applications, covering novel analogues, products and conjugates of dimethyltryptamine, methods and pharmaceutical compositions thereof. Any patents issuing from these pending patent applications, if granted, are expected to expire between 2042 and 2043, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Atai Life Sciences AG owns one U.S. provisional patent application, covering polymorphic forms of DMT. Any patents issuing from this pending patent application, if granted, are expected to expire in 2043, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. EmpathBio (EMP-01) Atai Life Sciences AG owns six U.S. pending patent applications, five PCT patent applications and two U.S. provisional patent applications, covering MDMA enantiomers and processes for the preparation of MDMA, its enantiomers and derivatives thereof. Any patents issuing from these pending patent applications, if granted, are expected to expire between 2042 and 2044, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Atai Life Sciences AG owns one U.S. provisional patent application, covering salts of R-MDMA and polymorphic forms. Any patents issuing from this pending patent application, if granted, are expected to expire in 2043, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Atai Life Sciences AG owns three U.S. provisional patent applications, covering salts of R-MDMA, the synthesis of R-MDMA and S-MDMA, and uses of MDMA for treating stress related disorders. Any patents issuing from these pending patent applications, if granted, are expected to expire in 2043, exclusive of possible patent term adjustments or extensions or other forms of exclusivity. Government Regulation and Product Approval The FDA, the U.S. Department of Health and Human Services Office of Inspector General, CMS, DEA, and comparable regulatory authorities in state and local jurisdictions and in other countries impose substantial and burdensome requirements upon companies involved in the clinical development, manufacture, marketing and distribution of drugs, such as those the company is developing. These agencies and other federal, state, local and foreign entities regulate, among other things, the research and development, testing, manufacture, quality control, safety, effectiveness, labeling, storage, record keeping, approval, advertising and promotion, distribution, post-approval monitoring and reporting, sampling and export and import of the company’s product candidates. Research and Development The company’s research and development expenses were $74.3 million for the year ended December 31, 2022. History Atai Life Sciences N.V., formerly known as Adripa Holding B.V., was founded in 2018. The company was incorporated pursuant to the laws of the Netherlands in 2020.