#1O atai LIFE SCIENCES Cognitive Impairment Associated with Schizophrenia - a KOL webinar January 2022#2Disclaimer This document 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: continued investor confidence in atai's platform and its potential to serve the growing mental health crisis; the success, cost and timing of development of our product candidates; and our business strategy and plans. 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We disclaim any obligation or undertaking to update or revise any forward-looking statements contained herein, which speak only as of the date on which they are made. Unless the context otherwise requires, all references herein to "we," "us," "our," "ATAI" or the "Company" refer to ATAI Life Sciences N.V. and its consolidated subsidiaries. This document is not an offer to buy or sell any security. atai LIFE SCIENCES 12#3Agenda atai LIFE SCIENCES 1 Introductions 2 CIAS background and landscape RL - 007 background and phase 2a data 3 4 Q&A Dr. Srini Rao, CSO, atai Life Sciences Dr. Richard Keefe, Professor Duke University Dr. Matt Pando, CEO, Recognify 12:00-12:05 12:05-12:20 12:20-12:40 12:40-1:00 13#4atai executive summary & key highlights atai LIFE SCIENCES 4 5 6 сл Mental health disorders have become one of largest global health burdens. Despite the unmet patient need, innovations remain limited. As a response to the technical risks associated with CNS drug development, atai focuses on compounds with prior evidence in humans. Our platform consists of 11 drug development programs and 6 enabling technologies, focusing on differentiated, potentially disease-modifying therapies. We employ a decentralized drug development process, leveraging the atai team and our enabling technologies to aim for improved safety, efficacy and probability of clinical success across our pipeline. Validation of atai's operating model: IPO of COMPASS Pathways and Otsuka partnership with Perception. We have a team of more than 200 highly experienced FTES/ consultants across our platform, and a strong cash position of approx. $430M. 14#5Development program overview: lead compounds, lead indications and stage of development Lead Compound PCN-101/R-ketamine RL - 007/Compound² DMX-1002/lbogaine GRX-917/Deuterated etifoxine NN-101/N-acetylcysteine KUR-101/Deuterated Generalized Anxiety Disorder Mild Traumatic Brain Injury Opioid Use Disorder mitragynine EMP-01/MDMA derivative Post-Traumatic Stress Disorder RLS-01/Salvinorin A VLS-01/DMT Lead Indication Treatment-Resistant Depression atai LIFE SCIENCES Cognitive Impairment Associated with Schizophrenia Opioid Use Disorder Preclinical Treatment-Resistant Depression Treatment-Resistant Depression Phase 1 Phase 2 E LIMITED TO EQUITY INTEREST Developing COMP360 therapy, with psychological support from special trained therapists, for treatment - resistant depression. Phase 2b topline data read out in Nov'21. Developing DMX-1001, a formulation of noribogaine, as a potential at-home maintenance therapy for OUD. Preclinical stage Note: DMT = N,N-dimethyltryptamine; MDMA = 3,4-Methylenedioxymethamphetamine. (1) Perception, Recognify, DemeRx IB and Neuronasal are all variable interest entities; GABA is a non-consolidated VIE with operational involvement through MSA model, including Srinivas Rao serving as CMO; EmpathBio, Revixia and Viridia are wholly-owned subsidiaries; COMPASS Pathways and DemeRx NB are non-controlling equity interests. (2) RL-007 compound is (2R, 3S)-2-amino-3-hydroxy-3-pyridin-4-yl-1-pyrrolidin-1-yl-propan-1-one(L)-(+) tartrate salt. Phase 3 Affiliate Company¹ Perception Neuroscience Recognify Life Sciences DemeRx IB GABA Therapeutics Neuronasal Kures Empath Bio Revixia Life Sciences Viridia Life Sciences COMPASS Pathways DemeRx NB 15#6Speaker bios atai LIFE SCIENCES Richard S.E. Keefe, PhD Professor at Duke University School of Medicine & CEO of VeraSci Dr. Keefe has over 25 years of experience in clinical psychology, neuroscience, and drug development. In addition to founding & service as CEO of VeraSci, Dr. Keefe is also a Professor of Psychiatry, Psychology, & Neurosciences at Duke University Medical Center. Furthermore, Dr. Keefe is also a Fellow of the American College of Neuropsychopharmacology and on the Scientific Board of the Brain & Behavior Research Foundation. Dr. Keefe received his PhD in Clinical Psychology from NYU. Matt Pando, PhD CEO of Recognify Life Sciences Dr. Pando has over 20 years of experience in private & public biotech companies. Prior to founding & serving as CEO of Recognify Life Sciences, Dr. Pando served as CSO of Diaxonhit and was most recently a consultant for ForSight Labs. In his previous roles, Dr. Pando contributed to the discovery and development of various products for CNS disease, oncology, & infectious disease. Dr. Pando preformed his thesis work at The Salk Institute and received his PhD in Biology from University of California, San Diego. 16#7The Opportunity of Cognitive Impairment in Schizophrenia (CIAS): Major Cause of Disability With No Approved Treatment Richard Keefe. PhD CEO, WCG VeraSci Professor, Duke University Medical Center#8Disclosure Dr. Keefe is CEO of WCG Vera Sci, a for-profit company that provides support for over 100 commercial and academic entities, most of which are drug companies doing clinical trials, and includes atai/Recognify, Boehringer-Ingelheim, Sunovion, and Neurocrine, which are mentioned in this presentation 8#9Worldwide, Schizophrenia is A Leading Cause of Disability " T 1 Leading global causes of years of life lived with disability in 15- to 44-year-olds *** **** www. (1) Unipolar depressive disorders (2) Alcohol-use disorders (3) Schizophrenia 4 Iron-deficiency anemia 5 Bipolar disorder 6 Hearing loss, adult onset 7 HIV/AIDS 8 Chronic obstructive pulmonary disease 9 Osteoarthritis 10 Road traffic accidents World Health Organization. The World Health Report 2001. Mental Health: New Understanding, New Hope. Geneva, Switzerland: World Health Organization; 2001. 2 O#10People With Schizophrenia in the United States Rarely Marry or Find Jobs and May End Up Homeless at Some Point Schizophrenia affects about 1% of the general population ¹ There are over a dozen medications approved to treat Schizophrenia² (primarily targeting positive symptoms) And yet, functional outcomes remain exceedingly poor in this population 66% Have Never Married³ <15% Hold Competitive Employment 20% Homeless At Any One Time5 ¹http://www.nimh.nih.gov/health/topics/schizophrenia/index.shtml 4Rosenheck et al. Am J Psychiatry. 2006;163(3):411-417. 2http://www.nami.org 5Folsom et al. Am J Psychiatry. 2005; 162(2):370-376. ³Tandon et al. Schizophr Res. 2009;110:1-23. Harvey et al. J Psychiatry Res. 2012;46:1546-1552. In a 2012 study of milestone achievements, only 19% had ever achieved all 3 milestones (marriage, employment and financial responsibility)6 10#11The Economic Burden of Schizophrenial In the United States, the economic burden of schizophrenia for 2013 was estimated at $155.7 billion: Excess direct health care costs of $37.7 billion (24%) Direct non-health care costs of $9.3 billion (6%) Indirect costs of $117.3 billion (76%) The largest components were excess costs associated with unemployment (38%), productivity loss due to caregiving (34%), and direct health care costs (24%). Cloutier et al, The economic burden of schizophrenia in the United States in 2013. J Clin Psychiatry 2016;77(6):764-771 11#12Severity and Profile of Cognitive Impairment in Schizophrenia T-Score 60 55 50 45 40 35 30 25 20 יװװטװן Keefe et al, Schiz Res, 2011 Healthy Normative Sample (N = 300; Mean = 50; SD = 10) Schizophrenia Patients (N = 323) kk 12#13Disability in Schizophrenia is Primarily Caused by Cognitive Impairment Large Medium Small Correlation With Outcome 0.8 0.6 0.4 0.2 0.0 Neurocognitive Deficits P<.0001 Verbal Memory Immediate Memory Executive Functions Community Functioning Instrumental and Problem-Solving Skills Psychosocial Rehabilitation Programs Attention/ Vigilance Composite cognitive scores more strongly related than individual test scores Summary Scores* *Relationship between outcome and summary scores based upon data on file, Dr Michael F Green, and previously presented in Medscape CME Unraveling the complexities of Schizophrenia: New targets, new opportunities. http://www.medscape.orgiview article/763725 transcript. Accessed April 25, 2014. Green MF, et al. Schizophr Bull. 2000;26(1):119-136. 13#14The Large Majority of Patients With Schizophrenia Have Cognitive Impairment % of Cases 100 35 30 25 20 15 10 7.2% 5 0 0% 22.8% 20.6% 0.4% 22.6% 1.6% 16.5% 7.0% <50-50 51-60 61-70 71-80 16.0% 25.0% 25.0% 7.9% 2.2% Schizophrenia (n=575) Normal controls (n=540) from standardization sample Wilk CM, et al. Schizophr Res. 2004;70(2-3):175-186. RBANS: Repeatable Battery for Assessment of Neuropsychological Status 16.0% 0.4% 0% 7.0% 0% 1.6% 0% 0.4% 81-90 91-100 101-110 111-120 121-130 131-140 140+ Total Scale Score 14#15Why Are There No Approved Treatments for CIAS? 200+ CIAS treatment trials listed on Clinical trials.gov Amount of investment that is being made in the development of treatments and opportunities for success NIH spend 25 times more on cancer than on schizophrenia Industry investment in clinical trials in 2017 was $71.5 billion, dwarfs government efforts. • There are over 1,000 ongoing clinical trials in cancer for every one in CIAS Progress from phase 1 to the US Food and Drug Administration (FDA) approval is 5.1% for cancer indications, very similar to psychiatry at 6.2%. ● ● ● Curing cancer is more likely to be more personally tangible and may appear to be more morally compelling to investors Keefe RSE. Why are there no approved treatments for Cognitive Impairment in Schizophrenia? World Psychiatry, 2019; Jun; 18(2): 167-168. (PMID: 31059617). 16#16Positive Developments. FDA clearly recognizes the severity of the unmet need and continues to be open to expediting CIAS drug development programs. The potential economic gain to society for a successful treatment of CIAS is enormous and likely to be welcomed by private and government payors.#17Key Phase 2 and 3 CIAS Programs in Progress Cognition as a Primary Endpoint Boehringer Ingelheim GlyT1 inhibitor Biogen positive allosteric modulator (potentiator) of the a-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor • Neurocrine/Takeda Luvadaxistat (Cognition secondary but changing to primary) ● ● ● Negative Outcome on Primary Endpoint Measured by the Change from Baseline on the Positive and Negative Syndrome Scale/Negative Symptom Factor Score (PANSS NSFS) • Positive Outcome on Cognitive Assessment Secondary Endpoints Support Potential Further Clinical Development of Luvadaxistat Cognition as Secondary Endpoint Several studies but cognition not listed on clinicaltrials.gov Lo Note that many of these programs have specific mechanisms of action while the Recognify compound has a more complex MoA that modulates multiple receptor systems. Other compounds that target multiple receptor systems, such as clozapine, have demonstrated powerful efficacy in schizophrenia. g 18#18Change From Baseline in the MCCB Overall Composite T-Score 5- Adjusted mean change from baseline in MCCB overall composite T-score with 95% CI 4- 3- 2 1 0- T Baseline I J Week 6 - * I Treatment Group: Placebo QD Week 12 (EoT) *p<0.05 vs placebo CI, confidence interval; EoT, end of treatment; MCCB, MATRICS Cognitive Consensus Battery; MMRM, mixed model repeated measures; QD, once daily Fleischhacker WW, et al. Efficacy and safety of the novel glycine transporter inhibitor BI 425809 once daily in patients with schizophrenia: a double-blind, randomised, placebo- controlled phase 2 study. Lancet Psychiatry. 2021 Mar;8(3):191-201. doi: 10.1016/S2215-0366 (20)30513-7. PMID: 33610228. BI 425809 2 mg QD BI 425809 5 mg QD BI 425809 10 mg QD BI 425809 25 mg QD 19#19RL - 007 development & phase 2a data atai DHE BOERONE | 20#20Recognify team members • Matt Pando, PhD - CEO, Co-founder + RL-007 Developer Gary Walker, PhD - VP Clinical Development, Co-founder John Donello, PhD - CSO + RL-007 Inventor/Developer Rolando Gutierrez-Esteinou, MD - CMO, atai Georgina Kilfoil, BS, MBA - Clinical Operations, atai Sarah McEwen, PhD - Clinical Scientist, atai Kelly Palmer, BS - Study Monitor ● ● ● atai LIFE SCIENCES | 21#21RL-007 is a potentially game changing compound atai LIFE SCIENCES RL-007: a well tolerated neuromodulator that potently enhances synaptic plasticity & elicits statistically significant & clinically meaningful effects on learning & memory | 22#22RL - 007: a de-risked pro-cognitive treatment for CIAS De-risked pharma developed product in-licensed with impressive ($100M) pre-clinical & clinical data package Human Phase 1 + 2 data show replicated, clinically significant learning and memory effects, consistent with broad pre-clinical pro-cognitive data Well tolerated (>500 subjects dosed), centrally acting oral drug Initial indication: Cognitive Impairment Associated with Schizophrenia (CIAS) is characterized by episodic learning and memory deficits -no approved treatment atai LIFE SCIENCES | 23#23RL - 007 de-risked through extensive & consistent translational data atai LIFE SCIENCES In vitro Enhanced synaptic plasticity In vivo Broad cognitive efficacy across species Predictive dose modeling Defined CNS drug exposure cognition relationship Phase 1, CSF concentration Well behaved PK confirms CNS exposures Phase 1b cognitive challenge Scopolamine challenge confirm cognition dose range Phase 2a, DPNP Showed cognitive improvements in metabolic syndrome Phase 2a, CIAS Confirmed CNS engagement and cognitive signal Consistent PK-PD relationship Confidence in active dose range Complete CMC package Excellent tolerability and safety Multiple clinical cognitive signals De-risked path forward 24#24Positive pre-clinical results (over 40 in vitro and in vivo models) Positive in broad range pre-clinical models & multiple species atai LIFE SCIENCES Neuroplasticity enhancement Cognition Functional recovery Non-sedating & no dose-limiting CNS tolerability effects O Anxiety | 25#25Neuromodulator discovered in vivo, pharmacologically defined using electrophysiology atai LIFE SCIENCES RL - 007 enhances basal neuronal signaling, glutamatergic synaptic transmission, and long- term potentiation (LTP) ✓ Discovered through an in vivo phenotypic screen ✓ Enhances basal glutamatergic tone, enhances LTP, and synergizes with ACHEIS ✓ In Vivo behavioral effects are blocked by GABAB and nACHR antagonists fEPSP slope (% of baseline) 240 fEPSP Ampl. (% Change from BL) 200- 160- 120- 80- 40 19 14 -1 0 O O O O ACSF 1 nM ** 10 nM 100 nM ** 1000 nM Veh. T 20 TBS RL-007 40 minutes Physo. P<0.005 * 007 ** 60 *: p< 0.001 P<0.04 80 007+ Physo. 126#26RL - 007 is active in a broad range of pre-clinical cognition models Enhances cognition in mouse, rat and dog species: Normal young animals Aged animals Aged mouse model of Alzheimer's Disease (3XTG-AD) ● ● ● Reverses scopolamine-induced memory deficit in both tox species Consistent inverted u-shaped PK/PD relationship across species atai LIFE SCIENCES Pro-cognitive effects translate to humans | 27#27O atai LIFE SCIENCES RL - 007 development: in CIAS, cognitive deficits have highest impact on everyday functioning & are a critical target for improving QOL | 28#28RL - 007 development: excellent PK, well tolerated with replicated cognitive signals atai LIFE SCIENCES Study HV PK Scopolamine Cognitive Challenge Peripheral Diabetic Neuropathy N=48 N=23 N=180 Phase 1 7 Day Multiple Dose DB Placebo, 4x ΧΟ Cognition Cognition Phase 2 Double Blind Placebo XO, 1 month, 5 month ext Cognition Excellent PK and CSF exposure >500 subjects exposed (9 prior Phase 1 and 2 studies) Safety to 6 month (300 mg TID) Multiple independent cognitive signals (30-80 mg dose range) Safety /PK ✓ ✓ ✓ Target Biphasic Engaged ✓ ✓ Cognitive improvements seen at the lowest doses in prior studies | 29#29Exploratory endpoint analysis shows clinically meaningful learning effects - ISLT (PK study - young caucasians) (Cohen's d effect size) 1.40 1.20 1.00 0.80 0.60 0.40 0.20 0.00 -0.20 -0.40 -0.60 -0.80 RL - 007 40 mg low dose enhanced learning with single & 7 day TID dosing (Phase 1 exploratory endpoints - 6 patients/dose) Single dose 7 day TID dosing atai LIFE SCIENCES 0.53 PBO-single 1.22 40-single I I I -0.57 150-single -0.29 450-single (Cohen's d effect size) 1.50 1.00 0.50 0.00 -0.50 -1.00 -1.50 -0.03 PBO-7d TID 0.97 140-7d TID -0.83 150-7d TID Cohen's d = 0.2 considered a 'small' effect size, 0.5 a 'medium' effect size & 0.8 a 'large' effect size -0.99 450-7d TID | 30#30RL-007 significant clinical learning & memory effects Phase 1-reverses cholinergic memory challenge better than market leader Aricept (donepezil) D .01 .05 .10 2 hr Placebo/Scopolamine vs Baseline Theta (UV) Alpha 1 (UV) Alpha 2 (UV) Beta (UV) .10 .06 .01 Delta (UV) Inhibited scopolamine induced EEG changes in Alpha and Theta atai LIFE SCIENCES Placebo (Cohen's d effect size) Diff. vs. 0.35 0.3 0.25 0.2 0.15 0.1 0.05 0 Pregabalin (50-100 mg TID) Time point RL-007 I RL-007 (40 or 80 mg TID) (150 or 300 mg TID) +1h +2b +4h 30 mg/Scop vs. Placebo/Scop [ RL-007 low doses enhanced learning and memory Verbal Learning (DPNP) Delayed Recall (DPNP) Delta (V) (Cohen's d effect size) Diff. vs. Placebo 0.4 0.3 0.1 -0.1 -0.2 II -0.3 TE Theta (V) ]} II Alpha 1 (V) 11 Dose (Phase 2 exploratory endpoints - 180 patients) Alpha 2 (V) Beta (V) ** RL-007 Pregabalin RL-007 (50-100 mg TID) (40 or 80 mg 1D) (150 or 300 mg TID) Dose Indicates direction of improvement * = P<0.05 vs Placebo; **missed significance (P=0.075); Diabetic Peripheral Neuropathic Pain (DPNP) n=60 patients/treatment group; dosed TID; randomized, cross-over design RL-007 significantly reverses memory deficits at lowest dose and delays recovery at extremely high dose Continuity of Attention Delayed Word Recall 0 -2 12 44 Pre-dose 15h 0 -S -15 -201 -25 Pre-dose 1.5h 3h 4.5h Placebo Phase 2 - exploratory endpoint analysis shows statistically significant & clinically meaningful positive learning & memory effects ■ 30mg RL-007 ► 150mg RL-007 ◄ 750mg RL-007 "The effects on delayed word recall were more marked than seen with the target clinical dose of Aricept (donepezil), the most widely prescribed anti-Alzheimer's drug" 1 *CSR 209323-502: P<0.05, n = 18; CNS effects also monitored by EEG 1: Keith Wesnes in CDR study report 131#31Clinical insights in cognition Clinically and statistically significant signals in learning and memory across multiple studies Phase 1 scopolamine challenge: reverses learning and memory deficits better than donepezil (30 mg TID) Phase 1 PK study: single and multi-dose (1 week) effects on learning (40 mg TID) Phase 2 DPNP pain study: statistically significant effects on learning and memory (40-80 mg TID) Phase 2 DPNP pain study: statistically significant effects on Cognitive and Physical Function Questionnaire (data not shown; 40-80 mg TID) atai LIFE SCIENCES | 32#32Objective of RL - 007 Phase 2a study Extend prior clinical data to CIAS patients Safety and tolerability Confirm CNS activity via EEG in schizophrenia population Define dose-response in pro-cognitive dose range (go lower than previous studies) Explore acute cognitive signals in CIAS patients ● ● atai LIFE SCIENCES | 33#33CIAS phase 2a: study schematic Evaluate independent cohorts dosed with 10, 20, 40, or 80 mg TID (5 doses TID reaches approximate CSF steady state) atai LIFE SCIENCES ● ● Screening 1-45 days Day: -1 In-patient at CRU PBO ECG Labs C-SSRS 1 RL-007 2 qEEG/ERP Cog. ECG Labs qEEG/ERP Cog. C-SSRS 3 4 Placebo dosing ◆RL-007 dosing 5 A single-center, single-arm, single blind, multiple dose study Schizophrenia patients stable on a protocol-allowed antipsychotic Patients blinded to the dose strength & sequence of active/placebo dosing Single site study - Collaborative Neuroscience Research, Dr. David Walling (PI) 8 Phone call, Exit C-SSRS 134#34Wide-spread beneficial qEEG changes at middle and high doses Endpoint Delta (2.0-4.0 Hz) Theta (4.0- 8.0 Hz) Alpha (8.0-12.0 Hz) Alpha 1 (8.0-10.0 Hz) Alpha 2 (10.0-12.0 Hz) Beta (12.0 25.0 Hz), Beta 1 (12.0-15.0 Hz) Beta 2 (15.0- 18.0 Hz) Beta 3 (18.0- 25.0 Hz) Alpha Slow wave index (ASI) Theta-Beta Ratio (TBR) Beta-Alpha Ratio (BAR) Dominant frequency, frontal (IAF1) Dominant frequency, occipital (IAF2) EO Condition Cohort 2 atai LIFE SCIENCES Cohort 4 Cohort 1 (40 mg) (80 mg) (10 mg) FCT POFCTPOFCTPOFCTPO 个 ↑ ↓↓ ↓↓↓↑↑↑↑↑↑↑↑↑ ↓↓↓↓↓ Cohort 3 (20 mg) ↓↓↓↓↓↓↓ ↑↓ ↓↓↓↓↓ ↓↓↓↓ 111111↑↑↑↑↑↑↑↑↑ 个一个 个 ↓↑↑↑↑↑↑↑↑↑↑↑↑↑↑ JIJIN NNNNNNNNNNNNNNNTNINN Eyes open qEEG change: day 2 to day 4 Small Large ↑ ↓ → S ↓↑ 7 V ↓↑ Increase only Decrease only Decrease then increase Increase then decrease Variable over time or regions Small <-0.10 or >0.10 Large <-0.15 or >0.15 Nothing >=-0.10 & <=0.10 +0.05 and ±0.10 for 1/F slope Orange-shaded and blue-shaded cells respectively indicate increases and decreases that were significant in the mixed model (MMRM) analysis. Increased alpha/ASI (middle & high doses), decreased beta (lowest dose) | 35#35Preliminary evidence for dose-dependent changes in ERP ERPS support physiological differences between acute administration of low and high dose groups RL - 007 may remediate SZ-related deficits in sensory memory at low to moderate doses With this acute treatment there was no consistent response across timepoints Significantly increased MMN amplitudes at the lower dose levels (10 & 20 mg) vs salient decrease in MMN amplitudes at 40 mg ● No effect on P300b at low doses vs sporadic significantly decreased in P300b amplitudes at the highest dose levels (40 & 80 mg) atai LIFE SCIENCES MMN8 trough exposure time-point D2 vs D4-PKAMP (20mg) FZ-LE MMN8_D2_Predose MMN8_D4_Predose μV min -2- 0- 2- 6- -100 -50 0 50 100 150 200 250 300 350 ms ● Mismatch negativity - passive auditory oddball event- related potential (ERP) Salient beneficial changes in MMN amplitude and latency observed in 20 mg cohort 136#36Cognitive testing: subset of tasks from MCCB MATRICS Consensus Cognitive Battery (MCCB): 10 tests measuring seven cognitive performance domains speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition Hopkins Verbal Learning Test-Revised (HVLT-R) - Positive in multiple previous studies Cognitive domain: verbal learning and memory Procedure: learn and recall a list of 12 words-given 3 trials, then 20-25 minutes later Outcome measurement: number of words recalled (immediate) Brief Assessment of Cognition in Schizophrenia (BACS): symbol coding test Cognitive domain: processing speed, attention & working memory Procedure: matching symbols and numbers (1-9) as quickly as possible Outcome measurement: number of correct responses ● ● ● ● Category fluency task Cognitive Domain: processing speed (verbal ability and executive control) Procedure: say as many words in 1 minute in a specific category (e.g. "animals") Outcome measurement: number of appropriate items provided in the category . ● atai LIFE SCIENCES U U 1 III X = X > ||| X = ^ = 2 ||| U U < III Y U 3 * 3 D > || = X 4 < X ^ * U < 5 X X כ < U = || 6 = X 3 ^ = * ||| = = ||| * = 8 7 U 8 8 m 8 = X ^ Y U Y X 8 9 3 * X 137#37Acute bell-shaped cognitive response T-scores (Normalized for age, gender, and education level) atai LIFE SCIENCES 10 8 6 4 2 0 -2 -4 + HVLT I I I I 1 I I 1 I 1 1 I I I 1 I I I I I I I I I I I I i I I I ! Symbol Coding 10mg 20mg 40mg n=7 n=8 n=8 n=8 Category Fluency 80mg -I I "Symbol coding is the most sensitive measure and it correlates well with the other tasks in MATRICS" - Rich Keefe Improved Cohen's d* (Symbol Coding): 20 mg: 0.79 40 mg: 0.56 80 mg: 0.38 *Day 4 vs Day 2 | 38#38Clinical insights in cognition Symbol coding a well-established and sensitive measure in CIAS Correlates well with overall movement of MATRICS battery Observed changes larger than expected from practice Effect size in range that correlates with improvement in work/school performance Immediate word recall effects similar to previous studies (20 mg) Longer duration of treatment may extend/strengthen initial findings in CIAS * Keefe, Harrison, Green, & Nuechterlein Encouraging bi-phasic trends in cognitive data atai LIFE SCIENCES | 39#39CIAS phase 2a result summary Extension of prior clinical data to CIAS Safe and well-tolerated in SZ population Dose dependent, widespread qEEG changes across brain regions EO - Increased alpha/ASI (middle & high doses), decreased beta (lowest dose) ● ● ● ● EC - Observed elevations in resting state alpha, increased ASI, and decreased TBR Suggesting a relaxed wakeful state without drowsiness at the mid to high dose levels ERP data suggests some dose-dependent cognition relevant changes Evidence of bell-shaped dose-response HVLT-R immediate recall effect size = 0.44 (20 mg) Symbol coding effect size -0.4-0.8 atai LIFE SCIENCES ● ● "Symbol coding response is at a level that would correlate with better work/school performance" – Keith Nuechterlein | 40#40Key considerations for future studies atai LIFE SCIENCES Study HV PK Scopolamine Cognitive Challenge Cognitive Impairment Associated with Schizo Peripheral Diabetic Neuropathy Cognitive Impairment Associated with Schizo ● N=48 N=23 N=32 N=180 N=X Phase 1 7 Day Multiple Dose DB Placebo, 4x ΧΟ Cognition Cognition Open Label, 2 Day Phase 2 Cognition Double Blind Placebo XO, 1 month, 5 month ext Cognition Double Blind Placebo Safety /PK ✓ ✓ Target Engaged ✓ ✓ ✓ Initial CIAS study: confirmed safety, target engagement & cognitive response Next study: demonstrate statistically significant improvement in cognition Key considerations: dose, effect size & treatment duration Optimum dose range: 20 mg - 80 mg TID Pro-cognitive: Cohen's d effect sizes of -0.2 - 1.0+ (verbal learning, symbol coding) Durations tested: single dose to 4 weeks TID Biphasic | 41#41RL - 007: future directions RL - 007 is well tolerated with the potential to address multiple areas of high patient need, starting with CIAS RL-007 is a potential central pillar for atai in neuropsych With additional high-value opportunities in CNS atai LIFE SCIENCES | 42#42atai DHE BOERONE | 43