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| Item 7.01. | Regulation FD Disclosure. |
ATAI Life Sciences N.V. (the “Company”) from time to time presents and/or distributes to the investment community at various industry and other conferences slide presentations to provide updates and summaries of its business. On August 11, 2021, the Company posted an updated corporate slide presentation in the “Investors” portion of its website at www.atai.life. A copy of its current corporate slide presentation is attached to this Form 8-K as Exhibit 99.1. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
The information contained in Item 7.01 of this Form 8-K (including Exhibit 99.1 attached hereto) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly provided by specific reference in such a filing.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
The following Exhibit 99.1 relating to Item 7.01 shall be deemed to be furnished, and not filed:
| Exhibit |
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| 99.1 | Corporate Slide Presentation of ATAI Life Sciences N.V. dated August 2021 | |
| 104 | Cover Page Interactive Data File (embedded within the inline XBRL document) | |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| ATAI LIFE SCIENCES N.V. | ||||||
| Date: August 11, 2021 | By: | /s/ Florian Brand | ||||
| Florian Brand | ||||||
| Chief Executive Officer | ||||||
Healingmental health disorders so that everyone everywhere can live a more fulfilled life. Company Overview Company Overview Exhibit 99.1
This presentation may include forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, industry dynamics, business strategy and plans and our objectives for future operations, are forward-looking statements. These statements represent our opinions, expectations, beliefs, intentions, estimates or strategies regarding the future, which may not be realized. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “targets,” “projects,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions that are intended to identify forward-looking statements. Forward-looking statements are based largely on our current expectations and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy, short term and long-term business operations and objectives and financial needs. These forward-looking statements involve known and unknown risks, uncertainties, changes in circumstances that are difficult to predict and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statement. Moreover, we operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. We caution you therefore against relying on these forward-looking statements, and we qualify all of our forward-looking statements by these cautionary statements. The forward-looking statements included in this presentation are made only as of the date hereof. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, neither we nor our advisors nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. Neither we nor our advisors undertake any obligation to update any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations, except as may be required by law. You should read this presentation with the understanding that our actual future results, levels of activity, performance and events and circumstances may be materially different from what we expect. Unless otherwise indicated, information contained in this presentation concerning our industry, competitive position and the markets in which we operate is based on information from independent industry and research organizations, other third-party sources and management estimates. Management estimates are derived from publicly available information released by independent industry analysts and other third-party sources, as well as data from our internal research, and are based on assumptions made by us upon reviewing such data, and our experience in, and knowledge of, such industry and markets, which we believe to be reasonable. In addition, projections, assumptions and estimates of the future performance of the industry in which we operate and our future performance are necessarily subject to uncertainty and risk due to a variety of factors, including those described above. These and other factors could cause results to differ materially from those expressed in the estimates made by independent parties and by us. Industry publications, research, surveys and studies generally state that the information they contain has been obtained from sources believed to be reliable, but that the accuracy and completeness of such information is not guaranteed. Forecasts and other forward-looking information obtained from these sources are subject to the same qualifications and uncertainties as the other forward-looking statements in this presentation. This presentation contains excerpts of testimonials from individuals who have been treated with compounds or derivatives of the compounds underlying our product candidates in the context of third-party studies or otherwise that are solely intended to be illustrative and not representative of the potential for beneficial results of such compounds. Our product candidates are in preclinical or clinical stages of development and none of our product candidates have been approved by the FDA or any other regulatory agency. Any trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of the products or services of the Company. 02 Disclaimer
We are a founder-led team aiming to develop differentiated treatments for patients suffering from mental health disorders Florian Brand Co-Founder & CEO Srinivas Rao, MD, PhD Co-Founder & CSO Christian Angermayer Founder & Chairman Lars Wilde Co-Founder Greg Weaver CFO Rolando Gutierrez, MD CMO 13 50+ IND applications NDAs through regulatory approval The atai team has collectively led 03
1 Mental health disorders have become one of largest global health burdens, exacerbated by the COVID-19 pandemic. Despite the unmet patient need, innovations remain limited, with only 7 new neuropsychiatric drugs approved since 2015. 2 As a response to lack of innovation, atai focuses on compounds with prior clinical evidence, including psychedelics whose therapeutic potential has become evident in recent academic studies and which have benefited from recent regulatory momentum. 4 3 Our platform consists of 11 drug development programs and 6 enabling technologies, focusing on differentiated and potentially disease-modifying mental health treatments. We intend to continue to grow our platform through acquisitions and incubations. 5 Validation of atai’s operating model: IPO of COMPASS Pathways and Otsuka partnership with Perception (first drug development partnership between big pharma and a biopharmaceutical company developing psychedelics). 6 Executive Summary and Key Investment Highlights Our pipeline is rich in R&D catalysts over the next 18 months, and we have a team of more than 200 highly experienced FTEs / consultants across our platform, and a strong pro-forma cash position of approx. $449M1. Our platform approach: Decentralized drug development process, leveraging the atai team and our enabling technologies such as digital therapeutics to aim for improved safety, efficacy and probability of clinical success across our pipeline. 04 (1) ~$104M cash & cash equivalents as of March 31, 2021 with ~$345M subsequently received in connection with the closing of Series D and IPO
Meaningful R&D catalysts over the next 18 months lead to a unique density of news flow, excluding potential for additional business development opportunities Empath partnered with Bionomics on PTSD drug development atai launched EmpathBio to develop EMP-01 for PTSD DemeRx received approval to start DMX-1002 Phase 1/2 in UK Perception announced positive Phase 1 results with PCN-101 COMPASS successfully IPO-ed on NASDAQ atai launched Introspect to develop Digital Therapeutics atai acquired majority stake in Recognify to develop RL-007 for CIAS Recent Milestones Anticipated Milestones next 18 months KUR-101 Phase 1 results EMP-01 Phase 1 results VLS-01 Phase 1 results IntroSpect app deployment EntheogeniX lead candidate Perception closed licensing deal with Otsuka for Japan atai entered strategic partnership with IntelGenx 2021 atai announced successful closing of Series D, raising $157m Psyber prototype deployment InnarisBio pilot Phase 1 results Launch of Revixia Life Sciences to develop RLS-01 RL-007 Phase 2b FSI PCN-101 Phase 2a results PCN-101 Phase 2a FSI RL-007 Phase 2a results GRX-917 Phase 2 FSI NN-101 Phase 1 results DMX-1002 Phase 1 results GRX-917 Phase 1 results NN-101 Phase 1 FSI DMX-1002 Phase 1/2 FSI PCN-101 (SQ vs. IV BA) results Notes: FSI = First subject in, SQ = Subcutaneous, IV = Intravenous, BA = Bioavailability Recognify started Phase 2a study in CIAS with RL-007 05 Legend Preclinical Phase 1 Phase 2 Enabling Technology
As a response to the significant unmet need and lack of innovation in the mental health treatment landscape, as well as the emergence of therapies that previously may have been overlooked or underused, including psychedelic compounds and digital therapeutics. Founded in 2018 06
SIGNIFICANT BURDEN Although mental health has become one of the largest global healthcare challenges, there has been little innovation for patients7 Affected people Global population with mental health disorders1 Of US population impacted Expected that more than half of US population will have a mental health disorder at some point in their lifetime2 Global economic impact Estimated global economic costs of mental health disorders by 20303 URGENT NEED FOR INNOVATION Respond inadequately A third of patients with depression respond inadequately or relapse with current treatments within certain indications5 Psychiatry approvals since 2015 Only 7 new drugs approved by the FDA for psychiatry disorders since 2015 – less than 10% relative to oncology (N=83)8 Ritchie, “Global mental health: five key insights which emerge from the data”, Our World In Data (2018). Kapil, “5 Surprising Mental Health Statistics”, National Council for Behavioral Health (2019). Patel et al., “The Lancet Commission on global mental health and sustainable development”, The Lancet (2018). Abbott, “COVID’s mental-health toll: how scientists are tracking a surge in depression, Nature (2021) Salzer, “National Estimates of Recovery-Remission From Serious Mental Illness”, Psychiatry Online (2018). Tew et al., “Impact of prior treatment exposure on response to antidepressant treatment in late life” Am J Geriatr Psychiatry (2006) Sinha, ”New Findings on Biological Factors Predicting Addiction Relapse Vulnerability” (2011) EvaluatePharma (as of 19.03.2021). New drugs include new molecular entities or new active ingredients. 7 ~33% ~75% Relapse rate Most of the patients treated for opioid use disorder (OUD) relapse7 Up to 12 wks Slow onset of treatment effect Frontline treatments for depression and anxiety have slow onset (4-12w)6 ~1bn >50% ~$16tn Recent impact of COVID-19 Percentage of US adults experiencing symptoms of depression and anxiety rose from 11% in 2019 to 42% end of 20204 ~4x 07
A resurgence in psychedelic therapies is emerging as promising disease-modifying drug candidates progress with regulatory momentum Early research suggested efficacy in mental health Novel results and regulatory support underscore therapeutic value LSD synthesized by Dr. Albert Hofmann at Sandoz research labs1 Psychedelic therapy developed by Dr. Abram Hoffer and Dr. Humphry Osmond, efficacious in treating alcoholics2 Dr. Stan Grof uses LSD to treat heroin addiction in Prague3 Psilocybin shows sustained decreases in depression and anxiety in cancer patients5 2016 FDA Breakthrough therapy designations for psilocybin for treatment of TRD.7 2018 FDA approval of intranasal S-ketamine for TRD8 2019 Drug Control Amendments forbid the manufacture and sale of psychedelic drugs (scheduling)4 FDA Breakthrough designation for MDMA-Assisted Psychotherapy and announcement of Phase 3 in PTSD6 “America’s public enemy number one is drug abuse.” PRESIDENT NIXON, 1971 2017 1938 1960s 1965 1953 Hofmann, MAPS (1996) Dyck, “’Hitting Highs at Rock Bottom’: LSD Treatment for Alcoholism” (2006) Williams, “Human Psychedelic Research: A Historical and Sociological Analysis” (1999) FDA, Drug Law History (2018) Griffiths et al., “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” (2016) MAPS, announcement breakthrough designation Phase 3 (2017) COMPASS, COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression (2018) FDA, FDA Approves New Nasal Spray (2019) Note: LSD = Lysergic acid diethylamide; TRD = Treatment-resistant depression; MDD = Major depressive disorder; PTSD = Post-traumatic stress disorder. 08
Griffiths et al., “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance” (2006) Schenberg et al., “Treating drug dependence with the aid of ibogaine: A qualitative study” (2017) Watts et al., “Patients’ Accounts of Increased ‘Connectedness’ and ‘Acceptance’ After Psilocybin for Treatment-Resistant Depression” (2017) Argento et al., “Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada” (2019) “When I had a craving, something in my head quickly thought about the good part, the taste, the feeling, the high, right? But if I think of the drug now... I quickly think about the downside. It changed the perception I have regarding the drug.”2 “It sort of relieved a lot of stress, a lot of negative thoughts within my body… opened my eyes to see where my stress and conflict is coming from… It is hard to explain but… it just brought a lot of grief up that I had inside me, it brought it out and I got rid of a lot of grief.”3 “I felt like, just like a whole new reborn person… I had not felt that happy in a long, long time. I felt way better about myself.”4 Male, 55 Psilocybin Male, 25 Ibogaine Female, 19 Ayahuasa Patient reports: In a study, more than half of the patients ranked psilocybin therapy among the top five most meaningful experiences of their lives1 09
The atai platform: Decentralized drug development process that leverages our team and enabling technologies to aim for improved probability of clinical success Enabling Technologies Formulation and biomarkers Digital Therapeutics AI-enabled drug discovery Process Disciplined selection criteria (including prior evidence in humans) Impactful capital allocation to acquired and incubated companies Strategic value capturing and high degree of optionality People Access to experienced group of strategic advisors and KOLs Operational involvement of interdisciplinary atai team Small teams with entrepreneurial autonomy develop our compounds 10
Rapid Growth via incubations and acquisitions: 6 psychedelic programs, 5 non-psychedelic programs and 6 enabling technologies Launched OCT 2020 Acquired stake in1 NOV 2018 Acquired stake in AUG 2019 Acquired stake in DEC 2019 Acquired larger stake in APR 2020 Launched JUN 2020 Launched JUN 2020 Acquired stake in AUG 2019 COMPASS Pathways IPO: $146m SEPT 2020 Launched JUN 2020 Acquired stake in NOV 2020 2021 2020 Launched NOV 2019 Acquired stake in DEC 2019 Lead investor AUG 2018 Launched InnarisBio MAR 2021 Launched PsyProtix MAR 2021 Acquired stake in MAR 2021 Acquired Psyber FEB 2021 Partnership Non-psychedelic Program Enabling Technologies Ketamine and S-ketamine are psychedelic/dissociative at therapeutic doses, while R-ketamine (the enantiomer that Perception Neuroscience is developing) is assumed to be nonpsychedelic at effective doses. & 11 Psychedelic Program partnered with MAR 2021
Development program overview: Our company ownership, lead compounds, lead indications and stage of development Ownership %1 50.1%2 51.9% 59.5% 56.5%4 100% 100% 54.1%5 100% Preclinical Phase 1 Phase 2 Phase 3 PCN-101 / R-ketamine RL-007 / Compound3 DMX-1002 / Ibogaine NN-101 / N-acetylcysteine VLS-01 / DMT EMP-01 / MDMA derivative KUR-101 / Deuterated mitragynine RLS-01 / Salvinorin A Lead Compound Lead Indication TRD CIAS OUD mTBI TRD PTSD OUD TRD Company Note: TRD = Treatment-resistant depression; CIAS = Cognitive impairment associated with schizophrenia; OUD = Opioid use disorder; GAD = Generalized anxiety disorder; mTBI = Mild traumatic brain injury; DMT = N,N-dimethyltryptamine; MDMA = 3,4-Methylenedioxymethamphetamine; PTSD = Post-traumatic stress disorder, VIE = Variable interest entity. VIE VIE VIE VIE Wholly Owned Wholly Owned VIE Wholly Owned Type 12 Developing COMP360 therapy, with psychological support from specially trained therapists, for TRD. Phase 2b trial is ongoing. ENTITIES LIMITED TO EQUITY INTEREST 19.4%7 6.3%8 Developing DMX-1001, a formulation of noribogaine, as a potential at-home maintenance therapy for OUD. Preclinical stage. OUR PROGRAMS 53.8%6 GRX-917 / Deuterated etifoxine GAD Majority Owned Equity Interest6 (1) Unless otherwise indicated herein, ownership percentage based on ownership of securities with voting rights as of May 30th, 2021. (2) Perception does not give effect to the shares of common stock issuable upon the conversion of outstanding convertible notes held by atai which may increase the ownership. (3) RL-007 compound is (2R, 3S)-2-amino-3-hydroxy-3-pyridin-4-yl-1-pyrrolidin-1-yl-propan-1-one(L)-(+) tartrate salt. (4) Neuronasal ownership does not give effect to the obligation to acquire further shares upon the achievement of specified development milestones which may increase the ownership to up to 64.5%. (5) Kures ownership does not give effect to the obligation to acquire further shares upon the achievement of specified development milestones which may increase the ownership to up to 67.9%. (6) Operational involvement through MSA model, including Srinivas Rao serving as GABA CMO; GABA ownership does not give effect to the obligation to acquire further shares upon the achievement of specified development milestones which may increase the ownership to up to 54.2%. (7) As of June 30, 2021, we held a 19.4% ownership interest in COMPASS. (8) DemeRx NB ownership does not give effect to option to acquire further shares upon the achievement of specified development milestones which may increase the ownership to up to 57.1%.
Early clinical signals have shown psilocybin therapy leads to rapid and sustained reduction in depressive symptoms Low Dose 1st – High Dose 2nd High Dose 1st – Low Dose 2nd Low Dose: 1 or 3mg High Dose: 22 or 30mg 46 cancer patients with depression symptoms GRID-HAMD (Depression) Assessment 1 & 2nd dose (~9w) Assessment 2 (~w14) 6 months 25 20 15 10 5 0 Baseline (w0) 1st Dose (~w4) PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY Oral Psilocybin (COMP360) 5-HT2A-R agonist Rapid onset, potential for sustained efficacy after single dose Primary: Treatment Resistant Depression Potential: Major Depressive Disorder, Anorexia, Autism, Bipolar Disorder, Chronic Cluster Headache, Body Dysmorphic Disorder COMP360 Phase 1 trial completed and results publicly available, Phase 2b trial results expected end of 2021 Proprietary formulation of synthetic psilocybin, COMP360 SUMMARY HIGHLIGHT Psilocybin demonstrated efficacy in reducing depressive symptoms in humans in an academic, third-party study p<0.05 p<0.05 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1) 13 19.4% OWNERSHIP Note: GRID-HAMD = GRID Hamilton Depression Rating Scale; COMP360 = a proprietary high-purity, polymorphic crystalline formulation of psilocybin; In COMPASS’s model of psilocybin therapy, COMP360 is administered in conjunction with psychological support from specially trained therapists. Griffiths et al., “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” (2016)
Note: MADRS = Montgomery-Asberg Depression Rate Scale, CADSS = Clinician-administered dissociative states scale, IV = Intravenous, PBO = Placebo. Leal et al., “Intravenous arketamine for treatment-resistant depression: open-label pilot study” (2020) PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1) DAY 93 patients with TRD: 3 cohorts Primary endpoint: MADRS at 24 hours PBO VS. 2 DOSES OF PCN-101 1 IN-CLINIC DOSING 2 PLANNED PCN-101 PHASE 2 TRIAL: Randomized, double blind, placebo-controlled (n=93) FOLLOW-UP -1 ~8 ~15 MADRS score Mean MADRS over 7 days and median CADSS scores of TRD patients after single IV dose (0.5mg/kg) of R-ketamine (n=7) 1 Pre-infusion 60min 240 min 1 day 3 days 7 days 40 30 25 20 15 10 5 0 35 120 min SUMMARY Subcutaneous R-ketamine (PCN-101) Glutamatergic modulator Rapid-acting, nonpsychedelic antidepressant with potential for at home use Primary: Treatment Resistant Depression Potential: Substance Use Disorder Phase 1 trial showed safety and tolerability of R-ketamine at doses of up to 150mg, Phase 2 trial initiation anticipated in mid ‘21 Issued methods of use of R-ketamine for treatment of depressive symptoms Third party study: Single IV dose (0.5 mg/kg) of R-ketamine led to a rapid and sustained decrease in MADRS in patients with TRD; dissociation was nearly absent1 We aim to develop PCN-101 as a rapid acting antidepressant with potential for at-home use Pre-infusion 40min 240 min 120 min 14 50.1% PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP
Deep-dive R-ketamine vs. S-ketamine: Higher-potency, longer lasting antidepressant effect and lower potential for abuse in preclinical models R-ketamine outperformed and outlasted S-ketamine in mice; confirmed in multiple other animal models in different labs Lower potential for abuse Conditioned place preference score test2 (third party study) R-ketamine showed less potential for abuse in mice models, while racemic and S-ketamine have significant risk Learned helplessness test Immobility time (s) * 240 180 120 60 0 * *** Forced swim test1 (third party study) 1 hour *** Escape failures SAL (S)-KET (mg kg-1) 1525 40 30 20 10 0 (R)-KET (mg kg-1) 1525 * *** 24 hours SAL 13 10 30 1 3 10 30 SAL 1 3 10 30 1 3 10 30 (S)-KET (mg kg-1) (R)-KET (mg kg-1) (R)-KET (mg kg-1) (S)-KET (mg kg-1) (S)-KET (mg kg-1) (R)-KET (mg kg-1) (R)-KET (mg kg-1) * * CPP Scores Saline (RS)-Ketamine (10mg/kg) 500 400 300 200 100 0 -100 CPP Scores Saline (S)-Ketamine * ** 5mg/kg10mg/kg 20mg/kg 500 400 300 200 100 0 -100 CPP Scores Saline (R)-Ketamine 5mg/kg10mg/kg 20mg/kg 500 R-Ketamine < abuse potential 100 0 -100 400 300 200 Superior and more durable R-ketamine S-ketamine Ketamine (racemate) R-ketamine lacks the psychotomimetic and abuse potential of S-ketamine at therapeutic doses in preclinical models. Like S-ketamine, R-ketamine’s mechanism involves increased neuroplasticity through glutamatergic modulation, with potency differences putatively arising from: Different active metabolite profiles Different pre- and post-synaptic sites of action Involvement of different intracellular pathways (mTORC1 vs. ERK) Profile of R- vs. S-ketamine Note: mTORC1 = Mechanistic target of rapamycin complex 1, ERK = Extracellular signal-regulated kinases. Sources: Wei et al., “A historical review of antidepressant effects of ketamine and its enantiomers” (2020); Chang et al., “Comparison of antidepressant and side effects in mice after intranasal administration of (R,S)-ketamine, (R)-ketamine, and (S)-ketamine Pharmacology Biochemistry and Behavior “ (2019); Zanos et al., “NDMAR inhibition-independent antidepressant actions of ketamine metabolites” (2016); Yang et al., “R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects” (2015). 15
Placebo Ayahuasca Double-blind, randomized placebo-controlled trial with Ayahuasca in 29 patients with TRD Note: MADRS: Montgomery-Asberg Depression Rate Scale. Palhano-Fontes et al. “Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression”, Psychol Med (2019) SUMMARY 45 40 35 30 25 20 15 10 5 0 p=.0001 Baseline Day 1 Day 2 Day 7 p<.05 p<.05 MADRS Score Dimethyltryptamine (DMT) in a buccal transmucosal film (VLS-01), DMT is the active psychedelic moiety in Ayahuasca 5-HT2A-R agonist Rapid onset, sustained efficacy after single dose, short duration of psychedelic effect (~30 to 45 minutes) Primary: Treatment Resistant Depression Potential: Eating Disorders, Substance Use Disorders Pre-clinical: Formulation work and safety testing in progress; Phase 1 clinical trial anticipated to initiate in mid-’22 Filed provisional on formulations of DMT VLS-01 is designed to have an improved duration of psychedelic effect while improving tolerability VLS-01 may increase patient accessibility by reducing patient and clinic time commitment PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1) 16 100% PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP
Study showed ability of S. divinorum leaf to reach hallucinogenic states of consciousness beyond serotonergic mechanisms. All six Hallucinogen Rating Scale (HRS) clusters were significantly elevated for participants given the active S. divinorum leaf. No significant adverse events were observed or reported by the participants. Five patients reported positive changes in relationships with living family members. Salvonorin A’s subjective effects were demonstrated to be similar to classical psychedelics RLS-01 is a buccal formulation of Salvinorin A (SalA), a naturally occurring psychedelic compound derived from the Salvia divinorum plant Non-orally bioavailable, non-nitrogenous agonist of the kappa-opioid receptor (KOR), no interaction with serotonergic mechanisms Rapid-acting hallucinogenic compound, no wash-out of SSRIs required Primary: Treatment Resistant Depression Potential: Substance Use Disorder, Pain Phase 1 clinical trial anticipated to initiate in H2 ’22 Filed provisional on formulation of SalA PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1) SUMMARY Participant ratings on Hallucinogen Rating Scale (HRS) completed 1h after drug administration (n=30) Cluster Placebo Active P value Affect 0.75 (0.47) 1.50 (0.58) <0.001* Cognition 0.37 (0.41) 1.61 (0.81) <0.001* Intensity 0.382 (0.76) 3.002 (0.77) <0.001* Perception 0.33 (0.36) 1.71 (0.73) <0.001* Somaesthesia 0.31 (0.33) 1.27 (0.54) <0.001* Volition 0.94 (0.53) 1.85 (0.46) <0.001* Hallucinogenic experiences demonstrated by all six significantly elevated HRS clusters on an active dose, and no significant adverse events (third party study).1 17 PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP 100% Note: Data are mean ratings with one standard deviation shown in parentheses (*P < 0.05). Addy, “Acute and post-acute behavioral and psychological effects of salvinorin A in humans” (2011) Median used instead of mean for nonparametric data
Note: 5HT2A-R = Serotonin 2A receptor, KOR = kappa-opioid receptor, NMDA-R = N-methyl-D-aspartate receptor, NET = Norepinephrine transporter, SERT = Serotonin Transporter, mGluR2 = Metabotropic glutamate receptor 2, GABA = Gamma-aminobutyric acid, DMT = Dimethyltryptamine, 5-MeO-DMT = 5-methoxy-N,N-dimethyltryptamine , SSRI = Selective Serotonin Reuptake Inhibitor, SNRI = Selective serotonin-norepinephrine reuptake Inhibitor., COMP360 = a proprietary high-purity, polymorphic crystalline formulation of psilocybin; In COMPASS’s model of psilocybin therapy, COMP360 is administered in conjunction with psychological support from specially trained therapists. Sources: GlobalData, Evaluate Pharma (both as of 2021), Uthaug, M. V. et al. Prospective examination of synthetic 5-methoxy-N,N-dimethyltryptamine inhalation: effects on salivary IL-6, cortisol levels, affect, and non-judgment. Psychopharmacology 237, 773–785 (2019). company websites 1. Rapid onset of treatment effect versus standard of care. Company Compound Potential for sustained efficacy Mechanism of Action Rapid onset of treatment effect1 Potential for at home use Depression positioning and landscape: atai’s programs are designed to be differentiated from one another and from competitors TRD treatments being developed by atai companies Marketed therapies Phase II and III competitors SSRI/SNRI SERT / NET blockade e.g. Lilly, Pfizer 5-MeO-DMT GH Research 5-HT1A- and 5-HT2A- agonist SAGE-217, Sage / Praxis GABAA positive allosteric modulator PRAX-114 tbd S-ketamine NMDA-R antagonist J&J COMP360 5-HT2A-R agonist Compass DMT 5-HT2A-R agonist Viridia R-ketamine Glutamatergic modulator Perception MIJ-821, NRX-102, JNJ-5515, AXS-05 NMDA-R / mGluR2 antagonists tbd tbd Various Salvinorin A KOR agonist Revixia 18
Stage 1: Maximum Tolerated Dose Subject cohort: Recreational opioid users (up to 30 subjects) Objective: Dose finding HCQN Subscale Pre-dose (N=75) 5 4 3 2 1 0 Stage 2: Proof of Concept TREATMENT (MULTIPLE DOSES) Patient cohort: Opioid dependent patients (approximately 80 subjects) Discharge (N=74) 1 Month (N=37) SUMMARY Emotionality (negative mood state) Compulsivity (lack of confidence in ability to quit) Purposefulness (desire of intent to use) Expectancy (expected positive benefits of drug use) Endpoints: Acute withdrawal, abstinence over 90 days SAFETY/PK TREATMENT VS PCB SAFETY/EFFICACY Ibogaine HCl capsules (DMX-1002), ibogaine is a naturally occurring psychedelic compound isolated from a West African shrub, iboga Opioid mediated, cholinergic, glutamatergic and monoaminergic receptor modulator A single dose of ibogaine may precipitate a rapid withdrawal and long-term abstinence in OUD patients Primary: Opioid Use Disorder Potential: Substance Use Disorder, Post-Traumatic Stress Disorder, Traumatic Brain Injury Phase 1/2 trial to initiate in mid ‘21 Pending method of treatment claims for OUD for ibogaine, issued method of treatment claims for OUD patients on methadone for noribogaine3 Potential sustained reduction in opioid craving with DMX-1002 single administration A single-dose of ibogaine showed sustained reductions in opioid cravings in 75 opioid-dependent patients PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1) ONGOING PHASE 1/2 TRIAL 19 59.5%2 PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP Note: HCQN = Heroin Craving Questionnaire, PTSD = Post-traumatic stress disorder, OUD = Opioid use disorder, PCB = Placebo, PK = Pharmacokinetics. Mash et al., “Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes” (2018) Refers to ownership in DemeRx IB. DemeRx NB ownership is 6.3%, which does not give effect to option to acquire further shares which may increase the ownership to up to 57.1% Noribogaine Intellectual property resides in DemeRx NB IB & NB
(5-7 COHORTS) DAY Up to 56 Schizophrenia patients Primary endpoint: Safety and tolerability Secondary endpoint: EEG-based biomarkers of cognition RL-007 TID FOLLOW-UP -1 1 2 4 8 3 Note: CIAS = Cognitive impairment associated with schizophrenia; RL-007 is (2R, 3S)-2-amino-3-hydroxy-3-pyridin-4-yl-1-pyrrolidin-1-yl-propan-1-one(L)-(+) tartrate salt; TID denotes 3x/day dosing Verbal learning was assessed by the "International Shopping List Task" (ISLT) Verbal delayed recall was assessed by ISLT with a delayed recall, as a parameter for short-term memory SUMMARY ** ** Verbal delayed recall2 Diff vs. Placebo (ISLT) Pregabalin (50-100mg TID) FSV7-007 (150 or 300 mg TID) FSV7-007 (40 or 80 mg TID) 0.4 0.3 0.2 0.1 0 -0.1 -0.2 -0.3 Verbal learning1 Pregabalin (50-100mg TID) FSV7-007 (150 or 300 mg TID) FSV7-007 (40 or 80 mg TID) ** 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0 Diff vs. Placebo (ISLT) (2R, 3S)-2-amino-3-hydroxy-3-pyridin-4-yl-1-pyrrolidin-1-yl-propan-1-one(L)-(+) tartrate salt oral capsules (RL-007) Cholinergic, glutamatergic and GABA-B receptor modulator No drug-related serious adverse events in over 500 study subject exposures, pro-cognitive effects demonstrated in two Phase 1 and one Phase 2 trials Primary: Cognitive Impairment Associated with Schizophrenia Potential: Autism, Alzheimer’s dementia Phase 2a trial initiated in H1’21 Issued composition of matter patent Previous Phase 2 showed pro-cognitive potential of RL-007 in 180 patients with diabetic peripheral neuropathic pain RL-007 has previously shown pro-cognitive effects in human clinical studies p<0.05 p<0.05 PRIOR EVIDENCE IN HUMANS ONGOING PHASE 2 TRIAL: Single-arm, single-blind dose-ranging clinical trial 20 51.9% PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP
Part 2: Multiple Ascending Dose Etifoxine has a strong safety record: a review of over 14m prescriptions in France found no cases of abuse, misuse or dependence2 Part 1: Single Ascending Dose Up to 40 healthy subjects: Up to 5 cohorts PD Endpoint: qEEG Up to 36 healthy subjects: Up to 3 cohorts PD Endpoint: qEEG SUMMARY SAFETY/PK/PD TREATMENT SAFETY/PK/PD TREATMENT Etifoxine works as rapidly as lorazepam, with etifoxine continuing its effects beyond treatment, while lorazepam shows rebound Non Inferiority Test Ham-A total score Day 0 Under treatment Safety Day 7 Day 28 Day 35 30 25 20 15 10 5 0 Etifoxine Lorazepam Deuterated etifoxine HCl oral dosage form (GRX-917) Etifoxine facilitates endogenous production of neurosteroids like allopregnanolone through agonist activity at the mitochondrial translocator protein (TSPO) GRX-917 is designed to have rapid onset activity of anxiolytic activity like benzodiazepines but without the sedating, addicting, or cognitive impairing properties Primary: Generalized Anxiety Disorder Potential: Social Anxiety Disorder, Postpartum Depression Phase 1 trial initiated in H1’21 Issued composition of matter on deuterated etifoxine (GRX-917) and corresponding methods of use GRX-917 is aimed to be an improved version of Etifoxine, which already showed promising results GRX-917 has the potential for benzodiazepine-like rapid-onset efficacy with improved safety and tolerability P=0.0001 P=0.0002 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1) ONGOING PHASE 1 TRIAL 21 53.8% PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP Note: HAM-A = Hamilton Anxiety Rating Scale, SD = standard deviation, qEEG = Quantitative electroencephalography, PK = Pharmacokinetics. PD = Pharmacodynamics. Nguyen et al., “Efficacy of etifoxine compared to lorazepam monotherapy” (2006) Cottin et al., “Safety profile of etifoxine: A French pharmacovigilance survey” (2016)
A: Placebo Count of patients None 1 2 3 4 30 20 10 0 5 B: Early oral NAC Count of patients None 1 2 3 4 30 20 10 0 5 Subject cohort: Healthy volunteers Objective: Identify optimized drug and device Primary endpoints: Brain bioavailability, safety, tolerability ESCALATING DOSE Treatment of 81 mTBI patients with NAC (24h post blast) increased probability of symptom resolution by ~2x (OR = 3.60, p = 0.0062 overall) REPEAT DOSING NN-101 pilot NN-101 was observed to be ~20x and ~100x more brain-penetrant compared to IV and oral NAC respectively SUMMARY FORMULATION COMPARISON RANDOMIZED OPEN LABEL Number of symptoms after 7 days Number of symptoms after 7 days Intranasal N-acetylcysteine (NN-101) N-acetylcysteine (NAC) stimulates glutathione production thus reducing oxidative damage Direct-to-brain intranasal administration showed to increase concentrations in the brain and reduce side effects associated with very high doses of oral or IV NAC Primary: mild Traumatic Brain Injury Potential: Parkinson’s Disease Pilot study completed in H2’20, Phase 1 trial anticipated to initiate in mid ’21 Pending patent on methods of use of NAC for treating post-concussion syndrome Improved brain-penetration of NN-101 and NAC effect in early mTBI NN-101 has the potential to become the first approved pharmacological treatment for mTBI PLANNED PHASE 1 TRIAL: Single-site, 4-part clinical trial PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1 AND NEURONASAL PILOT) 22 56.5% PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP Note: HAM-A = Hamilton Anxiety Rating Scale.. Hoffer et al., “Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetylcysteine: a double-blind, placebo-controlled study” (2013)
SUMMARY EMP-01 is an oral formulation of an MDMA derivative being developed for the treatment of PTSD A monoamine releaser and reuptake inhibitor with prominent effects on serotonin (5-HT) An entactogen; a compound class that increases feelings of empathy and closeness--with a potentially improved cardiovascular profile compared to MDMA Primary: Post-traumatic Stress Disorder Potential: General Anxiety Disorder Phase 1 trial anticipated to initiate in mid ’22 Filed provisional on formulation, combination approach EMP-01 is aimed to be an improved version of MDMA to treat PTSD symptoms, through an improved cardiovascular profile and potential digital therapeutic support MDMA-assisted psychotherapy significantly reduced PTSD symptoms in 90 severe PTSD patients PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY1) MDMA-assisted therapy significantly reduced CAPS-V scores in PTSD patients (primary endpoint), (n=90) MDMA-assisted therapy Placebo with therapy CAPS-5 total severity score Baseline (T1) 0 After session 1 (T2) After session 2 (T3) 10 20 30 40 50 After session 3 (T4), primary endpoint 23 100% PRODUCT PHARMA- COLOGY PRODUCT FEATURES INDICATIONS CURRENT STATUS INTELLECTUAL PROPERTY HIGHLIGHT OWNERSHIP Note: Change in CAPS-V total severity score from T1 to T4 (P < 0.0001, d = 0.91, n = 89 (MDMA n = 46)), as a measure of the primary outcome. Primary analysis was completed using least square means from a mixed model repeated measure (MMRM) analysis model; (n=90) Mitchell et al., “MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study” (2021)
Pear Tx created a precedent Positive regulatory sentiment atai’s opportunity reSET-O © from Pear Therapeutics is the first prescription digital therapeutic that obtained FDA approval for treatment of patients with OUD (2018) FDA is supporting and stimulating Digital Health initiatives1: Aimed at improved therapeutic outcomes Regulatory exclusivity possible through development of combination product (i.e., digital app + drug) Combination also provides opportunity for IP scope expansion Deep dive Introspect: Powerful digital therapeutics strategies across the pipeline with goal to improve treatment outcomes FDA, “Digital Health Innovation Action Plan” (2018) 24
Financial Position Issuer (ticker) ATAI Life Sciences N.V. (NASDAQ: ATAI) Market capitalization ~$2.7B(1) Outstanding shares 154.8M Cash & cash equivalents ~$104M cash & cash equivalents as of March 31, 2021 ~$345M subsequently received in connection with the closing of Series D and IPO atai is well financed to fund planned operations through 2023 As of July 20, 2021 25
Investor Contact: Greg Weaver Chief Financial Officer Email: greg.weaver@atai.life 26
Appendix ATAI PLATFORM INDICATION DEEP DIVES: Overview Depression CIAS SUD Anxiety mTBI MoA 27
The atai approach: We are leveraging a platform approach to to aim for improved probability of clinical success Process People Enabling Technologies 28
Disciplined New Program Selection Prior evidence in humans to increase probability of success Capital Allocation and Decentralized Operations Optionality and Strategic Value Capture Our process is designed to aim for effective program selection, drug development and value capturing Differentiated treatment effect to address unmet patient needs Significant commercial potential and complementary to drug candidates already in pipeline Access to milestone-based funding, shared services and enabling tech Small teams with entrepreneurial autonomy develop our drugs Economies of scope and cross-fertilization across our development programs IPO Strategic Partnerships Internal Development 29
Case study: COMPASS Pathways creates a precedent for atai’s companies: From foundation in 2017 to public company today 2017 2018 2020 2019 NOW Aug 2017: Seed round GBP 3m Post money valuation: GBP 15m atai as co-investor 1 Sept 2018: Series A GBP 27m Oct 2018: Breakthrough designation Post money valuation: GBP 77m atai as lead investor Apr 2020: Series B USD 80m Post money valuation: GBP 325m atai as lead investor Dec 2019: Positive Phase 1 results Sept 2020: IPO USD 146.6m Market Cap2: USD 1.5bn Successful IPO atai co-founder, Christian Angermayer (though his family office, Apeiron) was initial investor into Compass which shareholding was contributed to atai upon atai's incorporation Market Cap as of July 20, 2021 30
Our People: Over 50 atai professionals with strong track record and a group of experienced advisors support the CEOs of our companies with the execution of our trials 31 Ryan Barrett GC & Lead of Corporate Development Greg Bates VP, Regulatory Affairs Roman Dahl VP, Operations & Innovation Kasia Frankfort VP, FP&A Majed Fawaz, PhD VP, CMC Iqbal Husain VP, Project Direction Anne Johnson VP, Global Controller David Keene VP, Digital Therapeutics Georgina Kilfoil, PMP VP, Clinical Operations Glenn Short, PhD VP, Early Development Frank Stegert VP, Operations and Investment Arvind Tewari VP, Digital Strategy and Operations Vicki Klutzaritz Sr Director, Development Operations Sanjeev Kumar Sr Director, Technical Accounting Edmund Neuhaus, PhD Senior Director, Psychology Carrie Bowen, PhD Director, Neuroscience Josh Elliott Director, Communications Sebastian Giraldo Director, Treasury Sarah McEwen, PhD Director, Clinical Science Galyna Pidpruzhnykova, PhD Director, Innovation Strategy Anna Richardson Chief of Staff, Director Stakeholder Engagement Nicki Shah Director, Talent Acquisition Paul Simboli Director, IP Counsel Danny Talati Director, Business Development Terence A. Kelly, PhD CEO Perception Neuroscience Ian Massey CEO GABA Therapeutics Deborah Mash, PhD CEO DemeRx Tom Bradshaw CEO Neuronasal Matthew Pando, PhD CEO Recognify Pralahad Krishnan CEO Psyber Sabrina Martucci Johnson Supervisory Board Andrea Heslin Smiley Supervisory Board Jason Camm Supervisory Board Michael Auerbach Supervisory Board Alexis de Rosnay Supervisory Board Amir Kalali, MD Supervisory Board
Utilizes digital combination tools to empower atai’s programs, such as remote monitoring and remote counseling AI-enabled computational biophysics platform designed to optimize and accelerate drug discovery Potential to be a product engine for atai supporting the next generation of novel programs Digital Therapeutics AI Enabled Drug Discovery Wholly owned digital therapeutics platform dedicated to providing more comprehensive, personalized care management with potential to secure stronger IP protection Joint venture with Cyclica, with atai currently owning 80% Formulation & Biomarker Stratification Joint venture with Uniquest to advance direct-to-brain drug delivery technology Our enabling technologies are designed to drive efficient drug discovery and improved treatment outcomes InnarisBio Partnership with IntelGenx to develop Innovative transmucosal formulations Metabolomics based biomarker approach to develop precision psychiatry PsyProtix 32
~300m Patients with Depression (global)1 ~33% of patients are resistant to front line treatments ~18m Patients with Cognitive Impairment Associated with Schizophrenia (global)3 No pharmacological treatments approved for CIAS ~20m Patients with Substance Use Disorder (US)4 ~75% of patients relapse within one year of treatment ~1.7m Patients with TBI (US)5 No pharmacological treatments approved for mild TBI ~40m Patients with Anxiety Disorders (US)2 Current treatments have slow onset (4- 12 weeks) or side effects including sedation World Health Organization (2020) Anxiety and Depression Association of America (2020) Using CSCI Criterion; Reichenberg et al., “Neuropsychological Function and Dysfunction in Schizophrenia and Psychotic Affective Disorders” (2009) SAMSHA - National Survey on Drug Use and Health (2017) Georges et al, “Traumatic Brain Injury”, NCBI (2020) We are initially focused on mental health disorders (DSM-V) with current unmet patient need and significant market opportunities 33
Robust Ability to Block Strategy: IP, regulatory and restrictive covenants create framework for excluding would-be competitors New Chemical Entity Engine Drug & Digital Combo Therapeutics Exclusivity Strategy Differential De-scheduling Strategic Restrictive Covenants Leading IP and Regulatory Advisors Pursuit of Extensions of Patent Scope Robust Specialty Pharma IP Strategy 34
Additional DEA process for schedule 1 process, takes approx. 4 months Successful precedents include GHB and THC FDA evaluates NDAs and shares a recommendation with the DEA on down-scheduling of the particular compound Source: FDA website * GHB = y-hydroxybutyric acid Phase 3 Phase 1 Phase 2 NDA review FDA Review 6-10 months Typical new drug application process NDA review Change in Federal register 90 days Review down-scheduling recommendation Scheduling recommendation from FDA Parallel review of NDA documentation package 30 days Launch Brand name Compound Indication Sodium oxybate (sodium salt of GHB*) Narcolepsy Xyrem THC (delta-9-tetrahydrocannabinol in sesame oil) Chemotherapy-induced nausea Marinol (Dronabinol) Launch 2002 1985 35
Depression 36
Includes mood stabilizers, atypical antipsychotics, and esketamine. Includes rTMS (repetitive transcranial magnetic stimulation), tDCS (transcranial direct current stimulation), ECT (electroconvulsive therapy), and DBS (deep-brain stimulation). World Health Organization (2020) Hasler et al., Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose effect study (2004) Pandarakalam, 2018; Sussman et al., 2018; Gaynes et al., 2019 Evaluate Pharma (as of 19.03.2021) Depression Treatment resistant depression (TRD) is diagnosed after two failed courses of antidepressants. First onset depression (MDD) Persistent depression (MDD) Treatment resistant depression (TRD) ~300m Global sufferers of depression3 ~60-70% Likelihood of relapse from current SoC4 ~100m Global TRD patients5 Antidepressants Augmentation therapy1 S- Ketamine Somatic therapy2 High-intensity psychological interventions Opportunity Overview Treatment options for TRD 2 Approved drugs for TRD (Spravato, Symbyax) $8bn+ Relative market opportunity (antidepressant sales by 2025)6 37
atai is targeting depression via multiple complementary approaches Depression TRD 5-HT2A-R agonist 6-8 hours COMP360 Company Compound Indication MoA Target / Drug Class Potential for at home use In-clinic duration Distribution channels S-ketamine/ psilocybin clinics Population / Drug class Convenience / Use Commercial TRD ~2 hours DMT TRD Glutamatergic modulator N/A Pharmacies R-ketamine TRD Kappa opioid agonist ~2 hours Salvinorin A Potential for concomitant use with SSRIs New clinics infrastructure S-ketamine/ psilocybin clinics 5-HT2A-R agonist 38
Cognitive Impairment Associated with Schizophrenia 39
Cognitive Impairment Associated with Schizophrenia (CIAS) Schizophrenia is a chronic, psychiatric disorder characterized by a heterogeneous combination of symptoms, including psychosis, social withdrawal, flat emotional affect and cognitive impairment. Nearly all schizophrenia patients are affected by CIAS, limiting both social and non-social cognitive functions. ~21m Global sufferers of schizophrenia 1 ~84% of schizophrenia patients suffer from significant cognitive impairment2 ~20 yrs Lost life expectancy compared to general population (schizophrenia patients)3 To date, there are no pharmacological treatments approved for CIAS ~$155bn+ Estimated annual US economic burden due to schizophrenia4 $13bn+ Relative market opportunity (antipsychotic sales by 2025)5 Opportunity Overview Charlson et al., “Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study” (2016) Using CSCI Criterion; Reichenberg et al., “Neuropsychological Function and Dysfunction in Schizophrenia and Psychotic Affective Disorders” (2009) Laursen, Nordentoft & Mortensen, “Excess early mortality in schizophrenia” (2014) Cloutier et al., “The Economic Burden of Schizophrenia in the United States in 2013” (2016) EvaluatePharma (as of 19.03.2021) 40
RL-007 is well positioned, combining a history of safety with a signal of pro-cognitive effects in humans PIPELINE SUMMARY 9 Clinical Stage Therapies in Development for CIAS 12 Pre-Clinical Stage Therapies in Development 17 Different Mechanisms of Action Primary Indication MoA Current Phase Notes Therapy Schizophrenia TAAR1 agonist III Breakthrough therapy designation, being developed for schizophrenia but recently demonstrated small improvements in cognitive measures SEP-363856 CIAS GlyT1 inhibitor II Completed Phase II with positive results; recruiting for Ph III BI-425809 RL-007 CIAS GABA / nicotinic modulator II Previously assessed in over 500 subjects for other indications with no serious adverse events observed NBI-1065844 Schizophrenia DAAO inhibitor II Failed to achieve primary endpoint of easing the negative symptoms of schizophrenia, but met secondary endpoints of cognitive improvement PF-03463275 CIAS GlyT1 inhibitor II Ongoing Phase II BIIB-104 CIAS AMPA agonist II Ongoing Phase II, US and Japan Only Overview of Leading Clinical Stage Competitors for Cognitive Impairment Associated with Schizophrenia (CIAS) Note: GABA = Gamma aminobutyric acid; TAAR1 = trace amine-associated receptor; GlyT1 = Glycine Transporter 1,; AAO = D Amino Acid Oxidase; AMPA = α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; M4 = muscarinic acetylcholine 4; PAM = positive allosteric modulator Sources: GlobalData, Evaluate Pharma (both as of 2021) 41 Schizophrenia M4 PAM I Recently completed Phase Ib in patients with schizophrenia with positive results; progressing to Phase II CVL-231
Substance Use Disorder 42
Substance Substance use disorders are highly prevalent disorders characterized by an inability to control the use of a legal or illegal drug, medication or other psychoactive compound ~20m US sufferers of SUD in 20171 ~2m US sufferers of OUD in 20171 ~48k US deaths from opioid drug overdose in 20172 Synthetic opioid receptor agonists (methadone and buprenorphine) Opioid antagonists (naltrexone and naloxone) Treatment options for Opioid Use Disorder (OUD) $787bn Societal cost associated with OUD in US3 ~75% of patients undergoing OUD therapy experience relapse within one year4 Use Disorder (SUD) Opportunity Overview SAMSHA - National Survey on Drug Use and Health (2017) Wilson et al., “Drug and opioid-involved overdose deaths – United States, 2017-2018” (2020) Murphy, “The cost of opioid use disorder and the value of aversion” (2020) Sinha, “New Findings on Biological Factors Predicting Addiction Relapse Vulnerability” (2011) 43
DMX-1002 has the potential to become the first disease-modifying treatment for OUD, minimizing risk of relapse SUMMARY DMX-1002 could potentially become a paradigm-shifting therapy for Opioid Use Disorder Current standard of care for OUD is medication therapy, requiring opioid substitutes that carry significant side effects Medication Assisted Therapy1 Daily therapy given in substitution of opioid in outpatient setting in attempt to wean off from opioid Withdrawal Support2 Therapies given for symptomatic management during supervised withdrawal (detoxification) Disease Modification Single dose administered in monitored setting, providing both withdrawal support and oneiric experience with goal of complete remission Single Therapeutic Episode Minimal Abuse Potential No Opioid Side Effects High Adherence / Low Risk of Relapse Mu-agonist Partial Mu-agonist Mu-antagonist Mixed MoA Alpha-2 agonist Mechanism of Action Alpha-2 agonist Methadone Ibogaine (DMX-1002) Therapy Buprenorphine Naltrexone Clonidine Lofexidine Current strategies for withdrawal support have high rates of relapse Source: GlobalData, Evaluate Pharma (both as of 2021) Current Standard of Care Rarely used given high rates of relapse. Used primarily in institutional or penitentiary settings 44
Anxiety 45
Anxiety Generalized Anxiety Disorder (GAD) Social Anxiety Disorder (SAD) ~40m Anxiety disorder sufferers in the US1 #1 Most common mental health disorder in the US1 ~7m GAD sufferers in the US2 Antidepressants (SSRIs) Benzodiazepines Psychotherapy Treatment options for anxiety disorders Obsessive- Compulsive Disorder (OCD) Panic Disorder Post- Traumatic Stress Disorder (PTSD) <50% Less than half of patients with Anxiety disorder in the US receive treatment2 $42bn+ Annual societal cost of anxiety disorders in the US3 Opportunity Overview Anxiety disorders develop when feelings of apprehension and unease persist over an extended period and potentially worsen over time National Alliance on Mental Illness (2021) Anxiety and Depression Association of America (2021) DeVane et al., “Anxiety Disorders in the 21st Century: Status, Challenges, Opportunities, and Comorbidity With Depression”, AJMC (2005) 46
GRX-917 can fill unmet need in Generalized Anxiety Disorder (GAD) with rapid onset and favorable safety profile SUMMARY There is an unmet need in GAD for therapies with rapid onset, high efficacy, and minimal side effects SSRI’s are current standard of care for GAD but require 4-6 weeks for onset of effect and have several disadvantages1: SSRI/SNRI-specific inadequacy Lack of tolerability Patient nonadherence to medications that fail to relieve symptoms of anxiety quickly Benzodiazepines are second-line treatment, offering fast and effective relief, but carrying significant risk of: Sedation Impaired cognition Dependence/addiction Benzoxazine Venlafaxine Alprazolam Buspirone Pregablin deu-etifoxine (GRX-917) Escitalopram Imipramine Class Examples Mechanism of action Favorable safety profile Rapid Onset High Efficacy Minimal Side Effects Non-addictive Serotonin and Norepinephrine Reuptake Inhibitor (SNRI) Benzodiazepines Tricyclic Antidepressant (TCA) Azapirones Gabapentinoid Selective Serotonin Reuptake Inhibitor (SSRI) SERT AND NET blockade GABAA Potentiation partial 5-HT1A agonist VDCC inhibition GABAA Channel and TSPO Potentiation SERT blockade Mixed MoA Overview of Current Therapeutic Options for Generalized Anxiety Disorder Note: GABA = Gamma aminobutyric acid, SERT = serotonin transporter , NET = serotonin transporter; MoA = Mechanism of Action; 5HT1a = serotonin 1A receptor; VDCC = voltage dependent calcium channel; TSPO = mitochondrial translocator protein Source: GlobalData, Evaluate Pharma (both as of 19.03.2021) DeMartini et al., “Generalized Anxiety Disorder” (2019) Anticipated pharmacological profile based on etifoxine 47
Traumatic Brain Injury 48
Traumatic Brain Injury (TBI) Traumatic brain injury typically occurs when a sudden force impacts the head or body, resulting in damage and functional impairment of the brain. atai initially focuses on mild traumatic brain injuries. ~1.7m People sustain TBI each year in US1 ~57k Annual TBI-related deaths in US2 70-80% Mild TBI accounts for 70 - 80% of all reported TBIs 5.3m Americans live with TBI related disabilities3 70-90% of patients continue to exhibit prolonged neurocognitive dysfunctions4 Opportunity Overview To date, there are no pharmacological treatments approved for Traumatic Brain Injury Georges et al, “Traumatic Brain Injury”, NCBI (2020) CDC, “Surveillance Report of Traumatic Brain Injury-related Emergency Department Visits, Hospitalizations, and Deaths” (2014) Thurman et al., “Report to Congress: Traumatic Brain Injury in the United States”, CDC (1999) Hoffer et al., “Repositioning drugs for traumatic brain injury”, Journal of Biomedical Science (2017) 49
While mental health is the initial focus, adjacent indications may allow for significant expansion Anti-inflammatory properties make psychedelics potentially interesting for a variety of therapeutic indications1 Selected CNS indications of interest for psychedelic therapeutics * Company estimate based on worldwide incidence Source: EvaluatePharma for all indications with exception of Eating disorders, Autism spectrum disorder, and obsessive-compulsive disorder, for which there are no currently marketed therapies. Market size was calculated based on estimated worldwide incidence and current yearly average cost of antidepressant therapy 1. Flanagan & Nichols, “Psychedelics as anti-inflammatory agents” (2018). 2. Spriggs et al., “Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder” (2020). 3. Lea et al., “Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and substance use disorders” (2020). 4. De Gregorio et al., “Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission” (2021). 5. Moreno et al., “Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder” (2006). 6. Szabo et al., “The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells” (2016). 7. Vann Jones & O’Kelly, “Psychedelics as a Treatment for Alzheimer’s Disease Dementia” (2020) 8. Katchborian-Neto et al., “Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability to Parkinson's disease” (2020). 9. Thompson et al., “Psychedelics as a novel approach to treating autoimmune conditions” (2020). 10. Szabo A., “Psychedelics and immunomodulation: novel approaches and therapeutic opportunities” (2015). 11. Schindler et al., “Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin” (2020). 12. Sewell et al., “Response of cluster headache to psilocybin and LSD” (2006) Estimated 2026 Market Size ($BN) Indication Academic Publications 2.4 Parkinson’s Disease Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability to Parkinson's disease8 10.6 Alzheimer’s Disease Psychedelics as a Treatment for Alzheimer’s Disease Dementia7 Ischemic/ Hypoxic Brain Injury 20.0 The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells6 1.0 Amyotrophic lateral sclerosis Psychedelics as a novel approach to treating autoimmune conditions9 21.1 Multiple Sclerosis Psychedelics and immunomodulation: novel approaches and therapeutic opportunities10 1.4* Autism Spectrum Disorders Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory neurotransmission4 7.4* Eating disorders Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an eating disorder2 3.3 Attention Deficit Hyperactivity Disorder Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and substance use disorders3 Obsessive-Compulsive Disorder 3.7* Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive disorder5 9.6 Migraine Headache Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin11 Cluster Headache 0.3 Response of cluster headache to psilocybin and LSD12 80 50
atai aims to develop novel disease-modifying strategies to restore mental health by focusing on neuroplasticity SSRIs localized to serotoninergic pathways with slow onset, mainly ↓AN: reduced stress, emotional blunting. Standard of Care 1 Buprenorphine ↓RN Opioid receptor agonists for maintenance; drawbacks: respiratory depression and maintained dependency. 2 Pleiotropic re-set of DMN & AN. Increased neuroplasticity combined with psychedelic experience facilitates regaining control of CC and RN and “unlearning” negative behaviors. 1 2 Modulatory (+/-) effect on AN. Restoration of top-down control of emotions from CC. 3 Benzodiazepines ↓AN: sedation, amnesia, impaired motor performance; withdrawal Default Mode Network (DMN): Self awareness Cognitive Control (CC): Decision making, executive functions Reward Network (RN): Pleasure Affective Network (AN): Fear response, social interaction, learning, processing emotions 3 51
“Watching my best friend and business partner suffer, being let down by existing treatments and finally finding comfort in psychedelic therapies, was all the inspiration I needed to commit my life to this cause.” Florian Brand | CEO | atai life sciences 52