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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 July 13, 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 Current Report on 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 |
Description | |
| 99.1 | Corporate Slide Presentation of ATAI Life Sciences N.V. dated July 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: July 13, 2021 | By: | /s/ Florian Brand | ||||
| Florian Brand | ||||||
| Chief Executive Officer | ||||||
Exhibit 99.1 Company Overview Company Overview Exhibit 99.1 Company Overview Company Overview
02 Disclaimer This presentation may include forward-looking statements. All statements other statements. We caution you therefore against relying on these forward-looking necessarily subject to uncertainty and risk due to a variety of factors, including than statements of historical facts contained in this presentation, including statements, and we qualify all of our forward-looking statements by these those described above. These and other factors could cause results to differ statements regarding our future results of operations and financial position, cautionary statements. materially from those expressed in the estimates made by independent parties industry dynamics, business strategy and plans and our objectives for future and by us. Industry publications, research, surveys and studies generally state that operations, are forward-looking statements. These statements represent our the information they contain has been obtained from sources believed to be The forward-looking statements included in this presentation are made only as of opinions, expectations, beliefs, intentions, estimates or strategies regarding the reliable, but that the accuracy and completeness of such information is not the date hereof. Although we believe that the expectations reflected in the future, which may not be realized. In some cases, you can identify forward-looking guaranteed. Forecasts and other forward-looking information obtained from these forward-looking statements are reasonable, we cannot guarantee that the future statements by terms such as“may,”“will,”“should,”“expects,”“plans,” sources are subject to the same qualifications and uncertainties as the other results, levels of activity, performance or events and circumstances reflected in “anticipates,”“could,”“intends,”“targets,”“projects,”“contemplates,”“believes,” forward-looking statements in this presentation. the forward-looking statements will be achieved or occur. Moreover, neither we “estimates,”“predicts,”“potential” or“continue” or the negative of these terms nor our advisors nor any other person assumes responsibility for the accuracy and or other similar expressions that are intended to identify forward-looking completeness of the forward-looking statements. Neither we nor our advisors This presentation contains excerpts of testimonials from individuals who have statements. Forward-looking statements are based largely on our current undertake any obligation to update any forward-looking statements for any been treated with compounds or derivatives of the compounds underlying our expectations and projections about future events and financial trends that we reason after the date of this presentation to conform these statements to actual product candidates in the context of third-party studies or otherwise that are believe may affect our financial condition, results of operations, business strategy, results or to changes in our expectations, except as may be required by law. You solely intended to be illustrative and not representative of the potential for short term and long-term business operations and objectives and financial needs. should read this presentation with the understanding that our actual future beneficial results of such compounds. Our product candidates are in preclinical or These forward-looking statements involve known and unknown risks, results, levels of activity, performance and events and circumstances may be clinical stages of development and none of our product candidates have been uncertainties, changes in circumstances that are difficult to predict and other materially different fromwhat weexpect. approved by the FDAorany other regulatory agency. important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements Unless otherwise indicated, information contained in this presentation concerning Any trademarks included herein are the property of the owners thereof and are expressed or implied by the forward-looking statement. Moreover, we operate in our industry, competitive position and the markets in which we operate is based used for reference purposes only. Such use should not be construed as an a very competitive and rapidly changing environment. New risks emerge from on information from independent industry and research organizations, other endorsement ofthe products orservices ofthe Company. time to time. It is not possible for our management to predict all risks, nor can we third-party sources and management estimates. Management estimates are assess the impact of all factors on our business or the extent to which any factor, derived from publicly available information released by independent industry or combination of factors, may cause actual results to differ materially from those analysts and other third-party sources, as well as data from our internal research, contained in any forward-looking statements we may make. In light of these risks, and are based on assumptions made by us upon reviewing such data, and our uncertainties and assumptions, the forward-looking events and circumstances experience in, and knowledge of, such industry and markets, which we believe to discussed in this presentation may not occur and actual results could differ be reasonable. In addition, projections, assumptions and estimates of the future materially and adversely from those anticipated or implied in the forward-looking performance of the industry in which we operate and our future performance are02 Disclaimer This presentation may include forward-looking statements. All statements other statements. We caution you therefore against relying on these forward-looking necessarily subject to uncertainty and risk due to a variety of factors, including than statements of historical facts contained in this presentation, including statements, and we qualify all of our forward-looking statements by these those described above. These and other factors could cause results to differ statements regarding our future results of operations and financial position, cautionary statements. materially from those expressed in the estimates made by independent parties industry dynamics, business strategy and plans and our objectives for future and by us. Industry publications, research, surveys and studies generally state that operations, are forward-looking statements. These statements represent our the information they contain has been obtained from sources believed to be The forward-looking statements included in this presentation are made only as of opinions, expectations, beliefs, intentions, estimates or strategies regarding the reliable, but that the accuracy and completeness of such information is not the date hereof. Although we believe that the expectations reflected in the future, which may not be realized. In some cases, you can identify forward-looking guaranteed. Forecasts and other forward-looking information obtained from these forward-looking statements are reasonable, we cannot guarantee that the future statements by terms such as“may,”“will,”“should,”“expects,”“plans,” sources are subject to the same qualifications and uncertainties as the other results, levels of activity, performance or events and circumstances reflected in “anticipates,”“could,”“intends,”“targets,”“projects,”“contemplates,”“believes,” forward-looking statements in this presentation. the forward-looking statements will be achieved or occur. Moreover, neither we “estimates,”“predicts,”“potential” or“continue” or the negative of these terms nor our advisors nor any other person assumes responsibility for the accuracy and or other similar expressions that are intended to identify forward-looking completeness of the forward-looking statements. Neither we nor our advisors This presentation contains excerpts of testimonials from individuals who have statements. Forward-looking statements are based largely on our current undertake any obligation to update any forward-looking statements for any been treated with compounds or derivatives of the compounds underlying our expectations and projections about future events and financial trends that we reason after the date of this presentation to conform these statements to actual product candidates in the context of third-party studies or otherwise that are believe may affect our financial condition, results of operations, business strategy, results or to changes in our expectations, except as may be required by law. You solely intended to be illustrative and not representative of the potential for short term and long-term business operations and objectives and financial needs. should read this presentation with the understanding that our actual future beneficial results of such compounds. Our product candidates are in preclinical or These forward-looking statements involve known and unknown risks, results, levels of activity, performance and events and circumstances may be clinical stages of development and none of our product candidates have been uncertainties, changes in circumstances that are difficult to predict and other materially different fromwhat weexpect. approved by the FDAorany other regulatory agency. important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements Unless otherwise indicated, information contained in this presentation concerning Any trademarks included herein are the property of the owners thereof and are expressed or implied by the forward-looking statement. Moreover, we operate in our industry, competitive position and the markets in which we operate is based used for reference purposes only. Such use should not be construed as an a very competitive and rapidly changing environment. New risks emerge from on information from independent industry and research organizations, other endorsement ofthe products orservices ofthe Company. time to time. It is not possible for our management to predict all risks, nor can we third-party sources and management estimates. Management estimates are assess the impact of all factors on our business or the extent to which any factor, derived from publicly available information released by independent industry or combination of factors, may cause actual results to differ materially from those analysts and other third-party sources, as well as data from our internal research, contained in any forward-looking statements we may make. In light of these risks, and are based on assumptions made by us upon reviewing such data, and our uncertainties and assumptions, the forward-looking events and circumstances experience in, and knowledge of, such industry and markets, which we believe to discussed in this presentation may not occur and actual results could differ be reasonable. In addition, projections, assumptions and estimates of the future materially and adversely from those anticipated or implied in the forward-looking performance of the industry in which we operate and our future performance are
04 Christian Angermayer Florian Brand Srinivas Rao, MD, PhD Founder Co-Founder & CEO Co-Founder & CSO Lars Wilde Greg Weaver Rolando Gutierrez, MD Co-Founder CFO CMO NDAs through IND The atai team has collectively led regulatory approval applications04 Christian Angermayer Florian Brand Srinivas Rao, MD, PhD Founder Co-Founder & CEO Co-Founder & CSO Lars Wilde Greg Weaver Rolando Gutierrez, MD Co-Founder CFO CMO NDAs through IND The atai team has collectively led regulatory approval applications
05 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. 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. Since 2018 we have aggressively grown our platform to 6 psychedelic, 5 non- psychedelic drug development programs and 6 enabling technologies, focusing on differentiated and potentially disease-modifying mental health treatments. 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. Increased investor appetite as the IPO of COMPASS Pathways and the Otsuka partnership with our subsidiary Perception Neurosciences demonstrate our ability to capture value. With a team of more than 50 highly experienced professionals at atai, an additional 150 FTEs / consultants across our companies and a cash position as of March 31, 2021 of approx. 1 $449M , we are well positioned to achieve our upcoming anticipated value inflection points. (1) After giving effect to our Series D and IPO financings.05 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. 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. Since 2018 we have aggressively grown our platform to 6 psychedelic, 5 non- psychedelic drug development programs and 6 enabling technologies, focusing on differentiated and potentially disease-modifying mental health treatments. 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. Increased investor appetite as the IPO of COMPASS Pathways and the Otsuka partnership with our subsidiary Perception Neurosciences demonstrate our ability to capture value. With a team of more than 50 highly experienced professionals at atai, an additional 150 FTEs / consultants across our companies and a cash position as of March 31, 2021 of approx. 1 $449M , we are well positioned to achieve our upcoming anticipated value inflection points. (1) After giving effect to our Series D and IPO financings.
06 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.06 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.
07 SIGNIFICANT BURDEN URGENT NEED FOR INNOVATION Affected people Respond inadequately Global population with mental health A third of patients with depression respond 1 disorders inadequately or relapse with current 5 treatments within certain indications Of US population impacted Slow onset of treatment effect Expected that more than half of US population will have a mental health Frontline treatments for depression and 2 6 disorder at some point in their lifetime anxiety have slow onset (4-12w) Relapse rate Global economic impact Most of the patients treated for opioid use Estimated global economic costs of 7 disorder (OUD) relapse 3 mental health disorders by 2030 Psychiatry approvals since 2015 Recent impact of COVID-19 Only 7 new drugs approved by the FDA for Percentage of US adults experiencing psychiatry disorders since 2015 – less than symptoms of depression and anxiety rose 8 4 10% relative to oncology (N=83) from 11% in 2019 to 42% end of 2020 1. Ritchie, “Global mental health: five key insights which emerge from the data”, Our World In Data (2018). 5. Salzer, “National Estimates of Recovery-Remission From Serious Mental Illness”, Psychiatry Online (2018). 2. Kapil, “5 Surprising Mental Health Statistics”, National Council for Behavioral Health (2019). 6. Tew et al., “Impact of prior treatment exposure on response to antidepressant treatment in late life” Am J Geriatr Psychiatry (2006) 7. Sinha, ”New Findings on Biological Factors Predicting Addiction Relapse Vulnerability” (2011) 3. Patel et al., “The Lancet Commission on global mental health and sustainable development”, The Lancet (2018). 8. EvaluatePharma (as of 19.03.2021). New drugs include new molecular entities or new active ingredients. 4. Abbott, “COVID’s mental-health toll: how scientists are tracking a surge in depression, Nature (2021)07 SIGNIFICANT BURDEN URGENT NEED FOR INNOVATION Affected people Respond inadequately Global population with mental health A third of patients with depression respond 1 disorders inadequately or relapse with current 5 treatments within certain indications Of US population impacted Slow onset of treatment effect Expected that more than half of US population will have a mental health Frontline treatments for depression and 2 6 disorder at some point in their lifetime anxiety have slow onset (4-12w) Relapse rate Global economic impact Most of the patients treated for opioid use Estimated global economic costs of 7 disorder (OUD) relapse 3 mental health disorders by 2030 Psychiatry approvals since 2015 Recent impact of COVID-19 Only 7 new drugs approved by the FDA for Percentage of US adults experiencing psychiatry disorders since 2015 – less than symptoms of depression and anxiety rose 8 4 10% relative to oncology (N=83) from 11% in 2019 to 42% end of 2020 1. Ritchie, “Global mental health: five key insights which emerge from the data”, Our World In Data (2018). 5. Salzer, “National Estimates of Recovery-Remission From Serious Mental Illness”, Psychiatry Online (2018). 2. Kapil, “5 Surprising Mental Health Statistics”, National Council for Behavioral Health (2019). 6. Tew et al., “Impact of prior treatment exposure on response to antidepressant treatment in late life” Am J Geriatr Psychiatry (2006) 7. Sinha, ”New Findings on Biological Factors Predicting Addiction Relapse Vulnerability” (2011) 3. Patel et al., “The Lancet Commission on global mental health and sustainable development”, The Lancet (2018). 8. EvaluatePharma (as of 19.03.2021). New drugs include new molecular entities or new active ingredients. 4. Abbott, “COVID’s mental-health toll: how scientists are tracking a surge in depression, Nature (2021)
08 LSD synthesized by Dr. Stan Grof uses Psilocybin shows sustained FDA Breakthrough therapy Dr. Albert Hofmann at LSD to treat heroin decreases in depression and designations for psilocybin 1 3 5 7 Sandoz research labs addiction in Prague anxiety in cancer patients for treatment of TRD. Psychedelic therapy Drug Control PRESIDENT NIXON, 1971 developed by Dr. Abram Amendments forbid FDA Breakthrough FDA approval of Hoffer and Dr. Humphry the manufacture and designation for MDMA- intranasal S-ketamine Osmond, efficacious in sale of psychedelic 8 2 4 Assisted Psychotherapy for TRD treating alcoholics drugs (scheduling) and announcement of 6 Phase 3 in PTSD Novel results and regulatory support Early research suggestedefficacy in underscore therapeutic value mental health Note: LSD = Lysergic acid diethylamide; TRD = Treatment-resistant depression; MDD = Major depressive disorder; PTSD = Post-traumatic stress disorder. 1. Hofmann, MAPS (1996) 5. Griffiths et al., “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” (2016) 2. Dyck, “’Hitting Highs at Rock Bottom’: LSD Treatment for Alcoholism” (2006) 6. MAPS, announcement breakthrough designation Phase 3 (2017) 3. Williams, “Human Psychedelic Research: A Historical and Sociological Analysis” (1999) 7. COMPASS, COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression (2018) 4. FDA, Drug Law History (2018) 8. FDA, FDA Approves New Nasal Spray (2019)08 LSD synthesized by Dr. Stan Grof uses Psilocybin shows sustained FDA Breakthrough therapy Dr. Albert Hofmann at LSD to treat heroin decreases in depression and designations for psilocybin 1 3 5 7 Sandoz research labs addiction in Prague anxiety in cancer patients for treatment of TRD. Psychedelic therapy Drug Control PRESIDENT NIXON, 1971 developed by Dr. Abram Amendments forbid FDA Breakthrough FDA approval of Hoffer and Dr. Humphry the manufacture and designation for MDMA- intranasal S-ketamine Osmond, efficacious in sale of psychedelic 8 2 4 Assisted Psychotherapy for TRD treating alcoholics drugs (scheduling) and announcement of 6 Phase 3 in PTSD Novel results and regulatory support Early research suggestedefficacy in underscore therapeutic value mental health Note: LSD = Lysergic acid diethylamide; TRD = Treatment-resistant depression; MDD = Major depressive disorder; PTSD = Post-traumatic stress disorder. 1. Hofmann, MAPS (1996) 5. Griffiths et al., “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” (2016) 2. Dyck, “’Hitting Highs at Rock Bottom’: LSD Treatment for Alcoholism” (2006) 6. MAPS, announcement breakthrough designation Phase 3 (2017) 3. Williams, “Human Psychedelic Research: A Historical and Sociological Analysis” (1999) 7. COMPASS, COMPASS Pathways Receives FDA Breakthrough Therapy Designation for Psilocybin Therapy for Treatment-resistant Depression (2018) 4. FDA, Drug Law History (2018) 8. FDA, FDA Approves New Nasal Spray (2019)
09 “When I had a craving, “It sort of relieved a lot of “I felt like, just like a whole something in my head quickly stress, a lot of negative new reborn person… I had thought about the good part, thoughts within my body… not felt that happy in a long, the taste, the feeling, the high, opened my eyes to see where long time. I felt way better 4 right? But if I think of the drug my stress and conflict is about myself.” now... I quickly think about the coming from… It is hard to downside. It changed the explain but… it just brought a perception I have regarding the lot of grief up that I had inside 2 drug.” me, it brought it out and I got 3 rid of a lot of grief.” Female, 19 Male, 25 Male, 55 Ayahuasca Ibogaine Psilocybin 1. Griffiths et al., “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance” (2006) 2. Schenberg et al., “Treating drug dependence with the aid of ibogaine: A qualitative study” (2017) 3. Watts et al., “Patients’ Accounts of Increased ‘Connectedness’ and ‘Acceptance’ After Psilocybin for Treatment-Resistant Depression” (2017) 4. Argento et al., “Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada” (2019)09 “When I had a craving, “It sort of relieved a lot of “I felt like, just like a whole something in my head quickly stress, a lot of negative new reborn person… I had thought about the good part, thoughts within my body… not felt that happy in a long, the taste, the feeling, the high, opened my eyes to see where long time. I felt way better 4 right? But if I think of the drug my stress and conflict is about myself.” now... I quickly think about the coming from… It is hard to downside. It changed the explain but… it just brought a perception I have regarding the lot of grief up that I had inside 2 drug.” me, it brought it out and I got 3 rid of a lot of grief.” Female, 19 Male, 25 Male, 55 Ayahuasca Ibogaine Psilocybin 1. Griffiths et al., “Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance” (2006) 2. Schenberg et al., “Treating drug dependence with the aid of ibogaine: A qualitative study” (2017) 3. Watts et al., “Patients’ Accounts of Increased ‘Connectedness’ and ‘Acceptance’ After Psilocybin for Treatment-Resistant Depression” (2017) 4. Argento et al., “Exploring ayahuasca‐assisted therapy for addiction: A qualitative analysis of preliminary findings among an Indigenous community in Canada” (2019)
10 Small teams with entrepreneurial Disciplined selection criteria Digital Therapeutics (including prior evidence in humans) autonomy develop our compounds Impactful capital allocation to Operational involvement of Formulation and biomarkers acquired and incubated companies interdisciplinary atai team Strategic value capturing and AI-enabled drug discovery Access to experienced group of Enabling Process People high degree of optionality strategic advisors and KOLs Technologies10 Small teams with entrepreneurial Disciplined selection criteria Digital Therapeutics (including prior evidence in humans) autonomy develop our compounds Impactful capital allocation to Operational involvement of Formulation and biomarkers acquired and incubated companies interdisciplinary atai team Strategic value capturing and AI-enabled drug discovery Access to experienced group of Enabling Process People high degree of optionality strategic advisors and KOLs Technologies
11 Acquired stake in Launched Acquired larger stake in Acquired stake in Acquired stake in PsyProtix COMPASS Pathways MAR 2021 IPO: $146m MAR 2021 Launched APR 2020 AUG 2019 NOV 2020 Launched Acquired SEPT 2020 Lead investor JUN 2020 InnarisBio Psyber MAR 2021 FEB 2021 Acquired stake in Acquired stake in AUG 2018 Launched Launched AUG 2019 DEC 2019 JUN 2020 JUN 2020 Launched 1 Launched Acquired stake in Acquired stake in OCT 2020 & NOV 2019 DEC 2019 NOV 2018 Psychedelic Program Non-psychedelic Program Enabling Technologies 2020 2021 1. 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 Acquired stake in Launched Acquired larger stake in Acquired stake in Acquired stake in PsyProtix COMPASS Pathways MAR 2021 IPO: $146m MAR 2021 Launched APR 2020 AUG 2019 NOV 2020 Launched Acquired SEPT 2020 Lead investor JUN 2020 InnarisBio Psyber MAR 2021 FEB 2021 Acquired stake in Acquired stake in AUG 2018 Launched Launched AUG 2019 DEC 2019 JUN 2020 JUN 2020 Launched 1 Launched Acquired stake in Acquired stake in OCT 2020 & NOV 2019 DEC 2019 NOV 2018 Psychedelic Program Non-psychedelic Program Enabling Technologies 2020 2021 1. 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.
12 OUR PROGRAMS 1 Company Lead Compound Lead Indication Type Ownership % Preclinical Phase 1 Phase 2 Phase 3 PCN-101 / 2 TRD VIE 50.1% R-ketamine RL-007 / CIAS VIE 51.9% 3 Compound DMX-1002 / OUD VIE 59.5% Ibogaine NN-101 / 4 mTBI VIE 56.5% N-acetylcysteine KUR-101 / 5 OUD VIE 54.1% Deuterated mitragynine EMP-01 / PTSD Wholly Owned 100% MDMA derivative RLS-01 / Wholly Owned TRD 100% Salvinorin A VLS-01 / TRD Wholly Owned 100% DMT ENTITIES LIMITED TO EQUITY INTEREST Developing COMP360 therapy, with psychological support from 6 19.4% specially trained therapists, for TRD. Phase 2b trial is ongoing. Developing deuterated etifoxine HCl oral dosage form (GRX-917) as 7 53.8% potential therapy for GAD. Phase 1 trial initiated. Developing DMX-1001, a formulation of noribogaine, as a potential 8 6.3% at-home maintenance therapy for OUD. Preclinical stage. 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. th (1) Unless otherwise indicated herein, ownership percentage based on ownership of securities with voting rights as of May 30 , 2021. (5) Kures ownership does not give effect to the obligation to acquire further shares upon the achievement of specified developmen t milestones which may (2) Perception does not give effect to the shares of common stock issuable upon the conversion of outstanding convertible not es held by atai which may increase the ownership to up to 67.9%. increase the ownership. (6) As of June 30, 2021, we held a 19.4% ownership interest in COMPASS. (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. (7) GABA ownership does not give effect to the obligation to acquire further shares upon the achievement of specified develop ment milestones which may (4) Neuronasal ownership does not give effect to the obligation to acquire further shares upon the achievement of specified development mile stones increase the ownership to up to 54.2%. which may increase the ownership to up to 64.5%. (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%.12 OUR PROGRAMS 1 Company Lead Compound Lead Indication Type Ownership % Preclinical Phase 1 Phase 2 Phase 3 PCN-101 / 2 TRD VIE 50.1% R-ketamine RL-007 / CIAS VIE 51.9% 3 Compound DMX-1002 / OUD VIE 59.5% Ibogaine NN-101 / 4 mTBI VIE 56.5% N-acetylcysteine KUR-101 / 5 OUD VIE 54.1% Deuterated mitragynine EMP-01 / PTSD Wholly Owned 100% MDMA derivative RLS-01 / Wholly Owned TRD 100% Salvinorin A VLS-01 / TRD Wholly Owned 100% DMT ENTITIES LIMITED TO EQUITY INTEREST Developing COMP360 therapy, with psychological support from 6 19.4% specially trained therapists, for TRD. Phase 2b trial is ongoing. Developing deuterated etifoxine HCl oral dosage form (GRX-917) as 7 53.8% potential therapy for GAD. Phase 1 trial initiated. Developing DMX-1001, a formulation of noribogaine, as a potential 8 6.3% at-home maintenance therapy for OUD. Preclinical stage. 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. th (1) Unless otherwise indicated herein, ownership percentage based on ownership of securities with voting rights as of May 30 , 2021. (5) Kures ownership does not give effect to the obligation to acquire further shares upon the achievement of specified developmen t milestones which may (2) Perception does not give effect to the shares of common stock issuable upon the conversion of outstanding convertible not es held by atai which may increase the ownership to up to 67.9%. increase the ownership. (6) As of June 30, 2021, we held a 19.4% ownership interest in COMPASS. (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. (7) GABA ownership does not give effect to the obligation to acquire further shares upon the achievement of specified develop ment milestones which may (4) Neuronasal ownership does not give effect to the obligation to acquire further shares upon the achievement of specified development mile stones increase the ownership to up to 54.2%. which may increase the ownership to up to 64.5%. (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%.
13 19.4% OWNERSHIP 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Oral Psilocybin (COMP360) PRODUCT 46 cancer patients with depression symptoms 25 PHARMA- 5-HT2A-R agonist COLOGY 20 Rapid onset, potential for sustained efficacy PRODUCT 15 after single dose FEATURES p<0.05 p<0.05 Primary: Treatment Resistant Depression 10 st nd Low Dose 1 – High Dose 2 Potential: Major Depressive Disorder, Anorexia, INDICATIONS Autism, Bipolar Disorder, Chronic Cluster st nd High Dose 1 – Low Dose 2 Headache, Body Dysmorphic Disorder 5 Low Dose: 1 or 3mg COMP360 Phase 1 trial completed and results CURRENT publicly available, Phase 2b trial results High Dose: 22 or 30mg STATUS 0 expected end of 2021 Baseline Assessment 1 Assessment 2 6 months (w0) & 2nd dose (~w14) (~9w) INTELLECTUAL Proprietary formulation of synthetic psilocybin, st 1 Dose PROPERTY COMP360 (~w4) Psilocybin demonstrated efficacy in reducing 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. depressive symptoms in humans in an HIGHLIGHT 1. Griffiths et al., “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” (2016) academic, third-party study GRID-HAMD (Depression)13 19.4% OWNERSHIP 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Oral Psilocybin (COMP360) PRODUCT 46 cancer patients with depression symptoms 25 PHARMA- 5-HT2A-R agonist COLOGY 20 Rapid onset, potential for sustained efficacy PRODUCT 15 after single dose FEATURES p<0.05 p<0.05 Primary: Treatment Resistant Depression 10 st nd Low Dose 1 – High Dose 2 Potential: Major Depressive Disorder, Anorexia, INDICATIONS Autism, Bipolar Disorder, Chronic Cluster st nd High Dose 1 – Low Dose 2 Headache, Body Dysmorphic Disorder 5 Low Dose: 1 or 3mg COMP360 Phase 1 trial completed and results CURRENT publicly available, Phase 2b trial results High Dose: 22 or 30mg STATUS 0 expected end of 2021 Baseline Assessment 1 Assessment 2 6 months (w0) & 2nd dose (~w14) (~9w) INTELLECTUAL Proprietary formulation of synthetic psilocybin, st 1 Dose PROPERTY COMP360 (~w4) Psilocybin demonstrated efficacy in reducing 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. depressive symptoms in humans in an HIGHLIGHT 1. Griffiths et al., “Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer” (2016) academic, third-party study GRID-HAMD (Depression)
14 OWNERSHIP 50.1% 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Subcutaneous R-ketamine (PCN-101) PRODUCT 1 Mean MADRS over 7 days and median CADSS scores of TRD patients after single IV dose (0.5mg/kg) of R-ketamine (n=7) 40 35 PHARMA- Glutamatergic modulator 30 COLOGY 25 20 Rapid-acting, nonpsychedelic antidepressant PRODUCT 15 with potential for at home use FEATURES 10 5 0 Primary: Treatment Resistant Depression Pre-infusion 60min 120 min 240 min 1 day 3 days 7 days Pre-infusion 40min 120 min 240 min INDICATIONS Potential: Substance Use Disorder PLANNED PCN-101 PHASE 2 TRIAL: Randomized, double blind, placebo-controlled (n=93) Phase 1 trial showed safety and tolerability of R- CURRENT ketamine at doses of up to 150mg, PBO VS. 2 DOSES OF PCN-101 FOLLOW-UP STATUS Phase 2 trial initiation anticipated in mid ‘21 DAY -1 1 2 ~8 ~15 Issued methods of use of R-ketamine for INTELLECTUAL IN-CLINIC treatment of depressive symptoms DOSING PROPERTY 93 patients with TRD: Primary endpoint: 3 cohorts MADRS at 24 hours Third party study: Single IV dose (0.5 mg/kg) of Note: MADRS = Montgomery-Asberg Depression Rate Scale, CADSS = Clinician-administered dissociative states scale, IV = Intravenous, PBO = Placebo. R-ketamine led to a rapid and sustained decrease 1. Leal et al., “Intravenous arketamine for treatment-resistant depression: open-label pilot study” (2020) HIGHLIGHT in MADRS in patients with TRD; dissociation was 1 nearly absent MADRS score14 OWNERSHIP 50.1% 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Subcutaneous R-ketamine (PCN-101) PRODUCT 1 Mean MADRS over 7 days and median CADSS scores of TRD patients after single IV dose (0.5mg/kg) of R-ketamine (n=7) 40 35 PHARMA- Glutamatergic modulator 30 COLOGY 25 20 Rapid-acting, nonpsychedelic antidepressant PRODUCT 15 with potential for at home use FEATURES 10 5 0 Primary: Treatment Resistant Depression Pre-infusion 60min 120 min 240 min 1 day 3 days 7 days Pre-infusion 40min 120 min 240 min INDICATIONS Potential: Substance Use Disorder PLANNED PCN-101 PHASE 2 TRIAL: Randomized, double blind, placebo-controlled (n=93) Phase 1 trial showed safety and tolerability of R- CURRENT ketamine at doses of up to 150mg, PBO VS. 2 DOSES OF PCN-101 FOLLOW-UP STATUS Phase 2 trial initiation anticipated in mid ‘21 DAY -1 1 2 ~8 ~15 Issued methods of use of R-ketamine for INTELLECTUAL IN-CLINIC treatment of depressive symptoms DOSING PROPERTY 93 patients with TRD: Primary endpoint: 3 cohorts MADRS at 24 hours Third party study: Single IV dose (0.5 mg/kg) of Note: MADRS = Montgomery-Asberg Depression Rate Scale, CADSS = Clinician-administered dissociative states scale, IV = Intravenous, PBO = Placebo. R-ketamine led to a rapid and sustained decrease 1. Leal et al., “Intravenous arketamine for treatment-resistant depression: open-label pilot study” (2020) HIGHLIGHT in MADRS in patients with TRD; dissociation was 1 nearly absent MADRS score
15 Lower potential for abuse Superior and more durable Profile of R- vs. S-ketamine S-ketamine 1 2 Forced swim test (third party study) Conditioned place preference score test (third party study) 1 hour 24 hours *** 500 500 *** * * * ** 400 400 240 * * 300 300 180 200 200 120 Ketamine (racemate) 100 100 60 0 0 0 SAL 1 3 10 30 1 3 10 30 SAL 1 3 10 30 1 3 10 30 -100 -100 R-ketamine Saline (RS)-Ketamine Saline 5mg/kg 10mg/kg 20mg/kg (R)-KET (S)-KET (R)-KET (S)-KET -1 -1 -1 -1 (10mg/kg) (mg kg ) (mg kg ) (mg kg ) (mg kg ) (S)-Ketamine R-ketamine lacks the psychotomimetic and abuse potential R-Ketamine < abuse potential 500 of S-ketamine at therapeutic doses in preclinical models. Learned helplessness test 400 *** R-ketamine R-ketamine showed Like S-ketamine, R-ketamine’s mechanism involves increased * 300 40 neuroplasticity through glutamatergic modulation, with outperformed and less potential for abuse in 200 30 potency differences putatively arising from: outlasted S-ketamine mice models, while racemic 100 20 • Different active metabolite profiles in mice; confirmed in and S-ketamine have 0 10 • Different pre- and post-synaptic sites of action multiple other animal significant risk -100 0 Saline 5mg/kg 10mg/kg 20mg/kg SAL 1 5 25 1 5 25 models in different labs • Involvement of different intracellular pathways (S)-KET (R)-KET (R)-Ketamine -1 (mTORC1 vs. ERK) -1 (mg kg ) (mg kg ) 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); 1. Zanos et al., “NDMAR inhibition-independent antidepressant actions of ketamine metabolites” (2016); 2. Yang et al., “R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects” (2015). Escape failures Immobility time (s) CPP Scores CPP Scores CPP Scores15 Lower potential for abuse Superior and more durable Profile of R- vs. S-ketamine S-ketamine 1 2 Forced swim test (third party study) Conditioned place preference score test (third party study) 1 hour 24 hours *** 500 500 *** * * * ** 400 400 240 * * 300 300 180 200 200 120 Ketamine (racemate) 100 100 60 0 0 0 SAL 1 3 10 30 1 3 10 30 SAL 1 3 10 30 1 3 10 30 -100 -100 R-ketamine Saline (RS)-Ketamine Saline 5mg/kg 10mg/kg 20mg/kg (R)-KET (S)-KET (R)-KET (S)-KET -1 -1 -1 -1 (10mg/kg) (mg kg ) (mg kg ) (mg kg ) (mg kg ) (S)-Ketamine R-ketamine lacks the psychotomimetic and abuse potential R-Ketamine < abuse potential 500 of S-ketamine at therapeutic doses in preclinical models. Learned helplessness test 400 *** R-ketamine R-ketamine showed Like S-ketamine, R-ketamine’s mechanism involves increased * 300 40 neuroplasticity through glutamatergic modulation, with outperformed and less potential for abuse in 200 30 potency differences putatively arising from: outlasted S-ketamine mice models, while racemic 100 20 • Different active metabolite profiles in mice; confirmed in and S-ketamine have 0 10 • Different pre- and post-synaptic sites of action multiple other animal significant risk -100 0 Saline 5mg/kg 10mg/kg 20mg/kg SAL 1 5 25 1 5 25 models in different labs • Involvement of different intracellular pathways (S)-KET (R)-KET (R)-Ketamine -1 (mTORC1 vs. ERK) -1 (mg kg ) (mg kg ) 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); 1. Zanos et al., “NDMAR inhibition-independent antidepressant actions of ketamine metabolites” (2016); 2. Yang et al., “R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects” (2015). Escape failures Immobility time (s) CPP Scores CPP Scores CPP Scores
16 100% OWNERSHIP 1 Dimethyltryptamine (DMT) in a buccal PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) transmucosal film (VLS-01), DMT is the active PRODUCT psychedelic moiety in Ayahuasca Double-blind, randomized placebo-controlled trial with Ayahuasca in 29 patients with TRD 45 PHARMA- 5-HT2A-R agonist 40 COLOGY 35 Rapid onset, sustained efficacy after single PRODUCT dose, short duration of psychedelic effect 30 FEATURES (~30 to 45 minutes) 25 Primary: Treatment Resistant Depression INDICATIONS Potential: Eating Disorders, Substance Use 20 Disorders 15 Pre-clinical: Formulation work and safety testing CURRENT in progress; Phase 1 clinical trial anticipated to STATUS initiate in early ’22 10 p<.05 p=.0001 p<.05 5 INTELLECTUAL Filed provisional on formulations of DMT PROPERTY 0 Ayahuasca Placebo Baseline Day 1 Day 2 Day 7 VLS-01 is designed to have an improved HIGHLIGHT duration of psychedelic effect while improving Note: MADRS: Montgomery-Asberg Depression Rate Scale. 1. Palhano-Fontes et al. “Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression”, Psychol Med (2019) tolerability MADRS Score16 100% OWNERSHIP 1 Dimethyltryptamine (DMT) in a buccal PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) transmucosal film (VLS-01), DMT is the active PRODUCT psychedelic moiety in Ayahuasca Double-blind, randomized placebo-controlled trial with Ayahuasca in 29 patients with TRD 45 PHARMA- 5-HT2A-R agonist 40 COLOGY 35 Rapid onset, sustained efficacy after single PRODUCT dose, short duration of psychedelic effect 30 FEATURES (~30 to 45 minutes) 25 Primary: Treatment Resistant Depression INDICATIONS Potential: Eating Disorders, Substance Use 20 Disorders 15 Pre-clinical: Formulation work and safety testing CURRENT in progress; Phase 1 clinical trial anticipated to STATUS initiate in early ’22 10 p<.05 p=.0001 p<.05 5 INTELLECTUAL Filed provisional on formulations of DMT PROPERTY 0 Ayahuasca Placebo Baseline Day 1 Day 2 Day 7 VLS-01 is designed to have an improved HIGHLIGHT duration of psychedelic effect while improving Note: MADRS: Montgomery-Asberg Depression Rate Scale. 1. Palhano-Fontes et al. “Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression”, Psychol Med (2019) tolerability MADRS Score
17 100% OWNERSHIP RLS-01 is a buccal formulation of Salvinorin A 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) (SalA), a naturally occurring psychedelic PRODUCT compound derived from the Salvia divinorum plant Participant ratings on Hallucinogen Rating Scale (HRS) completed 1h after drug administration (n=30) Non-orally bioavailable, non-nitrogenous PHARMA- agonist of the kappa-opioid receptor (KOR), COLOGY no interaction with serotonergic mechanisms Cluster Placebo Active P value Study showed ability of S. divinorum leaf to reach Rapid-acting hallucinogenic compound, Affect 0.75 (0.47) 1.50 (0.58) <0.001* PRODUCT hallucinogenic states of consciousness beyond no wash-out of SSRIs required FEATURES serotonergic mechanisms. Cognition 0.37 (0.41) 1.61 (0.81) <0.001* All six Hallucinogen Rating Scale (HRS) clusters Primary: Treatment Resistant Depression INDICATIONS 2 2 were significantly elevated for participants given Intensity 0.38 (0.76) 3.00 (0.77) <0.001* Potential: Substance Use Disorder, Pain the active S. divinorum leaf. Perception 0.33 (0.36) 1.71 (0.73) <0.001* No significant adverse events were observed or CURRENT Phase 1 clinical trial anticipated to STATUS initiate in mid ’22 reported by the participants. Somaesthesia 0.31 (0.33) 1.27 (0.54) <0.001* Five patients reported positive changes in Volition 0.94 (0.53) 1.85 (0.46) <0.001* INTELLECTUAL relationships with living family members. Filed provisional on formulation of SalA PROPERTY Hallucinogenic experiences demonstrated by all six significantly elevated HRS clusters on an HIGHLIGHT Note: Data are mean ratings with one standard deviation shown in parentheses (*P < 0.05). active dose, and no significant adverse events 1. Addy, “Acute and post-acute behavioral and psychological effects of salvinorin A in humans” (2011) 1 (third party study). 2. Median used instead of mean for nonparametric data17 100% OWNERSHIP RLS-01 is a buccal formulation of Salvinorin A 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) (SalA), a naturally occurring psychedelic PRODUCT compound derived from the Salvia divinorum plant Participant ratings on Hallucinogen Rating Scale (HRS) completed 1h after drug administration (n=30) Non-orally bioavailable, non-nitrogenous PHARMA- agonist of the kappa-opioid receptor (KOR), COLOGY no interaction with serotonergic mechanisms Cluster Placebo Active P value Study showed ability of S. divinorum leaf to reach Rapid-acting hallucinogenic compound, Affect 0.75 (0.47) 1.50 (0.58) <0.001* PRODUCT hallucinogenic states of consciousness beyond no wash-out of SSRIs required FEATURES serotonergic mechanisms. Cognition 0.37 (0.41) 1.61 (0.81) <0.001* All six Hallucinogen Rating Scale (HRS) clusters Primary: Treatment Resistant Depression INDICATIONS 2 2 were significantly elevated for participants given Intensity 0.38 (0.76) 3.00 (0.77) <0.001* Potential: Substance Use Disorder, Pain the active S. divinorum leaf. Perception 0.33 (0.36) 1.71 (0.73) <0.001* No significant adverse events were observed or CURRENT Phase 1 clinical trial anticipated to STATUS initiate in mid ’22 reported by the participants. Somaesthesia 0.31 (0.33) 1.27 (0.54) <0.001* Five patients reported positive changes in Volition 0.94 (0.53) 1.85 (0.46) <0.001* INTELLECTUAL relationships with living family members. Filed provisional on formulation of SalA PROPERTY Hallucinogenic experiences demonstrated by all six significantly elevated HRS clusters on an HIGHLIGHT Note: Data are mean ratings with one standard deviation shown in parentheses (*P < 0.05). active dose, and no significant adverse events 1. Addy, “Acute and post-acute behavioral and psychological effects of salvinorin A in humans” (2011) 1 (third party study). 2. Median used instead of mean for nonparametric data
18 TRD treatments being developed by atai companies Marketed therapies Phase II and III competitors Perception Compass Viridia Revixia J&J Various GH Research Sage / Praxis e.g. Lilly, Pfizer Company SAGE-217, MIJ-821, NRX- Compound COMP360 R-ketamine S-ketamine 5-MeO-DMT DMT Salvinorin A SSRI/SNRI PRAX-114 102, JNJ-5515, AXS-05 Potential for at home use Potential for sustained tbd tbd efficacy Rapid onset of tbd 1 treatment effect NMDA-R / 5-HT1A- and GABA positiv A 5-HT2A-R Glutamatergic 5-HT2A-R KOR NMDA-R SERT / NET Mechanism of mGluR2 e allosteric 5-HT2A- agonist modulator agonist agonist antagonist blockade Action antagonists agonist modulator 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.18 TRD treatments being developed by atai companies Marketed therapies Phase II and III competitors Perception Compass Viridia Revixia J&J Various GH Research Sage / Praxis e.g. Lilly, Pfizer Company SAGE-217, MIJ-821, NRX- Compound COMP360 R-ketamine S-ketamine 5-MeO-DMT DMT Salvinorin A SSRI/SNRI PRAX-114 102, JNJ-5515, AXS-05 Potential for at home use Potential for sustained tbd tbd efficacy Rapid onset of tbd 1 treatment effect NMDA-R / 5-HT1A- and GABA positiv A 5-HT2A-R Glutamatergic 5-HT2A-R KOR NMDA-R SERT / NET Mechanism of mGluR2 e allosteric 5-HT2A- agonist modulator agonist agonist antagonist blockade Action antagonists agonist modulator 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.
19 IB & NB 2 OWNERSHIP 59.5% 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Ibogaine HCl capsules (DMX-1002), ibogaine is a naturally occurring psychedelic compound PRODUCT isolated from a West African shrub, iboga 5 Opioid mediated, cholinergic, glutamatergic PHARMA- 4 and monoaminergic receptor modulator COLOGY Emotionality 3 (negative mood state) A single dose of ibogaine may precipitate a Compulsivity 2 PRODUCT (lack of confidence in ability to quit) rapid withdrawal and long-term abstinence in FEATURES OUD patients Purposefulness 1 (desire of intent to use) Primary: Opioid Use Disorder Expectancy 0 Pre-dose Discharge 1 Month (expected positive benefits of drug use) INDICATIONS Potential: Substance Use Disorder, Post- (N=75) (N=74) (N=37) Traumatic Stress Disorder, Traumatic Brain Injury ONGOING PHASE 1/2 TRIAL CURRENT Stage 1: Maximum Tolerated Dose Stage 2: Proof of Concept Phase 1/2 trial to initiate in mid ‘21 STATUS TREATMENT (MULTIPLE DOSES) SAFETY/PK TREATMENT VS PCB SAFETY/EFFICACY Objective: Subject cohort: Patient cohort: Endpoints: Pending method of treatment claims for OUD for INTELLECTUAL Dose finding Recreational opioid users Opioid dependent patients Acute withdrawal, ibogaine, issued method of treatment claims for PROPERTY (up to 30 subjects) (approximately 80 subjects) abstinence over 90 days 3 OUD patients on methadone for noribogaine Potential sustained reduction in opioid craving Note: HCQN = Heroin Craving Questionnaire, PTSD = Post-traumatic stress disorder, OUD = Opioid use disorder, PCB = Placebo, PK = Pharmacokinetics. HIGHLIGHT 1. Mash et al., “Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Obse rvations and Treatment Outcomes” (2018) with DMX-1002 single administration 2. 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 t o 57.1% 3. Noribogaine Intellectual property resides in DemeRx NB HCQN Subscale19 IB & NB 2 OWNERSHIP 59.5% 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Ibogaine HCl capsules (DMX-1002), ibogaine is a naturally occurring psychedelic compound PRODUCT isolated from a West African shrub, iboga 5 Opioid mediated, cholinergic, glutamatergic PHARMA- 4 and monoaminergic receptor modulator COLOGY Emotionality 3 (negative mood state) A single dose of ibogaine may precipitate a Compulsivity 2 PRODUCT (lack of confidence in ability to quit) rapid withdrawal and long-term abstinence in FEATURES OUD patients Purposefulness 1 (desire of intent to use) Primary: Opioid Use Disorder Expectancy 0 Pre-dose Discharge 1 Month (expected positive benefits of drug use) INDICATIONS Potential: Substance Use Disorder, Post- (N=75) (N=74) (N=37) Traumatic Stress Disorder, Traumatic Brain Injury ONGOING PHASE 1/2 TRIAL CURRENT Stage 1: Maximum Tolerated Dose Stage 2: Proof of Concept Phase 1/2 trial to initiate in mid ‘21 STATUS TREATMENT (MULTIPLE DOSES) SAFETY/PK TREATMENT VS PCB SAFETY/EFFICACY Objective: Subject cohort: Patient cohort: Endpoints: Pending method of treatment claims for OUD for INTELLECTUAL Dose finding Recreational opioid users Opioid dependent patients Acute withdrawal, ibogaine, issued method of treatment claims for PROPERTY (up to 30 subjects) (approximately 80 subjects) abstinence over 90 days 3 OUD patients on methadone for noribogaine Potential sustained reduction in opioid craving Note: HCQN = Heroin Craving Questionnaire, PTSD = Post-traumatic stress disorder, OUD = Opioid use disorder, PCB = Placebo, PK = Pharmacokinetics. HIGHLIGHT 1. Mash et al., “Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Obse rvations and Treatment Outcomes” (2018) with DMX-1002 single administration 2. 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 t o 57.1% 3. Noribogaine Intellectual property resides in DemeRx NB HCQN Subscale
20 OWNERSHIP 51.9% PRIOR EVIDENCE IN HUMANS (2R, 3S)-2-amino-3-hydroxy-3-pyridin-4-yl-1- pyrrolidin-1-yl-propan-1-one(L)-(+) tartrate salt PRODUCT oral capsules (RL-007) 1 2 Verbal learning Verbal delayed recall 0.35 0.4 p<0.05 ** p<0.05 ** ** 0.30 0.3 Cholinergic, glutamatergic and PHARMA- GABA-B receptor modulator 0.25 0.2 COLOGY 0.20 0.1 No drug-related serious adverse events in over 0 0.15 500 study subject exposures, pro-cognitive PRODUCT -0.1 0.10 effects demonstrated in two Phase 1 and one FEATURES Phase 2 trials -0.2 0.05 -0.3 0 Pregabalin FSV7-007 FSV7-007 Primary: Cognitive Impairment Associated with Pregabalin FSV7-007 FSV7-007 (40 or 80 mg TID) (150 or 300 mg TID) (40 or 80 mg TID) (150 or 300 mg TID) (50-100mg TID) (50-100mg TID) INDICATIONS Schizophrenia Potential: Autism, Alzheimer’s dementia ONGOING PHASE 2 TRIAL: Single-arm, single-blind dose-ranging clinical trial CURRENT Phase 2a trial initiated in H1’21 STATUS (5-7 COHORTS) RL-007 TID FOLLOW-UP INTELLECTUAL DAY -1 1 2 3 4 8 Issued composition of matter patent PROPERTY Secondary endpoint: Primary endpoint: Up to 56 Schizophrenia EEG-based biomarkers of Safety and tolerability patients cognition Previous Phase 2 showed pro-cognitive 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 HIGHLIGHT potential of RL-007 in 180 patients with 1. Verbal learning was assessed by the International Shopping List Task (ISLT) 2. Verbal delayed recall was assessed by ISLT with a delayed recall, as a parameter for short-term memory diabetic peripheral neuropathic pain Diff vs. Placebo (ISLT) Diff vs. Placebo (ISLT)20 OWNERSHIP 51.9% PRIOR EVIDENCE IN HUMANS (2R, 3S)-2-amino-3-hydroxy-3-pyridin-4-yl-1- pyrrolidin-1-yl-propan-1-one(L)-(+) tartrate salt PRODUCT oral capsules (RL-007) 1 2 Verbal learning Verbal delayed recall 0.35 0.4 p<0.05 ** p<0.05 ** ** 0.30 0.3 Cholinergic, glutamatergic and PHARMA- GABA-B receptor modulator 0.25 0.2 COLOGY 0.20 0.1 No drug-related serious adverse events in over 0 0.15 500 study subject exposures, pro-cognitive PRODUCT -0.1 0.10 effects demonstrated in two Phase 1 and one FEATURES Phase 2 trials -0.2 0.05 -0.3 0 Pregabalin FSV7-007 FSV7-007 Primary: Cognitive Impairment Associated with Pregabalin FSV7-007 FSV7-007 (40 or 80 mg TID) (150 or 300 mg TID) (40 or 80 mg TID) (150 or 300 mg TID) (50-100mg TID) (50-100mg TID) INDICATIONS Schizophrenia Potential: Autism, Alzheimer’s dementia ONGOING PHASE 2 TRIAL: Single-arm, single-blind dose-ranging clinical trial CURRENT Phase 2a trial initiated in H1’21 STATUS (5-7 COHORTS) RL-007 TID FOLLOW-UP INTELLECTUAL DAY -1 1 2 3 4 8 Issued composition of matter patent PROPERTY Secondary endpoint: Primary endpoint: Up to 56 Schizophrenia EEG-based biomarkers of Safety and tolerability patients cognition Previous Phase 2 showed pro-cognitive 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 HIGHLIGHT potential of RL-007 in 180 patients with 1. Verbal learning was assessed by the International Shopping List Task (ISLT) 2. Verbal delayed recall was assessed by ISLT with a delayed recall, as a parameter for short-term memory diabetic peripheral neuropathic pain Diff vs. Placebo (ISLT) Diff vs. Placebo (ISLT)
21 OWNERSHIP 53.8% 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Deuterated etifoxine HCl oral dosage form PRODUCT (GRX-917) Etifoxine works as rapidly as lorazepam, Non Inferiority Test Etifoxine facilitates endogenous production of with etifoxine continuing its effects beyond 30 neurosteroids like allopregnanolone through PHARMA- P=0.0001 25 treatment, while lorazepam shows rebound agonist activity at the mitochondrial COLOGY P=0.0002 20 translocator protein (TSPO) 15 GRX-917 is designed to have rapid onset activity 10 Etifoxine of anxiolytic activity like benzodiazepines but PRODUCT 5 Etifoxine has a strong safety record: a review without the sedating, addicting, or cognitive FEATURES Lorazepam 0 of over 14m prescriptions in France found no impairing properties Day 0 Day 7 Day 28 Day 35 2 cases of abuse, misuse or dependence Under treatment Safety Primary: Generalized Anxiety Disorder INDICATIONS Potential: Social Anxiety Disorder, Postpartum Depression ONGOING PHASE 1 TRIAL CURRENT Phase 1 trial initiated in H1’21 Part 1: Single Ascending Dose Part 2: Multiple Ascending Dose STATUS TREATMENT SAFETY/PK/PD TREATMENT SAFETY/PK/PD Issued composition of matter on deuterated INTELLECTUAL Up to 40 healthy subjects: Up to 36 healthy subjects: PD Endpoint: PD Endpoint: etifoxine (GRX-917) and corresponding Up to 5 cohorts PROPERTY Up to 3 cohorts qEEG qEEG methods of use GRX-917 is aimed to be an improved version of Note: HAM-A = Hamilton Anxiety Rating Scale, SD = standard deviation, qEEG = Quantitative electroencephalography, PK = Pharmacokinetics. PD = Pharmacodynamics. HIGHLIGHT Etifoxine, which already showed promising 1. Nguyen et al., “Efficacy of etifoxine compared to lorazepam monotherapy” (2006) 2. Cottin et al., “Safety profile of etifoxine: A French pharmacovigilance survey” (2016) results Ham-A total score21 OWNERSHIP 53.8% 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) Deuterated etifoxine HCl oral dosage form PRODUCT (GRX-917) Etifoxine works as rapidly as lorazepam, Non Inferiority Test Etifoxine facilitates endogenous production of with etifoxine continuing its effects beyond 30 neurosteroids like allopregnanolone through PHARMA- P=0.0001 25 treatment, while lorazepam shows rebound agonist activity at the mitochondrial COLOGY P=0.0002 20 translocator protein (TSPO) 15 GRX-917 is designed to have rapid onset activity 10 Etifoxine of anxiolytic activity like benzodiazepines but PRODUCT 5 Etifoxine has a strong safety record: a review without the sedating, addicting, or cognitive FEATURES Lorazepam 0 of over 14m prescriptions in France found no impairing properties Day 0 Day 7 Day 28 Day 35 2 cases of abuse, misuse or dependence Under treatment Safety Primary: Generalized Anxiety Disorder INDICATIONS Potential: Social Anxiety Disorder, Postpartum Depression ONGOING PHASE 1 TRIAL CURRENT Phase 1 trial initiated in H1’21 Part 1: Single Ascending Dose Part 2: Multiple Ascending Dose STATUS TREATMENT SAFETY/PK/PD TREATMENT SAFETY/PK/PD Issued composition of matter on deuterated INTELLECTUAL Up to 40 healthy subjects: Up to 36 healthy subjects: PD Endpoint: PD Endpoint: etifoxine (GRX-917) and corresponding Up to 5 cohorts PROPERTY Up to 3 cohorts qEEG qEEG methods of use GRX-917 is aimed to be an improved version of Note: HAM-A = Hamilton Anxiety Rating Scale, SD = standard deviation, qEEG = Quantitative electroencephalography, PK = Pharmacokinetics. PD = Pharmacodynamics. HIGHLIGHT Etifoxine, which already showed promising 1. Nguyen et al., “Efficacy of etifoxine compared to lorazepam monotherapy” (2006) 2. Cottin et al., “Safety profile of etifoxine: A French pharmacovigilance survey” (2016) results Ham-A total score
22 56.5% OWNERSHIP 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY AND NEURONASAL PILOT) Intranasal N-acetylcysteine (NN-101) PRODUCT NN-101 pilot Treatment of 81 mTBI patients with NAC (24h post blast) increased probability of symptom resolution by ~2x (OR = 3.60, p = 0.0062 overall) NN-101 was observed to be ~20x and A: Placebo B: Early oral NAC N-acetylcysteine (NAC) stimulates glutathione ~100x more brain-penetrant PHARMA- 30 30 compared to IV and oral NAC production thus reducing oxidative damage COLOGY respectively 20 20 Direct-to-brain intranasal administration showed to increase concentrations in the brain PRODUCT 10 10 and reduce side effects associated with very FEATURES high doses of oral or IV NAC 0 0 None 1 2 3 4 5 None 1 2 3 4 5 Number of symptoms after 7 days Number of symptoms after 7 days Primary: mild Traumatic Brain Injury INDICATIONS Potential: Parkinson’s Disease PLANNED PHASE 1 TRIAL: Single-site, 4-part clinical trial Pilot study completed in H2’20, CURRENT Phase 1 trial anticipated to initiate in mid ’21 STATUS RANDOMIZED OPEN LABEL FORMULATION COMPARISON ESCALATING DOSE REPEAT DOSING INTELLECTUAL Pending patent on methods of use of NAC for Objective: Subject cohort: Primary endpoints: Identify optimized drug and device PROPERTY Healthy volunteers Brain bioavailability, safety, tolerability treating post-concussion syndrome Improved brain-penetration of NN-101 and Note: HAM-A = Hamilton Anxiety Rating Scale.. HIGHLIGHT 1. Hoffer et al., “Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetylcysteine: a double-blind, placebo-controlled study” (2013) NAC effect in early mTBI Count of patients Count of patients22 56.5% OWNERSHIP 1 PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY AND NEURONASAL PILOT) Intranasal N-acetylcysteine (NN-101) PRODUCT NN-101 pilot Treatment of 81 mTBI patients with NAC (24h post blast) increased probability of symptom resolution by ~2x (OR = 3.60, p = 0.0062 overall) NN-101 was observed to be ~20x and A: Placebo B: Early oral NAC N-acetylcysteine (NAC) stimulates glutathione ~100x more brain-penetrant PHARMA- 30 30 compared to IV and oral NAC production thus reducing oxidative damage COLOGY respectively 20 20 Direct-to-brain intranasal administration showed to increase concentrations in the brain PRODUCT 10 10 and reduce side effects associated with very FEATURES high doses of oral or IV NAC 0 0 None 1 2 3 4 5 None 1 2 3 4 5 Number of symptoms after 7 days Number of symptoms after 7 days Primary: mild Traumatic Brain Injury INDICATIONS Potential: Parkinson’s Disease PLANNED PHASE 1 TRIAL: Single-site, 4-part clinical trial Pilot study completed in H2’20, CURRENT Phase 1 trial anticipated to initiate in mid ’21 STATUS RANDOMIZED OPEN LABEL FORMULATION COMPARISON ESCALATING DOSE REPEAT DOSING INTELLECTUAL Pending patent on methods of use of NAC for Objective: Subject cohort: Primary endpoints: Identify optimized drug and device PROPERTY Healthy volunteers Brain bioavailability, safety, tolerability treating post-concussion syndrome Improved brain-penetration of NN-101 and Note: HAM-A = Hamilton Anxiety Rating Scale.. HIGHLIGHT 1. Hoffer et al., “Amelioration of acute sequelae of blast induced mild traumatic brain injury by N-acetylcysteine: a double-blind, placebo-controlled study” (2013) NAC effect in early mTBI Count of patients Count of patients
23 100% OWNERSHIP 1 EMP-01 is an oral formulation of an MDMA PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) derivative being developed for the PRODUCT treatment of PTSD MDMA-assisted therapy significantly reduced CAPS-V scores in PTSD patients (primary endpoint), (n=90) 50 A monoamine releaser and reuptake inhibitor PHARMA- with prominent effects on serotonin (5-HT) COLOGY 40 An entactogen; a compound class that increases feelings of empathy and closeness-- PRODUCT with a potentially improved cardiovascular FEATURES profile compared to MDMA 30 Primary: Post-traumatic Stress Disorder INDICATIONS Potential: General Anxiety Disorder 20 CURRENT Phase 1 trial anticipated to initiate in mid ’22 STATUS 10 MDMA-assisted therapy Placebo with therapy INTELLECTUAL Filed provisional on formulation, combination 0 PROPERTY approach Baseline (T1) After session 1 After session 2 After session 3 (T4), (T2) (T3) primary endpoint EMP-01 is aimed to be an improved version of MDMA to treat PTSD symptoms, through an 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 HIGHLIGHT outcome. Primary analysis was completed using least square means from a mixed model repeated measure (MMRM) analysis model; (n=90) improved cardiovascular profile and potential Mitchell et al., “MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study” (2021) digital therapeutic support CAPS-5 total severity score23 100% OWNERSHIP 1 EMP-01 is an oral formulation of an MDMA PRIOR EVIDENCE IN HUMANS (THIRD PARTY STUDY ) derivative being developed for the PRODUCT treatment of PTSD MDMA-assisted therapy significantly reduced CAPS-V scores in PTSD patients (primary endpoint), (n=90) 50 A monoamine releaser and reuptake inhibitor PHARMA- with prominent effects on serotonin (5-HT) COLOGY 40 An entactogen; a compound class that increases feelings of empathy and closeness-- PRODUCT with a potentially improved cardiovascular FEATURES profile compared to MDMA 30 Primary: Post-traumatic Stress Disorder INDICATIONS Potential: General Anxiety Disorder 20 CURRENT Phase 1 trial anticipated to initiate in mid ’22 STATUS 10 MDMA-assisted therapy Placebo with therapy INTELLECTUAL Filed provisional on formulation, combination 0 PROPERTY approach Baseline (T1) After session 1 After session 2 After session 3 (T4), (T2) (T3) primary endpoint EMP-01 is aimed to be an improved version of MDMA to treat PTSD symptoms, through an 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 HIGHLIGHT outcome. Primary analysis was completed using least square means from a mixed model repeated measure (MMRM) analysis model; (n=90) improved cardiovascular profile and potential Mitchell et al., “MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study” (2021) digital therapeutic support CAPS-5 total severity score
24 Pear Tx created a precedent Positive regulatory sentiment atai’s opportunity reSET-O © from Pear Therapeutics is FDA is supporting and stimulating Aimed at improved therapeutic 1 the first prescription digital therapeutic Digital Health initiatives : outcomes that obtained FDA approval for treatment of patients with OUD (2018) Regulatory exclusivity possible through development of combination product (i.e., digital app + drug) Combination also provides opportunity for IP scope expansion 1. FDA, “Digital Health Innovation Action Plan” (2018)24 Pear Tx created a precedent Positive regulatory sentiment atai’s opportunity reSET-O © from Pear Therapeutics is FDA is supporting and stimulating Aimed at improved therapeutic 1 the first prescription digital therapeutic Digital Health initiatives : outcomes that obtained FDA approval for treatment of patients with OUD (2018) Regulatory exclusivity possible through development of combination product (i.e., digital app + drug) Combination also provides opportunity for IP scope expansion 1. FDA, “Digital Health Innovation Action Plan” (2018)
25 Anticipated Milestones next 18 months Recent Milestones KUR-101 Phase 1 results Recognify started Phase 2a study in CIAS with RL-007 PCN-101 Phase 2a FSI DMX-1002 Phase 1/2 FSI EMP-01 Phase 1 results Perception closed licensing deal with Otsuka for Japan VLS-01 Phase 1 results atai entered strategic partnership with IntelGenx PCN-101 (SQ vs. IV BA) results DemeRx received approval to start DMX-1002 Phase 1/2 in UK IntroSpect app deployment 2021 NN-101 Phase 1 FSI EntheogeniX lead candidate atai announced successful closing of Series D, raising $157m RL-007 Phase 2a results Psyber prototype deployment PCN-101 Phase 2a results Perception announced positive Phase 1 results with PCN-101 InnarisBio pilot Phase 1 results Empath partnered with Bionomics on PTSD drug development DMX-1002 Phase 1 results atai acquired majority stake in Recognify to develop RL-007 for CIAS GRX-917 Phase 1 results NN-101 Phase 1 results Launch of Revixia Life Sciences to develop RLS-01 RL-007 Phase 2b FSI COMPASS successfully IPO-ed on NASDAQ GRX-917 Phase 2 FSI atai launched EmpathBio to develop EMP-01 for PTSD atai launched Introspect to develop Digital Therapeutics Notes: FSI = First subject in, SQ = Subcutaneous, IV = Intravenous, BA = Bioavailability25 Anticipated Milestones next 18 months Recent Milestones KUR-101 Phase 1 results Recognify started Phase 2a study in CIAS with RL-007 PCN-101 Phase 2a FSI DMX-1002 Phase 1/2 FSI EMP-01 Phase 1 results Perception closed licensing deal with Otsuka for Japan VLS-01 Phase 1 results atai entered strategic partnership with IntelGenx PCN-101 (SQ vs. IV BA) results DemeRx received approval to start DMX-1002 Phase 1/2 in UK IntroSpect app deployment 2021 NN-101 Phase 1 FSI EntheogeniX lead candidate atai announced successful closing of Series D, raising $157m RL-007 Phase 2a results Psyber prototype deployment PCN-101 Phase 2a results Perception announced positive Phase 1 results with PCN-101 InnarisBio pilot Phase 1 results Empath partnered with Bionomics on PTSD drug development DMX-1002 Phase 1 results atai acquired majority stake in Recognify to develop RL-007 for CIAS GRX-917 Phase 1 results NN-101 Phase 1 results Launch of Revixia Life Sciences to develop RLS-01 RL-007 Phase 2b FSI COMPASS successfully IPO-ed on NASDAQ GRX-917 Phase 2 FSI atai launched EmpathBio to develop EMP-01 for PTSD atai launched Introspect to develop Digital Therapeutics Notes: FSI = First subject in, SQ = Subcutaneous, IV = Intravenous, BA = Bioavailability
ATAI Life Sciences N.V. (NASDAQ: ATAI) Issuer (ticker) Market (1) ~$2.8B capitalization Outstanding 154.8M shares (2) Cash & cash • ~$449M cash & cash equivalents as of March 31, 2021 equivalents • In the second quarter of 2021, atai successfully completed an IPO and raised total gross proceeds of ~$258.8M (including the underwriters’ allotment) • atai is well financed to fund planned operations through 2023 (1) As of June 9, 2021 (2) After giving effect to our Series D and IPO financings.ATAI Life Sciences N.V. (NASDAQ: ATAI) Issuer (ticker) Market (1) ~$2.8B capitalization Outstanding 154.8M shares (2) Cash & cash • ~$449M cash & cash equivalents as of March 31, 2021 equivalents • In the second quarter of 2021, atai successfully completed an IPO and raised total gross proceeds of ~$258.8M (including the underwriters’ allotment) • atai is well financed to fund planned operations through 2023 (1) As of June 9, 2021 (2) After giving effect to our Series D and IPO financings.
Investor Contact: Greg Weaver Chief Financial Officer Email: greg.weaver@atai.lifeInvestor Contact: Greg Weaver Chief Financial Officer Email: greg.weaver@atai.life
27 ATAI PLATFORM INDICATION DEEP DIVES: • Overview • Depression • CIAS • SUD • Anxiety • mTBI • MoA27 ATAI PLATFORM INDICATION DEEP DIVES: • Overview • Depression • CIAS • SUD • Anxiety • mTBI • MoA
28 Process People Enabling Technologies28 Process People Enabling Technologies
29 Enabling Technologies People Process Small teams with entrepreneurial Disciplined selection criteria Digital Therapeutics autonomy develop our compounds (including prior evidence in humans) Operational involvement of Impactful capital allocation to Formulation and biomarkers interdisciplinary atai team acquired and incubated companies Strategic value capture and Access to experienced group of AI-enabled drug discovery high degree of optionality strategic advisors and KOLs29 Enabling Technologies People Process Small teams with entrepreneurial Disciplined selection criteria Digital Therapeutics autonomy develop our compounds (including prior evidence in humans) Operational involvement of Impactful capital allocation to Formulation and biomarkers interdisciplinary atai team acquired and incubated companies Strategic value capture and Access to experienced group of AI-enabled drug discovery high degree of optionality strategic advisors and KOLs
30 Disciplined New Optionality and Capital Allocation and Program Selection Strategic Value Capture Decentralized Operations Prior evidence in humans to Small teams with entrepreneurial Internal Development increase probability of success autonomy develop our drugs Access to milestone-based funding, Differentiated treatment effect Strategic Partnerships shared services and enabling tech to address unmet patient needs Significant commercial potential Economies of scope and cross- IPO and complementary to drug fertilization across our development candidates already in pipeline programs30 Disciplined New Optionality and Capital Allocation and Program Selection Strategic Value Capture Decentralized Operations Prior evidence in humans to Small teams with entrepreneurial Internal Development increase probability of success autonomy develop our drugs Access to milestone-based funding, Differentiated treatment effect Strategic Partnerships shared services and enabling tech to address unmet patient needs Significant commercial potential Economies of scope and cross- IPO and complementary to drug fertilization across our development candidates already in pipeline programs
31 Successful IPO 2 Sept 2020: Market Cap : IPO USD USD 1.5bn atai as lead investor 146.6m Apr 2020: Post money Series B valuation: USD 80m GBP 325m atai as lead investor NOW Sept 2018: Post money Series A valuation: 1 atai as co-investor GBP 27m GBP 77m 2020 Aug 2017: Post money Seed round valuation: GBP 3m GBP 15m 2019 2018 Dec 2019: Positive Phase 1 2017 results Oct 2018: Breakthrough designation 1. atai co-founder, Christian Angermayer (though his family office, Apeiron) was initial investor into Compass which shareholding w as contributed to atai upon atai's incorporation 2. Market Cap as of July 9, 202131 Successful IPO 2 Sept 2020: Market Cap : IPO USD USD 1.5bn atai as lead investor 146.6m Apr 2020: Post money Series B valuation: USD 80m GBP 325m atai as lead investor NOW Sept 2018: Post money Series A valuation: 1 atai as co-investor GBP 27m GBP 77m 2020 Aug 2017: Post money Seed round valuation: GBP 3m GBP 15m 2019 2018 Dec 2019: Positive Phase 1 2017 results Oct 2018: Breakthrough designation 1. atai co-founder, Christian Angermayer (though his family office, Apeiron) was initial investor into Compass which shareholding w as contributed to atai upon atai's incorporation 2. Market Cap as of July 9, 2021
32 Greg Bates Carrie Bowen, PhD Glenn Short, PhD Anne Johnson Ryan Barrett Anna Richardson VP, Regulatory Affairs Director, Neuroscience VP, Early Development VP, Global Controller GC & Lead of Chief of Staff, Director Corporate Development Stakeholder Engagement Georgina Kilfoil, PMP Majed Fawaz, PhD Roman Dahl David Keene Danny Talati Edmund Neuhaus, PhD VP, Clinical Operations VP, CMC VP, Operations & VP, Digital Therapeutics Director, Business Senior Director, Innovation Development Psychology Arvind Tewari Paul Simboli Galyna Pidpruzhnykova, PhD Sarah McEwen, PhD Frank Stegert Kasia Frankfort VP, Digital Strategy and Director, IP Counsel Director, Innovation Strategy Director, Clinical Science VP, Operations and VP, FP&A Operations Investment Alan Schatzberg, MD John Krystal, MD Frank Sasinowski Amir Kalali, MD Barbara Duncan Scientific Advisor Scientific Advisor Regulatory Advisor Business Advisor Business Advisor COMPASS and GABA Terence A. Kelly, PhD Ian Massey, DPhil Deborah Mash, PhD Tom Bradshaw Matthew Pando, PhD Atul Pande, MD CEO Perception CEO GABA CEO DemeRx CEO Neuronasal CEO Recognify Director Perception Neuroscience Therapeutics Neuroscience Professionals in FTEs / consultants Core atai team IND applications NDAs through regulatory approval atai core team across atai’s companies collectively led32 Greg Bates Carrie Bowen, PhD Glenn Short, PhD Anne Johnson Ryan Barrett Anna Richardson VP, Regulatory Affairs Director, Neuroscience VP, Early Development VP, Global Controller GC & Lead of Chief of Staff, Director Corporate Development Stakeholder Engagement Georgina Kilfoil, PMP Majed Fawaz, PhD Roman Dahl David Keene Danny Talati Edmund Neuhaus, PhD VP, Clinical Operations VP, CMC VP, Operations & VP, Digital Therapeutics Director, Business Senior Director, Innovation Development Psychology Arvind Tewari Paul Simboli Galyna Pidpruzhnykova, PhD Sarah McEwen, PhD Frank Stegert Kasia Frankfort VP, Digital Strategy and Director, IP Counsel Director, Innovation Strategy Director, Clinical Science VP, Operations and VP, FP&A Operations Investment Alan Schatzberg, MD John Krystal, MD Frank Sasinowski Amir Kalali, MD Barbara Duncan Scientific Advisor Scientific Advisor Regulatory Advisor Business Advisor Business Advisor COMPASS and GABA Terence A. Kelly, PhD Ian Massey, DPhil Deborah Mash, PhD Tom Bradshaw Matthew Pando, PhD Atul Pande, MD CEO Perception CEO GABA CEO DemeRx CEO Neuronasal CEO Recognify Director Perception Neuroscience Therapeutics Neuroscience Professionals in FTEs / consultants Core atai team IND applications NDAs through regulatory approval atai core team across atai’s companies collectively led
33 Formulation & Digital AI Enabled Therapeutics BiomarkerStratification Drug Discovery PsyProtix Metabolomics based biomarker approach Wholly owned digital therapeutics platform Joint venture with Cyclica, with to develop precision psychiatry dedicated to providing more comprehensive, atai currently owning 80% personalized care management with potential InnarisBio AI-enabled computational biophysics to secure stronger IP protection Joint venture with Uniquest to advance platform designed to optimize and accelerate direct-to-brain drug delivery technology drug discovery Potential to be a product engine for Utilizes digital combination tools to atai supporting the next generation of empower atai’s programs, such as remote Partnership with IntelGenx to develop novel programs monitoring and remote counseling Innovative transmucosal formulations33 Formulation & Digital AI Enabled Therapeutics BiomarkerStratification Drug Discovery PsyProtix Metabolomics based biomarker approach Wholly owned digital therapeutics platform Joint venture with Cyclica, with to develop precision psychiatry dedicated to providing more comprehensive, atai currently owning 80% personalized care management with potential InnarisBio AI-enabled computational biophysics to secure stronger IP protection Joint venture with Uniquest to advance platform designed to optimize and accelerate direct-to-brain drug delivery technology drug discovery Potential to be a product engine for Utilizes digital combination tools to atai supporting the next generation of empower atai’s programs, such as remote Partnership with IntelGenx to develop novel programs monitoring and remote counseling Innovative transmucosal formulations
34 Therapeutic area focus Traditional Decentralized development development (pipeline) (platform) Therapeutic area agnostic34 Therapeutic area focus Traditional Decentralized development development (pipeline) (platform) Therapeutic area agnostic
36 Patients with Patients with Anxiety Patients with Patients with Patients with TBI 1 2 5 Depression (global) Cognitive Impairment Substance Use (US) Disorders (US) 4 Associated with Disorder (US) 3 Schizophrenia (global) ~33% of patients are resistant No pharmacological ~75% of patients relapse No pharmacological Current treatments have slow to front line treatments treatments approved for CIAS within one year of treatment treatments approved for mild onset (4- 12 weeks) or side effects including sedation TBI 1. World Health Organization (2020) 4. SAMSHA - National Survey on Drug Use and Health (2017) 2. Anxiety and Depression Association of America (2020) 5. Georges et al, “Traumatic Brain Injury”, NCBI (2020) 3. Using CSCI Criterion; Reichenberg et al., “Neuropsychological Function and Dysfunction in Schizophrenia and Psychotic Affecti ve Disorders” (2009)36 Patients with Patients with Anxiety Patients with Patients with Patients with TBI 1 2 5 Depression (global) Cognitive Impairment Substance Use (US) Disorders (US) 4 Associated with Disorder (US) 3 Schizophrenia (global) ~33% of patients are resistant No pharmacological ~75% of patients relapse No pharmacological Current treatments have slow to front line treatments treatments approved for CIAS within one year of treatment treatments approved for mild onset (4- 12 weeks) or side effects including sedation TBI 1. World Health Organization (2020) 4. SAMSHA - National Survey on Drug Use and Health (2017) 2. Anxiety and Depression Association of America (2020) 5. Georges et al, “Traumatic Brain Injury”, NCBI (2020) 3. Using CSCI Criterion; Reichenberg et al., “Neuropsychological Function and Dysfunction in Schizophrenia and Psychotic Affecti ve Disorders” (2009)
37 Drug & Digital Combo Robust Specialty New Chemical Therapeutics Pharma IP Strategy Entity Engine Exclusivity Strategy Strategic Pursuit of Differential Restrictive Extensions of De-scheduling Covenants Patent Scope Leading IP and Regulatory Advisors37 Drug & Digital Combo Robust Specialty New Chemical Therapeutics Pharma IP Strategy Entity Engine Exclusivity Strategy Strategic Pursuit of Differential Restrictive Extensions of De-scheduling Covenants Patent Scope Leading IP and Regulatory Advisors
38 Additional DEA process for Typical new drug application process schedule 1 Phase 1 Phase 2 Phase 3 NDA review process, takes • FDA Review Scheduling approx. 4 months Parallel review of NDA recommendation from • 6-10 months documentation package FDA Successful Review down-scheduling NDA review Change in Federal register recommendation precedents • 90 days • 30 days include GHB and THC Brand name Xyrem Marinol (Dronabinol) Sodium oxybate THC (delta-9-tetrahydrocannabinol in sesame oil) Compound (sodium salt of GHB*) Indication Narcolepsy Chemotherapy-induced nausea 2002 1985 Launch Source: FDA website * GHB = y-hydroxybutyric acid38 Additional DEA process for Typical new drug application process schedule 1 Phase 1 Phase 2 Phase 3 NDA review process, takes • FDA Review Scheduling approx. 4 months Parallel review of NDA recommendation from • 6-10 months documentation package FDA Successful Review down-scheduling NDA review Change in Federal register recommendation precedents • 90 days • 30 days include GHB and THC Brand name Xyrem Marinol (Dronabinol) Sodium oxybate THC (delta-9-tetrahydrocannabinol in sesame oil) Compound (sodium salt of GHB*) Indication Narcolepsy Chemotherapy-induced nausea 2002 1985 Launch Source: FDA website * GHB = y-hydroxybutyric acid
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40 Opportunity Overview Treatment resistant depression (TRD) is diagnosed after two failed courses of antidepressants. Treatment First onset Persistent resistant depression depression depression (MDD) (MDD) (TRD) 5 Global sufferers of Likelihood of relapse Global TRD patients 3 4 depression from current SoC Treatment options for TRD Antidepressants 1 Augmentation therapy S-ketamine Approved drugs for TRD Relative market opportunity 2 (Spravato, Symbyax) (antidepressant sales by Somatic therapy 6 2025) High-intensity psychological interventions 1. Includes mood stabilizers, atypical antipsychotics, and esketamine. 4. Hasler et al., Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose effect study (2004) 2. Includes rTMS (repetitive transcranial magnetic stimulation), tDCS (transcranial direct current stimulation), ECT (electroconvulsive therapy), and DBS (deep-brain stimulation). 5. Pandarakalam, 2018; Sussman et al., 2018; Gaynes et al., 2019 3. World Health Organization (2020) 6. Evaluate Pharma (as of 19.03.2021)40 Opportunity Overview Treatment resistant depression (TRD) is diagnosed after two failed courses of antidepressants. Treatment First onset Persistent resistant depression depression depression (MDD) (MDD) (TRD) 5 Global sufferers of Likelihood of relapse Global TRD patients 3 4 depression from current SoC Treatment options for TRD Antidepressants 1 Augmentation therapy S-ketamine Approved drugs for TRD Relative market opportunity 2 (Spravato, Symbyax) (antidepressant sales by Somatic therapy 6 2025) High-intensity psychological interventions 1. Includes mood stabilizers, atypical antipsychotics, and esketamine. 4. Hasler et al., Acute psychological and physiological effects of psilocybin in healthy humans: a double-blind, placebo-controlled dose effect study (2004) 2. Includes rTMS (repetitive transcranial magnetic stimulation), tDCS (transcranial direct current stimulation), ECT (electroconvulsive therapy), and DBS (deep-brain stimulation). 5. Pandarakalam, 2018; Sussman et al., 2018; Gaynes et al., 2019 3. World Health Organization (2020) 6. Evaluate Pharma (as of 19.03.2021)
41 Depression Company Compound COMP360 DMT R-ketamine Salvinorin A Indication TRD TRD TRD TRD 5-HT2A-R 5-HT2A-R Glutamatergic Kappa opioid MoA Target / Drug Class agonist agonist modulator agonist Potential for at home use Concomitant SSRI therapy In-clinic duration 6-8 hours ~2 hours N/A ~2 hours S-ketamine/ S-ketamine/ Distribution channels New clinics infrastructure Pharmacies psilocybin clinics psilocybin clinics Convenience Population Commercial / Use / Drug class41 Depression Company Compound COMP360 DMT R-ketamine Salvinorin A Indication TRD TRD TRD TRD 5-HT2A-R 5-HT2A-R Glutamatergic Kappa opioid MoA Target / Drug Class agonist agonist modulator agonist Potential for at home use Concomitant SSRI therapy In-clinic duration 6-8 hours ~2 hours N/A ~2 hours S-ketamine/ S-ketamine/ Distribution channels New clinics infrastructure Pharmacies psilocybin clinics psilocybin clinics Convenience Population Commercial / Use / Drug class
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43 Opportunity Overview Global sufferers of of schizophrenia patients Lost life expectancy Schizophrenia is a chronic, psychiatric disorder 1 schizophrenia suffer from significant compared to general characterized by a heterogeneous combination 2 cognitive impairment population of symptoms, including psychosis, social 3 (schizophrenia patients) withdrawal, flat emotional affect and cognitive impairment. Nearly all schizophrenia patients are affected by CIAS, limiting both social and non-social cognitive functions. Estimated annual US Relative market opportunity To date, there are no economic burden due to (antipsychotic sales by pharmacological treatments 4 5 schizophrenia 2025) approved for CIAS 1. Charlson et al., “Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study” (2016) 3. Laursen, Nordentoft & Mortensen, “Excess early mortality in schizophrenia” (2014) 2. Using CSCI Criterion; Reichenberg et al., “Neuropsychological Function and Dysfunction in Schizophrenia and Psychotic Affecti ve Disorders” 4. Cloutier et al., “The Economic Burden of Schizophrenia in the United States in 2013” (2016) (2009) 5. EvaluatePharma (as of 19.03.2021)43 Opportunity Overview Global sufferers of of schizophrenia patients Lost life expectancy Schizophrenia is a chronic, psychiatric disorder 1 schizophrenia suffer from significant compared to general characterized by a heterogeneous combination 2 cognitive impairment population of symptoms, including psychosis, social 3 (schizophrenia patients) withdrawal, flat emotional affect and cognitive impairment. Nearly all schizophrenia patients are affected by CIAS, limiting both social and non-social cognitive functions. Estimated annual US Relative market opportunity To date, there are no economic burden due to (antipsychotic sales by pharmacological treatments 4 5 schizophrenia 2025) approved for CIAS 1. Charlson et al., “Global Epidemiology and Burden of Schizophrenia: Findings From the Global Burden of Disease Study” (2016) 3. Laursen, Nordentoft & Mortensen, “Excess early mortality in schizophrenia” (2014) 2. Using CSCI Criterion; Reichenberg et al., “Neuropsychological Function and Dysfunction in Schizophrenia and Psychotic Affecti ve Disorders” 4. Cloutier et al., “The Economic Burden of Schizophrenia in the United States in 2013” (2016) (2009) 5. EvaluatePharma (as of 19.03.2021)
44 PIPELINE SUMMARY 9 Clinical Stage Overview of Leading Clinical Stage Competitors for Cognitive Impairment Associated with Schizophrenia (CIAS) Therapies in Development for CIAS Therapy RL-007 SEP-363856 BI-425809 NBI-1065844 PF-03463275 BIIB-104 12 Pre-Clinical Stage Primary Indication CIAS Schizophrenia CIAS Schizophrenia CIAS CIAS Therapies in GABA / nicotinic MoA TAAR1agonist GlyT1 inhibitor DAAO inhibitor GlyT1 inhibitor AMPA agonist modulator Development Current Phase II III II II II II Notes Previously Breakthrough Completed Phase Failed to achieve Ongoing Phase II Ongoing Phase II, 17Different assessed in over therapy II with positive primary endpoint US and Japan Only 500 subjects for designation, results of easing the Mechanisms of Action other indications negative being developed with no serious symptoms of for schizophrenia adverse events schizophrenia, but but recently observed met secondary demonstrated endpoints of small cognitive improvements in improvement cognitive measures 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 Sources: GlobalData, Evaluate Pharma (both as of 2021)44 PIPELINE SUMMARY 9 Clinical Stage Overview of Leading Clinical Stage Competitors for Cognitive Impairment Associated with Schizophrenia (CIAS) Therapies in Development for CIAS Therapy RL-007 SEP-363856 BI-425809 NBI-1065844 PF-03463275 BIIB-104 12 Pre-Clinical Stage Primary Indication CIAS Schizophrenia CIAS Schizophrenia CIAS CIAS Therapies in GABA / nicotinic MoA TAAR1agonist GlyT1 inhibitor DAAO inhibitor GlyT1 inhibitor AMPA agonist modulator Development Current Phase II III II II II II Notes Previously Breakthrough Completed Phase Failed to achieve Ongoing Phase II Ongoing Phase II, 17Different assessed in over therapy II with positive primary endpoint US and Japan Only 500 subjects for designation, results of easing the Mechanisms of Action other indications negative being developed with no serious symptoms of for schizophrenia adverse events schizophrenia, but but recently observed met secondary demonstrated endpoints of small cognitive improvements in improvement cognitive measures 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 Sources: GlobalData, Evaluate Pharma (both as of 2021)
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46 Opportunity Overview Substance use disorders are highly prevalent disorders characterized by an inability to control the use of a legal or illegal drug, medication or US sufferers of US sufferers of US deaths from opioid other psychoactive compound 1 1 2 SUD in 2017 OUD in 2017 drug overdose in 2017 Treatment options for Opioid Use Disorder (OUD) Synthetic opioid receptor agonists Societal cost associated of patients undergoing OUD (methadone and buprenorphine) 3 with OUD in US therapy experience relapse 4 within one year Opioid antagonists (naltrexone and naloxone) 1. SAMSHA - National Survey on Drug Use and Health (2017) 3. Murphy, “The cost of opioid use disorder and the value of aversion” (2020) 2. Wilson et al., “Drug and opioid-involved overdose deaths – United States, 2017-2018” (2020) 4. Sinha, “New Findings on Biological Factors Predicting Addiction Relapse Vulnerability” (2011)46 Opportunity Overview Substance use disorders are highly prevalent disorders characterized by an inability to control the use of a legal or illegal drug, medication or US sufferers of US sufferers of US deaths from opioid other psychoactive compound 1 1 2 SUD in 2017 OUD in 2017 drug overdose in 2017 Treatment options for Opioid Use Disorder (OUD) Synthetic opioid receptor agonists Societal cost associated of patients undergoing OUD (methadone and buprenorphine) 3 with OUD in US therapy experience relapse 4 within one year Opioid antagonists (naltrexone and naloxone) 1. SAMSHA - National Survey on Drug Use and Health (2017) 3. Murphy, “The cost of opioid use disorder and the value of aversion” (2020) 2. Wilson et al., “Drug and opioid-involved overdose deaths – United States, 2017-2018” (2020) 4. Sinha, “New Findings on Biological Factors Predicting Addiction Relapse Vulnerability” (2011)
47 SUMMARY Single No Opioid Side Minimal Abuse High Adherence Therapy Mechanismof Action Therapeutic Effects Potential / Low Risk of Relapse Episode DMX-1002 could Disease Modification potentially become Single dose administered Ibogaine (DMX-1002) a paradigm-shifting in monitored setting, Mixed MoA providing both withdrawal therapy for Opioid support and oneiric experience Use Disorder with goal of complete remission Current standard of care 2 Clonidine Alpha-2 agonist Withdrawal Support for OUD is medication Therapies given for therapy, requiring opioid symptomatic substitutes that carry management during supervised withdrawal Lofexidine Alpha-2 agonist significant side effects (detoxification) Methadone Mu-agonist Current strategies for Medication 1 withdrawal support have Assisted Therapy high rates of relapse Daily therapy given in substitution of opioid in Buprenorphine Partial Mu-agonist outpatient setting in attempt to wean off from opioid Naltrexone Mu-antagonist Source: GlobalData, Evaluate Pharma (both as of 2021) 1. Current Standard of Care 2. Rarely used given high rates of relapse. Used primarily in institutional or penitentiary settings47 SUMMARY Single No Opioid Side Minimal Abuse High Adherence Therapy Mechanismof Action Therapeutic Effects Potential / Low Risk of Relapse Episode DMX-1002 could Disease Modification potentially become Single dose administered Ibogaine (DMX-1002) a paradigm-shifting in monitored setting, Mixed MoA providing both withdrawal therapy for Opioid support and oneiric experience Use Disorder with goal of complete remission Current standard of care 2 Clonidine Alpha-2 agonist Withdrawal Support for OUD is medication Therapies given for therapy, requiring opioid symptomatic substitutes that carry management during supervised withdrawal Lofexidine Alpha-2 agonist significant side effects (detoxification) Methadone Mu-agonist Current strategies for Medication 1 withdrawal support have Assisted Therapy high rates of relapse Daily therapy given in substitution of opioid in Buprenorphine Partial Mu-agonist outpatient setting in attempt to wean off from opioid Naltrexone Mu-antagonist Source: GlobalData, Evaluate Pharma (both as of 2021) 1. Current Standard of Care 2. Rarely used given high rates of relapse. Used primarily in institutional or penitentiary settings
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49 Opportunity Overview Anxiety disorders develop when feelings of apprehension and unease persist over an extended period and potentially worsen over time Social Obsessive- Generalized Anxiety Compulsive Anxiety Disorder Disorder Disorder (SAD) (OCD) (GAD) Anxiety disorder Most common mental GAD sufferers in 1 1 2 sufferers in the US health disorder in the US the US Post- Traumatic Panic Stress Disorder Disorder (PTSD) Treatment options for anxiety disorders Antidepressants (SSRIs) Less than half of patients with Annual societal cost of Benzodiazepines 3 Anxiety disorder in the US anxiety disorders in the US 2 receive treatment Psychotherapy 1. National Alliance on Mental Illness (2021) 2. Anxiety and Depression Association of America (2021) 3. DeVane et al., “Anxiety Disorders in the 21st Century: Status, Challenges, Opportunities, and Comorbidity With Depression”, AJMC (2005)49 Opportunity Overview Anxiety disorders develop when feelings of apprehension and unease persist over an extended period and potentially worsen over time Social Obsessive- Generalized Anxiety Compulsive Anxiety Disorder Disorder Disorder (SAD) (OCD) (GAD) Anxiety disorder Most common mental GAD sufferers in 1 1 2 sufferers in the US health disorder in the US the US Post- Traumatic Panic Stress Disorder Disorder (PTSD) Treatment options for anxiety disorders Antidepressants (SSRIs) Less than half of patients with Annual societal cost of Benzodiazepines 3 Anxiety disorder in the US anxiety disorders in the US 2 receive treatment Psychotherapy 1. National Alliance on Mental Illness (2021) 2. Anxiety and Depression Association of America (2021) 3. DeVane et al., “Anxiety Disorders in the 21st Century: Status, Challenges, Opportunities, and Comorbidity With Depression”, AJMC (2005)
50 SUMMARY Overview of Current Therapeutic Options for Generalized Anxiety Disorder Non- Favorable Minimal Side Mechanism There is an unmet need Class Examples High Efficacy Rapid Onset safety profile Effects addictive of action in GAD for therapies with rapid onset, high GABA Channel A deu-etifoxine Benzoxazine and TSPO efficacy, and minimal (GRX-917) Potentiation side effects Anticipated pharmacological profile based on etifoxine Selective Serotonin Reuptake Inhibitor Escitalopram SERTblockade SSRI’s are current standard of care (SSRI) for GAD but require 4-6 weeks for Serotonin and onset of effect and have several Norepinephrine SERTAND NET Venlafaxine 1 Reuptake Inhibitor disadvantages : blockade (SNRI) 1. SSRI/SNRI-specific inadequacy 2. Lack of tolerability GABA A Benzodiazepines Alprazolam Potentiation 3. Patient nonadherence to medications that fail to relieve symptoms of anxiety Tricyclic Antidepressant Imipramine Mixed MoA quickly (TCA) partial 5-HT1A Benzodiazepines are second-line Azapirones Buspirone agonist treatment, offering fast and effective relief, but carrying significant risk of: Gabapentinoid Pregablin VDCC inhibition 1. Sedation 2. Impaired cognition 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 3. Dependence/addiction Source: GlobalData, Evaluate Pharma (both as of 19.03.2021) 1. DeMartini et al., “Generalized Anxiety Disorder” (2019)50 SUMMARY Overview of Current Therapeutic Options for Generalized Anxiety Disorder Non- Favorable Minimal Side Mechanism There is an unmet need Class Examples High Efficacy Rapid Onset safety profile Effects addictive of action in GAD for therapies with rapid onset, high GABA Channel A deu-etifoxine Benzoxazine and TSPO efficacy, and minimal (GRX-917) Potentiation side effects Anticipated pharmacological profile based on etifoxine Selective Serotonin Reuptake Inhibitor Escitalopram SERTblockade SSRI’s are current standard of care (SSRI) for GAD but require 4-6 weeks for Serotonin and onset of effect and have several Norepinephrine SERTAND NET Venlafaxine 1 Reuptake Inhibitor disadvantages : blockade (SNRI) 1. SSRI/SNRI-specific inadequacy 2. Lack of tolerability GABA A Benzodiazepines Alprazolam Potentiation 3. Patient nonadherence to medications that fail to relieve symptoms of anxiety Tricyclic Antidepressant Imipramine Mixed MoA quickly (TCA) partial 5-HT1A Benzodiazepines are second-line Azapirones Buspirone agonist treatment, offering fast and effective relief, but carrying significant risk of: Gabapentinoid Pregablin VDCC inhibition 1. Sedation 2. Impaired cognition 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 3. Dependence/addiction Source: GlobalData, Evaluate Pharma (both as of 19.03.2021) 1. DeMartini et al., “Generalized Anxiety Disorder” (2019)
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52 Opportunity Overview Traumatic brain injury typically occurs when a sudden force impacts the head or body, resulting in damage and functional People sustain TBI Annual TBI-related Mild TBI accounts for impairment of the brain. atai initially focuses 1 2 each year in US deaths in US 70 - 80% of all on mild traumatic brain injuries. reported TBIs To date, there are no pharmacological treatments Americans live with TBI of patients continue to exhibit approved for Traumatic 3 related disabilities prolonged neurocognitive Brain Injury 4 dysfunctions 1. Georges et al, “Traumatic Brain Injury”, NCBI (2020) 3. Thurman et al., “Report to Congress: Traumatic Brain Injury in the United States”, CDC (1999) 2. CDC, “Surveillance Report of Traumatic Brain Injury-related Emergency Department Visits, Hospitalizations, and Deaths” (2014) 4. Hoffer et al., “Repositioning drugs for traumatic brain injury”, Journal of Biomedical Science (2017)52 Opportunity Overview Traumatic brain injury typically occurs when a sudden force impacts the head or body, resulting in damage and functional People sustain TBI Annual TBI-related Mild TBI accounts for impairment of the brain. atai initially focuses 1 2 each year in US deaths in US 70 - 80% of all on mild traumatic brain injuries. reported TBIs To date, there are no pharmacological treatments Americans live with TBI of patients continue to exhibit approved for Traumatic 3 related disabilities prolonged neurocognitive Brain Injury 4 dysfunctions 1. Georges et al, “Traumatic Brain Injury”, NCBI (2020) 3. Thurman et al., “Report to Congress: Traumatic Brain Injury in the United States”, CDC (1999) 2. CDC, “Surveillance Report of Traumatic Brain Injury-related Emergency Department Visits, Hospitalizations, and Deaths” (2014) 4. Hoffer et al., “Repositioning drugs for traumatic brain injury”, Journal of Biomedical Science (2017)
53 Estimated 2026 Academic Publications While mental Indication Market Size ($BN) health is the initial Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an Eating disorders 7.4* 2 eating disorder focus, adjacent Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive 3.7* Obsessive-Compulsive Disorder 5 indications may disorder allow for Attention Deficit Hyperactivity 3.3 Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and 3 substance use disorders Disorder significant 1.4* Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory Autism Spectrum Disorders expansion 4 neurotransmission 10 Multiple Sclerosis 21.1 Psychedelics and immunomodulation: novel approaches and therapeutic opportunities Anti-inflammatory Ischemic/ 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 Hypoxic Brain Injury properties make 6 iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells psychedelics Alzheimer’s Disease 7 10.6 Psychedelics as a Treatment for Alzheimer’s Disease Dementia potentially 11 Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin Migraine Headache 9.6 interesting for a Parkinson’s Disease 2.4 Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability variety of 8 to Parkinson's disease therapeutic 9 1.0 Psychedelics as a novel approach to treating autoimmune conditions Amyotrophic lateral sclerosis 1 indications 12 Response of cluster headache to psilocybin and LSD 0.3 Cluster Headache 80 * 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)53 Estimated 2026 Academic Publications While mental Indication Market Size ($BN) health is the initial Positive effects of psychedelics on depression and wellbeing scores in individuals reporting an Eating disorders 7.4* 2 eating disorder focus, adjacent Safety, tolerability, and efficacy of psilocybin in 9 patients with obsessive-compulsive 3.7* Obsessive-Compulsive Disorder 5 indications may disorder allow for Attention Deficit Hyperactivity 3.3 Perceived outcomes of psychedelic microdosing as self-managed therapies for mental and 3 substance use disorders Disorder significant 1.4* Lysergic acid diethylamide (LSD) promotes social behavior through mTORC1 in the excitatory Autism Spectrum Disorders expansion 4 neurotransmission 10 Multiple Sclerosis 21.1 Psychedelics and immunomodulation: novel approaches and therapeutic opportunities Anti-inflammatory Ischemic/ 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 Hypoxic Brain Injury properties make 6 iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells psychedelics Alzheimer’s Disease 7 10.6 Psychedelics as a Treatment for Alzheimer’s Disease Dementia potentially 11 Exploratory Controlled Study of the Migraine-Suppressing Effects of Psilocybin Migraine Headache 9.6 interesting for a Parkinson’s Disease 2.4 Neuroprotective potential of Ayahuasca and untargeted metabolomics analyses: applicability variety of 8 to Parkinson's disease therapeutic 9 1.0 Psychedelics as a novel approach to treating autoimmune conditions Amyotrophic lateral sclerosis 1 indications 12 Response of cluster headache to psilocybin and LSD 0.3 Cluster Headache 80 * 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)
54 SSRIs localized to serotoninergic Buprenorphine Benzodiazepines pathways with slow onset, mainly ↓RN Opioid receptor agonists for ↓AN: sedation, amnesia, impaired maintenance; drawbacks: respiratory motor performance; withdrawal ↓AN: reduced stress, emotional blunting. depression and maintained dependency. Default Mode Network (DMN): Self awareness Cognitive Control (CC): Decision making, executive functions Reward Network (RN): Pleasure Pleiotropic re-set of DMN & AN. Modulatory (+/-) effect on AN. Increased neuroplasticity combined with Restoration of top-down control of emotions Affective Network (AN): Fear response, social interaction, learning, psychedelic experience facilitates regaining from CC. control of CC and RN and “unlearning” processing emotions negative behaviors. Standard of Care54 SSRIs localized to serotoninergic Buprenorphine Benzodiazepines pathways with slow onset, mainly ↓RN Opioid receptor agonists for ↓AN: sedation, amnesia, impaired maintenance; drawbacks: respiratory motor performance; withdrawal ↓AN: reduced stress, emotional blunting. depression and maintained dependency. Default Mode Network (DMN): Self awareness Cognitive Control (CC): Decision making, executive functions Reward Network (RN): Pleasure Pleiotropic re-set of DMN & AN. Modulatory (+/-) effect on AN. Increased neuroplasticity combined with Restoration of top-down control of emotions Affective Network (AN): Fear response, social interaction, learning, psychedelic experience facilitates regaining from CC. control of CC and RN and “unlearning” processing emotions negative behaviors. Standard of Care
55 Florian Brand | CEO | atai life sciences55 Florian Brand | CEO | atai life sciences