Form 8-K - Current report

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

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FORM 8-K

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CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of report (Date of earliest event reported): June 5, 2024

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ATAI LIFE SCIENCES N.V.

(Exact name of registrant as specified in its charter)

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The Netherlands	001-40493	Not Applicable
(State or other jurisdiction of incorporation or organization)	(Commission File Number)	(I.R.S. Employer Identification No.)

Wallstraße 16

10179 Berlin, Germany

(Address of principal executive offices) (Zip Code)

[phone]

(Registrant’s telephone number, including area code)

N/A

(Former Name or Former Address, if Changed Since Last Report)

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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐	Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐	Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐	Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐	Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act

Title of each class		Trading Symbol(s)		Name of each exchange on which registered
Common shares, €0.10 par value per share		ATAI		The Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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Item 8.01

Other Events.

On June 5, 2024, atai Life Sciences N.V. (the “Company”) posted to the Company’s corporate website at www.atai.life an investor presentation (the “Investor Presentation”) to be used from time to time in meetings with investors and analysts. A copy of the Investor Presentation is attached as Exhibit 99.1 and is incorporated herein by reference.

Item 9.01.

Financial Statements and Exhibits.

(d) Exhibits

Exhibit No.		Description
99.1		Investor Presentation, dated June 5, 2024.
104		Cover Page Interactive Data File (embedded within the inline XBRL document).

 

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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:  June 5, 2024	By:	/s/ Florian Brand
	Name:	Florian Brand
	Title:	Chief Executive Officer

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Exhibit 99.1

 Healingmental health disorders so that everyone everywhere can live a more fulfilled life.  Company Overview   Company Overview – June 2024 

 

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 All references in this presentation to “we”, “us”, “our”, “atai”, or the “Company” refer to ATAI Life Sciences N.V. and its consolidated subsidiaries, unless the context otherwise requires. This presentation contains forward-looking statements within the meaning of the private Securities Litigation Reform Act of 1995. We intend such forward-looking statements to be covered under by the safe harbor provisions for forward-looking statements contained in Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended.” All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, industry dynamics, business strategy and plans and our objectives for future operations, are forward-looking statements. These statements represent our opinions, expectations, beliefs, intentions, estimates or strategies regarding the future, which may not be realized. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expects,” “plans,” “anticipates,” “could,” “intends,” “targets,” “projects,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions that are intended to identify forward-looking statements. Forward-looking statements are based largely on our current expectations and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy, short term and long-term business operations and objectives and financial needs. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including without limitation the important factors described in the section titled “Risk Factors” in our most recent Annual Report on Form 10-K filed with the Securities and Exchange Commission (“SEC”), as updated by our subsequent filings with the SEC, that may cause our actual results, performance or achievements to differ materially and adversely from those expressed or implied by the forward-looking statements. Moreover, we operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. We caution you therefore against relying on these forward-looking statements, and we qualify all of our forward-looking statements by these cautionary statements.  The forward-looking statements included in this presentation are made only as of the date hereof. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, neither we nor our advisors nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements. Neither we nor our advisors undertake any obligation to update any forward-looking statements for any reason after the date of this presentation to conform these statements to actual results or to changes in our expectations, except as may be required by law. You should read this presentation with the understanding that our actual future results, levels of activity, performance and events and circumstances may be materially different from what we expect.  Unless otherwise indicated, information contained in this presentation concerning our industry, competitive position and the markets in which we operate is based on information from independent industry and research organizations, other third-party sources and management estimates. Management estimates are derived from publicly available information released by independent industry analysts and other third-party sources, as well as data from our internal research, and are based on assumptions made by us upon reviewing such data, and our experience in, and knowledge of, such industry and markets, which we believe to be reasonable. In addition, projections, assumptions and estimates of the future performance of the industry in which we operate or of any individual competitor and our future performance are necessarily subject to uncertainty and risk due to a variety of factors, including those described above. These and other factors could cause results to differ materially from those expressed in the estimates made by independent parties and by us. Industry publications, research, surveys and studies generally state that the information they contain has been obtained from sources believed to be reliable, but that the accuracy and completeness of such information is not guaranteed. Forecasts and other forward-looking information obtained from these sources are subject to the same qualifications and uncertainties as the other forward-looking statements in this presentation.   This presentation contains excerpts of testimonials from individuals who have been treated with compounds or derivatives of the compounds underlying our product candidates in the context of third-party studies or otherwise that are solely intended to be illustrative and not representative of the potential for beneficial results of such compounds. Our product candidates are in preclinical or clinical stages of development and none of our product candidates have been approved by the FDA or any other regulatory agency.  Any trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of the products or services of the Company.   Disclaimer  02 

 

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 atai Life Sciences: Healing mental health disorders so that everyone everywhere can live a more fulfilled life  Highlights  03  1  Mental health disorders are one of the largest global health burdens; in 2019, 1 in every 8 people, or approx. 1 billion people around the world, were living with a mental disorder.1   3  Eight clinical-stage psychedelic and non-psychedelic programs and strategic investments, each with a robust package of prior clinical evidence.   2  atai’s objective is to enable mental health patients to achieve clinically meaningful and sustained behavioral change through developing innovative, rapid-acting and durable therapeutics.  4  Validated operating model and ability to capture value: IPO of COMPASS Pathways in 2020 and licensing deal between Otsuka and atai subsidiary Perception Neuroscience in 2021.  5  Cash and cash equivalents, marketable securities, and committed term loan funding expected to provide runway into 2026.2  1 World Health Organization  2 Committed term loan funding includes $45M of additional capital that can be drawn not subject to milestones under the facility with Hercules Capital; marketable securities includes money market funds, U.S. Treasury securities, commercial paper, corporate notes/bonds, U.S. government agencies securities, and public equities 

 

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 Our strategy to be delivered through a robust portfolio of psychedelic and non-psychedelic drug development programs and strategic investments   Drug Development Programs and Strategic Investments   PSYCHEDELIC PROGRAMS & STRATEGIC INVESTMENTS  Preclin  Phase 1  Phase 2  Phase 3  Programs / Investments  RL-007 / Pro-cognitive neuromodulator3  GRX-917 / Deuterated etifoxine  COMP3601 / Psilocybin  ELE-1012 / Psilocin  VLS-01 / DMT  EMP-01 / R-MDMA  EGX-A & EGX-B / Novel 5-HT2A Receptor Agonists  BPL-0032 / 5-MEO-DMT  IBX-210 / Ibogaine  Primary Indication  Cognitive Impairment Associated   with Schizophrenia  Generalized Anxiety Disorder  Treatment-Resistant Depression  Major Depressive Disorder  Treatment-Resistant Depression  Undisclosed  Undisclosed  Treatment-Resistant Depression  Opioid Use Disorder  NON-PSYCHEDELIC PROGRAMS  2 Strategic Investment in Beckley PsyTech  1 Strategic Investment in Compass Pathways  3 RL-007 compound is (2R, 3S)-2-amino-3-hydroxy-3-pyridin-4-yl 1-pyrrolidin-1-yl-propan-1-one(L)-(+) tartrate salts  Strategic Investment 

 

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 We expect to deliver several meaningful R&D milestones anticipated across our key programs and strategic investments through 2024 and 20251  Upcoming Catalysts  All dates provided are as estimated  05  Achieved and expected milestones1(2024-25)  BPL-003Ph 2a OL (TRD) Part 1 data  2025  H2’24  H1’24  VLS-01Ph 1b first participant dosed  ELE-101Ph 1/2a OL (MDD) initial data   COMP360Ph 3 (TRD) Pivotal Trial 1 topline data  COMP360Ph 3 (TRD) Pivotal Trial 2 topline data (mid’25)  COMP360Ph 2 (PTSD) data (Spring ’24)  BPL-003Ph 2a OL (AUD) data (mid’24)  RL-007Ph 2b (CIAS) topline data (mid’25)  VLS-01Ph 1b topline data  BPL-003Ph 2b (TRD) patient recruitment completed      IBX-210Ph 1/2a initiation    VLS-01Ph 2 initiation (around YE’24)  

 

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 Programs in Depression  BPL-003, VLS-01, COMP360, ELE-101  06 

 

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 A diverse portfolio of differentiated psychedelic assets to address the heterogeneity of patients who suffer from depression  atai’s Depression Portfolio Comparison  Associated Program  Compound  Primary Indication  Route of Administration  Receptor binding affinity (5-HT2A : 5-HT1A )1  Rapid Onset of Treatment Effect  Appr. Duration in clinic  VLS-01  DMT  TRD  Oral transmucosal film  3.4  ~2h  BPL-003  5-MeO-DMT  TRD  Intranasal  0.01  ~2h  ELE-101  Psilocin  MDD  Intravenous  2.0  ~2h  COMP360  Psilocybin2  TRD  Oral  2.0  ~6h  1 Besnard et al. 2012 // 2 Psilocybin is not present in the body in meaningful concentrations after oral consumption // Abbreviations: TRD = Treatment Resistant Depression; MDD = Major Depressive Disorder  07 

 

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 atai’s focus is on psychedelics with the potential to leverage the 2-hour interventional psychiatry treatment paradigm successfully established by Spravato®  Commercial Positioning  Anticipated in-clinic time based on duration of subjective effects1   (in hours) Illustrative  Spravato®  BPL-003 / VLS-01 / ELE-101  Multi-dose 5-MeO-DMT  Psilocybin + analogs  MDMA  LSD  ~2  ~2  ~2 to 6*  ~6  ~6 to 8  ~8 to 12  BPL-003, VLS-01 and ELE-101 have the potential in depression to offer a predictable, single-dose model administered within the 2-hour in-clinic treatment paradigm established by Spravato®  1  We anticipate this facilitates more scalable adoption and allows clinics to accommodate a greater number of patients daily, compared to psychedelics with longer duration subjective effects  2  Key Takeaways  This may ultimately drive improved patient convenience and treatment access in the >4,000 certified delivery clinics2 for Spravato® with proven reimbursement and logistics pathways  3  Subject to further validation through future clinical studies and real-world evidence  https://www.spravatohcp.com/#find-a-center  * If multi-dose required  Anticipated hours in-clinic1  08 

 

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 BPL-003   (5-MeO-DMT)   for TRD & AUD  09  Strategic Investment into Beckley Psytech 

 

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 Beckley Psytech’s BPL-003 had a favorable safety profile and was well tolerated in the Phase 1 SAD study, with no observed serious or severe adverse events  BPL-003: Phase 1 Results  1 n = number of subjects reporting at least one TEAE in that category, % - rounded proportion of cohort total   10  Placebo  N=13  BPL-003 dose (N=31)  GRX-917  150 mg  N=9  GRX-917  200 mg  N=9  GRX-917  300 mg  N=8  All  GRX-917  N=43  Total  N=44  1 mg  N=4  2.5 mg  N=4  4mg  N=4  6 mg  N=4  8 mg  N=5  10mg  N=5  12 mg  N=5  Any TEAEs   2   1  1  4   3   4   2  4   21     Nasal discomfort  1  2  2  2  3   10     Nausea  2  1  2  1  1   7      Vomiting  2  1  2  5   Headache  1  1   2  4  Administration   site pain  1  1  2   Chest discomfort  1  1   Dizziness  1  1   Pyrexia  1   1   Gastroenteritis  1   1   Back pain  1   1   Hypoesthesia  1   1   Limb discomfort  1  1   Tremor  1  1   Lacrimation  Increased  1  1   Restlessness  1   1   BPL-003 Phase 1 Treatment-Emergent Adverse Events (TEAEs)1  Results from the C-SSRS showed participants experienced no increase in suicidal thoughts,  intentions or behavior.   There were no severe or serious adverse events observed, and 89.5% TEAEs were mild and 10.5% were moderate in severity.  1  2  4  3  Key Takeaways  5  Blood pressure and heart rate increases were transient and resolved within 90 min without intervention. None were considered clinically significant.  Most common TEAEs (>10%) were nasal discomfort, nausea, vomiting, and headache. TEAEs did not appear to correlate with dose.   There were no clinically significant findings for laboratory parameters, vital signs, ECGs or physical examinations. 

 

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 12mg (n=5)  10mg (n=5)  8mg (n=5)  6mg (n=4)  4mg (n=4)  2.5mg (n=4)  1mg (n=4)  Mean plasma concentration levels (ng/ml)  Time post-dose (minutes)  BPL-003 Phase 1 Pharmacokinetic Profile  Pharmacokinetics (PK)  Exposure was dose-proportional  Rapid onset with mean Tmax of 6-17 min  Mean half life of 15-30 min  Pharmacodynamics (PD)  Subjects were psychedelic naive  All subjects on doses ≥6mg achieved intensity scores ≥7   Perceptual effects generally fully resolved within 60 - 90 mins  BPL-003 Phase 1 Subjective Intensity Ratings  0  12  30  60  90  12mg (n=5)  10mg (n=5)  8mg (n=5)  6mg (n=4)  Time post-dose (minutes)  Mean subjective drug   intensity (SDI)  Results from the completed BPL-003 Phase 1 study demonstrated a dose proportional PK/PD profile with perceptual effects generally resolving within 90 min  BPL-003: Phase 1 Results  0  12  30  60  90  Source: internal Beckley Psytech data  Abbreviations: SAD = Single Ascending Dose; PK = Pharmacokinetic; PD = Pharmacodynamic  11  Dose range taken forward to Phase 2  Key Takeaways 

 

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 Completed Part 1 of an open-label Phase 2a study investigating 10mg of BPL-003 as a monotherapy for TRD patients  BPL-003: Phase 2a Clinical Trial Design  Abbreviations: MADRS = Montgomery–Åsberg Depression Rating Scale  Screening  Part 1: Monotherapy  Open label   Day 2   85  Completed Q1 2024  Phase 2a study design  Single dose of BPL-003   29  STUDY DETAILS  Open-label study evaluating a single dose of BPL-003 nasal spray, in patients with moderate-to-severe TRD  KEY INCLUSION CRITERIA  Montgomery-Asberg Depression Rating Scale (MADRS) score ≥24  Part 1: willing and able to discontinue current antidepressants  Part 2: on current stable dose of antidepressant SSRI therapy  KEY OBJECTIVES  Primary Endpoint:   Safety and tolerability of BPL-003  Other Secondary Endpoints:  MADRS change through Week 12  Remission and response rates through Week 12  12  Part 2: Adjunct to SSRIs  Initiated Q1 2024 

 

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 BPL-003 produced meaningful clinical response and durable remission rates after just a single dose, and was generally well tolerated with no serious adverse events  BPL-003: Phase 2a Results  Source: internal Beckley Psytech data  Response rate defined as ≥50% reduction in MADRS score and Remission rate defined as MADRS score ≤10  * Prior to data analysis, one subject (from total of 12 patients) was determined not to meet multiple per protocol eligibility criteria and was excluded from the efficacy analysis.  13  BPL-003 PHASE 2A INITIAL RESULTS  Response and remission rate1 in TRD patients after a single dose of BPL-003  Response and Remission rate1,2  Time post-dose  55% of patients achieved clinical response on Day 2 and this rate of response was maintained at Week 12  1  Key Takeaways  At Week 4, 55% of patients achieved both clinical remission and response  2  Day 2  Week 4  Week 12  45%  Response Rate (n = 11*)  Remission Rate (n = 11*)  3  4  Acute effects resolved within an average time of less than 2 hours   Most common AEs (>10%) were nasal discomfort, headaches, nausea and vomiting, broadly consistent with Phase 1 findings 

 

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 BPL-003 is actively recruiting for its ongoing Phase 2b study, a randomized, quadruple-masked, monotherapy study in 225 moderate to severe TRD patients  BPL-003: Phase 2b Clinical Trial Design  1 Patients entering the open-label extension are randomized 1:1 to receive either a single 12mg dose or a biphasic 4mg and 8mg dose approximately 10 minutes apart  Abbreviations: MADRS = Montgomery–Åsberg Depression Rating Scale; CGI-S = Clinical Global Impressions-Severity; PGIC = Patient's Global Impression of Change; EQ-5D = EuroQol-5D  Randomization   (1:1:1; n=225)   Day 0  2  29  57   Wk-8  Washout  12 mg1  Core Study (8 weeks)  Primary   Analysis  29  57  Patient recruitment expected to be completed for Ph 2b (TRD) in 2H24   (first patient dosed Oct 2023)  Open label extension (8 weeks)  0.3 mg (n=75)  8 mg  (n=75)  12 mg  (n=75)  1st  Dose  2nd  Dose  KEY INCLUSION CRITERIA  Patients with moderate to severe TRD  Hamilton Depression Scale (HAM-D) >= 19  Willing and able to discontinue current antidepressants  KEY OBJECTIVES  Primary Endpoint:   MADRS change from baseline at Week 4  Other Secondary Endpoints:  MADRS change from baseline at Day 2, Week 1 and Week 8  CGI-S, PGIC, EQ-5D  8  14  1  1  2 

 

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 VLS-01   (DMT) for TRD  15 

 

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 Potential for rapid onset, durable efficacy, and designed to fit within 2-hour in-clinic treatment paradigm  VLS-01: Product Overview  World Health Organization  Salzer, “National Estimates of Recovery-Remission From Serious Mental Illness”, Psychiatry Online (2018)  Abbreviations: OTF = Oral transmucosal film; PK = Pharmacokinetic; PCT = Patent Cooperation Treaty  Lead indication overview  ~300m  Global sufferers of depression in 20191  33%  Patients who have inadequate response or relapse after current treatments2  Depression is a mood disorder that affects the thoughts and behavior of an individual, leading to psychological, physical, and social problems  Treatment resistant depression (TRD) is diagnosed after two failed courses of antidepressants  FDA approved depression treatments can be characterized by a slow onset, long-term side effects and inadequate response rate  Global disease burden  VLS-01 Key Product Features  Short duration of psychedelic effect with improved tolerability and convenience from OTF delivery relative to other psychedelics in development for depression  Designed for rapid onset, sustained efficacy, and to fit within a two-hour in-clinic treatment paradigm  Optimized OTF formulation is designed to improve the PK profile and the patient and provider experience   DMT (N,N-Dimethyltryptamine) in an oral transmucosal film (OTF)   Lead: Treatment Resistant DepressionPotential expansions: Eating Disorders, Substance Use Disorders  Phase 1b first participant dosed in 1Q’24  Phase 1b trial results anticipated in 2H’24  Phase 2 study anticipated to initiate around YE’24  PRODUCT  INDICATIONS  CURRENT STATUS  INTELLECTUAL PROPERTY  Granted U.S. patent covering OTF administration of DMT, supported by several pending U.S. and PCT patent applications  16 

 

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 Double-blind, randomized placebo-controlled trial with DMT in 29 patients with TRD demonstrated rapid & statistically significant changes on HAM-D & MADRS  VLS-01: Efficacy in Randomized Control Trial of DMT in TRD  PRIOR CLINICAL EVIDENCE (THIRD PARTY STUDY1)  Double-blind, randomized placebo-controlled trial of Ayahuasca (DMT is major active ingredient) in 29 patients with TRD   Placebo  N, N-DMT  P<.0001  p<.05  p<.05  Baseline  Day 1  Day 2  Day 7  45  40  35  30  25  20  15  10  5  0  MADRS Score  Note: TRD = Treatment Resistant Depression; DMT = N,N-Dimethyltryptamine  1. Palhano-Fontes et al. “Rapid antidepressant effects of the psychedelic ayahuasca in treatment-resistant depression”, Psychol Med (2019)  Summary: A single administration of .36 mg/kg met both primary and key secondary efficacy endpoints by demonstrating rapid and statistically significant changes on depression severity measures of HAM-D & MADRS   Primary endpoint (HAM-D - not shown): N,N-DMT arm achieved the primary endpoint of a statistically significant difference in depression severity relative to placebo (p<.05).   1  2  There were no serious adverse events reported.  4  Key secondary endpoint (MADRS – see left): rapid and statistically significant differences were observed at all timepoints assessed, including as early as Day 1 and through Day 7. MADRS is a potential registrational endpoint.  3  Key Takeaways  17 

 

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 Phase 1 results of VLS-01 showed it was safe and well-tolerated with dose-dependent increases in exposure  VLS-01: Phase 1 Clinical Trial Design & Results   Note: IV = Intravenous; OTF = Oral Transmucosal Film; PK / PD = Pharmacokinetic / Pharmacodynamic; DMT = N,N-Dimethyltryptamine; IV = Intravenous  Program status: Phase 1b first participant dosed in Q1 24. Topline results expected 2H 24.   Phase 2 study in TRD patients anticipated to initiate around YE’24   IV VLS-01: PK / PD results were consistent with the known pharmacological profile of DMT, producing robust exposure-dependent increases in the subject intensity of psychedelic experience.  Part 3 (OTF VLS-01)  Part 2 (OTF VLS-01)    Part 1 (IV VLS-01)    STUDY DESIGN:  OTF VLS-01: Produced generally dose-dependent increases in exposure, approaching that seen with IV administration, alongside subjective psychedelic experiences in most patients.  OTF VLS-01: 160mg with a backing layer via buccal administration experienced the most robust and consistent increases in exposure and subjective effects compared to the other OTF cohorts, with results comparable to the 30 mg IV cohort of DMT.  Phase 1 PK / PD RESULTS:    18 

 

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 COMP 360   (Psilocybin) for TRD, PTSD and Anorexia  19  Strategic Investment into Compass Pathways 

 

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 COMP360 Phase 2b trial showed a rapid, sustained reduction in depressive symptoms  PRODUCT  PHARMA-COLOGY  PRODUCT FEATURES  INDICATIONS  CURRENT STATUS  INTELLECTUAL PROPERTY  Oral Psilocybin (COMP360)  5-HT2A-R agonist  Rapid onset, potential for sustained efficacy after single dose  Primary: Treatment Resistant Depression, Anorexia Nervosa, PTSD  Potential: Major Depressive Disorder, Autism, Bipolar Disorder, Chronic Cluster Headache  Phase 3 pivotal trial 1 data expected summer-24  Phase 3 pivotal trial 2 data expected mid-25  Proprietary formulation of synthetic psilocybin, COMP360  SUMMARY: COMP360  HIGHLIGHT  COMP360 demonstrated efficacy in reducing depressive symptom severity with rapid and durable response in Phase 2b study  PRIOR EVIDENCE IN HUMANS (COMP360 PHASE 2b)  9,565,774 shares1  OWNERSHIP  Note: MADRS = Montgomery-Åsberg 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.  Ownership as of March 27th, 2024  Post-hoc analysis showed results were also positive at the other time points listed for 25mg dose, however, the nonsignificant finding for the comparison between the 10mg group and the 1mg group terminated significance testing based on the prespecified hierarchical test procedure for all subsequent key secondary efficacy end points.  20  Primary Endpoint 

 

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 COMPASS Pathways is currently conducting a Phase 3 pivotal program, with topline data expected in 4Q 2024 and mid 2025  COMP360: Phase 3 Trial Designs  Source: Compass Pathways Capital Markets Day presentation as of May 11th, 2023   Primary endpoint = Change from baseline in MADRS total score at week 6  The participant population (TRD definition and core inclusion / exclusion criteria) remains unchanged compared to Phase 2b  Week 6  Primary endpoint1  Week 3  Proceeded by long-term follow up  Pivotal study 1  Single dose monotherapy  (COMP 005)  COMP360  25mg  Placebo  Randomization = 2:1  Target N2 = 255   Topline data expected: 4Q 2024  Pivotal study 2  Fixed repeat dose monotherapy  (COMP 006)  COMP360  25mg  COMP360  25mg  COMP360  10mg  COMP360  10mg  COMP360  1mg  COMP360  1mg  Randomization = 2:1:1  Target N2 = 568  Topline data expected:   Mid 2025  Week 0  Week 0  Proceeded by long-term follow up  Pivotal Phase 3 Trial Designs  Week 6  Primary endpoint1  21 

 

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 Open-label phase 2 study of COMP360 in post-traumatic stress disorder demonstrated an early onset and sustained improvement in PTSD symptoms at week 4 and week 12  COMP360: Phase 2 PTSD Results  22  Source: Compass Pathways  NCT05312151  Response rate defined as a reduction of ≥ 15 points in CAPS-5 score  Remission rate defined as a total CAPS-5 ≤ 20  Mean SDS total score of 22.7 at baseline  COMP360 PHASE 2 PTSD STUDY TOPLINE RESULTS  Summary of change in CAPS-5 mean total score  Mean total score on CAPS-5 (+/- SD)  Time post-dose  Phase 2 study was a multicenter open-label, single administration of 25mg COMP360 with psychological support (n=22)1  1  Key Takeaways  81.8% response rate and 63.6% remission rate at week 4 with a 77.3% response and 54.5% remission rate at week 122,3  2  Baseline  Week 12  Week 4  3  4  Sheehan Disability Scale (SDS), a measure of functional impairment, improved with a reduction from baseline of 11.7 points at week 4 and 14.4 points at week 124  Administration was well tolerated, with no serious adverse events observed  CAPS-5 mean total score 

 

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 ELE-101   (Psilocin) for MDD  23  Strategic Investment into Beckley Psytech 

 

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 Potential benefits of psilocybin’s active moiety in an optimized delivery and treatment model  ELE-01: IV Psilocin  1 Psilocin simulations based on primary data from Brown et al. 2017, Madsen et al . 2019, Hasler et al. 1997, and Carhart-Harris et al. 2011.  2 Holze F. et al (2023). Pharmacokinetics and Pharmacodynamics of Oral Psilocybin Administration in Healthy Participants. Clin Pharmacol Ther.   Psilocin pharmacokinetics for   IV psilocin (simulated) vs. oral psilocybin1  Typical plasma psilocin concentrations at effective dose of 25mg psilocybin1  Perceptual threshold2  Expected benefits of IV psilocin vs oral psilocybin:  Reduced variability  Shorter-half life = shorter duration of psychedelic effect, anticipated to be <2 hours  24 

 

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 Randomized, Phase 1 dose-escalation study in healthy volunteers followed by Phase 2a open-label study in MDD  ELE-101: Phase 1/2a Clinical Trial Design  ELE-101 Phase 1/2a – Part A  Key Objectives:   Safety and tolerability  Assessment of PK & PD   Target concentration of psilocin in <2 minutes  Consistency of subjective intensity  Key Objectives:   Safety and tolerability of ELE-101 in patients with moderate to severe MDD  Key Secondary Endpoints:  Assessment of MADRS change (Day 2, 4, 6, 15, 29)  CGI-S, PGIC  Single Ascending Dose  ELE-101 Phase 1/2a – Part B  Open-label MDD cohort  Initial results anticipated in H1 2024  Screening  Dose to be selected  Open label   Day 1  Day 29  Dose 1  Placebo  Dose 2  Placebo  Dose 3  Placebo  Dose 4  Placebo   Day 1  Day 7  Abbreviations: MADRS = Montgomery–Åsberg Depression Rating Scale; PK = Pharmacokinetics; PD = Pharmacodynamics; CGI-S = Clinical Global Impressions-Severity; PGIC = Patient's Global Impression of Change; MDD = Major Depressive Disorder  25 

 

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 IBX-210  (IV-Ibogaine) for Substance Use Disorder  26 

 

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 Post traumatic stress disorder and traumatic brain injury, respectively  World Health Organization  Salzer, “National Estimates of Recovery-Remission From Serious Mental Illness”, Psychiatry Online (2018)  A single dose of ibogaine may support withdrawal and long-term relapse prevention in OUD patients  Product Overview: IBX-210 for Opioid Use Disorder  Lead indication overview  ~3m  US OUD Incidence in 20202  >100k  Opioid-related deaths in US in 2022  Substance use disorders are highly prevalent and characterized by an inability to control the use of a legal or illegal drugs, such as opioids (including prescription opioids) or alcohol.   Current standard of care for OUD primarily consists of psychosocial support and synthetic full and partial opioid receptor agonists (methadone & buprenorphine), where approximately 30% of patients achieve treatment success (defined as >80% illicit opioid free weeks). In addition, long-acting opioid antagonists (naltrexone) lead to a proportion of patients achieving treatment success.  Global disease burden  IBX-210 Key Product Features  A single dose of ibogaine delivered in a monitored setting may support withdrawal and long-term relapse prevention in Opioid Use Disorder patients  Prior clinical evidence:   In third-party open label studies, ibogaine was associated with significantly reduced opioid cravings, both at discharge and at one month post treatment, as well as improved mood in patients with OUD  In addition, a double-blind, placebo-controlled study in subjects with cocaine use disorder demonstrated a statistically significant benefit on urine confirmed relapse of a single administration of ibogaine compared to placebo  Lead: Opioid Use Disorder (“OUD”)Potential expansions: Add’l Substance Use Disorders, PTSD, TBI1  Phase 1 oral ibogaine study completed in 3Q 23  IBX-210 Phase 1/2a study anticipated to initiate in H2 2024  PRODUCT  INDICATIONS  CURRENT STATUS  INTELLECTUAL PROPERTY  Issued and pending method of treatment claims for OUD   IBX-210 is a novel IV formulation of ibogaine, which is an indole alkaloid with potential for clinical benefit through oneirophrenic effects  27 

 

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 Results from an open-label study of 8-12 mg/kg of ibogaine in patients seeking detoxification from opioids and cocaine  Clinical Evidence: Efficacy of ibogaine in Open-Label Safety & Efficacy Study  PRIOR CLINICAL EVIDENCE (THIRD PARTY STUDY1)  Note: TRD = Treatment Resistant Depression; DMT = N,N-Dimethyltryptamine; HCQ = Heroin Craving Questionnaire  1 Mash et al., “Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes” (2018)  1  2  Safety: Ibogaine was reported to be well tolerated with no serious adverse events.   4  Key Takeaways  HCQ-29 Subscale  Pre-dose (N=75)  5  4  3  2  1  0  Discharge (N=74)  1 Month (N=37)  Emotionality(negative mood state)  Compulsivity(lack of confidence in ability to quit)  Purposefulness(desire of intent to use)  Expectancy(expected positive benefits of drug use)  Self-reported dimensions of craving  Efficacy – Post-Acute Withdrawal Syndrome: signs and symptoms at post dose assessments were reduced compared to pre-dose baseline withdrawal severity measures. Objective signs of opioid withdrawal were mild and none were exacerbated at later time points.  3  Efficacy – Relapse Prevention (shown left): Opioid dependent patients had significant reductions in the mean scores of four HCQ-29 domains of craving measured at program discharge and out to 1 month for patients continuing through study completion. Cravings are an important mediator of relapse.  Summary: A single-dose of ibogaine showed reductions in self-reported opioid cravings in 74 opioid dependent patients.   28 

 

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 IBX-210 has the potential to become the first & best in-class treatment for OUD, minimizing risk of relapse  SUMMARY  IBX-210 could potentially become a paradigm-shifting therapy for Opioid Use Disorder (OUD)  Current standard of care for OUD is medication therapy, requiring opioid substitutes that carry significant side effects  Sustained relapse prevention  Single dose administered in monitored setting, providing both withdrawal support and oneiric experience driving sustained remission  Single Therapeutic Episode  Minimal Abuse Potential  No Opioid Side Effects  High Adherence  / Low Risk of Relapse  Cholinergic, glutamatergic and monoaminergic receptor modulator  Mechanism of Action  Ibogaine (IBX-210)  Therapy  Medication Assisted Therapy1  Daily therapy given in substitution of opioid in outpatient setting in attempt to wean off from opioid  Mu-agonist  Partial Mu-agonist  Mu-antagonist  Methadone  Buprenorphine  Naltrexone  Withdrawal Support2  Therapies given for symptomatic management during supervised withdrawal (detoxification)  Alpha-2 agonist  Alpha-2 agonist  Clonidine  Lofexidine  Current strategies for withdrawal support have high rates of relapse  Note: OUD = Opioid Use Disorder  Source: Publicly available information, including company websites and clinicaltrials.gov, GlobalData, Evaluate Pharma (both as of 2022)  Current Standard of Care  Rarely used given high rates of relapse. Used primarily in institutional or penitentiary settings  DemeRx  29 

 

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 RL-007 for Cognitive Impairment  30 

 

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 World Health Organization  Schaffer et al., 2013  Bora et al, Cognitive Impairment in Schizophrenia and Affective Psychoses: Implications for DSM-V Criteria and Beyond  GlobalData (as of 31/12/2023)  Demonstrated consistent pro-cognitive effects in prior clinical trials, with a favorable safety profile in >500 subjects  Product Overview: RL-007 for Cognitive Impairment   Lead indication overview  ~24m  Global sufferers of Schizophrenia¹  >80%  Patients with Schizophrenia experiencing significant cognitive impairment3  Cognitive impairment associated with schizophrenia (CIAS) is characterized by attention, learning, memory, and exec function deficits  Such deficits result in cognitive function around 2.5 standard deviations below the mean of the general population2  CIAS is a common and major cause of disability in schizophrenia, with more than 80% of patients showing significant impairment3  No FDA approved treatments4  Global disease burden  RL-007 Key Potential Product Features  Pro-cognitive effects demonstrated across four prior clinical studies, including two Phase 1 and two Phase 2 trials  Consistent “inverted-U” dose response across clinical & preclinical studies  Demonstrated safety & tolerability with no evidence of sedative side effects across the 10 clinical studies in >500 subjects  Oral, pro-cognitive neuromodulator  Lead: Cognitive impairment associated with schizophrenia (CIAS)Potential expansions: Cognitive disorders including Alzheimer’s dementia and/or Autism  Phase 2a CIAS trial completed in H2’21Phase 2b first patient dosed in 1Q’23  Phase 2b data expected in mid’25  PRODUCT  INDICATIONS  CURRENT STATUS  INTELLECTUAL PROPERTY  Issued composition of matter, formulation and method of use IP  31 

 

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 Third-Party Phase 2 study in DPNP showed statistically significant positive cognitive signals (exploratory endpoints)  Note: * = P< 0.05 vs Placebo;   N=60 patients/treatment group; dosed TID = 3x/day dosing; randomized, cross-over design  Clinical Evidence: Efficacy on Cognitive Endpoints in a Phase 2 Study  Phase 2, randomized, placebo-controlled, crossover clinical study in subjects with diabetic peripheral neuropathic pain (DPNP) that assessed improvements in verbal learning and memory as an exploratory endpoint  4-week placebo periods were compared to 4-week RL-007 periods   “Intermediate-dose escalation” RL-007 40mg (first week) to 80mg (n=60)  “High-dose escalation” RL-007 150mg (first week) to 300mg (n=60)  Background  RL-007 showed statistically significant pro-cognitive effects on learning and memory within the “Intermediate-Dose escalation” 40mg to 80mg arm.   1  2  Key Takeaways  Delayed recall  0.4  0.3  0.2  0.1  0  -0.1  -0.2  -0.3  0.35  0.3  0.25  0.2  0.15  0.1  0.05  RL-007  (40 & 80 mg TID)  RL-007  (150 & 300 mg TID)  RL-007  (40 & 80 mg TID)  RL-007  (150 & 300 mg TID)  Cohen’s d effect size  Diff. vs. Placebo  Cohen’s d effect size  Diff. vs. Placebo  *  *  Direction of   Improvement  Direction of   Improvement  0  3  The 40 to 80mg arm patients also reported a statistically significant improvement on the Cognitive and Physical Function Questionnaire (p = 0.021)  Inverted U-shaped dose response whereby intermediate doses yield greater clinical activity is replicated and consistent with from prior clinical and preclinical studies  Verbal learning  32 

 

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 PHASE 2a TRIAL - EFFICACY DATA ON COMPONENTS MCCB COMPOSITE  Signal of improvement  n=7 n=8 n=8 n=8  Cohen’s d* (Symbol Coding):  20 mg: 0.79  40 mg: 0.56  80 mg: 0.38  *Active vs pbo  T-Scores (Normalized for age, gender, and education level)  atai’s Phase 2a study in CIAS demonstrated positive cognitive signals on a subset of MCCB neurocognitive endpoints  Clinical Evidence: Efficacy Signals Reproduced in Phase 2a Study in CIAS  Study demonstrated dose-related trends for improvements on each MCCB neurocognitive endpoints, including a Cohen’s d effect size of 0.79, 0.56 and 0.38 at the 20mg, 40mg, and 80mg, respectively, on the BACS Symbol Coding test.   1  Importantly, Symbol Coding is the most sensitive subcomponent and correlates with overall performance on the MCCB neurocognitive composite, the latter being a registrational endpoint and the primary endpoint for the on-going Phase 2b study of RL-007.  2  In addition, qEEG data was consistent with the prior clinical evidence and demonstrated increases in amplitude in the alpha band and in the alpha-slow wave index, markers of alertness believed to correlate with aspects of cognition.  3  Cognitive function was assessed in 31 patients with CIAS across four RL-007 cohorts (10, 20, 40 & 80mg). Patients received four doses of placebo followed by six doses of RL-007 over 4-days. Day 2 “pre-RL-007” was compared to Day 4 “post-RL-007”.   The primary objectives of the single-blinded study was to confirm safety on-top of SOC and to identify signals of cognitive benefit in patients with CIAS, including on three MCCB sub-component neurocognitive tests, HVLT1, BACS Symbol Coding & Category Fluency  Background  Key Takeaways  1. Hopkins Verbal Learning Test  33 

 

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 Clinical Trial Design: RL-007 Phase 2b Study  Note: MCCB = MATRICS Consensus Cognitive Battery; BACS = Brief Assessment of Cognition in Schizophrenia; CIAS = Cognitive Impairment Associated with Schizophrenia; TID = 3x/day dosing  Trial status: First patient dosed in 1Q’23,   Topline data anticipated mid’25  Randomized, placebo-controlled study of RL-007 in ~234 patients with CIAS  RL-007 TID (40mg)  RL-007 TID (20mg)  Placebo  R  Randomized  1:1:1  Primary Endpoint:   MCCB neurocognitive composite score at Week 6  Key Secondary Endpoints:  Select Individual Components of MCCB, including BACS Symbol Coding  Clinical Global Impression Score  Week 6  Day 1  34 

 

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 GRX-917 for Anxiety Disorders  35 

 

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 World Health Organization  Anxiety and Depression Association of America (2021)  GlobalData (as of 6/1/2023) - All recent approvals by the FDA have been reformulations of long-standing antidepressant and benzodiazepine options  Designed to have rapid onset of anxiolytic activity but without the negative side effects seen with benzodiazepines  Product Overview: GRX-917 for Anxiety Disorders  Lead indication overview  ~300m  Anxiety disorder sufferers in 20191  #1  Most common mental health disorder1  Anxiety disorders develop when feelings of apprehension and unease persist over an extended period and potentially worsen over time  50% of US patients go untreated as a result of sub-optimal treatment options2  No FDA approved novel treatments over the past decade3  Global disease burden  GRX-917 Key Product Features  Demonstrated rapid onset activity of anxiolytic activity (non-deuterated etifoxine approved in France)  Review of ~14m prescriptions in France underscores the strong safety track record for etifoxine  Differentiated tolerability profile, with limited sedative, addictive and/or cognitive impairing properties, unlike benzodiazepines  Deuterated etifoxine HCl oral dosage form (GRX-917)  Lead: Anxiety Disorders (e.g., GAD, SAD, PTSD, etc.)  Phase 1 trial completed in H2’22  Exploring partnership and external funding opportunities  PRODUCT  INDICATIONS  CURRENT STATUS  INTELLECTUAL PROPERTY  Issued composition of matter on deuterated etifoxine (GRX-917) and corresponding methods of use  36 

 

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 Nasdaq: ATAI  

 

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Document and Entity Information	Jun. 05, 2024
Cover [Abstract]
Document Type	8-K
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Document Period End Date	Jun. 05, 2024
Entity File Number	001-40493
Entity Registrant Name	ATAI LIFE SCIENCES N.V.
Entity Central Index Key	0001840904
Entity Incorporation, State or Country Code	P7
Entity Tax Identification Number	00-0000000
Entity Address, Address Line One	Wallstraße 16
Entity Address, City or Town	Berlin
Entity Address, Country	DE
Entity Address, Postal Zip Code	10179
City Area Code	49 89
Local Phone Number	2153 9035
Title of 12(b) Security	Common shares, €0.10 par value per share
Trading Symbol	ATAI
Security Exchange Name	NASDAQ
Entity Emerging Growth Company	true
Entity Ex Transition Period	false
Written Communications	false
Soliciting Material	false
Pre-commencement Tender Offer	false
Pre-commencement Issuer Tender Offer	false

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