Protagenic Therapeutics, Inc. · OTC:PTIX

Protagenic Therapeutics — Protagenic Therapeutics, Inc.\new — Investor Presentation (April 2021)

28 slides from Protagenic Therapeutics's investor presentation, Apr 21, 2021

1. Slide 1: Breakthrough Therapeutics for Stress-Related Neuropsychiatric Disorders

   Breakthrough Therapeutics fOl Stress-Related Neuropsychiatric Disorders Corporate Overview April 2021

2. Slide 2: Cautionary Statements

   Cautionary Statements This presentation has been prepared by Protagenic Therapeutics. Inc. (the “Company’) solely for informational purposes based on its own information, as well as information from publi¢ sources. This presentation has been prepared to assist interested parties in making their own

3. Slide 3: Corporate Highlights

   Corporate Highlights v Strong safety/efficacy signal in all relevant preclinical models v Phase |/lla clinical study anticipated to be underway by 3Q 2021 by leading psychiatrist Dr. Maurizio Fava (Psychiatrist-in-Chief at MGH) v Potential Candidate for Breakthrough Designation by the FDA and put on

4. Slide 4: Stress Related Disorders are Rapidly Growing

   Stress Related Disorders are Rapidly Growing Current Pharmacotherapies have suboptimal efficacy and have toxicities Depression Anxiety PTSD Drug & Alcohol Addiction 19 Million 9 Million 11 Million 20 Million Americans Americans Americans Americans 50% 43% Only 2 approved Only Available drugs treated

5. Slide 5: The Stress Feedback Loop

   The Stress Feedback Loop * A person with past trauma or a history of c substance abuse is more prone or sensitive to stress, which commences a vicious cycle STRESS PSYCHOLOGICAL & * When met with a stressor, this causes brain LEVEL PHYSIOLOGICAL HARM impairment, and physical & emotional harm * This

6. Slide 6: TCAP is the body's natural regulator of stress response

   TCAP is the body’s natural regulator of stress response, breaking the vicious cycle of stress overdrive TCAP restores stress response is a in the brain to e healthy levels Taps into a biological system Works ona newly-discovered that has evolved over millions receptor system in the brain of yearsacr

7. Slide 7: Stress Signaling and TCAP's Mechanism of Action

   Stress Signaling and TCAP’s Mechanism of Action 1 Asstress signal increases levels of brain hormones CRF and AVP, these hormones are associated with increased anxiety, disrupted sleep, overall dysphoria, and key CNS-related symptoms' 2) Additionally, these hormones trigger the release of ACTH?, whic

8. Slide 8: TCAP Reverses or Prevents Stress-Induced Disorders in Relevant Models

   TCAP Reverses or Prevents Stress-Induced Disorders in Relevant Models Extensive Pharmacological Experiments with PTOO1 14 Corroborate its Activity « TCAP leads to increases in activity of the neuronal circuitry implicated in depression, demonstrated by increases in the utilization of glucose, a surr

9. Slide 9: TCAP as a platform technology in Neuronal Health

   TCAP as a platform technology in Neuronal Health TCAP has the potential to preserve, protect, and repair nerve circuits, making it a possible treatment for not only neuropsychiatric disorders but also neurodegenerative diseases |» tas « TCAP has been shown to be active in the regulation of cell ' pr

10. Slide 10: PT00114 Has Demonstrated Profound Efficacy and Safety in Extensive Preclinical Models

    PTOO114 Has Demonstrated Profound Efficacy and Safety in Extensive Preclinical Models of Stress-Related Disorders « Multiple preclinical animal studies conducted in a range of stress- induced behavioral distortions using objective behavioral and biochemical biomarkers « Administration of PTOO114 res

11. Slide 11: Saelens Test: Significant Reduction in Opioid Withdrawal Symptoms

    Saelens Test: Significant Reduction in Opioid Withdrawal Symptoms and Harmful Behavioral Response With Subcu-Administered PTOO1 14 * The Saelens Test is a standard animal model of Drug Withdrawal Response, whereby mice are addicted to an opioid (Morphine in this experiment) , and after several days,

12. Slide 12: PT00114's Potential Advantages Over Marketed Psychiatric Therapies

    PTOO1 14's Potential Advantages Over Marketed Psychiatric Therapies are Numerous Based on Observed Pharmacology Data and Preclinically Corroborated Mechanism of Action 12 Naturally crosses the blood brain barrier Rapid onset of action in animal anxiety and depression models as compared with other TR

13. Slide 13: Phase I/II Trial in 1H 2021 Advancing with Clinical and Operational Leaders

    Phase I/II Trial in 1H 2021 Advancing with Clinical and Operational Leaders | Double-Blind Study of PT00114 In Major Indications Sequential dose escalation with cohort replication for dose & biologic activity in 1, Major Depressive Disorder (MDD) who have suboptimal response to or poorly tolerated t

14. Slide 14: Phase I/II Trial Cohort 1: Normal Volunteers

    Phase I/II Trial Cohort 1: Normal Volunteers (NV) Screening Baseline v1 v2 v3 v4 vs ve v7 Day -21 to-1 Day O Day 1 Day 7 Day 8 Day 14 Day 15 Day 21 48 hour in-patient stay 48 hour in-patient stay 48 hour in-patient stay 2 Placebo 2 Placebo 2 Placebo Same subjects Same subjects Follow-up 6 active 6 a

15. Slide 15: Phase I/II Trial Cohorts 2-5: MDD, GAD, and PTSD

    Phase I/II Trial Cohorts 2 — 5: MDD, GAD, and PTSD MDD-(3:1) Play the winner Low (eee) PTSD-(3:1) Each subject 28 days treatment Date Range Mid July— Mid August Cohort 4 Ho) A) HE) A OP A-(S:1) Play the winner ———— Cohort 2, 3, and4 Each subject 28 days treatment Date Range: Early October to Early N

16. Slide 16: PTIX Owns Worldwide Exclusive Rights to Commercialize TCAP

    PTIX Owns Worldwide Exclusive Rights to Commercialize TCAP; Current Patent Estate Across Six Families of COM & Methods of Use Patents easel han uss Teneurin C-Terminal Associated Peptides (TCAP) and Methods 1 Pebaa May 2, 2023 2 ‘A Method of Regulating Neurite Growth May 2, 2023 Method for Modulatin

17. Slide 17: PTIX's Management Team Has Decades of Combined Experience

    PTIX’s Management Team Has Decades of Combined Experience Building Biopharma Companies From Discovery Through Development Garo H. Armen, Ph.D., Co-Founder, Executive Chairman Andrew Slee, Ph.D., Chief Operating Officer Mizobiology from Syracuse Universty Robert B. Stein, M.D. PhD., Dir vief Medical

18. Slide 18: PTIX's Key Strategic and Tactical Goals Over the Next Eight Quarters

    PTIX’s Key Strategic and Tactical Goals Over the Next Eight Quarters Align With Its Transition Into a Clinical-stage Company Rapidly advance PTOO114 through clinical trials in TRD, GAD, PTSD, and substance use disorder Explore efficacy in additional stress-related neuropsychiatric and mood disorders

19. Slide 19: PTIX Has Multiple Clinical Development-Related Catalysts Over the Next 12M

    PTIX Has Multiple Clinical Development-Related Catalysts Over the Next 12M 19 IND Filing Initiation of Phase I/II study Presentation at CNS conference Initial Readout of Phase I/II study Final Readout of Phase I/II study Plans for subsequent confirmatory/registrational studies (and/or any regulatory

20. Slide 20: Public Comparable Companies — Neuropsychiatric / Neurodegenerative

    Public Comparable Companies — Neuropsychiatric / Neurodegenerative Logo Name Market Cap ($M) Lead Candidate Phase CO AC\mmune AC Immune SA (NasdaqGM:ACIU) 6147 Crenezumab 2 A ADAMas" amas Pharmaceuticals, Inc. (NasdaqGM:ADMS) 167.4 ADS-5102 3 x SMAYVEX — Araver Life Sciences Corp. (NasdaqCMAVXL) 871

21. Slide 21: TCAP is a Platform With Potential to Deliver Therapeutic Impact

    21 ——_—— TCAP is a Platform With Potential to Deliver Therapeutic Impact to Millions of Patients With Unmet Need Globally Acts through the body's intrinsic mechanism to regulate stress Compelling preclinical data in animal models of Depression, PTSD, Anxiety, and Addiction Powerfully addresses voids

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23. Slide 23: Appendix

24. Slide 24: PT00114 Alleviates Physical and Emotional Impacts of Addiction, PTSD, and Depression

    PTOO114 Alleviates Physical and Emotional Impacts of Addiction, PTSD, and Depression in Animal Models Observed substantial reduction in behavioral and biochemical impacts of disease with no impact to motor function Saelens Test (standard animal model of Drug Withdrawal Response) « Mice are addicted

25. Slide 25: Saelens Test: Significant Reduction in Opioid Withdrawal Symptoms

    25 Saelens Test: Significant Reduction in Opioid Withdrawal Symptoms and Harmful Behavioral Response With Subcu-Administered PTOO114 # of Jumps per 20 Minutes (average) wal Py (oS in —_— t severe Ww sympton untreated mouse Maximal response seen with Pfizer's failed CRF-R1 antagonist PTOO114 treated

26. Slide 26: Open Field Test: Substantial Reduction in Stress-Related Anxious Behavior

    Open Field Test: Substantial Reduction in Stress-Related, Anxious Behavior With No Impact to Motor Function Motion Traces of Tube Stressed Mice, Day 8 Vehicle (untreated) 2 Doses PT00114 Intranasal (Days 1 & 2) PTO0114 treated mice moved freely through field, exhibiting significantly lower stress be

27. Slide 27: TCAP's Novel Mechanism of Action Suggests its Central Role in Counterbalancing Stress

    TCAP’s Novel Mechanism of Action Suggests its Central Role in Counterbalancing Stress Within the Brain’s Stress Response Cascade CRISPR-Based gene knockdown experiment confirms that PTOO1 14 acts through Latrophilin receptors TCAP interacts with Latrophilins via several proteins Latrophilins are hig

28. Slide 28: Integrated Development Plan

    Integrated Development Plan |Workstream / Activi [Clinical Development Phase I/lla Subsequent Studies cmc Formulation Development Drug Substance & Product Dev R&D Additional Pr00114 Pharmacology Studies| TCAP Platform Gmppse pp Complete Interim Data Readout Initiation of Sublingual & Intranasal Dosa

Protagenic Therapeutics, Inc.\new — Investor Presentation (April 2021) on 6ix