Protagenic Therapeutics, Inc. · OTC:PTIX
Protagenic Therapeutics — Protagenic Therapeutics, Inc.\new — Investor Presentation (April 2021)
28 slides from Protagenic Therapeutics's investor presentation, Apr 8, 2021
Slide 1: Breakthrough Therapeutics: Stress-Related Neuropsychiatric Disorders
Breakthrough Therapeutics. fo) Stress-Related Neuropsychiatric Disorders Corporate Overview April 2021
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 public sources. This presentation has been prepared to assist interested parties in making their own
Slide 3: Corporate Highlights
Corporate Highlights Sa Strong safety/efficacy signal in all relevant preclinical models v BtMGH) clinical study anticipated to be underway by 3Q 2021 by leading psychiatrist Dr. Maurizio Fava (Psychiatrist-in-Chief at x Potential Candidate for Breakthrough Designation by the FDA and put on an accel
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 Only Available drugs 0, 0, 50% 43% Only 2 approved t
Slide 5: The Stress Feedback Loop
The Stress Feedback Loop “ ¢ A person with past trauma or a history of substance abuse is more prone or sensitive to stress, which commences a STRESS aa PSYCHOLOGICAL & vicious cycle LEVEL PHYSIOLOGICAL + When met with a stressor, this causes HA\ brain impairment, and physical & emotional harm vy «
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 5 a response in the brain to - Taps into a biological system Works on a newly-discovered hea Ithy levels that has evolved over receptor system in the brain == millions of year
Slide 7: 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’ Additionally, these hormones trigger the release of ACTH2, which initiates the release of Cortisol, a steroid hor
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 PT00114 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 surro
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 + TCAP has been shown to be active in the regulation of cell proliferati
Slide 10: PT00114 Has Demonstrated Profound Efficacy and Safety in Preclinical Models
PT00114 Has Demonstrated Profound Efficacy and Safety in Extensive Preclinical Models of Stress-Related Disorders Safely 10 Multiple preclinical animal studies conducted in a range of stress-induced behavioral distortions using objective behavioral and biochemical biomarkers Administration of PT0011
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 * 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, withdrawa
Slide 12: PT00114's Potential Advantages Over Marketed Psychiatric Therapies
PT00114’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 TRD
Slide 13: Phase I/II Trial in 1H 2021 Advancing
Phase I/II Trial in 1H 2021 Advancing with Clinical and Operational | aaders Maurizio Fava, MD Psychiatrist-In-Chief, Department of Psychiatry Director, Division of Clinical Research Massachusetts General Hospital/Harvard Medical School Michael Murphy, MD, PhD Chief Medical and Scientific Officer at
Slide 14: Phase I/II Trial Cohort 1: Normal Volunteers
Phase I/II Trial Cohort 1: Normal Volunteers (NV) Screening Baseline M1 v2 v3 v4 V5 ve vw Day -21to-1 Dayo 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 Same Same Follow-up 6 active 6 active isit 6 (same (same V
Slide 15: Phase I/II Trial Cohorts 2-5: MDD, GAD, and PTSD
Phase I/II Trial Cohorts 2 — 5: MDD, GAD, and PTSD MDD4(3:1) Play the winner I) reythe winner Cohort 2 Cohort 2 and 3 GAD-(3:1) > Mid hmm | B-(3:1) > ee.) eTsD-(3:1) dese | ie -(1:1) Each subject 28 days treatment Each subject 28 days treatment Est Dates: 25 Jun 2021 to 6 Aug 2021 Est Dates: 7 Aug 2
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 Teneurin C-Terminal Associated Peptides (TCAP) and 1 Methods and Uses Thereof May 2, 2023 = A Method of Regulating Neurite Growth May 2, 2023 Method for Modulating In
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 Robert B. Stein, M.D., Ph.D. Director, Chief Medical Officer 17 Garo H. Armen, Ph.D., Co-Founder, Executive Chairman + Joined in 2004 + Chairman and CEO of Agenus Inc. + Former C
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 Com pany « Rapidly advance PT00114 through clinical trials in TRD, GAD, PTSD, and substance use disorder « Explore efficacy in additional stress-related neuropsychiatric and mood diso
Slide 19: Multiple Clinical Development-Related Catalysts Over the Next 12M
19 PTIX Has Multiple Clinical Development-Related Catalysts Over the Next 12M 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
Slide 20: Public Comparable Companies — Neuropsychiatric / Neurodegenerative
Public Comparable Companies — Neuropsychiatric / Neurodegenerative Weneavex CASSAVA sciences Catalyst harmaceatals JENALT © MINERVA &? Relmada Name AC Immune SA (NasdaqG@V-ACiu) ‘Adamas Pharmaceuticals, Inc. (Nasdaq@VADMS) ‘Anavex Life Sciences Corp. (NasdaqCM:AVXL) Cassava Sciences, Inc. (NasdaqCM:
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 in
Slide 22: Thank You
Slide 23: Appendix
Slide 24: PT00114 Alleviates Physical and Emotional Impacts of Addiction, PTSD, and Depression
PT00114 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
Slide 25: Saelens Test: Significant Reduction in Opioid Withdrawal Symptoms
Saelens Test: Significant Reduction in Opioid Withdrawal Symptoms and Harmful Behavioral Response With Subcu- Administered PT00114 # of Jumps per 20 Minutes (average) severe withdrawal 20 aac symptoms in i 1 untreated mouse Maximal response seen 0 of with Pfizer's failed CRF-R1 so ‘ 3! antagonist vo
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 Cortisol Level in Blood 8 PT00114 treated mice 140 | rset Cortical levels or — moves ey 130 stressed, untreated rough field, mice are almost exhibiting
Slide 27: TCAP's Novel Mechanism of Action Suggests its Central Role
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 PT00114 acts through Latrophilin receptors et = Posteyaote cal, 20 a-dystogyean—_{ tC ~ Neurexin 11 P-ystoaen 2 mC een
Slide 28: Integrated Development Plan
Integrated Development Plan Workstream / Activit Clinical Development Phase I/Ila Subsequent Clinical Studies Formulation Initiation of Sublingual & Development Intranasal Dosage Form Development Drug Substance & GMP Drug Product ss) Product Dev ‘Stability Studies R&D Additional PT00114 Pharmacology
Protagenic Therapeutics, Inc.\new — Investor Presentation (April 2021) on 6ix