Capo Therapeutics, Inc.

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1 Capo Therapeutics, Inc. Vaccine Therapies for Debilitating Diseases of the Brain San Diego, CA 1

2 SCIENTIFIC ADVISORY BOARD M. Flint Beal, M.D. Dr. Beal is an internationally recognized authority on neurodegenerative disorders. He is the Chairman of the Department of Neurology and Neuroscience at Weill Medical College of Cornell University and Director of the Neurology service at the New York Presbyterian Cornell Campus. He joined the neurology faculty at Harvard in 1983 and was Professor of Neurology at the Harvard Medical School. Dr. Beal's research has focused on the mechanism of neuronal degeneration in Alzheimer's Disease, Huntington's Disease, Parkinson's Disease and amyotrophic lateral sclerosis (ALS). Dr. Beal is the author or co-author of more than 300 scientific articles and more than 125 books, book chapters and reviews and a member of many professional organizations, including the Institute of Medicine of the National Academy of Sciences. Lon Schneider, M.D. - Professor of psychiatry, neurology and gerontology at USC. He directs the USC State of California Alzheimer s Disease Center and the clinical core and pharmacology program of the USC NIH/NIA Alzheimer s Disease Research Center. He has enormous expertise in clinical trials methods, instruments and rating scales for dementia trials, meta-analyses, and drug development. He serves on the steering committees of the NIH ADCS, the NIH ADNI, and the Alzheimer Prevention Initiative. He is internationally recognized in clinical drug development for AD, neuropsychiatric, and behavioral disorders, has led numerous clinical trials for AD and MCI therapeutics, consults with numerous development programs, participated in the design and operations of several early and later phase proprietary development programs for AD, and directed multicenter trials in AD and major depression. 2

3 Scientific Advisory Board David Cribbs, Ph.D. - Professor in Residence, Neurology, UCI School of Medicine and Associate Director of the MIND Institute at University of California, Irvine is an expert on age-related factors responsible for the initiation and the progression of AD, antibody-mediated clearance of Aß, identifying risk factors associated with immunotherapy in elderly AD patients. He has been appointed to the Department of Veterans Affairs Joint Biomedical Laboratory Research and Development and Clinical Science Research and Development Services. Dr. Cribbs is longtime collaborator of Dr. Agadjanyan and he is directly involved in their AD/PD vaccine projects. 3

Key Statistics for Alzheimer s Disease (AD) Epidemiology and Statistics By mid-century, someone in the United States will develop the disease every 33 seconds. 5.

4 Key Statistics for Alzheimer s Disease (AD) Epidemiology and Statistics By mid-century, someone in the United States will develop the disease every 33 seconds. 5.3 million Americans have this disease, 44 million worldwide Cost of AD $226 billion in the US (2015) and $604 billion worldwide $1.2 trillion projected in 2050 Current Market $6 billion for no effective treatments Should an effective treatment become available, the valuation is astronomical Therefore, Eli Lilly, Johnson & Johnson and Roche are actively buying companies and developing their own programs. They are spending billions. 4

5 Valuations in the AD Market Year Developer Licensee/Buyer/Co- Developer Deal Type Deal size (Millions) 2016 Heptares Allergan Licensing $3, Avanir Otsuka America M&A $3, Trophos Roche M&A $ Neurimmune Biogen Alliance $ AC Immune Janssen Pharmaceutical Co-Development $ Bionomics Merck Licensing $ Astra Zeneca Lilly Licensing $ ipierian Bristol- Myers M&A $ Rinat Pfizer Licensing $ AC Immune Roche/Genentech Licensing $ Affiris GlaxoSmithKline Licensing $ Medivation Pfizer Licensing $225+$500 5

6 Valuations as a Function of Maturity Capo After Investment Capo Now 6

Business Strategy Capitalize on tremendous need for AD treatment Capo Therapeutics IP has some of the most promising pre-clinical data available

7 Business Strategy Capitalize on tremendous need for AD treatment Capo Therapeutics IP has some of the most promising pre-clinical data available and is based on extensive R&D supported by the NIH IND s are ready to be written File IND s and begin Phase 1 trials Build to sell Help patients 7

Capo s Scientific Strategy Many ongoing clinical trials using vaccines for AD All of these vaccines have failed and those still ongoing will fail DUE TO DIFFICULTY TO GET HIGH TITERS OF THERAPEUTIC

8 Capo s Scientific Strategy Many ongoing clinical trials using vaccines for AD All of these vaccines have failed and those still ongoing will fail DUE TO DIFFICULTY TO GET HIGH TITERS OF THERAPEUTIC ANTIBODIES IN HUMANS (AS OPPOSED TO MICE) Capo IP has overcome this obstacle (competitive advantage) We have combined three key elements: Strong Multi-TEP platform, Novel proprietary adjuvant (Advax) and Aβ immunogen Using this, we can generate titers of therapeutic antibodies 1000x higher than competitors including in monkeys We can use this cocktail for AD and also for Parkinson s Disease Pre-clinical and experimental animal data rock solid. Pre-IND with FDA suggested that FDA will not question our clinical application 8

9 CAPO S TREATMENT STRATEGY Aβ &/or tau α-syn Aβ tau and/or tau/aβ Targeting the Right Pathology at the Right Time Vaccination strategy is to target appropriate pathological molecules, such as Aβ, tau, α-syn & their combinations at specific disease stages 9

10 MultiTEP Immunogenicity Comparison Table Vaccine Sponsor B cell epitope Carrier/ vaccine platform/ adjuvant Anti-Aβ B cells immune responses Mice Monkeys Humans Status** ACC001 Pfizer/Elan/ Janssen Aβ 1-7 Dithteria toxin/ QS21 NR* +/- Discontinued V950 Merck Aβ 1-15 Carrier unknown+ ISCOMATRIX NR Discontinued AD02 Affiris & GlaxoSmithKline Aβ 1-6 KLH/Alum + NR +/- Discontinued AD03 Affiris & GlaxoSmithKline Aβ pyrogluta mate KLH/Alum NR NR NR Discontinued CAD106 Cytos/Novartis Aβ 1-6 Bacteriophage Qβ Alum +++ +/- -/+ Phase 2 completed ACI-24 ACImmune/ Roche/Genentech Aβ 1-16 Liposome/MPLA +++ NR NR Phase 1/2 UB311 United Biomedical Inc Aβ Th epitopes (UBITh Aum/CpG) NR +++ NR Phase 2 initiated in 2015 LU AF20515 Lundbeck/Otsuca Tested IMM/UCI Aβ 1-12 P30/P2 TT Th epitopes (developed by IMM group) + ++ NR Phase 1 AV1959 Capo Therapeutics 3 copies Aβ 1-11 MultiTEP platform Advax/CpG for mice DNA for monkeys not started IND Pending 10

11 Antibody responses in Tg2576 vaccinated with AV-1959R formulated in Advax CpG vs LU AF Alum (600 times stronger) Anti-Aβ antibody conc. (µg/ml) Tg2576 mice T5x mice Antibody titers in Tg2576 mice LU AF20515 AV-1959R 3µg/ml 1800µg/ml (Davtyan et al., 2014) 11

12 Antibody responses in PS19 vaccinated with AV-1980R formulated in Advax CpG vs ACI-35+ Alum (1600 times stronger) Anti-tau antibody level (OD 450 ) Tg4510 mice PS19 mice T5x mice Vaccinated with AV-1980R+Advax CpG. Sera was diluted 1: Antibody titers in Tau PS19 Tg mice ACI-35 AV-1980R 1:100 1:

AV-1959R MultiTEP-Based Epitope Vaccine Prevents

Escape Latency, sec 80 60 40 20 The escape latency to

Non-vaccinated Irrelevant antigen AV-1959R vaccinated

Control **** AV-1959R Number of ThS-positive plaques

13 AV-1959R MultiTEP-Based Epitope Vaccine Prevents Cognitive Dysfunction and Aβ-plaques in APP/Tg Mice Escape Latency, sec The escape latency to reach the platform *** *** *** *** *** *** Non-vaccinated Irrelevant antigen AV-1959R vaccinated Wild-type 6E10-positive Aβ-load Control **** AV-1959R Number of ThS-positive plaques Control **** AV-1959R Days of Training 13

AV-1980R MultiTEP-Based Epitope Vaccine Prevents the Development of Motor, Learning and Memory Deficits in Tau/Tg Mice Learning and Memory Motor % of time spent in Novel Arm Y-maze activity: PERCENT

14 AV-1980R MultiTEP-Based Epitope Vaccine Prevents the Development of Motor, Learning and Memory Deficits in Tau/Tg Mice Learning and Memory Motor % of time spent in Novel Arm Y-maze activity: PERCENT of TIME SPENT in the NOVEL ARM Mice Normal Tau/Tg Tau/Tg * Treatment Non-vaccinated Advax CpG AV-1980R/ Advax CpG *** Latency to fall (second) Rota-Rod Performance Test ACCELERATION *** ** Normal Tau/Tg Tau/Tg Non-vaccinated Advax CpG AV-1980R/ Advax CpG 14

15 MultiTEP-based AD Epitope Vaccine Active Component 3 copies of Tau 2-18 B cell epitope Targeting Tau MultiTEP Platform AV-1980R PADRE P23 P32 P21 P30 P2 HBV nc HBsAg MT P7 P17 P28 Active Component 3 copies of Aβ 1-11 B cell epitope Targeting Aβ MultiTEP Platform AV-1959R PADRE P23 P32 P21 P30 P2 HBV nc HBsAg MT P7 P17 P28 MultiTEP Platform: Universal Th cell epitopes: synthetic (PADRE) or TT (P epitopes), HBV (nc and sag) and Flu (MT) 21

16 Capo s Therapeutics Pipeline Lead Vaccine Products Disease Vaccine Target epitope Type of Vaccine (DNA or Protein) Pre-clinical Immunogenicity & Efficacy Preclinical Safety IND Phase I Trial AD AV-1959D N terminus of Aβ 1-11 DNA DONE Funded by NINDS R01 and U44 Ongoing Funded NIA U01 Funded by NIA U01 AD AV-1959R N terminus of Aβ 1-11 adjuvant Protein + Advax CpG DONE Funded by NINDS * R01 AD AV-1980R AV-1980D N terminus of Tau 2-18 Protein + Advax CpG adjuvant DNA DONE Funded by NINDS R01 * Use of funds 16

17 Capo Therapeutics Pipeline (cont d) Next Generation of Vaccine Products for AD/PD/DLB/FTD Disease Vaccine Target B cell epitope Type of Vaccine (DNA or Protein) Pre-clinical Immunogenicity & Efficacy Pre- clinical Safety IND AD AV-1960CP Pyroglutamated Aβ 3p-11 Chemically modified protein Chemically AD AV-1991CP Phosphorylated Tau 396/404 modified protein Chemically AD AV-1992CP Acetylated Tau K174 modified protein PD AV-1947D a-syn (Epitope ) DNA PD AV-1948D a-syn (Epitope ) DNA PD AV-1949D a-syn (Epitope ) DNA PD AV-1950R AV-1950D a-syn (85-88/ / ) Protein +Advax CpG DNA In progress Funded by IMM In progress Funded by IMM In progress Funded by IMM In progress Funded by NIA R01 In progress Funded by NIA R01 In progress Funded by NIA R01 In progress Funded by R01 * * * * * * * * * * * * * * 17

18 Milestones and Timing Prepare and submit IND for AV-1959D (Q1 2017): Funding in place, toxicology studies ongoing, pre-ind meeting with FDA completed and another pre-ind FDA meeting will be scheduled after receiving safety/toxicology data (funds from NINDS U01) Prepare and submit IND for AV-1959R (Q1-Q3 2017): Dependent on fundraising Prepare and submit IND for AV-1980R (Q3 2017): Dependent on fundraising Design Phase I clinical trial for AV-1959D, work with CRO s to identify best partner, begin Phase I (Q Q2 2018): Dependent on fundraising 18

Engaging stakeholders for a holistic therapy in Alzheimer s disease

Engaging stakeholders for a holistic therapy in Alzheimer s disease Brain Forum l Lausanne, May 26, 2016 l Prof. Andrea Pfeifer 2016 AC Immune. Not to be used or reproduced without permission. www.acimmune.com