CORPORATE OVERVIEW Developing a new class of targeted tolerizing treatments for autoimmune diseases Immusan-T Corporate Highlights

Antigen-specific immunotherapy is considered to be the definitive treatment of autoimmune disease

Platform • Discovery and development of tolerizing antigen-specific immunotherapies for auto- Technology immune diseases and beyond

• Up-dosing followed by ongoing weekly subcutaneous self administration Proof of Concept • Dosed over 150 celiac patients with Nexvax2 and demonstrated greatly reduced gluten-mediated Demonstrated in immune responses and disease symptoms Celiac Disease • Currently conducting Phase 2 clinical program, Fast track designation granted

Major Unmet • Celiac disease (CeD) represents a >$1B market in US with no approved pharmaceutical treatment Need and Market available Opportunities • Type 1 Diabetes represents a ~$5B market with a CAGR of 5.2% by 2028 in US alone

Patent • Robust patent IP estate of >130 granted, pending and licensed patents Protection

Corporate • Founded in 2010 History • Major investors: Vatera Healthcare Partners, ARCH Ventures, JDRF T1D Fund

2 Experienced Leadership Team

• Founded Immusan-T in 2010 • Over 25 years of experience in healthcare, executive Leslie Williams, BS, RN, MBA management, commercial product development and marketing: Chief Executive Officer & INO Therapeutics, Merck, GSK, DatexOhmeda President • Former President & CEO, Ventaira Pharmaceuticals • Venture Partner, Battelle Ventures • Clinical experience – Critical Care, Duke University • Inventor of Immusan-T’s technology Bob Anderson, MBChB, PhD, • Lab Head, Immunology, Walter and Eliza Hall Institute in FRACP Melbourne Chief Scientific Officer • Gastroenterologist; led Celiac Disease Clinic at the Alfred Hospital and Royal Melbourne Hospital • Post Doctoral Scientist, Nuffield Dept. of Medicine, Oxford University • Over 20 years in drug development, spanning pre-IND through Ken Truitt, MD NDA: Merck & Co, Daiichi Sankyo Pharma Chief Medical Officer • Experience across multiple therapeutic areas including cardiometabolic, immunology & inflammation, rare diseases • Background in rheumatology and immunology • Training: UCSD, Johns Hopkins, UCSF

• Over 30 years of professional financial experience in Tom Shea biopharmaceutical industry Chief Financial Officer • Raised approximately $1B • Former CFO: Alberio Pharmaceuticals ,Tolerx, Cubist Immune-System Imbalance Leads to Autoimmunity

T cells moderate and augment immunity

Healthy

Immunity Tolerance

Effector T cell Suppressor T cells (Tregs) (Teffs)

Loss of tolerance to self

Immunity

Imbalance between effector and suppressor arms of adaptive immunity results in autoimmune conditions 4 ESIT Platform Differentiators

• Epitope mapping and selection: For relevant autoantigens, we use Targeted Immune fresh patient blood and post translational modifications to identify Tolerance the most relevant immune-dominant epitope combination

• Patient Stratification: By HLA type II, ensuring the right combination of peptides is delivered to the right patient group Precision Toolkit • Biomarker Guided Discovery: Immune response to peptides is validated and monitored via patients’ biomarkers

• Accurate ESIT Dosing and Regimen: Guided by PK/PD studies in previously dosed patients Clinical Experience • Platform Validation: We are leveraging key learning from our celiac disease program, a widely recognized model for autoimmune disease

• Fast: Discovery to composition – 1 year; Discovery to Phase I – 2 Optimized R&D years Process • Streamlined: Minimal use of animal models; No added adjuvants - straight forward CMC

5 Celiac disease Is a Recognized Model for Autoimmune Disease to Develop ESIT™ Platform potential in Autoimmune disease

Celiac Disease attributes GI / Hepatology Rheumatology • Primary Biliary Cholangitis • Rheumatoid Arthritis (RA) (PBC) • Systemic Lupus • Exogenous antigen – ability • Autoimmune Hepatitis Erythematosus (SLE) to challenge and withhold in (AIH) • Sjogren’s Syndrome clinical setting • Access to target organ We will implement learnings from the CeD Neurology Endocrinology (inflamed small intestine) via program to streamline our duodenal biopsy discovery & development • Multiple Sclerosis (MS) • Type 1 Diabetes • Strong HLA class II platform • Myasthenia Gravis (MG) • Graves’ Disease association • Narcolepsy • Hashimoto’s Thyroiditis • Blood based immune monitoring Dermatology Hematology • Prevalent -1% of population • Pemphigus Vulgaris (PV) • Thrombotic Thrombocytopenic Purpura • Vitiligo (TTP)

6 Platform Potential Beyond Autoimmune Disease By selecting the most relevant, immune-dominant epitopes for targeted tolerogenic therapies, we believe we can engage our platform across multiple applications:

Therapeutic Inflammation Viral Vectors CRISPR Payload Cell Therapy Oncology* & Allergy (Protein)

• Gene therapy • Neutralizing Ab’s • Gene therapy • Adaptive Cell • Asthma • Neoantigens: • Oncolytic viruses against CRISPR • Protein therapy therapy (i.e. CAR-T) • Food/Peanut functional (Anti drug Ab’s) • Stem cell therapy allergy hierarchy of • mRNA immune- relevant targets

7 * In oncology, our immunomodulatory approach will be applied to activate the immune response (rather than tolerizing) Immusan-T’s Pipeline First-in-class ESIT™ for autoimmune diseases

Development Stage Product Modality Indication Status Partner Discovery Pre-Clinical Ph. 1 Ph. 2 Ph. 3

ESIT™ Celiac • 5 proof-of-principle P1 studies Nexvax2® • Dose regimen established Vaccine Disease • Phase 2 trial underway

• Pilot discovery complete ESIT™ Type 1 • Preliminary fine mapping IMST-02 complete Vaccine Diabetes • Epitope hierarchy to be mapped by mid 2019

ESIT™ Multiple • Pilot discovery IMST-03 Vaccine Sclerosis underway

ESIT™ AAV Tolerance • Pilot discovery IMST-04 Not disclosed Vaccine Induction underway

• Diagnostic markers identified Celiac Disease • Supplementary studies Standalone To be licensed (expands Nexvax2® completed GC-2 Diagnostic out market) • Assay optimization close to completion

8 Confidential & Proprietary CELIAC DISEASE Nexvax2® Celiac Disease Represents a Serious Medical Condition… • Prevalence of about 1% of US/EU population • Clear genetic association: 90% of patients with HLA DQ2.5 Genotype Epidemiology • Rapid expansion in medical awareness and diagnosis in the last decade, but still up to 50% undiagnosed • Dietary exposure to gluten (antigen), the major protein component in wheat, rye and barley drives a pathogenic autoimmune response Pathogenesis • CD4+ T-cell specific targeting gluten peptides are activated → release of cytokines & initiation of an immunologic cascade → acute and chronic symptoms • Serology: specific antibody titers (i.e. tTG) Diagnosis • For confirmation, guidelines require small bowel biopsy that demonstrates villous atrophy, crypt elongation and lymphocytic infiltration Acute Chronic Normal Small Bowel Celiac Disease >2wks with GI: nausea; Malnutrition and failure Gluten vomiting; bloating, to thrive; anemia; GI Symptoms 1yr strict diarrhea; pain cancer; osteoporosis GFD Non GI: headache; infertility; ataxia; (likely) fatigue increased mortality rate

10 Source: NICE clinical guideline 86. Celiac disease. Recognition and assessment of celiac disease; London: National Institute for Health and Clinical Excellence, 2009. …With a Significant Unmet Medical Need

• There are no approved drugs to treat Celiac disease Treatment • Current standard of care is lifelong, strict gluten free diet (GFD) • Aim is to lower gluten intake in patients to levels below 10 mg/day (bread crumb)1

• Gluten and its byproducts are pervasive: strict GFD is hard to achieve and harder to maintain • Even in patients doing their best to adhere to a gluten free diet, inadvertent exposure to gluten is estimated at > 150-400 mg/day (1/10th slice of bread)2 well above the Challenges recommended level • GFD has a negative impact on patients’ quality of life, and celiac patients rate their burden of treatment comparably to how end stage renal disease patients view hemodialysis3

GFD is inadequate at managing inadvertent exposure even in compliant patients, exposing them to serious complications.

1Laurikka P, et al. Dietary Factors and Mucosal Immune Response in Celiac Disease Patients Having Persistent Symptoms Despite a Gluten-free Diet. J Clin Gastroenterol. 2018 Mar 2. 11 2Syage JA, et al. Determination of gluten consumption in celiac disease patients on a gluten-free diet. Am J Clin Nutr. 2018 Feb 1; 107(2): 201-207. 3Shah S, et al. Patient perception of treatment burden is high in celiac disease compared with other common conditions. Am J Gastroenterol. 2014; 109(9): 1304–1311. Gluten Ingestion Causes Symptoms and Systemic Cytokine Release in Celiac Patients

T = 0: patient consumed 3 g gluten in a 10) - liquid slurry

Severity (0 Severity 36yo HLA-DQ2.5 homozygous, 6yrs GFD - very good adherence (CDAT score 8), tTG-IgA and DGP-IgG in

normal range

Fold change Fold Fold change Fold

12 Source: Tye-Din JA et al., ICDS 2017 Celiac Disease Is a CD4+ T Cell-Mediated Disease Treatment should selectively target gluten-specific CD4+ T cells, the underlying cause of disease

Antigen-specific CD4+ T cells are activated by antigenic peptides with single exposure…

…However, with regular chronic exposure, these T-cells are inactivated (e.g. similar to allergy desensitization therapy)

13 Nexvax2® Epitope-Specific Immunotherapy (ESIT™)

An equimolar mix of 3 peptides that contain overlapping, immunodominant HLA-DQ2.5-restricted T-cell receptor gluten epitopes, including post-translational modifications, to enhance bioactivity and bioavailability

HLA-DQ2·5-restricted 9 amino acid Nexvax2 Peptide Amino acids T-cell epitopes epitope sequences

NPL001 16 DQ2·5-glia-α1a PFPQPELPY DQ2·5-glia-α2 PQPELPYPQ DQ2.5-glia-α2 NPL002 15 DQ2·5-glia-ω1 PFPQPEQPF DQ2·5-glia-ω2 PQPEQPFPW HLA-DQ2.5 NPL003 16 DQ2·5-hor-3 PIPEQPQPY var DQ2·5-glia-γ5 EQPIPEQPQ

Selection based on hierarchy of immunodominance identified from 17,000 candidate peptides using patient fresh blood samples TCR-footprint

14 Source: Anderson RP et al. Nat Med. 2000 Mar;6(3):337-42; Tye-Din JA et al. Sci Transl Med. 2010 Jul 21;2(41):41ra51; Goel G. et al. Lancet Gastroenterol Hepatol. 2017 Jul;2(7):479-493; Nexvax2 Associated Cytokine Response Disappears After Repeat Doses – Consistent Effect on Symptoms

1st Dose 3rd Dose 16th Dose Nexvax2 150 μg (N = 23) Weekly Dosing (N = 8) 2xWeekly Dosing (N = 15)

IL-2 MCP-1 IP-10 IL-8 IL-10 IL-2 MCP-1 IP-10 IL-8 IL-10 IL-2 MCP-1 IP-10 IL-8 IL-10

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Plasma levels and PK profiles for Nexvax2 at last dose were same as first dose PK

15 Nexvax2 but Not Placebo Induces Immunologic and Symptomatic Tolerance Treated patients challenged with 9 gm/day gluten for 3 days

Gluten challenge after 8 weeks of treatment

Nexvax2 Placebo 0% Treatment Responders* Placebo 150ug Randomized 7 8

Nexvax2 150µg 75% Treatment Responders* Initiated GC 7 (100%) 8 (100%) Completed GC 3 (43%) 8 (100%) Treatment Patient not Patient 0 (0%) 6 (75%) Failed to Responders complete immunotolerant to immunotolerant to gluten Nexvax2/gluten Nexvax2/gluten challenge p = 0.021 vs placebo

Treatment Responder = Completed gluten challenge + No Cytokine excursion

16 Source: Goel G. et al. Lancet Gastroenterol Hepatol. 2017 Jul;2(7):479-493. Nexvax2 Dose Regimen Established: Escalation Avoids Cytokine Response and Allows for Higher Top Dose

After incremental escalation, no cytokine release with 1st dose Nexvax2 3μg or 900 μg maintenance dose

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900 μg dose contains the antigenic load of ~ 2 loaves of bread

17 Phase 2 Clinical Trial Overview (Q4 ‘19 Top Line Data)

• Randomized, double-blind, placebo-controlled study in HLA-DQ2.5+ celiac patients on a gluten-free diet (N=180) – Primary endpoint - change in GI symptoms following gluten challenge ➢ Validated celiac disease patient reported outcomes (CeD PRO) tool ➢ Clinical model replicates inadvertent gluten exposure – Secondary endpoint - change in cytokines following gluten challenge – Endoscopy (biopsy) subgroup – safety – Total duration = 26 weeks (16 weeks on treatment) – 40 sites: US, AUS, NZ

18 TYPE 1 DIABETES: Targeted Immune Tolerance Immusan-T’s Targeted Approach Has Potential to Create the First Disease Modifying Therapy for Type 1 Diabetes

• Immusan-T Focus: Selective tolerance to Current auto-antigens without systemic immuno- Genetic (HLA) therapeutic suppression predisposition window

• IMST-02 (vaccine for type 1 diabetes): Preserve endogenous insulin production & improve glycemic control - in combination with exogenous insulin

therapy C-peptide present • Potential to be the first disease modifying therapy: Anticipated endpoints will reflect b-cell mass in addition to glucose homeostasis

• Learnings from celiac program de-risk T1D clinical development Goal to expand the window to earlier timepoints in the disease course

20 Contact Information

Immusan-T, Inc. Building 700, Suite 7102 One Kendall Square Cambridge, MA 02139

Leslie J Williams, President & CEO Phone: 617-515-6755 Email: [email protected]

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