Developing a new class of targeted tolerizing treatments for autoimmune diseases

CORPORATE OVERVIEW

Major Unmet

Need and Market

Opportunities

Corporate

History

Proof of Concept

Demonstrated in

Celiac Disease

Platform

Technology

• Up-dosing followed by ongoing weekly subcutaneous self administration

• Dosed over 150 celiac patients with Nexvax2 and demonstrated greatly reduced gluten-mediated

immune responses and disease symptoms

• Currently conducting Phase 2 clinical program, Fast track designation granted

• Founded in 2010

• Major investors: Vatera Healthcare Partners, ARCH Ventures, JDRF T1D Fund

• Discovery and development of tolerizing antigen-specific immunotherapies for auto-

immune diseases and beyond

Patent

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

• Celiac disease (CeD) represents a >$1B market in US with no approved pharmaceutical treatment

available

• Type 1 Diabetes represents a ~$5B market with a CAGR of 5.2% by 2028 in US alone

Immusan-T Corporate Highlights

2

Antigen-specific immunotherapy is considered to be the

definitive treatment of autoimmune disease

Leslie Williams, BS, RN, MBA

Chief Executive Officer &

President

• Founded Immusan-T in 2010

• Over 25 years of experience in healthcare, executive

management, commercial product development and marketing:

INO Therapeutics, Merck, GSK, DatexOhmeda

• Former President & CEO, Ventaira Pharmaceuticals

• Venture Partner, Battelle Ventures

• Clinical experience – Critical Care, Duke University

Ken Truitt, MD

Chief Medical Officer

• Over 20 years in drug development, spanning pre-IND through

NDA: Merck & Co, Daiichi Sankyo Pharma

• Experience across multiple therapeutic areas including

cardiometabolic, immunology & inflammation, rare diseases

• Background in rheumatology and immunology

• Training: UCSD, Johns Hopkins, UCSF

Bob Anderson, MBChB, PhD,

FRACP

Chief Scientific Officer

• Inventor of Immusan-T’s technology

• Lab Head, Immunology, Walter and Eliza Hall Institute in

Melbourne

• Gastroenterologist; led Celiac Disease Clinic at the Alfred

Hospital and Royal Melbourne Hospital

• Post Doctoral Scientist, Nuffield Dept. of Medicine, Oxford

University

Experienced Leadership Team

Tom Shea

Chief Financial Officer

• Over 30 years of professional financial experience in

biopharmaceutical industry

• Raised approximately $1B

• Former CFO: Alberio Pharmaceuticals ,Tolerx, Cubist

Immune-System Imbalance Leads to Autoimmunity

4

T cells moderate and

augment immunity

Tolerance

Healthy

Effector T cell

(Teffs)

Loss of tolerance to

self

Suppressor T cells (Tregs)

Immunity

Immunity

Imbalance between effector and suppressor arms of

adaptive immunity results in autoimmune conditions

ESIT Platform Differentiators

5

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

Targeted Immune Tolerance

Precision Toolkit

• Patient Stratification: By HLA type II, ensuring the right combination of peptides is delivered to the right patient group

• Biomarker Guided Discovery: Immune response to peptides is validated and monitored via patients’ biomarkers

Optimized R&D Process

• Fast: Discovery to composition – 1 year; Discovery to Phase I – 2 years

• Streamlined: Minimal use of animal models; No added adjuvants -straight forward CMC

Clinical Experience

• Accurate ESIT Dosing and Regimen: Guided by PK/PD studies in previously dosed patients

• Platform Validation: We are leveraging key learning from our celiac disease program, a widely recognized model for autoimmune disease

Celiac disease Is a Recognized Model for Autoimmune Disease to Develop ESIT™

6

Rheumatology

• Rheumatoid Arthritis (RA)

• Systemic Lupus

Erythematosus (SLE)

• Sjogren’s Syndrome

Neurology

• Multiple Sclerosis (MS)

• Myasthenia Gravis (MG)

• Narcolepsy

GI / Hepatology

• Primary Biliary Cholangitis

(PBC)

• Autoimmune Hepatitis

(AIH)

Dermatology

• Pemphigus Vulgaris (PV)

• Vitiligo

Endocrinology

• Type 1 Diabetes

• Graves’ Disease

• Hashimoto’s Thyroiditis

Hematology

• Thrombotic

Thrombocytopenic Purpura

(TTP)

We will implement

learnings from the CeD

program to streamline our

discovery & development

platform

• Exogenous antigen – ability

to challenge and withhold in

clinical setting

• Access to target organ

(inflamed small intestine) via

duodenal biopsy

• Strong HLA class II

association

• Blood based immune

monitoring

• Prevalent -1% of population

Celiac Disease attributes

Platform potential in Autoimmune disease

Platform Potential Beyond Autoimmune Disease

7

Viral Vectors CRISPR Cell Therapy

• Gene therapy• Oncolytic viruses

Oncology*

• Adaptive Cell therapy (i.e. CAR-T)

• Stem cell therapy

• Neutralizing Ab’s against CRISPR

Therapeutic

Payload

(Protein)

• Gene therapy• Protein therapy

(Anti drug Ab’s)• mRNA

Inflammation

& Allergy

• Neoantigens: functional hierarchy of immune- relevant targets

By selecting the most relevant, immune-dominant epitopes for targeted tolerogenic therapies, we

believe we can engage our platform across multiple applications:

* In oncology, our immunomodulatory approach will be applied to activate the immune response (rather than tolerizing)

• Asthma• Food/Peanut

allergy

Immusan-T’s Pipeline First-in-class ESIT™ for autoimmune diseases

GC-2Standalone

Diagnostic

Celiac Disease

(expands Nexvax2®

market)

• Diagnostic markers identified• Supplementary studies

completed • Assay optimization close to

completion

To be licensed

out

Product Modality IndicationDevelopment Stage

Status PartnerDiscovery Pre-Clinical Ph. 1 Ph. 2 Ph. 3

Nexvax2® ESIT™

Vaccine

Celiac

Disease

• 5 proof-of-principle P1 studies

• Dose regimen established

• Phase 2 trial underway

IMST-02ESIT™

Vaccine

Type 1

Diabetes

• Pilot discovery complete• Preliminary fine mapping

complete• Epitope hierarchy to be

mapped by mid 2019

IMST-03ESIT™

Vaccine

Multiple

Sclerosis• Pilot discovery

underway

IMST-04ESIT™

Vaccine

AAV Tolerance

Induction• Pilot discovery

underwayNot disclosed

Confidential & Proprietary8

Nexvax2®

CELIAC DISEASE

Celiac Disease Represents a Serious Medical Condition…

Source: NICE clinical guideline 86. Celiac disease. Recognition and assessment of celiac disease; London:

National Institute for Health and Clinical Excellence, 2009.10

Epidemiology

• Prevalence of about 1% of US/EU population

• Clear genetic association: 90% of patients with HLA DQ2.5 Genotype

• Rapid expansion in medical awareness and diagnosis in the last decade, but still up to

50% undiagnosed

Pathogenesis

• Dietary exposure to gluten (antigen), the major protein component in wheat, rye and

barley drives a pathogenic autoimmune response

• CD4+ T-cell specific targeting gluten peptides are activated → release of cytokines &

initiation of an immunologic cascade → acute and chronic symptoms

Diagnosis

• Serology: specific antibody titers (i.e. tTG)

• For confirmation, guidelines require small bowel biopsy that demonstrates villous

atrophy, crypt elongation and lymphocytic infiltration

Acute Chronic

GI: nausea;

vomiting; bloating,

diarrhea; pain

Non GI: headache;

fatigue

Malnutrition and failure

to thrive; anemia; GI

cancer; osteoporosis

infertility; ataxia; (likely)

increased mortality rate

Normal Small Bowel Celiac Disease

1yr strict

GFD

>2wks with

Gluten

Symptoms

…With a Significant Unmet Medical Need

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 2.2Syage 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.

11

Treatment

Challenges

• 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

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

• There are no approved drugs to treat Celiac disease

• 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

GFD is inadequate at managing inadvertent exposure even in compliant

patients, exposing them to serious complications.

Gluten Ingestion Causes Symptoms and Systemic Cytokine Release in Celiac Patients

12

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

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

Source: Tye-Din JA et al., ICDS 2017

Severi

ty (

0-1

0)

Fo

ld c

han

ge

Fo

ld c

han

ge

Celiac Disease Is a CD4+ T Cell-Mediated Disease

13

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)

Nexvax2® Epitope-Specific Immunotherapy (ESIT™)

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;

Selection based on hierarchy of immunodominance identified from

17,000 candidate peptides using patient fresh blood samples

Nexvax2 Peptide Amino acidsHLA-DQ2·5-restricted

T-cell epitopes

9 amino acid

epitope sequences

NPL001 16 DQ2·5-glia-α1a PFPQPELPY

DQ2·5-glia-α2 PQPELPYPQ

NPL002 15 DQ2·5-glia-ω1 PFPQPEQPF

DQ2·5-glia-ω2 PQPEQPFPW

NPL003 16 DQ2·5-hor-3 PIPEQPQPY

var DQ2·5-glia-γ5 EQPIPEQPQ

DQ2.5-glia-α2

T-cell receptor

HLA-DQ2.5

TCR-footprint

An equimolar mix of 3 peptides that contain overlapping, immunodominant HLA-DQ2.5-restricted

gluten epitopes, including post-translational modifications, to enhance bioactivity and bioavailability

Nexvax2 Associated Cytokine Response Disappears After Repeat Doses – Consistent Effect on Symptoms

15

Nexvax2 150 μg (N = 23)

1st Dose 3rd Dose2xWeekly Dosing (N = 15)

16th Dose

0 1 2 3 4 5 6

1

10

2

3

5

7

15

Hours

Fold

change

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

0 1 2 3 4 5 6

1

10

2

3

5

7

15

Hours

Fold

change

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

0 1 2 3 4 5 6

1

10

2

3

5

7

15

Hours

Fold

change

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

Weekly Dosing (N = 8)

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

Nexvax2 but Not Placebo Induces Immunologic and Symptomatic Tolerance

Source: Goel G. et al. Lancet Gastroenterol Hepatol. 2017 Jul;2(7):479-493.16

Treated patients challenged with 9 gm/day gluten for 3 days

Failed to

complete

gluten

challenge

Patient not

immunotolerant to

Nexvax2/gluten

Patient

immunotolerant to

Nexvax2/gluten

0% Treatment Responders*Placebo

75% Treatment Responders*Nexvax2 150µg

Treatment Responder = Completed gluten challenge + No Cytokine excursion

Gluten challenge after 8 weeks of treatment

PlaceboNexvax2

150ug

Randomized 7 8

Initiated GC 7 (100%) 8 (100%)

Completed GC 3 (43%) 8 (100%)

Treatment

Responders0 (0%) 6 (75%)

p = 0.021 vs placebo

Nexvax2 Dose Regimen Established: Escalation Avoids Cytokine Response and Allows for Higher Top Dose

17

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

maintenance dose

Pre 2h 4h 6h0.1

1

10

100

Hours

IL2 (

pg/m

l)

Screening Food Challenge

0h 2h 4h 6h 8h0.1

1

10

100

Hours

IL2 (

pg/m

l)

Nexvax2 3mgNexvax2 3μg (initial dose)

0h 2h 4h 6h 8h0.1

1

10

100

Hours

IL2 (

pg/m

l)

Nexvax2 900mg (1st SC dose)Nexvax2 900μg (maintenance dose)

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

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

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Targeted Immune Tolerance

TYPE 1 DIABETES:

Immusan-T’s Targeted Approach Has Potential to Create the First Disease Modifying Therapy for Type 1 Diabetes

• Immusan-T Focus: Selective tolerance to

auto-antigens without systemic immuno-

suppression

• IMST-02 (vaccine for type 1 diabetes):

Preserve endogenous insulin production

& improve glycemic control - in

combination with exogenous insulin

therapy

• 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

20

Current

therapeutic

windowGenetic (HLA)

predisposition

C-peptide present

Goal to expand the window to earlier

timepoints in the disease course

Contact Information

21

Immusan-T, Inc.

Building 700, Suite 7102

One Kendall Square

Cambridge, MA 02139

Leslie J Williams, President & CEO

Phone: 617-515-6755

Email: leslie@immusant.com