Targeting Neuroinflammation: The Common Thread in Neurodegenerative Disease Progression

200 Clarendon Street, 17th Floor

Boston, MA 02116

www.aztherapies.com

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Innovative Approach and Compelling Opportunity

Robust IP Estate with More Than 100 Patents and Applications

Late Stage Lead Program – Fully Enrolled

ALZT-OP1 in Early Stage Alzheimer’s Disease;Completion Expected Q1 2021

Experienced Leadership Team

Growing Pipeline with Near-term Clinical Milestones

Multiple Programs Targeting Neuroinflammation to Address Neurodegeneration

Novel Approach

Targeting Neuroinflammation by Multimodal Mechanisms as a Key Driver of Neurodegeneration

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Experienced Leadership Team

David R. Elmaleh, PhD

Founder, Chairman, and CEO

Karen Reeves, MD

President and CMO

Jay Mohr

COO and CBO

Head of Commercial Development

Rudolph E. Tanzi, PhD

Chairman, Scientific Advisory Board

Brian Bartlett

Chief Financial & Accounting Officer

Philip Ashton-Rickardt, PhD

Senior Vice President, Immunology

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Program Discovery Pre-clinical Phase 1 Phase 2 Phase 3 Expected Milestones

ALZT-OP1Early Alzheimer’s Disease

COGNITE Phase 3 trial fully enrolled, data readout in earlyQ1 2021

AZT-101ALS – Phase 2a Ready

Initiation in 1H 2020(IND Approved)

AZT-101Ischemic Stroke – Phase 2 Ready

Initiation 1H 2021

AZT-211 (Next-Gen)Neurodegenerative Diseases

IND expected 2H 2020

Universal Donor

CAR-Treg ProgramNeurodegenerative Diseases

Pre-clinical proof-of-concept in 1H 2020

Microbiome ProgramAlzheimer’s Disease

Observational study to initiate in 1H 2020

Robust Pipeline with Phase 3 Trial and Multiple Follow-on Opportunities

COGNITE Phase 3 Trial

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The Resilient Brain: Inflammation is Associated with Decreased Cognitive Function

Source: Perez-Nievas et al. Dissecting phenotypic traits linked to human resilience to Alzheimer’s pathology, Brain 2013; Isabel Barroeta-Espar et al. Distinct cytokine profiles in human brains resilient to Alzheimer’s pathology. Neurobiol Dis. 2019.

Neuroinflammation is potentially a key predictor of neurodegenerative disease and progression

Aβ Plaques Activated Microglia NeuronsActivated AstrocytesTau Tangles

ResilientNo Alzheimer’s

SymptomaticAlzheimer’s

Inflammation

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ALZT-OP1: A Multimodal CombinationApproach to Treat Complex Progression of AD

✓ A novel, inhalable cromolyn with a low dose formulated oral ibuprofen

✓ Re-engineered physical delivery to cross the blood brain barrier

✓ Well characterized safety profile

✓ Ongoing COGNITE Phase 3 clinical trial fully enrolled with trial completion in Q1 2021

✓ 505(b)2 pathway conducted under FDA Special Protocol Assessment (SPA)

✓ Speed-to-market strategy

17.1 mg capsule for daily inhalation via dry powder inhaler

Targets neuroinflammation and neurotoxic peptides

Shifts microglia into neuroprotective, phagocytic state

Inhibits pro-inflammatory cytokine production; oligomerization of Aβ peptides; and mast cell degranulation

Cromolyn

10 mg tablet for oral administration

Targets neuroinflammation as a COX1/COX2 non-specific NSAID

May boost cromolyn efficacy by promoting microglial recruitment to Aβ plaques

Ibuprofen

Oral Tablet

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Anti-amyloid Aggregation: Cromolyn inhibits amyloid fibrillization and increases amyloid clearance

Anti-inflammatory: Cromolyn induces a

protective, phagocytic state in

microglia versus neuroinflammation

Cromolyn: Dual Mechanisms to Reduce Neuronal Death in Alzheimer’s Disease

Source: Zhang, C et al. Cromolyn Reduces Levels of the Alzheimer’s Disease-Associated Amyloid ß-Protein by Promoting Microglial Phagocytosis. Scientific Reports, January 2018. Hori. Journal of Biological Chemistry, 2015.

Aβ oligomers form, plaques accumulate, trap in

synapses; Tau tangles form

Neuronal degeneration& death

Alzheimer’s disease progression and dementia

Microglial activation and aggravated

neuroinflammation

Amyloid protein precursor (APP) cleavage and Aβ

(40 – 42) peptides released

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Role of ALZT-OP1 Treatment

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Pro-inflammatory Microglia Damage Neurons and Synapses

Source: “Alzheimer’s in a Dish; Park et al., Nature Neurosci. (2018); Hoozemans et al (2011) CNS & Neurol Disorders–Drug Targets, 10: 57-67; Heneka et al (2005) Brain 128, 1442-1453.

Neurotoxic Microglia (M1) Attack Neurons

“Beyond the amyloid approach, an alternate line of thought based on the role of mast cells and microglia is neuroinflammation and the potential targeting of these cells for the treatment of AD represents a paradigm shift in therapeutic strategies.” - GlobalData Dec 2018

Microglia in Brain During AD Progression

Multi-modal approach aligns with current views on neuroinflammation as a leading

cause of neurodegenerative disease and progressive brain damage

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ALZT-OP1: Improving Memory Capabilities in Preclinical Model of AD

Source: Data on file, Mass General Hospital.

Morris Maze Memory Test

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1

2

3

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Mock-trt tg ALZT-OP1a trt tg WT controlNon-treated Control(APP/PS1 Mice Without Drug

Treatment)

Treatment Group(APP/PS1 Mice With

ALZT-OP1 Treatment)

Healthy Control (Wild Type Mice

Without Drug Treatment)

# Ti

me

s R

eac

hin

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p = 0.03Transgenic APP/PS1 mice (4-month-old) or same-age healthy

controls (wild type mice) were treated weekly with I.P. injections

for 6 months, trained on the Morris Maze Memory Test for 7

days, and then tested on day 8 for their ability to recall their training

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Cromolyn Anti-inflammatory Effect Validated in Multiple Recent Publications

2019

2018

2017

2016

2015

Independent AZTherapies

2015

2019

2019

2018

2019

2016

2019

2016

2016

2017

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ALZT-OP1: Phase 1 Studies Confirmed Crossed the Blood-Brain-Barrier

• AZT-002 Phase 1a study1:

– Cromolyn (17.1 mg) and ibuprofen (10 mg) pharmacokinetics in healthy volunteers – cromolyn and ibuprofen reached desired concentrations in plasma and CSF, the latter indicating blood brain barrier crossing

• AZT-004 Phase 1b study2:

– Cromolyn (17.1 mg) and ibuprofen (10 mg) pharmacokinetics in healthy volunteers and AD patients – cromolyn and ibuprofen reached desired concentrations in plasma and CSF, the latter indicating blood brain barrier crossing

1 Brazier, et al: Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Volunteers; Clin Drug Investig (2017).2 Data on file, AZTherapies, Inc.

Study Patients Cmax Tmax

Cro

mo

lyn

AZT-002(4 Hour CSF)

Healthy Adults 0.24 ng/mL 3.7 hours

AZT-004(8 Hour CSF)

Healthy Adults 0.4 ng/mL 3.6 hours

AD Patients 1.4 ng/mL 3.8 hours

Ibu

pro

fen

AZT-002(4 Hour CSF)

Healthy Adults 3.9 ng/mL 2.6 hours

AZT-004(8 Hour CSF)

Healthy Adults 4.1 ng/mL 3.0 hours

AD Patients 6.0 ng/mL 4.0 hours

ALZT-OP1 Pharmacokinetics (CSF)

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Primary Endpoint: Mean change from baseline in Clinical

Dementia Rating-Sum of Boxes (CDR-

SB) at week 72, comparing

combination treatment to monotherapy

cromolyn and monotherapy ibuprofen

Conducted under Special Protocol

Assessment (SPA)

Exploratory Biomarkers

Study Completion:Anticipated Trial Completion

in Q1 2021

ALZT-OP1: COGNITE Phase 3 Trial –Fully Enrolled

Randomization

Eligibility Criteria &

Assessments

Week 4

Safety &

Compliance

Check

Week 48

CDR-SB

MMSE

Safety

Day 1

Initial Drug

Dispense

Week 12

CDR-SB

MMSE

Safety

Week 24

CDR-SB

MMSE

Safety

Week 72

CDR-SB

MMSE

Safety

Biomarkers

n = 620

• Aged 55-79

• Confirmed early AD

• Aß-42 180-690 pg/mL

• Global CDR 0.5

• Memory Box ≥ 0.5

• WMS LMII

• CDR-SB

• MMSE

Ibuprofen

Placebo

Cromolyn

ALZT-OP1

While there are four-arms in the trial design, ~50% of the patients are receiving cromolyn

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AZT-101 Demonstrates Significant Potential in ALS

Source: Granucci. Cromolyn sodium delays disease onset and is neuroprotective in the SOD1G93A Mouse Model of amyotrophic lateral sclerosis. Scientific Reports. 2019; Note: Study performed on 149 male and female age- and litter-matched transgenic (Tg) SOD1G93A and wild-type (Wt) SOD1G93A mice.

Key Results Provide Evidence ofAZT-101 Activity in SOD1 ALS Model

Delayed disease onset and progression

Reduced motor deficits in the Paw Grip Endurance (PaGE) task

Spared lumbar spinal cord motor neurons & preserved neuro-muscular-junction integrity

Reduced pro-inflammatory cytokine levels in the spinal cord and plasma

Significant effect on motor symptoms as measured by age at paresis onset

**** p<0.0001

Onset of Paresis

Neuro-muscular-Junction Denervation

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Universal Donor CAR-Treg: Immense Potential in Treating Neurodegeneration

Source: AZTherapies Data; Appel. Neurol Neuroimmunol Neuroinflamm. 2018; scFv: Single-chain Variable Fragment.

Concentration (nM)

Fronto-temporal Dementia

(FTD)

Alzheimer’s Disease

Multiple Sclerosis

(MS)

ALS

Progressive Supranuclear

Palsy (PSP)

Parkinson’sDisease

Pre-clinical

Validation

Identify scFv`

Glia-binding scFv

Signaling &Co-stimulation

Domains CD28CD3zGlia

CAR Technology Increases Treg Localization to CNS, Enhancing Anti-Inflammation Effects and Limiting Off-

Target Suppression, Compared to Autologous Treg Infusions

Assess Efficacy`Validate Construct`

Identified seven unique human scFv and assessed

binding via ELISA

All CAR constructs are stably expressed on

surface of Tcells

In vitro and in vivo validation of CAR-Tregconstructs is ongoing

ALS Progression Slowed During Autologous Treg

Infusions in P1 Trial

Clinical Rationale`

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IP Portfolio: Select Examples

1 Listed pending applications are in the public domain, with additional pending applications that have yet to be disclosed.

Alzheimer’s Disease (ALZT-OP1, AZT-101)

TBD

Method of Use: Cromolyn + Ibuprofen for Treating AD; Exp: 2030

Formulation: Cromolyn +/- Ibuprofen Formulations; Exp: 2034

Composition of Matter: AZT-211 Exp: 2030

Method of Use: Cromolyn +/- Ibuprofen (IP, IV, SubQ) for Treating AD; Exp: 2030

Method of Use: Cromolyn + Cholinesterase Inhibitor/Select Aβ Antibody for Treating AD; Exp: 2033

Composition of Matter: CAR-Tregs for Treating Neurodegenerative Disease;Exp: ~2039

Method of Use: Cromolyn for Treating ALS; Exp: ~2037

Granted

Pending1

Key examples demonstrate the robust portfolio with IP protection well beyond 2030; additional patent applications not yet in the public domain further extending our exclusivity timeline

Non-Exhaustive IP Examples

Additional Programs (NCE, ALS, CAR-Treg)

Formulation: Cromolyn Formulations;Exp: 2034

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ALZT-OP1 WW Revenue Forecast

Note: Based on a detailed forecast of the US. A scale up factor was used to estimate ROW revenues.Source: Health Advances model.

U.S. + ROW Revenue Forecast2030 WW Revenue $4.5 B

$0.9$1.3

$1.8$2.0

$2.3 $2.4 $2.5 $2.7$0.6

$0.9

$1.2

$1.4

$1.5$1.6

$1.7$1.8

$0.0

$0.5

$1.5

$2.2

$3.0

$3.4

$3.8 $4.0

$4.3

$4.5

$0.0

$0.5

$1.0

$1.5

$2.0

$2.5

$3.0

$3.5

$4.0

$4.5

2021 2022 2023 2024 2025 2026 2027 2028 2029 2030

Reve

nu

es

(U

SD

B)

Rest-of-World Revenue

U.S. Revenue

Based on the strength of the product profile shared

with physicians and payers, ALZT-OP1 can expect to

generate WW peak revenues of ~$4.5B

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2020

Upcoming Milestones

✓ Submit IND for AZT-101 in ALS(IND Approved)

❏ Initiate and Complete Phase 2a Trial in ALS Patients

❏ Conduct Preclinical Proof-of-Concept with CAR-Treg Platform

❏ Submit IND for AZT-211

❏ Perform Scale-up Manufacturing of ALZT-OP1

❏ Initiate Microbiome Observational Study

❏ Continue Corporate Financings

2021

❏ Complete Phase 3 ALZT-OP1 Early AD Trial in Q1 2021

❏ Submit NDA and Gain FDA Approval in Early AD for ALZT-OP1

❏ Complete Commercial Preparation and Readiness for ALZT-OP1 in Early AD

❏ Initiate and Complete AZT-101 Phase 2 Stroke Trial

❏ Initiate Phase 1 Trial for AZT-211

❏ Submit First IND for CAR-Treg

❏ Complete Microbiome Observational Study

❏ Continue Corporate Financings

2020 – 2021

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CosineIBS CapitalInvestors

Strong Institutional and Investor Support

Institutional Partners

Wooshin

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Board of Directors and Advisory Boards

Board of Directors

Business Advisory Board

Scientific Advisory Board

David R. Elmaleh, PhD, Chair CEO, AZTherapies, Inc.

George D. Behrakis Investor/Former Biopharma Executive

Peter Conti, MD, PhD Prof. of Radiology, USC

Keith Greenfield The Dover Group

Gillian Sandler Cosine Capital, LLC

David Taft IBS Capital, LLC

Ronald Tompkins, MD, ScD Prof. of Surgery, Harvard

Rudolph E. Tanzi, PhD, Chair Prof. of Neurology, Harvard

Adam Boxer, MD, PhD Prof. of Neurology, UCSF

Martin R. Farlow, MD Prof. of Neurology, Indiana University

Seth P. Finkelstein, MD Assoc. Prof./Neurologist, Mass General

Bradley T. Hyman, MD Prof. of Neurology, MGH Inst of Neurodegenerative Disease Center

Keith A. Johnson, MD Prof. of Radiology/Neurology, Harvard

Scott E. Kasner, MD Chief Vascular Neurology, UPenn

Vijay K. Kuchroo, DVM, PhD Prof. of Neurology, Harvard

Megan Levings, PhD Prof., Department of Surgery, University of British Columbia

Ziv Neeman, PhD Director of Diagnostic Imaging Institute, Technion Medical School

Eran Segal, PhD Prof. of Computer Science, Weizmann Institute of Science

Sangram S. Sisodia, PhD Prof. of Neurobiology, University of Chicago

Shahin Tabatabaei, MD Assoc Prof. Urology, Mass General

Steven L. Wagner, PhD Assoc Prof. of Neurosciences, UCSD

Michael Porter, Chair Prof., Harvard Business School

Isabelle Bajeux-Besnainou Prof. of Finance, McGill

William S. Belichick New England Patriots

Noah Gottdiener Chair/CEO, Duff and Phelps

David H.P. King Co-founder and Managing Partner Peak Capital Holdings

Thierry Porté Managing Director, JC Flowers

Thank You

200 Clarendon Street, 17th Floor

Boston, MA 02116

www.aztherapies.com