Investor Presentation

Nasdaq: DMAC

Investor Presentation

2

This presentation contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, which are based on the beliefs of management and reflect management’s current expectations. When used in this presentation, the words “estimate,” “believe,” “anticipate,” “intend,” “expect,” “plan,” “continue,” “look forward,” “will,” “may” or “should”, the negative of these words or such variations thereon or comparable terminology and the use of future dates are intended to identify forward-looking statements and information. The forward-looking statements in this presentation include statements regarding the anticipated clinical benefits of DM199 as a potential treatment for chronic kidney disease (CKD) and acute ischemic stroke (AIS), the safety and efficacy of DM199; the assessment of the data from the ReMEDy study and the future publication and sharing of the full study results, and regulatory path forward, the timing and requirements of its clinical programs, including enrollment and clinical results and ability to achieve clinical milestones. By their nature, forward-looking statements involve known and unknown risks, uncertainties and other factors which may cause actual results, performance or achievements, or other future events, to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Applicable risks and uncertainties include, but are not limited to, DiaMedica’s plans to develop, obtain regulatory approval for its DM199 product candidate for the treatment of CKD or AIS and its expectations regarding the benefits of DM199; the possibility of unfavorable results from additional clinical trials of DM199 or from subsequent analysis of existing data from the ReMEDy study or existing or new data received from additional ongoing and future studies of DM199; the risk that existing preclinical and clinical data may not be predictive of the results of ongoing or later clinical trials; the perceived benefits of DM199 over existing treatment options for CKD; the potential size of the markets for DM199 and the Company’s ability to serve those markets; the success, cost and timing of planned clinical trials, as well as reliance on collaboration with third parties to conduct clinical trials; its ability to obtain funding for its operations, including funding necessary to complete planned clinical trials and obtain regulatory approvals for DM199; the impact of the COVID-19 pandemic on DiaMedica’s business, including in particular the conduct of clinical trials and the timing thereof; and the risks identified under the heading “Risk Factors” in DiaMedica’s annual report on Form 10-K for the fiscal year ended December 31, 2019 filed with the U.S. Securities and Exchange Commission (SEC) and subsequent SEC filings. Except as required by applicable securities laws, DiaMedica undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of existing or new information, future events, or otherwise.

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Strong scientific rationale

Ø Novel biology with lead candidate DM199 in diseases with high unmet medical needs

Ø Low KLK1 levels associated with diseases targeted

Ø KLK1 sourced from human urine and pig pancreas is approved in Japan, China & Korea • Millions treated in Asia, est. >400K patients treated per year (25+ companies)

DM199 is first recombinant KLK1 protein for human use

Ø Benefits of recombinant protein: improve safety and pharmacokinetics/efficacy

Ø Safely dosed in over 200 participants

Ø Chronic kidney diseases: Phase 2 study for three causes of kidney disease ongoing

• Early signals for improving kidney function: ↑eGFR and ↓albuminuria in kidney patients

Ø Acute ischemic stroke: Phase 2 completed; preparing for FDA meeting and phase 2/3 study • 2.5x improvement in excellent outcomes with 24-hour treatment window

Untapped market opportunity

Ø Underserved market opportunity, high unmet medical need and limited competition Ø Worldwide, exclusive development and commercial rights; IP protection to at least 2033

Nasdaq listed (DMAC)

Ø $31 million cash and investments (September 30, 2020)

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DM199: PROTEIN REPLACEMENT THERAPY

DM199: 1

st

_{Recombinant Form of KLK1 for Clinical Use}

• Reduced risk profile for immunogenicity, endotoxins & impurities

• Improved efficacy with optimized drug (PK) levels, dosing and convenience of subcutaneous delivery

Promoting homeostasis: Improving blood flow and reducing inflammation throughout the body

Retinopathy

Chronic Kidney Disease Acute Ischemic Stroke Hypertension Autoimmune

↑ renal function ↑ vasodilation ↑ renal blood flow ↓ inflammation ↓ inflammation ↓ oxidative stress ↓ Glucose ↓ ischemic damage ↑ vasodilation

↑ cerebral blood flow ↓ inflammation

↑ neurovascular coupling

suppresses autoimmune ↑T-regs, CD4, CD25 & Fox3 ↓ IgG and IgA levels potential ↑ beta cells ↓ transplantation rejection ↑ blood pressure control ↓ hyperkalemia ↑ vasodilation ↓ retinal damage ↑ visual acuity ↓ VEGF in eyes ↓ inflammation

DM199

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Program Asset/_ROA DEVELOPMENT STAGE

PRE-CLINICAL PHASE I PHASE 2 PHASE 3 Kidney Diseases

Diabetic Kidney Disease

(DKD) DM199SC

IgA Nephropathy

(IgAN) DM199SC

African Americans with

CKD (APOL1)1 DM199_SC Neurological Diseases

Acute Ischemic Stroke DM199 _IV/SC Phase 2/3: Initiate H1 2021 Phase 2: Enrolling

Phase 2: Topline H1 2021

Phase 2: Enrolling

1. Due to the heightened risk of African Americans with the APOL1 genetic mutation to progress to end-stage renal disease, participants in this cohort will be tested for the presence of the APOL1 genetic mutation.

6 LMWK BRADYKININ (BK) SYNTHESIS Direct activation of BK2 receptors BK1 receptors BK2 receptors EFFECTS ON

BRADYKININ (BK) BK RECEPTORSEFFECTS ON KIDNEY & BRAINEFFECTS ON

Plasma Kallikrein (PK) Tissue Kallikrein(KLK1) endothelial cell EFFECTS ON CELLS BRADYKININ

Improve Stroke Outcomes

↑ Improve Kidney Function

↑ Blood Flow1

↓ Inflammation

↓ Fibrosis/ scarring

↓ Oxidative Stress

Regulated & controlled increase of BK levels HMWK No cough No angioedema No hyperkalemia High Heredity Angioedema Low Kidney disease

↑ Nitric Oxide _{- cAMP} ↑ Prostaglandins _{- cGMP}

↑ Inflammation

LMWK - low molecular weight kininogen HMWK - high molecular weight kininogen

DM199 MECHANISM OF ACTION

DM199

recombinant KLK1

↑

1. Through dilatation of blood vessels and new blood vessel formation

Restores Low KLK1 Levels to Release

88

1. Centers for Disease Control, Chronic Kidney Disease in the US 2019 2. National Institute of Health Fact Sheet, 2010

3. USRD, CKD and ESRD (https://www.usrds.org/2018/view/v1_07.aspx)

Opportunity to Target Rare and/or DKD Markets

$114 Billion Overall CKD Related Costs in US

3

Rare Chronic Kidney Diseases

US Market Opportunity : >500,000

130,000 160,000 125,000 70,000 40,000 IgA Nephropathy T1D CKD APOL1 AA HT Lupus Nephritis FSGS

REDUX P2

REDUX P2

IgA Nephropathy (IgAN)

§ Rare CKD damaging the glomerulus

§ IgA & IgG antibodies build up cause inflammation § No FDA approved therapies

Diabetic Kidney Disease (DKD)

§ 12 million in US

§ Most frequent cause of ESRD worldwide

§ Anti-hypertensives & SGLT2i slow disease progression

Hypertensive African Americans with CKD

§ ~6 million African Americans with CKD

§ 3–4x more likely kidney failure than Caucasians § APOL1 gene mutation patients = higher risk of ESRD

o Potential rare disease § No FDA approved therapies

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DM199 MECHANISM WITHIN KIDNEYS

KLK1 Predominately Produced in Kidneys

and Regulates Multiple Interrelated Mechanisms

1

Potential Benefits of DM199

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Regulate blood flow:

§ Improve micro vascularization § Increase oxygen and nutrients

1 1

Improve glomerular function:

§ Reduce inflammation, oxidative stress and fibrosis § Prevent or reduce thickening of glomerular

basement membrane

§ Inhibit mesangial cell proliferation

2

5

Regulate epithelial sodium channel (ENaC):

§ Regulate salt & water reabsorption and excretion

3

5

Increase T-regs (CKD autoimmune diseases)

§ Halt pathological autoimmune attack on glomerulus § Potential to decrease IgA and IgG levels

4

Glomerulu s

Afferent

Arteriole Efferent Arteriole

FILTRATION

Renal Tubule 2 3 Autoimmune CKD Diseases 5 4 Unfiltered Blood Peritubular Capillaries (PTCs) 1 Filtered Blood

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KLK1 (porcine) Lowered Albuminuria

3

1. Clinical Studies not conducted or sponsored by DiaMedica,

2. Immunopharmacology 44 1999. 183–192. 3. Chin J Diabetes, August 2011, Vol 19, No 8

KLK1 Correlated to Severity of CKD

2

Albumin leaking into the urine indicates kidneys not properly filtering and signals kidney disease.

GROWING BODY OF CLINICAL EVIDENCE OF POTENTIAL

FOR KLK1 TO TREAT PATIENTS WITH CKD

1

Potential CKD biomarker

Porcine KLK1 Clinical Studies (30+) Show Improvements in CKD (eGFR and Albuminuria)

Normal Kidney Function Restored

Opportunity to Personalize Treatment

KL K1 L EV EL S ng /µg

11 3.69 4.59 2.29 0 1 2 3 4 5 6 Hrs 24 Hrs 72 Hrs (1.6%) (23.3%) (5.0%) (25%) (20%) (15%) (10%) (5%) 0% 6 Hrs 24 Hrs 72 Hrs

UACR (n=12)

2

eG

FR

C

ha

ng

e

(m

L/

M

in

/1

.7

3

2

)

* P = <0.05, t-test

Greatest Improvements in eGFR, UACR (Albuminuria), NO and PGE2 Occurred at 24 Hours

1. https://casehippo.com/apps/symposium/national-kidney-foundation-2020-spring-clinical-meetings/event/gallery/abstracts?abstractId=1025

2. Excludes participants with normal baseline UACR levels (<30)

* *

%

Ch

an

ge

Prostaglandin E2 (n=23)

%

Ch

an

ge

eGFR (n=24)

19.4% 40.6% 26.8% 0% 10% 20% 30% 40% 6 Hrs 24 Hrs 72 Hrs Median Mean

DM199 PHASE Ib CKD SINGLE DOSE STUDY

1

Stage 3 CKD Cohort, Single Doses of 3, 5 or 8

µ

g/kg (8 participants per dose)

1.1% 27.2% (10.1%) (15%) (5%) 5% 15% 25% 6 Hrs 24 Hrs 72 Hrs

Nitric Oxide (n=24)

%

Ch

an

ge

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ANALYSIS OF DKD PARTICIPANTS IN PHASE II AIS STUDY

1

DKD Participants Defined as eGFR <90 mL/Min/1.73

2

_{& Glucose >7 mmol at Baseline}

Statistically Significant +12.7mL/Min Improvement in eGFR

1. See slide “DM199 REMEDY PHASE II AIS STUDY” for study design

Change in eGFR – Day 22 (Last Dose)

mL /M in /1 .7 3 2 10.4 -2.3 -4 -2 0 2 4 6 8 10 12 +12.7 mL p=0.03 DM199 (n=9) Placebo (n=16)

•

Subgroup analysis of patients with

diabetic kidney disease (DKD)

•

Patients treated for 21 days at 3 µg/kg

•

Retained eGFR benefit trend of mean

+8.8 mL/Min observed at day 56

o

34 days of wash out

•

Also observed mean Glucose reduction of

-2.3 mmol/L in DM199 vs Placebo

v

Results supported addition of DKD

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DM199 REDUX PHASE 2 CKD STUDY IN 3 COHORTS

IgA Nephropathy, DKD and African Americans with CKD

Targeting Rare and Large Unmet Causes of CKD

Phase 2, Multi-Center US, Randomized Study

§

Three cohorts – 90 participants:

o

IgA Nephropathy n=30

o

African Americans n=30

o

Diabetic Kidney Disease (DKD) n=30

§

Eligibility criteria: eGFR 30-90 mL/min, Albuminuria: 150 – 5,000

§

95 days treatment

§

SC dosing, 2x week

§

Multi-center - 14 US sites

DM199 2 µg/kg DM199 5 µg/kg Randomized Top-line data Day 1 Day 95

Study endpoints at day 95:

§ Proteinuria (UACR) and eGFR

§ Safety, tolerability and pharmacodynamics (IgG, IgA), blood pressure

Enrollment started:

Dec 2019

DKD Topline results:

H1 2021

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Stroke and CKD closely linked: 34% of Stroke Patients have CKD

15 million

strokes per

year

globally

~600,000: DM199 US target market

Stroke related costs in US: $46 billion

800,000

strokes per

year in US

87% acute

ischemic

strokes

Blockage of blood flow in brain

Ø 25% of strokes are recurrent strokes Ø 2nd leading cause of death worldwide Ø Leading cause of adult disability

Ø ~10% of AIS patients receive Alteplase® (tPA) or mechanical thrombectomy (MT)

o tPA must be administered within

3-4.5 hours of AIS

~90% of AIS Patients have no Direct Treatment Options

Acute Ischemic Stroke (AIS)

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DM199 MECHANISM OF ACTION IN STROKE

Promotes Microvascular Circulation, Inhibits Apoptosis and Inflammation.

Improves Neuron Plasticity

THERAPY INITIATION

Within 24 hours

PROMOTES

Microcirculation &

anti-inflammation

(short-term blood flow)

+

IMPROVES

Neurovascular Coupling

(brain activity-blood flow balance)

THERAPY CONTINUATION

For 21 days

INHIBIT

Neuronal Apoptosis &

Inflammation in area at risk

(protects neuro cell)

+

PROMOTE

Accelerates Network

Reconstitution

(improving neuron plasticity)

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1. tPA (Tissue Plasminogen Activator).

tPA1 (Activase®₎

ONSET

3 – 4.5 hours

24 HOURS Most stroke patients should

reach hospital by 24 hours Mechanical Thrombectomy

DM199

12 6 18

Less than 10% of

stroke patients treated

up to 24 hours

Treatment Window Post Stoke Critical

Recent extension limited to specific types of patients

6+ hours

DM199 is a Potential Treatment Option for ~90% of AIS Patients

Who do Not Have a Treatment Option Today

DM199 Treatment Window of 24 hours Post Stroke

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600,000+ patients treated in China

•

National first-class drug

•

Included in National Basic Medical Insurance

on January 1, 2020

2

200+ clinical studies demonstrated efficacy in

multiple stroke clinical studies including

•

NIHSS, mRS and BI

•

Blood Flow

•

Inflammation (CRP)

1. New England Journal of Medicine, Volume 333, Number 24, December 14, 1995 2. Chen et al. Brain Behav. 2020;10:e01461.

KAILIKANG

®

_{(HUMAN URINARY KLK1) & ACTIVASE}

®

_(tPA)

CLINICAL EFFICACY RATES

Urinary KLK1 and tPA Efficacy

Excellent Outcomes: NIHSS 0-1

Urinary KLK1 (

Kailikang

®

₎

Urinary KLK1 has Demonstrated Improved Efficacy Compared to tPA

with up to 72 Hour Treatment Window Compared to 3 Hours for tPA

Ex ce lle nt O ut co m es : N IH SS 0 -1 11% 19% Kailikang®2 Urinary KLK1 Clinical study, N=260 Hours <72 tPA1 Phase 3, N=333 Hours <3

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Endpoint

DM199 IV, followed by SC

Placebo IV, followed by SC

Study endpoints at 90 days:

§ Safe and well tolerated § Improved stroke function –

NIHSS, mRS, and BI

§ Improved Kidney function: eGFR § Reduced inflammation, CRP DM199 IV

administration enrolled ≤24 hours from symptom onset

Randomization 1:1

Double blinded

DM199 subcutaneous (SC) admin. Day 1 & every 3rd day over 22 days Day 22 Day 90 24 hours Dosing complete Follow-up days 22 to 90 Follow-up days 22 to 90 Endpoint

First dose IV within 24 hrs of AIS followed by 21 days of SC treatment

§

92 participants enrolled; 91 evaluable participants (safety data set)

§

Mild-moderate stroke severity (NIHSS score 6 to 25) at treatment

o

Patients who received mechanical thrombectomy (MT), tPA or both, with eligible NIHSS

score measured up to the 24 hours post stroke event, were allowed into the study

(46 participants received MT prior to enrollment)

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1 Journal of Evidence-Based Medicine (2012) 5: 31-39. 2. Journal of International Medical Research 48(9) 1–10 2020

DM199 Phase 2 AIS NIHSS SHIFT

Non-MT Cohort

DM199 Increased Full and Near-Full Recoveries, NIHSS 0-1 (+22%), and Reduced Deaths (-12%)

24 Hour Therapeutic Window (~5x longer than tPA)

DM199 Improved Excellent Outcomes and Reduced Deaths

DM199 REMEDY PHASE 2 AIS EFFICACY

OVER 2.5X IMPROVEMENT IN EXCELLENT OUTCOMES

14% 36% 57% 36% 5% 16% 24% 12% 0% 20% 40% 60% 80% 100% Placebo (N=21) DM199 (N=25) 0-1 2-8 >9 Death 90 day NIHSS Excellent Outcomes = NIHSS 0-1

2.5x (+22%)

11%

19%

Urinary KLK1 Clinical study, N=260 Hours <72 (tPA) Phase 3, N=333 Hours <3 1 DM1993 Recombinant KLK1 Phase 2, N=46 Hours <24

22%

Kailikang®2

DM199, Urinary KLK1 and tPA Efficacy,

Excellent Outcomes: NIHSS 0-12

21

4 of 7 Fatal

Reduced Severe Recurrent Strokes

Over 90 Days

DM199 REMEDY PHASE 2 AIS SAFETY PROFILE AND

REDUCED SEVERE RECURRENT STROKES

P=0.028

§

No serious adverse events related to DM199

§

No discontinuations or dosing interruptions due to

tolerability

§

No hypotension difference compared to placebo

§

Most common related adverse events observed

and all self-resolved:

o

Constipation, nausea and headache

§

Reduced severe stroke recurrences

Safety Summary

250+ Participants Dosed DM199 over Multiple Studies

DM199

n=46 Placebon=44

1

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DiaMedica overcame manufacturing challenges in KLK1 protein manufacturing Glycosylation is critical for optimal activity

§Identified correct configuration of high & low molecular weight glycoforms

§5+ companies unsuccessful moving to clinical, including Amgen & Takeda-Techpool

Protein Development

Produced at up to 250L (potential commercial scale)

§ High-efficiency production based on proprietary cell line technology for creating and growing cells that release large amounts of KLK1

o Exclusivity with manufacturer

§Proprietary cell line, expression system, composition & know-how

Manufacturing & Trade Secrets

Multi-layered IP Position with Potential for Regulatory Exclusivity

INTELLECTUAL PROPERTY PORTFOLIO AND MANUFACTURING

Composition of Matter Patent Expires 2033

§ Issued composition of matter – glycosylation (2033) § Issued delivery - subcutaneous and improved PK (2033) § Pending dosing - dose range to restore KLK1 levels,

route of delivery and formulation (2038)

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RICK PAULS, MBA PRESIDENT & CEO Former venture capitalist with two early stage funds, including co-founder & Managing Director of life sciences VC fund.

SYDNEY GILMAN, Ph.D. VP REGULATORY AFFAIRS

30+ years regulatory and drug develop experience with multiple products through product approval. Positions with Elan, Amylin and Bristol Myers Squibb. Also spent 6 years as FDA reviewer.

LEADERSHIP

SCOTT KELLEN, CPA (INACTIVE)

CFO & VP FINANCE 25+ years in life sciences industry. Held senior leadership roles including CFO and COO for several private and pubic (Nasdaq) companies.

HARRY ALCORN JR., PHARM.D CHIEF MEDICAL OFFICER 30+ years biopharma experience. Principle Investigator of over 150 clinical studies with focus on kidney diseases. Former Chief Scientific Officer at DaVita Clinical Research.

EDWARD CALAMAI, Ph.D. CONSULTING HEAD OF MANUFACTURING 30+ years CMC experience including head-CMC and VP at Niiki Pharma, Sensus Drug Development of Seragen.

KIDNEY ADVISORY BOARD

RAJIV AGARWAL, M.D. Tenured Professor of Medicine at Indiana University School of Medicine. Published 250 original papers and reviews in Nephrology.

GEORGE BAKRIS, M.D. Professor of Medicine and Director of the American Heart Association Comprehensive Hypertension Center at the University of Chicago.

GLENN CHERTOW, M.D. Chief, Division of Nephrology at Stanford University School of Medicine, Norman S. Coplon Satellite Healthcare Professor of Medicine and (by courtesy) of Health Research and Policy.

CHARLES HERZOG, M.D. Professor of medicine at the University of Minnesota, and cardiologist at Hennepin County Medical Center “HCMC” for 34 years.

ALDO PEIXOTO, M.D. Professor of Medicine in the Section of Nephrology at the Yale University School of Medicine.

STROKE ADVISORY BOARD

PHILIP BATH, M.D., DSC Stroke Association Professor of Stroke Medicine, and Chair and Head of the Division of Clinical Neuroscience at the University of Nottingham.

SCOTT KASNER, M.D. Professor of Emergency Medicine and Director of Comprehensive Stroke Center at the University of

Pennsylvania.

POOJA KHATRI, M.D. Professor of Neurology and Director of Acute Stroke at the University of Cincinnati.

JOHN VOLPI, M.D.

Co-Director of the Eddy Scurlock Stroke Center at Houston Methodist and Associate Professor of Clinical Neurology at the Institute for Academic Medicine.

BRUCE CAMPBELL, M.D. Head of Stroke in the Department of Neurology at the Royal Melbourne Hospital.

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WE SEEK TO OFFER TREATMENT OPTIONS FOR UNMET

MEDICAL NEEDS BY RESTORING DEPLETED PROTEIN LEVELS

Strong scientific rationale

Ø Novel biology with lead candidate DM199 in diseases with high unmet medical needs

Ø Low KLK1 levels associated with diseases targeted

Ø KLK1 sourced from human urine and pig pancreas is approved in Japan, China & Korea • Millions treated in Asia, est. >400K patients treated per year (25+ companies)

DM199 is first recombinant KLK1 protein for human use

Ø Benefits of recombinant protein: improve safety and pharmacokinetics/efficacy

Ø Safely dosed in over 200 participants

Ø Chronic kidney diseases: Phase 2 study for three causes of kidney disease ongoing

• Early signals for improving kidney function: ↑eGFR and ↓albuminuria in kidney patients

Ø Acute ischemic stroke: Phase 2 completed; preparing for FDA meeting and phase 2/3 study • Data showed 2.5x improvement in excellent outcomes with 24-hour treatment window

Untapped market opportunity

Ø Underserved market opportunity, high unmet medical need and limited competition Ø Worldwide, exclusive development and commercial rights; IP protection to at least 2033

Nasdaq listed (DMAC)

Thank you!

Nasdaq: DMAC

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DM199 KEY PAPERS AND LINKS

KLK1 Mechanism

• Genetically-modified stem cells in treatment of human diseases: Tissue kallikrein (KLK1) - Review

o https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5819898/

• Role of nitric oxide and prostacyclin as vasoactive hormones released by the endothelium

o https://physoc.onlinelibrary.wiley.com/doi/full/10.1113/expphysiol.2007.038588

• Mechanisms of Disease: the tissue kallikrein–kinin system in hypertension and vascular remodeling

o https://pubmed.ncbi.nlm.nih.gov/17389890/

• Tissue kallikrein in cardiovascular, cerebrovascular and renal diseases and skin wound healing

o https://www.degruyter.com/view/journals/bchm/391/4/article-p345.xml

Kidney Papers

• Exogenous kallikrein protects against diabetic nephropathy – Preclinical KLK1 mechanism paper

o https://www.kidney-international.org/article/S0085-2538(16)30307-6/fulltext

• The Effect of Pancreatic Kininogenase Combined with Valsartan for the Treatment of Early DN

o Chin J Lab Diagn, December 2013, Vol 17, No. 12

Stroke Papers:

• Human Tissue Kallikrein in treatment in the treatment of acute ischemic stroke – review paper

o https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348491/

• Human Urinary Kallidinogenase (KLK1) therapy for acute ischemic stroke – 260 patient clinical study

o https://onlinelibrary.wiley.com/doi/full/10.1002/brb3.1461

• Human urinary kallidinogenase (KLK1) in treating acute ischemic stroke patients: analyses of pooled data from a randomized double-blind placebo-controlled phase IIb and phase III clinical trial