Diamedica Therapeutics Inc. · NASDAQ:DMAC

Diamedica Therapeutics — Q2 2025 Earnings Presentation

46 slides from Diamedica Therapeutics's earnings presentation, Aug 13, 2025

Slide 2: Cautionary Note Regarding Forward-Looking Statements
Cautionary Note Regarding Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995 and forward-looking information that are based on the beliefs of management and reflect management’s current expe
Slide 3: Life-transforming Therapy for Patients with Severe Ischemic Diseases
OUR MISSION Life-transforming Therapy for Patients with Severe Ischemic Diseases 01 Preeclampsia (PE) 02 Acute Ischemic Stroke (AIS) © 2025 DiaMedica Therapeutics. All Rights Reserved. 3
Slide 4: Company Overview
Lead Program: DM199 - Novel, Late-Stage Biologic Therapy Company 〉 Recombinant KLK1 (rhKLK1) protein with FDA Fast-Track Designation 〉 IP until ‘39 (+ potential 5-year ext.) & expected 12 years regulatory exclusivity Overview 〉 >300 patients have been dosed with DM199 across multiple studies Cash: $
Slide 5: DiaMedica Pipeline
DiaMedica Pipeline COMPOUND INDICATION PRECLINICAL PHASE 1 PHASE 2 PHASE 2/3 UPCOMING MILESTONES Phase 21: Part 1A Dose-Selection / Part 1B Expansion Cohort Part 1A Preeclampsia Phase 21: Parts 2 & 3 Expected Management FPI 2025 Study DM199 (rinvecalinase alfa) Fetal Growth Recombinant KLK1 Phase 21
Slide 7: Early-Onset PE and FGR: Severe Conditions with a $5B+ U.S. Market
Early-Onset PE and FGR: Severe Conditions with a $5B+ U.S. Market Disease Overview Annual Incidence in U.S. 〉Preeclampsia (PE): A life-threatening high blood pressure disorder accompanied by 325,000+ multi-system organ damage that occurs FGR & PE1,2 only during pregnancy. – Early onset PE is a sever
Slide 8: Limited and Insufficient Preeclampsia Treatments – A Major Unmet Need
Limited and Insufficient Preeclampsia Treatments – A Major Unmet Need 〉There are no disease modifying agents currently available for preeclampsia 〉First-line antihypertensives, ACE inhibitors and ARBs, are CONTRAINDICATED in pregnancy Medication Drug Comments Alpha-blocker 〉Reduce blood pressure and
Slide 9: Stage of Preeclampsia: Placental Disease
Stage 1 of Preeclampsia: Placental Disease Inadequate spiral artery development in the first trimester leads to placental hypoxia Normal Pregnancy Preeclampsia → Widened Spiral Arteries (5- to 10-fold)1 → Narrow Spiral Arteries → Healthy Blood Flow → Low Blood Flow Maternal Spiral Arteries Maternal
Slide 10: Stage of Preeclampsia: Endothelial Dysfunction & Maternal Disease
Stage 2 of Preeclampsia: Endothelial Dysfunction & Maternal Disease Noxious factors released from the ischemic placenta cause endothelial dysfunction BRAIN Oxidative stress RAAS-Activating • Eclampsia Factor Pro-inflammatory • Hemorrhagic stroke O 2- O 2- cytokines • Seizures O 2- O 2- TNF⍺ VASCULAT
Slide 11: DM199 May Offer a Disease-Modifying Solution for Preeclampsia
DM199 May Offer a Disease-Modifying Solution for Preeclampsia DM199 produces all three major endothelial derived vasodilating factors through the bradykinin pathway Nitric Oxide - cGMP DM199 (rhKLK1) Kininogen Bradykinin BK2R Prostacyclin - cAMP EDHFs DM199 may address root causes of PE by improving
Slide 12: Preeclampsia Potential Mode of Actions
DM199 Preeclampsia Potential Mode of Actions DM199 Nitric Oxide Prostacyclin EDHF VEGF Increase Placental Perfusion Repair Endothelium & Reduce Blood Pressure Pro-inflammatory 01 UPSTREAM O2- Oxidative stress cytokines Endothelial Repair /Angiogenesis RAAS-Activating O2- O2- O2- ROS Factor Reduce BP
Slide 13: DM199 Preeclampsia Phase 2 IST Trial – Part 1a
Part 1 Overview DM199 Preeclampsia Phase 2 IST Trial – Part 1a 〉 27-42 weeks gestation (singleton) Women planned for delivery within 72 hours 〉 >150 systolic blood pressure 〉 Receiving standard of care Part 1A - Dose Escalation (3x3 Design) 〉 <72 hours scheduled for delivery C10 2.5ug/kg IV + 15.0ug
Slide 15: DM199 Was NOT Detected in Umbilical Cord Blood in Any Dose Cohort
DM199 Was NOT Detected in Umbilical Cord Blood in Any Dose Cohort 〉At delivery, DM199 was not detected in any cord blood samples, while a clear dose-dependent increase in DM199 was observed in maternal plasma. 〉Data suggests DM199 does not cross the placental barrier, a potentially unique safety adv
Slide 16: DM199 Was Generally Safe and Well Tolerated
DM199 Was Generally Safe and Well Tolerated 〉No serious TEAEs were reported in response to any dose Maternal Treatment-Emergent Adverse Events TEAE N=28 [n(%)] Dose Cohorts Nausea 4 (14%) C8 (n=2), C9 (n=2) Headache 3 (11%) C3 (n=1), C6 (n=2) Flushing 1 (4%) C9 〉No events of hypotension 〉No patient
Slide 17: Blood Pressure Was Reduced at 5-Minute Post-Infusion Endpoint
Blood Pressure Was Reduced at Prespecified 5-Minute Post-Infusion Endpoint Pooled Cohorts C6–C9 achieved statistically significant reductions in SBP (-25 mmHg) and DBP (-15 mmHg) Systolic Diastolic Cohorts 6 – 9 10 Cohorts 6 – 9 5 Dose Range For Further Clinical Investigation Dose Range For Further
Slide 18: Blood Pressure Was Reduced at 30-Minute Post-Infusion Endpoint
Blood Pressure Was Reduced at Prespecified 30-Minute Post-Infusion Endpoint Pooled Cohorts C6–C9 achieved statistically significant reductions in SBP (-15 mmHg) and DBP (-13 mmHg) Systolic Diastolic 5 Cohorts 6 – 9 Cohorts 6 – 9 Dose Range For Further Clinical Investigation Dose Range For Further Cl
Slide 19: Drove Statistically Significant Systolic Blood Pressure Reduction
DM199 Drove Statistically Significant Systolic Blood Pressure Reduction Pooled analysis of Cohorts 6 to 9 1.0-2.0 μg/kg IV (Cohorts 6-9) n=122 Systolic Blood Pressure 175 170 165 167 Severe hypertension (AJOG) Average1 SBP (mmHg) 160 -15 -14 -17 -18 155 -22 -20 150 -25 152** 153** 149** 150** 145 14
Slide 20: Drove Statistically Significant Diastolic Blood Pressure Reduction
DM199 Drove Statistically Significant Diastolic Blood Pressure Reduction Pooled analysis of Cohorts 6 to 9 1.0-2.0 μg/kg IV (Cohorts 6-9) n=122 Diastolic Blood Pressure 110 105 104 Average1 DBP (mmHg) 100 -11 -10 -13 -13 -13 -13 95 -17 94** 94* 90 91** 92** 91** 91** 85 88** 80 (p=0.0007) (p=0.0002)
Slide 21: Reduced Uterine Artery Resistance, Suggesting Enhanced Placental Perfusion
DM199 Reduced Uterine Artery Resistance, Suggesting Enhanced Placental Perfusion Overall1,2 (n=25) 2.5 2 2 〉Dilation of the uterine arteries was assessed by Doppler ultrasound at baseline and two hours after Uterine Artery Pulsatility Index Reduced blood flow resistance Cohorts 1&2 1.5 Cohort 3 IV i
Slide 22: Fetal Growth Restriction: DM199's Indication Expansion
Fetal Growth Restriction: DM199’s Indication Expansion Strong mechanistic rationale based on Interim Part 1a PE data 〉Fetal Growth Restriction is a Major Unmet Medical 〉DM199 Offers the Potential to Improve Challenge Uteroplacental Blood Flow – Placental insufficiency—particularly impaired – Like pr
Slide 23: DM199 Phase 2 Preeclampsia IST Next Steps
DM199 Phase 2 Preeclampsia IST Next Steps All parts can enroll concurrently Part 1b (n=30) Part 2 (n=30) Part 3 (n=30) Planned Delivery in 72 Hrs Expectant Management Fetal Growth Restriction ▪ Recruiting the same population as ▪ Recruiting women with early onset ▪ Recruiting women with early onset
Slide 25: High Unmet Need in Acute Ischemic Stroke
High Unmet Need in Acute Ischemic Stroke >7.5 million acute ischemic strokes occur globally each year5 DM199 US Estimated Market Opportunity = $10+ Billion Low Treatment Rates Limited Treatment Options US Annual Acute Ischemic Strokes1,2,3 0 No New Pharmaceuticals Approved in Over 25 Years ~20% tPA
Slide 26: DM199 Initial Target in AIS – Significant Whitespace Opportunity
DM199 Initial Target in AIS – Significant Whitespace Opportunity >500k patients in the U.S. with no treatment option 〉The 4.5-hour time window for tPA treatment significantly limits patient eligibility 〉~ 90%1 of patients can reach the hospital emergency department within 24 hours HOURS Stroke Type
Slide 27: Human Urinary KLK1 (HUK): Safe and Efficacious Treatment for AIS
Human Urinary KLK1 (HUK): Safe and Efficacious Treatment for AIS HUK guided DM199 development, informing optimal dosing, target patients, & treatment protocols 〉HUK for AIS: – Marketed by Shanghai Pharmaceuticals under Kailikang® – Ameliorates neurological symptoms with few adverse events1 〉Up to 1
Slide 28: DM199 (rhKLK1 – rinvecalinase alfa) Novel Mechanism of Action
DM199 (rhKLK1 – rinvecalinase alfa) Novel Mechanism of Action DM199 produces all three major endothelial derived vasodilating factors Nitric Oxide - cGMP DM199 (rhKLK1) Kininogen Bradykinin BK2R Prostacyclin - cAMP EDHFs 〉 KLK1 is made predominately in kidneys (present also in the vasculature and br
Slide 29: Ischemia Naturally Induces Upregulation of Bradykinin Receptors (BK2R)
Ischemia Naturally Induces Upregulation of Bradykinin 2 Receptors (BK2R) DM199 has potential to enhance BK2R activation & promote focal vasodilation in the penumbra Brain Artery Under Different Conditions 1 2 3 Normal Conditions Ischemic Conditions Ischemic Conditions + DM199 ENDOTHELIAL CELL ENDOTH
Slide 30: DM199: May Improve Collateral Circulation in Acute Ischemic Stroke
DM199: May Improve Collateral Circulation in Acute Ischemic Stroke Novel mechanism with potential to improve stroke outcomes & reduce risk of stroke recurrence Early stroke No DM199 treatment DM199 treatment DM199 does not need to pass the blood-brain barrier to deliver therapeutic benefit. DM199 fa
Slide 31: Phase 2 Results: Improved Excellent Outcomes in Non-MT Subgroup
DM199 Phase 2 Results: Improved Excellent Outcomes in Non-MT Subgroup Patient population closely aligns with ReMEDy2 Phase 2/3 trial mRS ≤ 1 at 90 Days (Non-MT Participants) Target Population % of Participants at Day 90 +19% +15% Placebo DM199 Placebo DM199 N=21 N=24 N=15 N=19 MT – Mechanical Thromb
Slide 32: Phase 2 AIS Results Comparison with tPA Data
DM199 Phase 2 AIS Results Comparison with tPA Data Clinically relevant outcomes with DM199 extending treatment window from 4.5 to 24 hours Comparison of Absolute Improvements in mRS ≤ 1 vs Placebo (DM199 Phase 2 and tPA analysis; excludes MT treated participants) 20 % of Participants at Day 90 vs Pl
Slide 33: Pivotal Phase 2/3 AIS Trial
DM199 Pivotal Phase 2/3 AIS Trial Overview Endpoints at Day 90 DM199 (rhKLK1) 〉 Moderate AIS: NIHSS: 5-15 Primary: 〉 Adaptive Design Modified Rankin Score (mRS) ≤1 R 1:1 randomization – Interim analysis @ N=200 Secondary: – Intended to enroll N=~300 Placebo mRS shift, mortality, NIHSS, BI and 〉 Up t
Slide 35: Multi-layered IP and Exclusivity Position
DM199 Multi-layered IP and Exclusivity Position Key manufacturing challenges solved: protein activity, stability and economical scale Protein Development Patents and Exclusively Regulatory & Trade Secrets Licensed Technology Exclusivity DM199 (rhKLK1): Excellent Enzymatic Patents1 U.S.: Anticipate 1
Slide 36: Leadership and Board of Directors
Leadership Board of Directors James Parsons, Chairman of the Board 20+ years as a life sciences CFO for several companies. Former CFO Trillium Rick Pauls, President & Chief Executive Officer Therapeutics (Acquired by Pfizer for ~$2.2B). CEO of DiaMedica since 2010. Former venture capitalist with two
Slide 37: Company Overview
Lead Program: DM199 - Novel, Late-Stage Biologic Therapy Company 〉 Recombinant KLK1 (rhKLK1) protein with FDA Fast-Track Designation 〉 IP until ‘39 (+ potential 5-year ext.) & expected 12 years regulatory exclusivity Overview 〉 >300 patients have been dosed with DM199 across multiple studies Cash: $
Slide 40: Relative Contribution of Major Endothelial Derived Vasodilating Factors
Relative Contribution of 3 Major Endothelial Derived Vasodilating Factors1 EDHF is critical in microvasculature and compensates when NO and PGI2 signaling are compromised Conduit Arteries Terminal Branches Arterioles 〉Arterioles are the primary site of resistance in the vascular tree and the most si
Slide 41: DM199: Enhancing Vascular Health Beyond Blood Pressure Control
DM199: Enhancing Vascular Health Beyond Blood Pressure Control 〉Vasodilation Nitric Oxide cGMP 〉Anti-thrombotic 〉Endothelial protection 〉Angiogenesis (VEGF Cross-talk) 〉Vasodilation DM199 Prostacyclin cAMP 〉Anti-thrombotic 〉Endothelial protection EDHFS 〉Vasodilation (microvasculature) © 2025 DiaMedi
Slide 42: DM199 Targets All Key Vasodilatory Agonists: NO, PGI2 and EDHF
DM199 Targets All 3 Key Vasodilatory Agonists: NO, PGI2 and EDHF 01 Potential to increase placental perfusion & reduce placental-released noxious factors UPSTREAM Vasodilation During Pregnancy Varies by Size and Role of Arteries NO/PGI2 EDHF 〉 Agonist-induced vasodilation Ovarian artery Placental Fe
Slide 43: DM199 Potential to Augment VEGF Signaling in Endothelial Cells
DM199 Potential to Augment VEGF Signaling in Endothelial Cells 02 DOWN STREAM Potential to bypass sFlt-1 antagonism to improve endothelial health & blood flow Circulating sFlt-1 Increases Significantly in Preeclampsia BK2R Activation Can Directly Transactivate VEGF2R sFlt-1 sFlt-1 sFlt-1 sFlt-1 DM19
Slide 44: KLK1 Promotes Neovascularization Despite sFlt-1 Antagonism
KLK1 Promotes Neovascularization Despite sFlt-1 Antagonism 02 DOWN STREAM KLK1 Gene Transfer Increased Capillary and Arteriole Density1 Capillary Density Arteriole Density 2 weeks Adenoviral Tissue Kallikrein-1 Injected into adductor muscles 8 weeks Arteriole density remained elevated for 8 weeks, l
Slide 45: DM199 Has Been Shown To Lower Blood Pressure
DM199 Has Been Shown To Lower Blood Pressure IV Dose 〉 Has been show to rapidly (within minutes) lower blood pressure at higher dosages Subcutaneous Dose (SC) 〉 Sustained, clinically relevant and statistically significant SBP reduction in CKD patients with elevated SBP at Baseline Subcutaneous Injec
Slide 46: Clinical Summary: >300 patients dosed with DM199 to date
Clinical Summary: >300 patients dosed with DM199 to date Single Ascending Dose (n=30) Multiple Ascending Dose (n=7) 14-day Study in Type 2 Diabetics (n=12) 〉Generally safe and well tolerated, in both IV and SC formulations 28-day Study in Type 2 Diabetics (n=25) – Most common related adverse events

DiaMedica Therapeutics — Q2 2025 Earnings Presentation on 6ix

Diamedica Therapeutics — Q2 2025 Earnings Presentation

Slide 1: Corporate Presentation

Slide 2: Cautionary Note Regarding Forward-Looking Statements

Slide 3: Life-transforming Therapy for Patients with Severe Ischemic Diseases

Slide 4: Company Overview

Slide 5: DiaMedica Pipeline

Slide 6: Preeclampsia

Slide 7: Early-Onset PE and FGR: Severe Conditions with a $5B+ U.S. Market

Slide 8: Limited and Insufficient Preeclampsia Treatments – A Major Unmet Need

Slide 9: Stage of Preeclampsia: Placental Disease

Slide 10: Stage of Preeclampsia: Endothelial Dysfunction & Maternal Disease

Slide 11: DM199 May Offer a Disease-Modifying Solution for Preeclampsia

Slide 12: Preeclampsia Potential Mode of Actions

Slide 13: DM199 Preeclampsia Phase 2 IST Trial – Part 1a

Slide 14: Interim Phase 2 (Part 1a) Results

Slide 15: DM199 Was NOT Detected in Umbilical Cord Blood in Any Dose Cohort

Slide 16: DM199 Was Generally Safe and Well Tolerated

Slide 17: Blood Pressure Was Reduced at 5-Minute Post-Infusion Endpoint

Slide 18: Blood Pressure Was Reduced at 30-Minute Post-Infusion Endpoint

Slide 19: Drove Statistically Significant Systolic Blood Pressure Reduction

Slide 20: Drove Statistically Significant Diastolic Blood Pressure Reduction

Slide 21: Reduced Uterine Artery Resistance, Suggesting Enhanced Placental Perfusion

Slide 22: Fetal Growth Restriction: DM199's Indication Expansion

Slide 23: DM199 Phase 2 Preeclampsia IST Next Steps

Slide 24: Acute Ischemic Stroke Phase 2/3 Trial

Slide 25: High Unmet Need in Acute Ischemic Stroke

Slide 26: DM199 Initial Target in AIS – Significant Whitespace Opportunity

Slide 27: Human Urinary KLK1 (HUK): Safe and Efficacious Treatment for AIS

Slide 28: DM199 (rhKLK1 – rinvecalinase alfa) Novel Mechanism of Action

Slide 29: Ischemia Naturally Induces Upregulation of Bradykinin Receptors (BK2R)

Slide 30: DM199: May Improve Collateral Circulation in Acute Ischemic Stroke

Slide 31: Phase 2 Results: Improved Excellent Outcomes in Non-MT Subgroup

Slide 32: Phase 2 AIS Results Comparison with tPA Data

Slide 33: Pivotal Phase 2/3 AIS Trial

Slide 34: Corporate Summary

Slide 35: Multi-layered IP and Exclusivity Position

Slide 36: Leadership and Board of Directors

Slide 37: Company Overview

Slide 38: Thank You!

Slide 39: Appendix

Slide 40: Relative Contribution of Major Endothelial Derived Vasodilating Factors

Slide 41: DM199: Enhancing Vascular Health Beyond Blood Pressure Control

Slide 42: DM199 Targets All Key Vasodilatory Agonists: NO, PGI2 and EDHF

Slide 43: DM199 Potential to Augment VEGF Signaling in Endothelial Cells

Slide 44: KLK1 Promotes Neovascularization Despite sFlt-1 Antagonism

Slide 45: DM199 Has Been Shown To Lower Blood Pressure

Slide 46: Clinical Summary: >300 patients dosed with DM199 to date