10-K: DiaMedica 2025 Annual Report: DM199 Trials Advance Amid Delays

DiaMedica Therapeutics' 2025 annual report details progress in DM199 clinical trials for preeclampsia and stroke, alongside financial losses and enrollment challenges.

Summary

• DiaMedica Therapeutics Inc. is a clinical-stage biopharmaceutical company focused on severe ischemic diseases, with its lead candidate DM199 (rinvecalinase alfa) for preeclampsia (PE)/fetal growth restriction (FGR) and acute ischemic stroke (AIS).
• DM199 has been granted Fast Track Designation by the U.S. Food and Drug Administration (FDA) for the treatment of AIS.
• The PE clinical program includes an investigator-sponsored Phase 2 study in South Africa. Interim results from Part 1a (N=28 subjects) in July 2025 showed DM199 was safe, well-tolerated, had no evidence of placental transfer, and demonstrated rapid, statistically significant reductions in blood pressure (e.g., Cohort 9: -35 mmHg SBP, -15 mmHg DBP at 5 min) and a 13.2% reduction in uterine artery pulsatility index at 2 hours.
• A global Phase 2 study for early-onset PE is planned for North America (US & Canada) and the UK. Health Canada approved the study in March 2026, with site activation planned for H2 2026. The FDA requested an additional non-clinical ePPND study in a rabbit model, which was unsuccessful due to antibody response, leading to evaluation of alternate animal models and potential delays.
• The AIS program centers on the ReMEDy2 Phase 2/3 adaptive design trial, targeting 300-728 participants at up to 100 global sites, with an interim analysis planned after 200 participants.
• The ReMEDy2 trial has experienced slower than expected site activations and enrollment due to various factors, including hospital staffing shortages, protocol criteria, logistics, prior clinical hold concerns, AI/telemedicine impact, and competition.
• The company expanded its internal clinical team and globalized the ReMEDy2 trial, now conducting it in the United States, Canada, Georgia, the United Kingdom, and initiating sites in six European countries after receiving regulatory approval from the European Medicines Agency.
• Net loss for the year ended December 31, 2025, was $32.8 million, an increase from $24.4 million in 2024.
• Cash, cash equivalents, and marketable securities totaled $59.9 million as of December 31, 2025.
• The company raised approximately $43.9 million in gross proceeds during 2025 from a private placement ($30.1 million gross) and an at-the-market (ATM) offering ($13.8 million gross).
• The company believes current cash resources are sufficient to fund planned operations for at least the next 12 months.
• DM300, a recombinant human ulinastatin, is in early preclinical development for severe acute pancreatitis.

Sentiment

Score: 6

Explanation: StockSavvy.ai views this as a moderately positive report, driven by promising interim clinical data for DM199 in PE and successful capital raises, but tempered by ongoing enrollment delays in the AIS trial and new regulatory hurdles for the PE program in the US.

Positives

• DM199 received Fast Track Designation from the FDA for Acute Ischemic Stroke (AIS).
• Interim results from the Phase 2 Preeclampsia (PE) trial (Part 1a, N=28) demonstrated DM199 was safe, well-tolerated, showed no placental transfer, and achieved rapid, statistically significant reductions in blood pressure (e.g., Cohort 9: -35 mmHg SBP, -15 mmHg DBP at 5 min; Pooled Cohorts 6-9: -25 mmHg SBP, -13 mmHg DBP at 5 min).
• The PE trial also showed improved uterine artery blood flow, with a 13.2% (p=0.0003) mean reduction in pulsatility index at the 2-hour mark.
• Health Canada approved the initiation of a Phase 2 study for early-onset PE in Canada.
• Regulatory approval was received from the European Medicines Agency to initiate ReMEDy2 study sites in six European countries.
• DM199's large protein size (approximately 26 kilodaltons) suggests it may not cross the placental barrier, offering a potential safety advantage in PE treatment over small molecules.
• The ReMEDy2 trial protocol was amended to allow patients treated with tPA or TNK (thrombolytic agents) to be eligible if they continue to experience a persistent neurological deficit, expanding the eligible patient population.
• A Phase 1C open-label study confirmed DM199 blood concentration levels and safety, including in ACEi patients, addressing prior hypotension concerns.
• Prior Phase 2 ReMEDy1 trial data, excluding mechanical thrombectomy patients, showed a 22% absolute increase in full or nearly full recovery (NIHSS: 0-1) and a 50% relative reduction in deaths (12% vs. 24%) in the active treatment group compared to placebo.
• A significant reduction in recurrent ischemic stroke was noted in the ReMEDy1 active treatment group (0% vs. 13% on placebo, p=0.012).
• The company successfully raised approximately $43.9 million in gross proceeds during 2025 through a private placement and an at-the-market (ATM) offering, strengthening its financial position.

Negatives

• The company incurred substantial net losses of $32.8 million in 2025 and $24.4 million in 2024, with an accumulated deficit of $172.8 million as of December 31, 2025.
• Slower than expected site activations and enrollment continue to affect the ReMEDy2 trial for AIS.
• The FDA requested an additional non-clinical, 10-day modified embryo-fetal development and preand postnatal development (ePPND) study in a rabbit model for the planned Phase 2 PE study in the US.
• Preliminary results from the rabbit ePPND study indicated animals developed an antibody response to DM199, preventing study completion and necessitating evaluation of alternate animal models, which may cause substantial delays.
• The initial investigator-sponsored PE trial is conducted in South Africa, and there is a risk that its safety and pharmacodynamic results, differing standards of care, and dosing regimens may not translate or generalize to typical PE populations in North America or other parts of the world.
• The adaptive design of the ReMEDy2 trial could potentially require enrolling up to 728 patients, increasing the time and costs to complete the trial.
• DM199 has been associated with clinically significant, transient hypotension during IV infusion, which previously led to a clinical hold on the ReMEDy2 trial.
• The company has no revenue from product sales and does not expect any for at least two to three years.
• The company was classified as a Passive Foreign Investment Company (PFIC) for 2025, 2024, and 2023, which may have adverse U.S. federal income tax consequences for U.S. shareholders.

Risks

• Difficulty enrolling patients in the ReMEDy2 trial or other clinical testing delays/setbacks.
• The adaptive design of the ReMEDy2 trial could result in a requirement to enroll more patients than anticipated, increasing time and costs.
• Expansion of the DM199 clinical development program into PE and reliance on investigator-sponsored trials involve risks related to timing, regulatory approvals, costs, and enrollment.
• DM199 and any other product candidates may cause undesirable side effects or have other properties that could delay or prevent regulatory approval, limit commercial profile, or result in negative consequences post-approval.
• Risk of product liability claims exceeding insurance coverage, depleting cash resources, and leading to clinical trial delays.
• International trials (South Africa, Canada, EU) introduce risks related to differing standards of care, regulatory requirements, sanctions, anti-corruption laws, currency fluctuations, and data privacy.
• FDA or comparable foreign regulatory authorities may not accept trial data from countries located outside the United States.
• Interim, topline, and preliminary results from clinical trials may change as more data become available and are subject to audit and verification.
• Failure of ReMEDy2 or PE trials to adequately demonstrate safety and efficacy would prevent required regulatory approvals.
• Clinical trials may be suspended, repeated, or terminated if not conducted in accordance with regulatory requirements, if results are negative or inconclusive, or if the trial is not well designed.
• Prospects depend on the clinical and commercial success of DM199, which is subject to many factors outside of control.
• Need for additional funding to continue clinical development activities and operations, which may not be available on acceptable terms or at all.
• Substantial losses incurred since inception, with no expectation of profitability for at least two to three years.
• The regulatory approval process is expensive, time-consuming, and uncertain.
• Any approved product candidate could be subject to post-marketing restrictions, recall, or withdrawal from the market, and the company may face penalties for non-compliance.
• Inability to obtain regulatory acceptances necessary to conduct clinical trials in expected jurisdictions or on expected timelines.
• Fast Track designation may not lead to faster development or FDA review/approval, and may be rescinded.
• Current and future legislation (e.g., ACA, Inflation Reduction Act) may increase difficulty and cost for obtaining marketing approval and affect prices.
• Changes in funding or disruptions at the FDA and other government agencies could hinder their ability to perform functions.
• Reliance on third parties (CROs, CDMOs) for preclinical/clinical trials and manufacturing, with risks of delays, quality issues, and supply disruptions.
• Single source of supply for drug substance and product, increasing risk of interruption or delays.
• Inability to enter into or maintain future development collaborations.
• Loss of important intellectual property rights if license obligations are not met or relationships with licensors are disrupted.
• Inability to adequately protect technology and enforce intellectual property rights, or competitors taking advantage of development efforts.
• Need for additional third-party licenses to develop, manufacture, and commercialize DM199, which might not be available on commercially acceptable terms.
• Changes in patent law and its interpretation could diminish the value of patents.
• Intellectual property litigation may be expensive, time-consuming, and cause delays.
• Reliance on key executives, clinical personnel, and advisors, with the loss of any potentially affecting development ability.
• Difficulties in managing company growth and expanding operations.
• Failure to achieve market acceptance for DM199, if approved.
• Failure to obtain coverage and adequate reimbursement for DM199.
• Competition from other biotechnology and pharmaceutical companies with substantially greater resources.
• DM199 may face biosimilar competition sooner than expected.
• Estimates of market opportunity for DM199 may prove inaccurate.
• Volatility in common share price.
• Limited active trading market for common shares.
• Dilution from future equity issuances.
• Substantial sales of common shares or the perception of such sales could cause market price decline.
• Limited number of shareholders possess substantial voting power.
• Governed by British Columbia corporate laws, which differ from U.S. laws.
• Classification as a passive foreign investment company (PFIC) for U.S. federal income tax purposes.
• Difficulty for non-Canadian shareholders or investors to obtain and enforce judgments against the company.
• Failure to achieve publicly announced milestones according to schedule.
• Information technology (IT) systems failures, network disruptions, breaches in data security, and cyber-attacks.
• Securities class action litigation, which is expensive and could divert management attention.
• Insurance policies are expensive and protect only from certain business risks, potentially leaving significant uninsured liabilities.
• Widespread outbreaks of communicable diseases could delay clinical trials and adversely affect business.
• Actions by activist shareholders could negatively affect business or share value.

Future Outlook

DiaMedica plans to advance DM199 through clinical trials to establish its clinical and commercial potential for preeclampsia (PE), fetal growth restriction (FGR), and acute ischemic stroke (AIS). Longer term, the company intends to develop DM300 for severe acute pancreatitis. Research and development expenses are expected to increase as DM199 development continues and clinical trials expand globally. The company anticipates filing a clinical trial application in Q2 2026 to expand the Phase 2 PE study to the UK and expects to commence site activation for the Canadian PE study in H2 2026. The interim analysis for the ReMEDy2 trial is estimated to be completed in H2 2026. Management believes current cash resources are sufficient for at least the next 12 months but may seek additional funding if market conditions are favorable. The company expects to partner with a large pharmaceutical company for sales execution if DM199 is approved.

Management Comments

• Our mission is to improve the lives of people suffering from serious ischemic diseases.
• We believe DM199 has the potential to lower blood pressure, enhance endothelial health and improve perfusion to maternal organs and the placenta.
• We believe DM199 has the potential to treat a variety of diseases where restoring healthy function requires sufficient activity of KLK1 and the kallikrein-kinin system (KKS).
• We believe higher regulatory standards and the potential for impurities, endotoxins and chemical byproducts due to the inherent variability in the isolation and purification process are the primary reasons why urinaryor animal-derived KLK1s are not currently available and or approved in the United States or Europe.
• We believe that the results of this work suggest that the therapeutic action of DM199 will be the same or potentially better than that of the human urinary and porcine forms of KLK1 marketed in Asia.
• We believe that the ReMEDy2 trial has the potential to serve as a pivotal registration study of DM199 in this patient population.
• We believe these findings from our Phase 2 ReMEDy1 trial, which are consistent with the use of Kailikang in China, provide a signal that recombinant human KLK1 appears safe and may have promise as a new treatment for physicians who have limited options for the treatment of patients following an AIS.
• We believe that our proprietary technology, along with trade secrets and specialized knowledge of the manufacturing process, will provide substantial protection from third-party competitors.
• We believe that DM199 cannot be easily reverse engineered for the production of a copycat version.
• We expect our current cash resources of $59.9 million in cash, cash equivalents and marketable securities as of December 31, 2025 to be sufficient to allow us to continue our Phase 2/3 trial in patients with AIS, the PE trial and to otherwise fund our planned operations for at least the next 12 months from the date of issuance of the consolidated financial statements included in this report.

Industry Context

StockSavvy.ai notes that DiaMedica operates in a highly competitive biopharmaceutical landscape, targeting significant unmet medical needs in preeclampsia and acute ischemic stroke. The company's focus on a recombinant form of KLK1 (DM199) aims to overcome limitations of animalor urine-derived KLK1 therapies currently used in Asia, positioning it for potential entry into Western markets with higher regulatory standards. The challenges in trial enrollment and the need for additional non-clinical studies reflect the inherent difficulties and regulatory scrutiny in developing novel therapies for complex conditions like PE and AIS, where existing treatments have narrow windows or significant drawbacks. The expansion of the ReMEDy2 trial globally and the initiation of new PE studies indicate a strategic push to accelerate development and de-risk the clinical pipeline, a common approach for clinical-stage companies seeking to maximize market opportunity.

Comparison to Industry Standards

• The interim Phase 2 PE trial results showing statistically significant blood pressure reductions and improved uterine artery blood flow are promising, especially given the lack of FDA-approved therapeutics for PE. This positions DM199 favorably against symptomatic management approaches and contraindicated first-line hypertension medications (ACEi/ARBs) in pregnant patients.
• The observed safety profile with no placental transfer for DM199 in PE is a critical advantage compared to small molecule drugs like sildenafil (PDE5 inhibitors) which cross the placental barrier and have shown mixed or negative results in PE trials (e.g., the TRUFFLE trial for sildenafil in FGR was stopped due to increased risk of fetal death).
• For AIS, DM199's proposed 24-hour therapeutic window significantly extends beyond the 3-4.5 hour window for FDA-approved thrombolytics like alteplase (tPA, Activase) and tenecteplase (TNK, TNKase). This addresses a major unmet need for the 80% of AIS patients ineligible for current acute interventions.
• The ReMEDy1 trial's observed 22% absolute increase in full/nearly full recovery and 50% relative reduction in deaths in non-mechanical thrombectomy patients compares favorably to the limited efficacy of supportive care, which is the only option for many AIS patients outside the tPA/TNK or mechanical thrombectomy windows.
• The company's strategy to develop a recombinant KLK1 (DM199) aims to overcome the impurity and regulatory challenges associated with human urine-derived KLK1 (e.g., Kailikang in China) and porcine-derived KLK1 (used in Asia for hypertension), which are not approved in the US or Europe. This could provide a significant competitive edge in Western markets.

Management Changes

Corporate Governance

Legal Proceedings

• In October 2025, the company entered into a Settlement Agreement with Pharmaceutical Research Associates Group B.V. (acquired by ICON plc) to settle all disputes, claims, and liabilities arising from their relationship, including pending legal proceedings.
• The company is not currently engaged in or aware of any other threatened legal actions.

Stakeholder Impact

• Shareholders face potential for long-term value creation if DM199 trials succeed and regulatory approvals are obtained, but also risks from ongoing losses, potential future dilution from capital raises, share price volatility, and the PFIC classification's adverse U.S. federal income tax consequences.
• Employees may benefit from growth opportunities due to the expansion of the internal clinical team and administrative headcount, with share-based compensation plans aligning interests.
• Future patients stand to gain from DM199 addressing significant unmet medical needs in PE, FGR, and AIS, potentially offering new therapeutic options where none currently exist or current options are limited.
• Creditors face a higher risk profile due to the company's reliance on equity financing and accumulated deficit, though current cash resources are deemed sufficient for 12 months.
• Suppliers and vendors (CROs, CDMOs) will continue to have business with the company due to its reliance on third parties for R&D and manufacturing, but past issues with CRO performance highlight potential for disputes.

Next Steps

• Complete Part 1a, Part 1b, Part 2, and Part 3 of the Phase 2 investigator-sponsored trial for DM199 in PE/FGR.
• Initiate a global Phase 2 trial in early-onset preeclampsia in North America (Canada site activation in H2 2026) and the United Kingdom (anticipate filing CTA in Q2 2026).
• Engage regulatory agencies in multiple countries regarding the PE development program and submit applications for Fast Track and/or Breakthrough designations where available.
• Evaluate alternate animal models to address the FDA's ePPND study request for the US PE program.
• Continue to execute the ReMEDy2 Phase 2/3 trial for DM199 in AIS, including activating up to 100 global clinical sites and continuing participant enrollment.
• Monitor and implement additional actions to enhance site activations and enrollment in the ReMEDy2 trial.
• Complete interim analysis for the ReMEDy2 trial in H2 2026.
• Continue manufacturing process development to support anticipated applications for commercial approval of DM199.
• Identify strategic partner(s) to assist with future clinical development and commercialization of DM199.

Key Dates

Recommendation

The company presents a mixed bag of developments. The positive interim Phase 2 data for DM199 in preeclampsia and the successful capital raises provide a degree of confidence in the company's ability to advance its pipeline. However, significant challenges remain, including persistent enrollment delays in the pivotal ReMEDy2 AIS trial and new regulatory hurdles for the US PE program, which could lead to substantial delays and increased costs. The company's continued substantial losses and reliance on future financing, coupled with the inherent high-risk nature of clinical-stage biopharmaceutical development, suggest a 'hold' recommendation. Investors should monitor progress in both key clinical programs and regulatory interactions closely.

Keywords

DiaMedica Therapeutics, DM199, Rinvecalinase alfa, Preeclampsia, Fetal Growth Restriction, Acute Ischemic Stroke, Clinical Trials, Biopharmaceutical, Kallikrein-1 (KLK1), Recombinant Protein, Phase 2 Study, Phase 2/3 Trial, Fast Track Designation, Drug Development, Biotech, SEC Filing, 10-K