DiaMedica Therapeutics (NASDAQ:DMAC) executives used the company’s fiscal 2025 earnings call on Monday to highlight clinical progress for its lead asset DM199 and review an improved year-end cash position following financing activity in 2025.
DM199 mechanism and pipeline focus
President and CEO Rick Pauls described DM199 as “a recombinant form of the naturally occurring KLK1 protein,” which acts through bradykinin B2 receptors in blood vessel endothelium and increases nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor. Pauls said the company believes this “triple-pathway” mechanism may enhance blood flow and vascular health and supports development in preeclampsia, fetal growth restriction, and acute ischemic stroke.
Preeclampsia: interim phase 2 signals and next steps
According to Krop, interim data from cohorts 6 through 9 in hypertensive women with preeclampsia planned for delivery within 72 hours showed:
- “Clear dose-dependent and statistically significant sustained reductions” in systolic and diastolic blood pressure.
- A statistically significant reduction in uterine artery pulsatility index, which Krop described as a Doppler-based measure of arterial resistance suggesting improved uteroplacental perfusion.
- Evidence that DM199 “did not cross the placental barrier.” Krop added that additional analysis showed DM199 also does not pass through breast milk.
Krop said the company views these findings as an “on-target mechanistic response” and argued the safety profile could allow earlier initiation and longer treatment duration, potentially enabling meaningful prolongation of pregnancy.
On trial operations, Krop said enrollment continued in the Part 1-A expansion cohort, which may include up to 12 additional patients, and the company anticipates completing that cohort in the first half of 2026. In the Q&A, Pauls attributed slower-than-expected expansion cohort enrollment to “some staffing challenges” at the site led by Professor Catherine Cluver, adding that DiaMedica recently provided additional financial support for hiring new nurses and expects enrollment to pick up.
Krop said protocol amendments are being finalized for subsequent portions of the South Africa study:
- Part 1-B, which would enroll up to 30 hypertensive women with late-stage preeclampsia expected to deliver within 72 hours, using continuous IV dosing titrated to keep blood pressure in a targeted range.
- Part 2, which would enroll up to 30 women with early-onset preeclampsia eligible for expectant management, with the goal of prolonging pregnancy and improving blood flow for fetal outcomes.
Pauls said the company expects Parts 1-B and 2 to initiate “later in Q2” 2026 while the Part 1-A expansion continues, and he suggested the expansion could complete in Q2 as well.
Krop also said a fetal growth restriction cohort—enrolling patients without preeclampsia but with impaired placental function—is expected to dose its first patient in Q2 2026.
Health Canada clearance and FDA reproductive toxicology discussions
Krop said the company recently received regulatory clearance from Health Canada to initiate a global Phase 2 open-label, dose-finding trial in early-onset preeclampsia, with plans to begin site activation in the second half of 2026. The trial is designed to enroll about 30 participants between 24 and 32 weeks of gestation and evaluate safety, tolerability, and preliminary efficacy with dosing continuing until delivery. Krop said the study will assess three dose levels to inform Phase 3 regimen selection, with primary endpoints including maternal pharmacokinetics and confirmation that DM199 does not cross the placental barrier.
Additional endpoints will include prolongation of pregnancy, blood pressure control, uterine artery blood flow, circulating pathogenic biomarkers, and renal function, Krop said. She added the company is preparing to seek approval to expand the study to U.K. sites.
Addressing an FDA request for an additional reproductive toxicology study in rabbits, Krop said preliminary results from a dose range-finding rabbit study suggest rabbits may not be a suitable model for DM199 due to an unusual immune response to the recombinant human protein. She noted that teratogenic effects were not observed in a prior rabbit study involving “approximately 200 pups,” with no external, visceral, or skeletal malformations reported.
In the Q&A, Krop said the FDA’s concern is “finding a NOEL,” or a dose without adverse effects, given maternal toxicity believed to be driven by immunogenicity in rabbits. She said the company has submitted a package to the FDA and is discussing alternative models, but called it “premature” to identify the species until those discussions progress.
Pauls also addressed questions about placental transfer risk in earlier-onset preeclampsia. He said the company does not expect DM199 to cross the placenta, citing data from “over 35+ patients” in later-onset preeclampsia without evidence of crossing, along with a rat study. Pauls contrasted the approximate size threshold for crossing (“about 500 daltons”) with DM199’s size (“about 26 kilodaltons”), saying it would be “very shocking” if meaningful transfer occurred.
Stroke program: ReMEDy2 enrollment progress and interim analysis framework
Krop said DiaMedica’s ReMEDy2 trial in acute ischemic stroke saw improving enrollment momentum in recent months following increased engagement with sites, added resources to support enrollment and follow-up, and continued global site activations.
She reported the company has achieved “almost 70%” of the 200 participants required for the interim analysis. Krop said there are close to 61 active sites, including four in the U.K. and 12 across Europe, with roughly 25 additional sites expected to activate in the coming quarter. DiaMedica reiterated its guidance to complete the interim analysis in the second half of 2026.
Krop added that an independent Data Safety Monitoring Board reviewed safety data after enrollment of 100 patients and “unanimously recommended that enrollment continue without modification.”
Pauls provided additional detail on the interim analysis decision rules, saying that if the study is not showing a drug effect, DiaMedica “will terminate the study for lack of efficacy.” Otherwise, the trial includes a sample-size re-estimation, with the total sample size ranging from 300 to 728. He said the company’s “base case” expectation—if the observed effect is comparable to the prior Phase 2 experience—would be a total sample size “ideally in the 300-350 range.” If the trial would need to exceed 500 patients, Pauls said management would evaluate next steps “in light of” the company’s view of the preeclampsia opportunity.
In response to questions about enrollment acceleration, Pauls said the recent improvement is being driven by both higher per-site enrollment and an increased number of sites. He also addressed commercialization questions, arguing that DM199’s safety profile should support broad use across both community hospitals and academic centers, even though earlier enrollment challenges were associated with hub-and-spoke dynamics.
Financial results and cash runway
Chief Financial Officer Scott Kellen said DiaMedica ended 2025 with $59.9 million in cash equivalents and short-term investments, compared with $44.1 million at the end of 2024. He reported current liabilities of $5.1 million and working capital of $55.5 million at December 31, 2025, versus current liabilities of $5.4 million and working capital of $39.2 million a year earlier.
Kellen attributed the higher cash balance to net proceeds from a July 2025 private placement and the company’s at-the-market offering program. He said management “feel[s] confident” the cash position will fund planned clinical studies and corporate operations “through the end of 2027.”
Net cash used in operating activities was $29.1 million in 2025, compared with $22.1 million in 2024, which Kellen said primarily reflected a higher net loss.
On expenses, Kellen reported:
- R&D expense rose to $24.6 million in 2025 from $19.1 million in 2024, driven by continued ReMEDy2 activities and global expansion, clinical team expansion, and higher non-cash share-based compensation, partially offset by reduced manufacturing process development spending that had been completed in the prior year.
- G&A expense increased to $9.8 million from $7.6 million, reflecting higher non-cash share-based compensation, personnel costs, investor relations expense, and patent prosecution costs.
Pauls also referenced a Journal of Hypertension publication on “Endothelial Triple-Pathway Vasorelaxation as an Adjunctive Strategy in Resistant Hypertension,” which he said included resistant hypertension key opinion leader Dr. Luke Laffin and highlighted findings from DiaMedica’s earlier Phase 2 REDUX trial. Pauls said REDUX showed DM199 significantly reduced blood pressure over three months and lowered serum potassium in patients with elevated potassium levels. However, in the Q&A he emphasized that the company’s near-term focus remains on preeclampsia and stroke, with chronic kidney disease-related hypertension viewed as a future opportunity.
About DiaMedica Therapeutics (NASDAQ:DMAC)
DiaMedica Therapeutics, Inc (NASDAQ: DMAC) is a clinical‐stage biopharmaceutical company focused on developing novel therapies for acute and chronic central nervous system conditions. The company’s lead product candidate, DM199, is a recombinant form of human tissue kallikrein-1 designed to promote neuroprotection and tissue repair through modulation of the kallikrein‐kinin system. DiaMedica’s research and development efforts are centered on translating the regenerative potential of DM199 into effective treatments for disorders with high unmet medical need.
DM199 is being evaluated in acute ischemic stroke, where preclinical studies have demonstrated potential benefits in blood flow restoration, inflammation reduction and neuronal survival.
