8-K: Breakthrough Preeclampsia Drug Shows Promising Phase 2 Results

A biopharmaceutical company announced positive interim Phase 2 study results for its investigational drug DM199 in treating preeclampsia, demonstrating statistically significant reductions in blood pressure and no placental transfer.

Summary

• DiaMedica Therapeutics Inc. announced positive interim results from Part 1a of the Phase 2 study of DM199 for the treatment of preeclampsia.
• DM199 demonstrated highly statistically significant and clinically meaningful reductions in systolic and diastolic blood pressure for combined cohorts 6-9.
• DM199 did not cross the placental barrier and was generally safe and well tolerated, with no serious treatment emergent adverse events reported.
• Cohort 9 (n=3; highest dose) achieved substantial mean reductions at 5 minutes post-infusion: SBP reductions of -35 mmHg (p<0.05) and DBP reductions of -15 mmHg (p<0.05).
• Pooled cohorts 6-9 (n=12) exhibited statistically significant mean blood pressure reductions at 5 minutes, 30 minutes, and 24 hours post-infusion, showing a durable response over time.
• For pooled cohorts 6-9, SBP reductions were -25mmHg (p=0.0003) at 5 minutes, -15mmHg (p=0.0018) at 30 minutes, and -20 mmHg (p=0.0031) at 24 hours.
• For pooled cohorts 6-9, DBP reductions were -13mmHg (p=0.0007) at 5 minutes, -13mmHg (p=0.0002) at 30 minutes, and -10 mmHg (p=0.0294) at 24 hours.
• DM199 produced a statistically significant reduction in pulsatility index (PI) measures, with a 13.2% (p=0.0003) mean reduction in blood flow resistance at the 2-hour mark, indicating improved uterine artery blood flow and placental perfusion.
• Mild treatment emergent adverse events were limited to nausea (14%), headache (11%), and flushing (4%), with no discontinuations of treatment or inductions of early labor.

Sentiment

Score: 9

Explanation: The document reports highly positive interim Phase 2 clinical trial results for DM199 in preeclampsia, demonstrating statistically significant efficacy in blood pressure reduction and improved placental perfusion, coupled with a favorable safety profile including no placental transfer. This addresses a significant unmet medical need with no currently approved pharmacological treatments, indicating strong therapeutic potential.

Positives

• DM199 achieved pre-specified safety and efficacy endpoints for the Part 1a dose escalation phase of the Phase 2 study for preeclampsia.
• Demonstrated highly statistically significant and clinically meaningful reductions in both systolic and diastolic blood pressure.
• DM199 did not cross the placental barrier, which is a significant safety advantage for both mothers and babies and addresses a historical safety hurdle in developing preeclampsia treatments.
• The drug was generally safe and well tolerated, with no serious treatment emergent adverse events reported across all cohorts.
• Produced a statistically significant reduction in pulsatility index (13.2% mean reduction), indicating improved uterine artery blood flow and placental perfusion.
• Robust evidence supports DM199's potential as a best-in-class mechanism for enhancing placental perfusion, protecting the endothelium, and reducing blood pressure.
• No discontinuations of treatment and no inductions of early labor were observed during the study.

Risks

• The possibility of unfavorable results from ongoing or future clinical trials of DM199.
• The risk that existing preclinical and clinical data may not be predictive of the results of ongoing or later clinical trials.
• Reliance on collaboration with third parties to conduct clinical trials.
• Ability to continue to obtain funding for operations, including funding necessary to complete current and planned clinical trials and obtain regulatory approvals for DM199 for preeclampsia.
• General risks and uncertainties identified in the company's annual report on Form 10-K for the fiscal year ended December 31, 2024, and quarterly report on Form 10-Q for the quarterly period ended March 31, 2025.

Future Outlook

The Phase 2 study of DM199 for preeclampsia will proceed with enrollment of the dose expansion cohort (Part 1b). Additionally, based on the observed pulsatility index reductions in Part 1a, enrollment in the fetal growth restriction (FGR) cohort (Part 3 of the study) will also be initiated. DM199 is positioned as a potential first-in-class, disease-modifying therapy for preeclampsia.

Management Comments

• "These interim results exceeded our expectations demonstrating DM199s potential to be a first-in-class, disease modifying therapy for preeclampsia, coupled with a promising fetal exposure profile." Rick Pauls, President and CEO of DiaMedica Therapeutics.
• "We believe that the statistically significant reductions in blood pressure and pulsatility index represent on-target responses consistent with DM199s mechanism of action signaling the potential of DM199 to greatly benefit this underserved patient population." Rick Pauls.
• "These results are bolstered by data showing that DM199 did not cross the placental barrier, which historically has been a safety hurdle faced in developing treatments for PE. DM199 could potentially offer a significant safety advantage for both mothers and their babies." Rick Pauls.
• "With hypertension being the leading cause of delivery, often prematurely, in early onset preeclampsia, DM199s ability to safely reduce blood pressure represents an exciting development in the search for an effective treatment for preeclampsia and I look forward to continuing our trial." Professor Cathy Cluver, principal investigator of the Phase 2 preeclampsia trial.

Industry Context

Preeclampsia is a serious pregnancy disorder affecting up to 8% of pregnancies worldwide, characterized by high blood pressure and organ damage. Currently, there are no approved pharmacological treatments for the management of preeclampsia in the United States and Europe, representing a significant global unmet medical need. DM199's positive interim results position it as a potential first-in-class, disease-modifying therapy to address this critical gap.

Comparison to Industry Standards

• Currently, there are no approved pharmacological treatments for the management of preeclampsia in the United States and Europe, positioning DM199 as a potential first-in-class therapy to address this significant unmet medical need.
• DM199's demonstrated ability to not cross the placental barrier is a crucial safety advantage, addressing a historical hurdle faced by other potential treatments for preeclampsia, which often struggle with fetal exposure concerns.

Stakeholder Impact

• Shareholders: The highly positive clinical trial results are likely to significantly increase investor confidence and could lead to a positive impact on the company's share price due to the potential for a first-in-class drug in an unmet medical need.
• Patients (Mothers with Preeclampsia): DM199 offers a potential first-in-class pharmacological treatment option for a serious and life-threatening condition that currently lacks approved therapies, potentially improving maternal health outcomes.
• Patients (Babies): The finding that DM199 does not cross the placental barrier suggests a safer treatment profile for the fetus, potentially reducing risks associated with preeclampsia and its management.
• Healthcare Providers: A new, effective, and safe treatment for preeclampsia could provide a much-needed tool for managing the disease, potentially reducing the need for premature deliveries and improving patient care.

Next Steps

• Proceed with enrollment of the dose expansion cohort (Part 1b) of the Phase 2 study of DM199 for preeclampsia.
• Initiate enrollment in the fetal growth restriction (FGR) cohort (Part 3 of the study) based on observed pulsatility index reductions.
• DiaMedica Management will host a conference call and webcast on July 17, 2025, to discuss the interim Phase 2 preeclampsia study results.

Key Dates

Recommendation

Keywords

Preeclampsia, DM199, rinvecalinase alfa, Clinical trial, Phase 2, Biopharmaceutical, Blood pressure reduction, Placental transfer, Pulsatility index, Maternal health, Fetal growth restriction, KLK1 protein, Vascular health