DiaMedica Therapeutics has unveiled groundbreaking insights into the mechanism of action of DM199 (rinvecalinase alfa) for treating acute ischemic stroke (AIS) in a peer-reviewed publication in the February 2025 issue of Stroke. The research illuminates how this recombinant form of human tissue kallikrein-1 could potentially revolutionize stroke treatment through its unique approach to enhancing brain perfusion.
Mechanism of Action and Scientific Rationale
The study reveals that DM199 functions as a bradykinin-producing enzyme, with particularly notable effects in ischemic brain tissue. Animal studies demonstrated a remarkable 36-fold increase in bradykinin B2 receptor expression on brain endothelial cells within ischemic regions. This heightened expression enables DM199 to trigger potent local vasodilation through three synergistic signaling pathways downstream of the B2 receptor, ultimately improving brain perfusion.
Importantly, DM199's selective action on ischemic tissue minimizes the risk of systemic adverse effects such as hypotension when properly dosed. The drug's therapeutic benefits extend beyond immediate vasodilation, as it also promotes long-term improvements in brain perfusion by stimulating new blood vessel formation.
Clinical Development Progress
"DM199 treatment showed favorable impact on clinical outcomes in AIS patients who were not eligible for mechanical thrombectomy in the prior Phase 2 ReMEDy1 trial," noted Dr. Scott Kasner, Chief of the Division of Neurology at the University of Pennsylvania and principal investigator of the ReMEDy2 trial. "This publication provides valuable scientific insight into how DM199 may improve clinical outcomes in AIS, offering a novel approach to enhancing blood flow in stroke treatment."
ReMEDy2 Trial Design and Scope
The ongoing Phase 2/3 ReMEDy2 trial represents a significant step forward in evaluating DM199's therapeutic potential. This adaptive design, randomized, double-blind, placebo-controlled study aims to enroll between 300 and 728 patients across up to 100 global sites. The trial protocol includes:
- Treatment initiation within 24 hours of AIS symptom onset
- Three-week treatment duration with either DM199 or placebo
- 90-day follow-up period
- Inclusion of patients treated with tissue plasminogen activator (tPA) or tenecteplase (TNK) who show persistent neurological deficit
The study excludes patients who received mechanical thrombectomy or have large vessel occlusions in specific arterial segments. DiaMedica anticipates that this trial could serve as a pivotal registration study for DM199 in the acute ischemic stroke patient population.
