DiaMedica Therapeutics has reported positive interim results from Part 1a of its Phase II clinical trial for DM199, a potential first-in-class therapy targeting preeclampsia (PE).

The data showed significant reductions in blood pressure and improved uterine artery blood flow, while avoiding placental transfer—a key safety concern in pregnancy therapeutics.

Preeclampsia, a life-threatening hypertensive disorder affecting up to 8% of pregnancies globally, currently lacks US Food and Drug Administration (FDA) approved treatments. The only intervention is often premature delivery, which carries significant risks for both mother and child.

“These interim results exceeded our expectations, demonstrating DM199’s potential to be a disease-modifying therapy for preeclampsia, coupled with a promising fetal exposure profile,” said Rick Pauls, DiaMedica’s President, CEO, and Director, during an investor call.

Following the news, the Minneapolis (US)-based company’s stock rose 10.3% in trading on 17 July, compared to the previous day’s market close.

Promising Efficacy and Safety Data

The trial, conducted at Tygerberg Hospital in Cape Town, South Africa, is an open-label, single-center, single-arm study designed to assess DM199’s safety and pharmacodynamics. Participants included women with severe preeclampsia requiring delivery within 72 hours.

In Cohort 9, the highest dose group (n=3), patients experienced a mean systolic blood pressure (SBP) reduction of 35 mmHg and diastolic blood pressure (DBP) reduction of 15 mmHg five minutes post-infusion. Combined cohorts 6–9 (n=12) demonstrated statistically significant and durable reductions at multiple time points:

• SBP: -25 mmHg (p=0.0003) at 5 minutes, -15 mmHg (p=0.0018) at 30 minutes, and -20 mmHg (p=0.0031) at 24 hours.
• DBP: -13 mmHg (p=0.0007), -13 mmHg (p=0.0002), and -10 mmHg (p=0.0294), respectively.

“We had a dose-dependent reduction in both systolic and diastolic blood pressure, and we are especially encouraged by the sustained effects over 24 hours,” Pauls noted. “None of these patients’ systolic pressures exceeded 160 mmHg at any point—a critical threshold for obstetricians.”

The therapy also produced a 13% reduction in uterine artery pulsatility index (PI), a Doppler ultrasound measure of blood flow resistance (p=0.0003). This suggests improved placental perfusion and potential disease-modifying effects.

Importantly, DM199 showed no evidence of crossing the placental barrier—a major hurdle for previous therapies. Cord blood samples revealed no detectable DM199, supporting a favorable fetal safety profile. Treatment-emergent adverse events (TEAEs) were mild, including nausea (14%), headache (11%), and flushing (4%), with no discontinuations or early labor inductions.

Expert Perspective and Patient Impact

Dr. Catherine Cluver, principal investigator and Professor of Maternal-Fetal Medicine at Stellenbosch University, shared her frontline experience: “A number of patients who I thought would deteriorate actually improved. They became less swollen, and many felt remarkably well. It’s something I don’t usually see with such severe disease.”

Cluver emphasized DM199’s potential advantages over current antihypertensives, which cross the placenta and only manage symptoms: “DM199 is different. It targets the pathophysiology of preeclampsia by improving endothelial dysfunction, while sparing the fetus from exposure.”

She also highlighted patient enthusiasm: “Many of the women were thankful for the chance to be included in the study. The fact that DM199 can be given as a subcutaneous injection with a relatively long half-life is an added benefit.”

Next Steps for DM199

The trial will now proceed to Part 1b, a dose expansion cohort with 30 additional patients, and plans to initiate enrollment in a fetal growth restriction (FGR) cohort. FGR often co-occurs with preeclampsia and is linked to inadequate placental blood flow.

“With these results, we feel DM199 is emerging as a potential breakthrough candidate for both preeclampsia and fetal growth restriction,” Pauls said. “We are preparing to engage with the FDA later this year regarding a global Phase II/III study.”

The potential impact of DM199 extends beyond blood pressure management. Enhanced placental perfusion could translate into prolonged gestation and improved fetal outcomes, offering hope for reducing the high rates of preterm births and maternal complications associated with PE.

DM199 (rinvecalinase alfa) is a recombinant form of human tissue kallikrein-1 (rhKLK1). KLK1 increases nitric oxide and prostacyclin production, promoting vasodilation and improved endothelial function. DiaMedica is also studying DM199 for acute ischemic stroke.

Preeclampsia remains a leading cause of maternal and neonatal morbidity and mortality. Affecting over 10 million women annually worldwide, it can lead to eclampsia, organ failure, and death. Current management relies on controlling symptoms and delivering the baby, often prematurely.

“We believe DM199 has the potential to change the treatment paradigm for preeclampsia by addressing its root causes rather than just managing symptoms,” said Pauls.