DiaMedica’s novel biologic basal dilator: Bringing hope to preeclampsia and ischaemic stroke

Last month, DiaMedica Therapeutics announced they received a No Objection Letter (NOL) from Health Canada, granting regulatory clearance to start their Phase 2 study of DM199 (rinvecalinase alfa), a novel biologic, in patients with early-onset preeclampsia (EOPE). The company plans to start the Phase 2 trial during 2026 and expand into the United States and United Kingdom as regulatory clearances are obtained.

Preeclampsia is a serious pregnancy disorder, affecting nearly 10 millionwomen globally each year, and can strike without warning, threatening mothers and babies with high blood pressure, organ damage, preterm birth; even death. Despite being the leading cause of maternal death worldwide, though, there are still no FDA-approved therapies that address the root cause.

DiaMedica Therapeutics is a company committed to improving the lives of individuals battling serious vascular diseases by developing innovative therapies that reduce ischaemia. With an initial focus on preeclampsia (PE) and foetal growth restriction (FGR), as well as acute ischaemic stroke (AIS), DiaMedica seeks to advance patient care through a novel approach that centres around reversing the effects of the ischaemic injury to improve patient outcomes.

To this end, DM199 (rhKLK1) is a recombinant form of the human tissue KLK1 protein, which enhances blood flow and vascular health by increasing the available levels of nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarising factor (EDHF). Through this novel mechanism of action, DM199 has the potential to modify disease progression in not only preeclampsia, but foetal growth restriction, and potentially enhance collateral circulation in acute ischaemic stroke.

With DM199 having achieved positive results in a Phase 2 study in patients with PE in July 2025, the results showing a significant drop in blood pressure and dilated intrauterine arteries without crossing the placental barrier – and as we head towards May and Preeclampsia Awareness Month – in order to find out more, pharmaphorum spoke with DiaMedica’s CEO, Rick Pauls.

Beyond merely treating symptoms

In the preeclampsia setting, what DiaMedica is seeking with DM199 is to move beyond the current landscape of simply symptom treatment.

“The challenge is, we can't give drugs like ACE inhibitors, ARBs [angiotensin-II receptor blockers], because they're contraindicated and they've been shown to cross the placenta and cause harm to the baby,” explained Pauls. “So, as soon as the systolic blood pressure gets over 160, the OB/GYN starts to prepare for delivery.”

“Just for context, the last clinical trial for preeclampsia, an early onset patient [(EOPE)…] between weeks 24 and 34 – the average time from randomisation to delivery was about five days. If you deliver a baby at 28 weeks, I mean, 40% of those babies will develop cerebral palsy. That baby will likely be in the NICU for many months. It’s a huge cost to the system, but more so, [the baby] can have lifelong challenges […] But there are no treatments for this disease today.”

Indeed, the primary treatment for preeclampsia is delivery of the baby, with additional management including blood pressure control, seizure prevention, and close maternal-foetal monitoring. For mild preeclampsia, delivery is often considered after 37 weeks, while more severe cases require much earlier delivery, as Pauls discussed. As the Mayo Clinic states, close monitoring is essential in all cases: frequent blood pressure checks, laboratory tests (platelets, liver enzymes, kidney function, proteinuria), and foetal assessments (ultrasound, heart rate monitoring, growth evaluation, amniotic fluid assessment) to track disease progression and foetal well-being.

According to a study published in The International Journal of Molecular Sciences, early-onset preeclampsia (EOPE) and late-onset pre-eclampsia (LOPE) are “distinct clinical entities” that “require different management strategies.” EOPE arises from “abnormal placentation with inadequate spiral artery remodelling and impaired uteroplacental perfusion, whereas LOPE [late-onset preeclampsia] is mainly related to maternal cardiovascular and metabolic predisposition.”

“Preeclampsia, really, is a disease of not getting enough blood flow to the placenta. In a normal pregnancy, we've got the spiral arteries, and what happens is that trophoblast cells come in, strip the smooth muscle cells, strip the endothelial cells, and basically create this 10-lane highway. So, that's where all the nutrients, everything basically from the mother to the foetus, goes through the placenta. For a reason we don't fully understand, [in preeclampsia] this doesn't happen and these spiral arteries do not open up. So, then what happens is that, sometime after week 20, the demands of the baby outstrip the supply of nutrients and everything else that's being supplied. And then you get a hypoxic placenta, [which] then releases noxious factors that come in and damage the endothelium.”

According to another study published in The International Journal of Molecular Sciences, hypoxia has been shown to be associated with several pregnancy disorders. Yet, “in the early stages of a healthy pregnancy, a hypoxic microenvironment is actually essential for the trophoblast stem cells, or progenitor cells, to maintain homeostasis, prevent DNA damage, and differentiate selectively” and “also plays a key role in regulating immunity and inflammation.” Nonetheless, from mid- to late-term pregnancy, a hypoxic placenta is high risk for mother and baby.

As ever with patients who are pregnant, a key concern with any therapy is the risk of placental crossover.

“To cross the placental barrier […] takes about 500 Daltons, where our drug is 26 kilodaltons, so, we're able to show very clearly that our drug does not cross the placental barrier,” explained Pauls.

DiaMedica is aiming to have DM199 on the market for preeclampsia in “2029 to 2030”, according to Pauls.

“If we could get literally a few extra days, five, seven days, extending gestational age, that could have a profound impact in terms of reducing many of these severe neonatal events,” he insisted. “Every day you can keep that baby in the mother's womb has an impact in terms of how the ultimate outcome will be for that baby.”

Applicability in the stroke setting

DiaMedica is also currently recruiting patients in the US for a Phase 2 study that will assess DM199 in patients with stroke. If successful, this could potentially extend the window for therapeutic intervention from 4.5 hours to 24 hours, and ultimately lead to billions of dollars of savings in post stroke recovery costs.

“[DM199] is a very potent basal dilator [and] the challenge is that basal dilators have repeatedly failed in stroke; many indications have failed,” stated Pauls. “What we know works for stroke is blood flow: you dissolve the clots, blood flow gets reestablished, patients improve. In stroke, we talk about bradykinin 2 receptors.”

Bradykinin receptor 2 (B2R) is a G-protein-coupled receptor that mediates the effects of bradykinin, regulating vascular tone, calcium signalling and pain perception, and metabolic homeostasis. DM199 given systemically releases bradykinin and, in the ischaemic setting, “brings into that part of the brain what it needs – the blood flow and oxygen.”

“What's unique about the stroke programme is we're developing a recombinant protein,” continued Pauls. “But in China, there is a human urine source of this protein that today is treating about a million patients a year for acute ischemic stroke. So, we've just made the synthetic form [in the West]. For both of these programmes, it’s about vasodilation and blood flow. There's just a huge unmet medical need. All these patients have our hopes and prayers.”

About the interviewee

Rick Pauls has served as president and CEO of DiaMedica Therapeutics since 2009 and has been a Board member since 2005, including as Chair from 2008 to 2014. Previously, he co-founded and led CentreStone Ventures, an early-stage life sciences VC fund, and worked as an analyst at Centara Corporation. Earlier in his career, he specialised in asset-backed securitisation and structured finance at General Motors Acceptance Corporation. He has also served on the boards of several public and private companies. Pauls received his BA in Economics from the University of Manitoba and his MBA in Finance from the University of North Dakota.