DiaMedica Begins Phase 2 Clinical Evaluation of DM199 in Fetal Growth Restriction as First Patients Receive Treatment
DiaMedica Therapeutics has reached an important clinical milestone in its effort to address serious pregnancy-related complications, announcing that the first two patients have been dosed in an investigator-sponsored Phase 2 study of DM199 (rinvecalinase alfa) for the treatment of fetal growth restriction (FGR). The study marks the first time DM199 is being clinically evaluated in FGR, a severe obstetric condition with no approved drug therapies and substantial risks for both mother and baby.
DiaMedica, a clinical-stage biopharmaceutical company focused on developing novel therapies for conditions including preeclampsia, fetal growth restriction, and acute ischemic stroke, said the newly launched trial will explore the safety and potential activity of DM199 in women with early-onset fetal growth restriction, one of the most challenging forms of the disease. The open-label, single-arm Phase 2 study is designed to test three dose levels of DM199 in up to 30 patients, with the goal of generating early evidence on whether the therapy can improve placental blood flow, support fetal development, and potentially prolong pregnancy.
The company’s announcement reflects a growing effort within maternal-fetal medicine to move beyond monitoring and early delivery as the only options for pregnancies complicated by fetal growth restriction. If successful, DM199 could represent a new therapeutic approach for a condition that remains one of the most urgent unmet needs in obstetric care.
A serious pregnancy complication with limited options
Fetal growth restriction occurs when a fetus does not reach its expected growth potential during pregnancy, typically because the placenta is not functioning adequately and cannot deliver enough oxygen and nutrients to support normal fetal development. In many cases, the problem is tied to poor placental perfusion and reduced maternal uterine blood flow, which compromise the fetus’s ability to grow appropriately in the womb.
The burden of the condition is substantial. Globally, fetal growth restriction is estimated to affect about 10% of pregnancies, making it a major contributor to poor pregnancy outcomes worldwide. It is associated with an increased risk of stillbirth, preterm birth, neonatal complications, and long-term health consequences for children who survive. The risks are even more severe in early-onset fetal growth restriction, which affects an estimated 1 in 500 pregnancies and is linked to neonatal mortality rates of 15% to 20%, as well as a heightened likelihood of long-term neurodevelopmental complications.
Despite the seriousness of the condition, treatment options remain extremely limited. There are currently no approved pharmacologic therapies specifically indicated for fetal growth restriction. Instead, clinicians typically rely on close surveillance of fetal growth, Doppler assessments of placental and fetal circulation, and difficult decisions regarding the timing of delivery. In severe cases, physicians are often forced to deliver the baby prematurely to avoid fetal demise, even though early delivery itself carries significant risks related to prematurity.
That therapeutic gap is one reason DiaMedica and its academic collaborators see DM199 as a potentially meaningful new intervention in the field.
DM199’s mechanism and its potential relevance in fetal growth restriction
DM199 is a recombinant form of human tissue kallikrein-1 (KLK1), an enzyme that plays a role in the regulation of blood flow through activation of natural vasodilatory pathways. According to DiaMedica, the therapy works by promoting bradykinin-mediated signaling, which in turn stimulates the production of several biologically active molecules involved in vascular relaxation, including nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor.
These signaling molecules help blood vessels relax and widen, increasing blood flow through the vascular system. In the context of fetal growth restriction, that mechanism is particularly relevant because impaired uterine blood flow and poor placental perfusion are central drivers of disease pathology. If DM199 can dilate maternal blood vessels supplying the placenta, it may improve the delivery of oxygen and nutrients to the placenta and fetus, with the potential to support fetal growth and extend the duration of pregnancy.
The company has emphasized that this approach is rooted in the underlying biology of FGR rather than simply addressing symptoms or consequences of the disorder. In theory, restoring blood flow to the placenta could help modify the course of the disease itself—something current clinical management strategies do not achieve.
DiaMedica also highlighted a potentially important safety-related feature of DM199: as a large recombinant protein therapeutic, it has been shown not to cross the placental barrier into fetal circulation. In pregnancy-related drug development, minimizing direct fetal exposure can be an important consideration, and the company believes this characteristic could provide an advantage as DM199 is studied in maternal conditions such as fetal growth restriction and preeclampsia.
First patients dosed as DiaMedica expands maternal-fetal medicine strategy
The newly announced Phase 2 trial is being conducted as an investigator-sponsored study, reflecting collaboration between DiaMedica and experts in maternal-fetal medicine who are seeking new approaches for high-risk pregnancies. The study is open-label and single-arm in design, with patients receiving one of three DM199 dose levels. By enrolling women with early-onset fetal growth restriction, the study aims to generate insights in a patient population where the unmet need is especially high and where even modest improvements in placental function or pregnancy duration could have meaningful clinical implications.
Rick Pauls, DiaMedica’s President and Chief Executive Officer, said the start of dosing represents a significant step for the company’s pregnancy-focused pipeline and underscores its commitment to addressing conditions for which patients currently have few or no therapeutic options.
According to Pauls, fetal growth restriction remains one of the most pressing challenges in maternal-fetal medicine because clinicians can monitor disease progression but have no treatment capable of altering the underlying course of the condition. He noted that observations from DiaMedica’s ongoing preeclampsia study have provided early signals that support the scientific rationale for evaluating DM199 in fetal growth restriction as well.
That crossover is notable because both preeclampsia and fetal growth restriction are linked to abnormalities in placental vascular function and maternal blood flow. DiaMedica appears to be positioning DM199 as a therapy with potential utility across multiple pregnancy-related disorders characterized by vascular dysfunction, placental insufficiency, and compromised maternal-fetal circulation.
Clinical investigators see potential for a shift in standard care
The Phase 2 study is being led by Catherine Cluver, MD, PhD, a Professor of Maternal-Fetal Medicine at Stellenbosch University in Cape Town, South Africa, and the lead investigator of the trial. Cluver described fetal growth restriction as one of the most difficult and emotionally devastating conditions encountered in obstetric practice because current management is largely limited to surveillance and deciding when delivery is necessary—often much earlier than would be ideal for fetal development.
She pointed to the central role of placental perfusion deficits and abnormal maternal uterine vascular function in the disease process, noting that a therapy capable of restoring blood flow to the placenta could represent a fundamental change in how physicians approach fetal growth restriction. Rather than simply watching the fetus deteriorate and intervening with premature delivery, clinicians might one day have an option aimed at improving placental function and buying valuable time in the pregnancy.
That possibility is particularly important in early-onset disease, where each additional day or week in utero can influence neonatal outcomes, organ development, and long-term health. Even incremental extensions in gestational age may translate into lower risks of respiratory complications, neurological injury, and intensive care burden after birth.
New white paper outlines scientific rationale for DM199 in FGR
Alongside the announcement of first patient dosing, DiaMedica also said it has released a new white paper titled “The Potential of DM199 to Treat Fetal Growth Restriction.” The paper was authored by maternal-fetal medicine experts Stephen Tong, Susan Walker, and Catherine Cluver and is available through the company’s pregnancy disorders resources on its website.
According to DiaMedica, the white paper reviews the biological rationale for using DM199 in fetal growth restriction and compiles evidence supporting its potential role as a first-in-class therapy for the condition. The publication appears intended to provide scientific context for the program as the Phase 2 study moves forward, while also drawing attention to the broader unmet need in placental disease and high-risk pregnancy management.
The release of the paper may help frame DM199 not just as another investigational asset in development, but as part of a larger strategy to address diseases of placental insufficiency through vascular-targeted intervention.
A potentially important step in a difficult area of drug development
Drug development in pregnancy-related disorders has historically lagged behind many other therapeutic areas, in part because of scientific complexity, safety considerations, and the challenge of designing studies in vulnerable patient populations. As a result, conditions such as fetal growth restriction have long lacked disease-modifying treatment options despite their profound impact on maternal and neonatal health.
DiaMedica’s advancement of DM199 into a clinical study for fetal growth restriction therefore represents more than a routine trial update. It signals a push toward therapeutic innovation in a field where progress has been limited and where physicians and patients have had to rely largely on monitoring, supportive care, and difficult delivery decisions.
While the Phase 2 study remains early-stage and much more work will be required to establish safety, dosing, and efficacy, the initiation of patient dosing is a notable milestone for the program. If DM199 can demonstrate an ability to improve placental perfusion, support fetal growth, or safely prolong pregnancy in women with early-onset fetal growth restriction, it could open the door to a new treatment paradigm for one of obstetrics’ most serious and unresolved complications.
For now, the start of clinical dosing offers an early but meaningful sign of momentum for DiaMedica’s maternal-fetal medicine strategy—and renewed hope that a pharmacologic therapy for fetal growth restriction may finally be moving closer to reality.
About the Phase 2 Fetal Growth Restriction Trial
The open-label Phase 2 investigator-sponsored trial is expected to enroll up to 30 women with early-onset FGR between 27 and 32 weeks of gestation. The primary objective is to assess safety and tolerability. Exploratory efficacy endpoints include uterine artery vascular resistance, umbilical artery Doppler findings, fetal growth trajectory, birthweight centile, pregnancy prolongation and DM199 levels in umbilical cord blood at birth.
About Fetal Growth Restriction
Fetal growth restriction occurs when a fetus fails to reach its genetic growth potential in the womb, most commonly because of placental insufficiency. FGR affects approximately 10% of pregnancies globally and is associated with increased risk of stillbirth, preterm birth, neonatal morbidity and long-term neurodevelopmental, cardiovascular and metabolic complications. Severe early-onset FGR often requires delivery before 32 weeks of gestation.
Current management is limited to monitoring and determining the optimal timing of delivery. Additional detail on the scientific rationale for evaluating DM199 in FGR is available in a white paper in the Clinical Trials: Preeclampsia and Fetal Growth Restriction section of the Company’s website at Preeclampsia & Fetal Growth Restriction: DiaMedica Therapeutics, Inc. (DMAC).
About DM199 (rinvecalinase alfa)
DM199 (rinvecalinase alfa) is a recombinant form of human tissue kallikrein-1 (rhKLK1) in clinical development for preeclampsia, fetal growth restriction, and acute ischemic stroke. KLK1 is a serine protease enzyme that plays an important role in the regulation of diverse physiological processes via a molecular mechanism that increases production of nitric oxide, prostacyclin and endothelium-derived hyperpolarizing factor.
About DiaMedica Therapeutics Inc.
DiaMedica Therapeutics Inc. is a clinical-stage biopharmaceutical company committed to improving the lives of people suffering from serious ischemic diseases with a focus on preeclampsia, fetal growth restriction, and acute ischemic stroke. DiaMedica’s lead candidate DM199 is the first pharmaceutically active recombinant (synthetic) form of the KLK1 protein, an established therapeutic modality in Asia for the treatment of acute ischemic stroke, preeclampsia and other vascular diseases. For more information, visit the Company’s website at www.diamedica.com.
