DM199 (KLK1) is believed to improve overall endothelial health by stimulating potentially beneficial signaling pathways causing the production of nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factors. Enhancing endothelial health and lowering blood pressure yield numerous benefits for both mother and baby, potentially facilitating the extension of gestational days.
| Indication | Compound | Route of Admin | Development Stage | |||
|---|---|---|---|---|---|---|
| Preclinical | Phase 1 | Phase 2 | Phase 2/3 | |||
| Preeclampsia | ||||||
| Preeclampsia | DM199 (rinvecalinase alfa) | IV/SC |
Phase 2 Ready
Preclinical complete
|
Phase 1 complete
|
Phase 2 in progress
|
Phase 2/3 not started
|
Preeclampsia is a serious and potentially life-threatening disease in pregnancy that typically emerges after 20 weeks of gestation, impacting both the mother and unborn child. Traditional indicators of preeclampsia are hypertension and severe injury to the mother’s vascular system, which has the potential to damage multiple vital organs. Currently there are no FDA-approved therapies for preeclampsia, and the only ‘cure’ is to deliver the baby, often prematurely.
The two most common variants of preeclampsia are maternal vascular disease and endothelial dysfunction. Damage to the mother’s blood vessels can compromise the mother’s blood supply to her uterus and placenta, ultimately affecting the unborn baby. Treating preeclampsia can be very challenging due to its dual classification as a placental disease and maternal vascular disease.
Throughout the early stages of pregnancy, maternal vasculature in the uterus is remodeled by the developing placenta in order to gain nutrients from the maternal blood stream. This process occurs in the first trimester (up to 13 weeks of gestation) and catalyzes the transferring of nutrients and oxygen from the maternal bloodstream to the placenta. Poor placental implantation promotes the release of damaging anti-angiogenic factors such as soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng), oxidative stress factors (ROS), pro-inflammatory cytokines, and exosomes or cellular debris for the duration of pregnancy leading to stage two of the disease.
During the second stage of preeclampsia, an overproduction of harmful factors in the placenta leads to maternal vascular disease and subsequent endothelial dysfunction and hypertension prompting widespread injury to the mother’s blood vessels. A hallmark of endothelial cell dysfunction is the impaired signaling of nitric oxide, which drives the progression and severity of the disease.
DM199 treatment is intended to counterbalance the evolution of preeclampsia by triggering the release of endothelial nitric oxide (NO), prostacyclin (PGI2), and endothelium-derived hyperpolarizing factors (EDHF). We believe that the activation of these signaling pathways promote the relaxation of blood vessels and as a result, reduce blood pressure. We believe that DM199, a protein replacement therapy, has the potential to change the treatment paradigm of preeclampsia.
DiaMedica is collaborating with world leaders from Stellenbosch University, the University of Melbourne, and the University of Gothenburg to conduct an investigator-sponsored trial.
