Our Focus

Restoring the Body's Supply of an Essential Protein

DiaMedica Therapeutics is developing DM199 (rhKLK1), a recombinant protein replacement therapy intended to restore normal, healthy levels of the protein known as human tissue kallikrein-1 (KLK1). KLK1 is a naturally-occurring protein believed to stimulate the production of nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factors - critical local hormones that are believed to work synergistically to improve blood flow and reduce inflammation. We believe that DM199 (rhKLK1) has the potential to treat several acute diseases.

KLK1 Replenishes Key Signaling Molecules

KLK1 is a serine protease (enzyme) primarily produced in the kidneys, as well as in the pancreas and salivary glands. KLK1 is believed to be responsible for producing nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factors, so-called “signaling molecules,” that work together to play a critical role in regulating many bodily systems. Nobel Prizes in Physiology and Medicine were awarded in 1982 and 1998 to scientists that researched the importance of these signaling molecules. KLK1 is the key protein in the Kallikrein-Kinin system, the system which promotes local blood flow and vasodilation and may also mitigate inflammation and oxidative stress by selectively delivering these signaling molecules when and where they are needed.

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DM199 and KLK1

DM199 (rhKLK1) is a synthetic form of the human tissue kallikrein-1 (KLK1) protein. We developed DM199 in part due to the success of forms of KLK1 produced from human urine and pig pancreas in combatting a variety of diseases associated with reduced or low levels of KLK1 in Asia. Our initial focus is on clinically studying DM199 as a treatment for acute ischemic stroke and preeclampsia.

The Potential Therapeutic Effects of KLK1 Replacement

DM199 (rhKLK1) can be administered intravenously or subcutaneously. It is intended to restore an individual’s KLK1 to normal, healthy levels. KLK1 activates bradykinin receptors, primarily the bradykinin 2 receptor, which stimulates the production of nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factors. Together, these signaling molecules may ultimately improve collateral circulation and stroke outcomes, as well as reduce maternal blood pressure and address both upstream placental hypoxia and downstream endothelial dysfunction.

DM199’s Effect on Acute Ischemic Stroke

DM199 therapy is intended to increase production of bradykinin and thereby activate a greater number of the increased bradykinin 2 receptors present in arteries affected by AIS, referred to as the ischemic penumbra, thus improving collateral circulation in the ischemic penumbra. By delivering vital oxygen and nutrients to brain tissues in need, there is the potential to preserve/restore neuronal function and reduce the size of the ischemic penumbra, minimizing tissue death (infarction) and brain damage.

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DM199's Effect on Hypertension and Preeclampsia

KLK1 has the potential to lower blood pressure, enhance endothelial health, and improve perfusion to maternal organs and the placenta. This mode of action is believed to occur through the increased production of endothelial nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factors (EDHFs). These pathways are typically depressed or impaired in preeclampsia. DM199 holds the potential to be disease modifying for preeclampsia patients if it can effectively increase placental perfusion and reduce hypoxia, a significant contributor to the pathophysiology of preeclampsia.

Novel Approaches to Ischemic Vascular Diseases

At DiaMedica, we are developing DM199 (rhKLK1) as a novel and promising new therapy to restore normal levels of KLK1 and healthy function of the Kallikrein-Kinin system to address multiple serious diseases associated with KLK1 deficiencies. We believe that DM199 (rhKLK1) is the only KLK1 protein replacement therapy in clinical development outside of Asia.

DM199: Restoring Our Natural Ability to Heal

DM199 (rhKLK1) is designed to boost KLK1 levels in the body to restore the normal, physiologic function of the Kallikrein-Kinin system and to restore the body’s natural production of nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factors.

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The safety and effectiveness of DM199 for the treatment of acute ischemic stroke or preeclampsia has not been established and is limited to investigational use only.