Potential to Treat More Stroke Patients
Our investigational drug product candidate, DM199 (rhKLK1), aims to preserve valuable brain tissue during the hours to weeks after an acute ischemic stroke by promoting collateral circulation in the ischemic penumbra. DM199 is being clinically studied with treatment initiated up to 24 hours after the onset of stroke symptoms, a treatment window five times longer than any existing therapeutic. DM199, a synthetic version of the naturally occurring KLK1 protein, may provide a safer alternative treatment for a wider range of stroke patients.
Pipeline
| Indication | Compound | Route of Admin | Development Stage | |||
|---|---|---|---|---|---|---|
| Preclinical | Phase 1 | Phase 2 | Phase 2/3 | |||
| Neurological | ||||||
| Acute Ischemic Stroke | DM199 (rinvecalinase alfa) | IV/SC |
ReMEDy2 Study
Preclinical complete
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Phase 1 complete
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Phase 2 complete
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Phase 2/3 in progress
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About Acute Ischemic Stroke
Acute ischemic stroke (AIS) occurs when a blood clot blocks a vessel supplying blood to the brain, leading to a sudden loss of oxygen and nutrients and, if not corrected, ultimately neuronal cell death. According to the U.S. Center for Disease Control, stroke causes approximately one out of every 20 deaths in the U.S. each year, and nearly nine out of 10 strokes are ischemic. No new therapeutics have been approved for acute ischemic stroke in over 25 years.
When a blood vessel in the brain becomes blocked during a stroke, a core area of the affected brain tissue will typically suffer a nearly complete loss of blood flow, while the surrounding area (the “ischemic penumbra”) receives only about 20-40% of normal blood flow. Cells in the core area are rapidly depleted of their oxygen and glucose stores, leading, often within minutes, to cell death. The cells in the penumbral area may remain viable for several hours but are eventually at risk of damage.
A stroke can lead to permanent brain damage, including memory loss, speech problems, reading and comprehension difficulties, physical disabilities, and emotional/behavioral problems. Many patients require extended hospitalization, physical therapy or rehabilitation, or long-term institutional or family care.
A Mechanism to Enhance Collateral Circulation
DM199 (rhKLK1), as demonstrated in the graphics below, is intended to increase production of bradykinin which in turn activates a greater number of the increased bradykinin 2 receptors present in the arteries affected by the 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, DM199 may preserve/restore neuronal function and reduce the size of the ischemic penumbra, minimizing neuronal cell death (infarction) and brain damage.
