A near bankrupt Minneapolis biotech is staking its survival on a re engineered version of a human vasodilator protein (kallikrein 1, or KLK1) for acute ischemic stroke — and the ReMEDy2 Phase II/III trial readout before year end will test whether
Thousands of stroke patients reach the hospital outside the 3- to 4.5-hour tissue plasminogen activator (tPA) window every day, with no approved alternative to restore blood flow. A small Minneapolis biotech has spent two decades chasing a different answer, a recombinant version of a human vasodilator protein called kallikrein-1, or KLK1. DiaMedica Therapeutics' lead candidate DM199 is months from a Phase II/III interim readout in acute ischemic stroke, with a separate early-stage program in preeclampsia behind it. Whether the bet pays off depends on a piece of cell biology most coverage ignores: how the sugar molecules attached to the protein determine whether it actually dilates blood vessels.
Acute ischemic stroke affects roughly 700,000 people in the U.S. each year, and only a fraction receive tPA or mechanical thrombectomy in time. Preeclampsia complicates 2-8% of pregnancies globally and remains a leading cause of maternal mortality, with delivery as the only definitive treatment. The mechanism DiaMedica is testing addresses both: inadequate perfusion in the small vessels that feed the brain or the placenta.
The biology traces back to a 1990s rat experiment that seeded DiaMedica's program. Researchers cut the vagus nerve in diabetic rats and saw the animals' metabolic profile worsen, pointing to a liver-derived signaling molecule later identified as tissue kallikrein-1. KLK1 cleaves a circulating protein called kininogen to release bradykinin, which in turn drives nitric oxide (NO) release from the endothelial lining of blood vessels. The result is what DiaMedica calls a "basal dilator," not a clot-buster, but a steady-state opener of small vessels that the company says can improve perfusion in the ischemic phase of stroke and reduce reperfusion injury when blood flow returns.
KLK1 was the active ingredient in a decades-old product extracted from porcine pancreas and approved in parts of Asia for conditions including diabetic nephropathy. DiaMedica rebuilt it: a recombinant human KLK1 with two amino-acid sequence changes for manufacturability and a specific glycosylation pattern, the branched sugar trees attached to the protein after it is made, that the company links directly to enzymatic activity and circulatory half-life. CEO Rick Pauls frames the engineering step as the unlock that earlier attempts lacked. Independent peer-reviewed work has begun to characterize recombinant human tissue kallikrein-1's neurovascular protection in the hours after stroke onset, supporting the mechanistic case outside the company's own pipeline documents.
DiaMedica partnered with Catalent to produce DM199 using GPEx technology, a gene insertion platform that builds stable, high-yielding Chinese Hamster Ovary (CHO) cell lines. CHO cells are the workhorse of the biologics industry because they make human-compatible proteins at industrial scale. The arrangement lets the company run denser cell cultures, lowering per-batch cost, and locks in a process that the company says consistently yields the glycoform pattern linked to activity. For a near-bankrupt Phase II/III biotech, that process is what turns a research candidate into a salable product.
DiaMedica started in diabetes and ran two failed Phase II trials of DM199 in Type II diabetic neuropathy and kidney disease. The company at one point received a Nasdaq listing deficiency notice over its share price, before management repositioned the asset toward acute ischemic stroke, where preclinical data suggested the vasodilator mechanism could reach patients outside the tPA window. The pivot is unfinished: the lead indication has not yet produced a positive Phase III, and analysts will treat the upcoming interim as a go/no-go event.
The pipeline is built around two trials. ReMEDy2 is a Phase II/III study of DM199 in acute ischemic stroke patients who present outside the tPA window or who are ineligible for mechanical thrombectomy. The company is also running a Phase I/II open-label study in preeclampsia, where the same perfusion mechanism is being tested against a disease that has no approved disease-modifying therapy. Both programs are run on the manufactured glycoform of KLK1 that came out of the Catalent partnership.
The ReMEDy2 interim readout is expected before year-end and will dictate whether the trial continues, expands, or stops for futility. The preeclampsia Phase I/II is enrolling and is likely to produce an early pharmacodynamic and safety update in the same window. If the stroke readout is positive, DiaMedica's 20-year bet on KLK1 as a basal dilator becomes a commercial conversation. If it is negative, the manufacturing breakthrough is still real, but the company will need a new indication to justify the platform.
Decades of KLK1 failure in diabetes were at least partly a glycosylation problem, and solving it was the precondition for any clinical read in stroke or preeclampsia. The next readout tests both the molecule and that thesis at once.