Rick Pauls
DiaMedica (OTCQB:DMCAF; TSX-V:DMA) is preparing to begin a bridging study in the first half this year to determine the relative potency, and best dose and delivery of its lead recombinant protein, DM199.
“Our near-term focus is advancing DM199 into clinical studies for the treatment of acute ischemic stroke and positioning DM199 to provide a treatment option for stroke patients beyond the currently limited four-hour treatment window with clot buster, tissue plasminogen activator, (tPA),” Rick Pauls, president & CEO, says in an interview with BioTuesdays.com.
Mr. Pauls explains that DM199 is a recombinant human tissue kallikrein-1 protein (rKLK-1) designed to treat vascular and metabolic diseases, such as acute kidney injury and diabetic kidney disease.
A urine-derived form of human tissue kallikrein-1 (uKLK1) has been approved in China for up to 48 hours post-stroke by promoting cerebral vascular circulation, angiogenesis, inhibiting apoptosis, and decreasing inflammation, he points out. Published clinical studies have found uKLK1 also has been shown to be effective either alone or in combination with tPA in stroke patients.
Urine-source KLK1 is sold in China under the brand name, Kailikang, by Techpool Bio-Pharma, itself a joint venture of Takeda Pharmaceutical and Shanghai Pharmaceuticals. Kailikang is not approved for sale in the U.S. or Europe.
“As a result, we believe our DM199 is a substantially de-risked asset for development in acute ischemic stroke,” he contends.
DM199 has been administered in approximately 100 patients and demonstrated a safe and well tolerated profile. “The data we obtain in the second half of 2016 from the bridging study will determine optimum dosing and delivery route for Phase 2 and 3 clinical trials to follow,” he adds.
Only 5% to 7% of stroke victims reach hospital within four hours to receive tPA and “we are positioning DM199 to offer a treatment option up to 48 hours after a stroke and thereby, providing a treatment option for patients,” Mr. Pauls suggests.
Ischemic stroke is a leading cause of death globally, with about two million patients annually in the U.S., Europe and Japan. About 87% of strokes are ischemic, which is the result of formation of an acute clot, leading to blood vessel blockage in the brain. The resulting reduction in blood flow leads to brain damage and death.
DiaMedica’s lead recombinant protein, DM199, is believed to activate the bradykinin receptor when therapy is initiated within 48 hours of a stroke and for seven-to-21 days, promoting short-term blood flow and reducing inflammation
Mr. Pauls says the bridging study, in about 40 healthy volunteers will measure pharmacokinetics and pharmacodynamics of DM199 administered subcutaneously and intravenously, versus Kailikang which is given by IV.
“This is almost a biosimilar play because we are very comfortable that the underlying protein is quite effective in stroke patients,” he adds. “The key will be how to get dosing correct.”
DiaMedica hopes to proceed to a Phase 2b clinical study in about 200 stroke patients at 15 sites in the U.S. and Europe by early 2017. The treatment course will be to start daily administrations of DM199 within 48 hours of a stroke and continue treatment for seven-to-21 days, with primary endpoints examined after 90 days.
The study’s clinical endpoints include the National Institute of Health Stroke Scale, which measures levels of consciousness, visual acuity, facial palsy, motor abilities and language skills; activities of daily living on the Barthel Index; the modified Rankin Scale; and the recurrence rate of acute cerebral infarction.
According to Mr. Pauls, DM199’s product profile offers significant benefits over Kailikang. For one thing, he says DM199 is expected to have a longer half-life than Kailikang so it should stay in the blood system several hours longer.
Ischemic stroke is a leading cause of death globally, with about two million patients annually in the U.S., Europe and Japan
“We believe that DM199 offers significant benefits over the urine-sourced Kailikang product, including the removal of product supply constraints, very low manufacturing costs and a product capable of meeting the regulatory requirements for worldwide use,” he contends.
“These benefits could allow for significant growth over the existing Kailikang sales in China, greatly expanding the use of this therapy for the treatment of stroke in China, and provide for the first time a treatment option for the rest of the world.”
DiaMedica is currently holding discussions with several pharmaceutical companies about licensing DM199 in China. “We believe our product has the potential to replace Kailikang sales in China, which were in the tens of millions of dollars in 2014. We look at it like insulin. First, there was porcine insulin, which was eventually replaced by synthetic insulin.”
DiaMedica has produced 250 liters of commercial scale DM199 under cGMP, which may support as many as one million patients for acute ischemic stroke, Mr. Pauls suggests.
He explains that DM199 is believed to activate the bradykinin receptor when therapy is initiated within 48 hours of a stroke and for seven-to-21 days, promoting short-term blood flow and reducing inflammation. As therapy is continued, DM199 is expected to prevent brain cell death and promote long-term blood flow.
According to a meta analysis of 24 clinical trials and 2,433 patients published in the Journal of Evidence-Based Medicine in 2012, human urinary KLK1 appears to ameliorate neurological deficits for patients with acute ischemic stroke and improve long-term outcomes, though a few treated patients suffered from transient hypotension.
Regarding the company program in metabolic disorders, Mr. Pauls says the role of KLK1 in kidney disorders is well documented in the literature.
“Mechanistically, a number of opinion leaders and pharmaceutical companies we’ve spoken to appear to be very optimistic about the potential role of DM199 to treat these disorders,” he says.
“Prior to the availability of DM199, there was no form of KLK1 acceptable to the western world. We are excited that DM-199 may be a game changer if the results of clinical science support current theory.”
DiaMedica Product Pipeline
