DMAC

Moreover, we operate in a highly competitive and rapidly-changing environment.
Business Overview We are a clinical-stage biopharmaceutical company committed to improving the lives of people suffering from severe ischemic disease with two main clinical programs focused on preeclampsia (PE) / fetal growth restriction (FGR) and acute ischemic stroke (AIS).
Our lead candidate DM199 (rinvecalinase alfa), is the first pharmaceutically active recombinant (synthetic) form of the human tissue kallikrein-1 (rhKLK1) protein to be clinically studied in patients and has been granted Fast Track Designation by the U.S.
We plan to advance DM199 through required clinical trials to create shareholder value by establishing its clinical and commercial potential as a therapy for PE, FGR and AIS.
KLK1 is a serine protease enzyme that plays an important role in the regulation of diverse physiological processes via a molecular mechanism believed to enhance endothelial health, microcirculatory blood flow and tissue perfusion by increasing production of nitric oxide (NO), prostacyclin (PGI 2 ) and endothelium-derived hyperpolarizing factor (EDHF).
In PE and FGR, DM199 is intended to lower blood pressure, enhance endothelial health and improve perfusion to maternal organs and the placenta, potentially disease modifying results that improve both maternal and perinatal outcomes.
Our clinical development program in PE currently centers around an investigator-sponsored safety, tolerability and pharmacodynamic, proof-of-concept Phase 2 study in PE patients being conducted at the Tygerberg Hospital in Cape Town, South Africa.
This Phase 2 study consists of three studies in PE (Part 1a, dose-escalation; Part 1b, dose-expansion; and Part 2, expectant management) and a fourth study in fetal growth restriction (FGR, Part 3, expectant management).
Part 1a topline study results are intended to identify a suitable dose for Parts 1b, 2, and 3.
Up to approximately 100 women with PE and potentially an additional 30 subjects with fetal growth restriction may be evaluated.
The first subject in Part 1a was enrolled in the fourth quarter of 2024 and interim results from Part 1a of the study were released in July 2025.
The interim results (N=28 subjects) demonstrate that DM199 appears safe and well-tolerated with clinically-relevant pharmacodynamic activity with no evidence of placental transfer.
Additionally, subjects exhibited rapid, statistically significant reductions in blood pressure with duration of effect that was sustained up to 24 hours post-infusion compared to pre-treatment baseline.
An extension cohort of approximately 10 subjects is currently being enrolled at the expected therapeutic dose levels.
Preparations are underway to initiate Part 1b where up to 30 subjects with PE and expected delivery within 72 hours will be treated with a dose regimen identified from Part 1a.
Based in part upon these interim results, we believe DM199 has the potential to lower blood pressure, enhance endothelial health and improve perfusion to maternal organs and the placenta.
We are preparing for an open-label, dose-ranging Phase 2 study of DM199 in participants with early onset preeclampsia to be conducted in North America (United States & Canada) and the United Kingdom (UK).
In March 2026, we received approval from Health Canada to initiate this Phase 2 study and we are currently finalizing plans to commence site activation in the second half of this year.
In the second quarter of 2026, we anticipate filing a clinical trial application to expand this Phase 2 study to include sites in the UK.
Regarding the status of this clinical program in the United States, in the fourth quarter of 2025, we participated in a productive, in-person pre-investigational new drug (IND) meeting with the FDA to discuss the planned Phase 2 study, at which the FDA requested an additional non-clinical, 10-day modified embryo-fetal development and pre- and postnatal development (ePPND) study in a rabbit model, a non-rodent species.
Preliminary results of the rabbit study suggest that the animals developed an antibody response to DM199, a humanized recombinant protein, preventing us from completing the requested ePPND study in the rabbit model.
In earlier pregnant rabbit studies, there was no evidence of teratogenicity (i.e., no external, visceral or skeletal malformations in developing rabbit fetuses) attributable to DM199 in the approximately 200 rabbit offspring produced.
The fetal effects with pregnant rabbits that were observed, embryo/fetal lethality and decreased fetal body weights, were considered secondary to frank maternal toxicity that was observed at all doses.
We are currently evaluating alternate animal models to address the FDA’s ePPND study request.
Depending on the alternative species, and its gestational period, results from the ePPND study may be substantially delayed.
Our clinical program in AIS centers on our ReMEDy2 clinical trial (NCT05065216) of DM199 for the treatment of AIS.
Importantly, human urinary-derived KLK1 has been shown to be generally safe and well tolerated and does not increase the risk of severe intracranial hemorrhage.
Similarly, in the use of KLK1 to treat PE, preliminary evidence from several Asia-based studies using KLK1 derived from pig pancreas has shown reductions in maternal blood pressure and improvements in placental perfusion.
We further note that there are numerous regulatory, commercial and clinical drawbacks associated with KLK1 derived from these sources which we believe can be overcome by developing a recombinant version of KLK1 (rhKLK1) such as DM199.
We believe higher regulatory standards and the potential for impurities, endotoxins and chemical byproducts due to the inherent variability in the isolation and purification process are the primary reasons why urinary- or animal-derived KLK1s are not currently available and or approved in the United States or Europe.
We are not aware of any recombinant version of KLK1 with regulatory approval for clinical use in any country, nor are we aware of any recombinant version in development, other than our drug candidate, DM199.
The most well-characterized activity of KLK1 is the enzymatic cleavage of low molecular weight kininogen (LMWK) to produce bradykinin (BK) which activates BK receptors (primarily BK2R since the BK1R is typically only activated in pathological situations).
As illustrated below, activation of BK receptors by kinins sets in motion metabolic pathways which locally produce NO, prostaglandins (primarily PGI 2 in endothelial cells) and EDHF.
Increased nitric oxide and prostacyclin work through the cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways, to preferentially relax smooth muscle cells and improve blood flow (through vasodilation), potentially protecting tissues and end-organs from ischemic damage.
Although individual pharmacologic activators of each pathway—such as NO donors, PGI₂ analogues, and EDHF stimulators—show preclinical promise; however, none have achieved regulatory approval, and no current therapy targets all three pathways simultaneously.
DM199, as a protein augmentation therapy, is intended to increase KLK1 levels to more fully activate the KKS driving the local generation of all three endothelial pathways, NO, PGI 2 and EDHF, to promote endothelial health and protect the brain and kidney from damage.
By providing additional supply of the KLK1 protein, DM199 treatment could potentially improve blood flow to the placenta and brain while reducing inflammation in damaged end-organs, such as the brain and the kidneys, supporting their structural integrity and normal functioning.
Supporting Data for Use of DM199 (KLK1) Preeclampsia and Fetal Growth Restriction: Studies have shown that KLK1 levels are reduced in women suffering from preeclampsia.
Further, the lowest levels are observed in women with preeclampsia with severe features.
KLK1 plays a central physiological role in regulating vascular tone and perfusion through the generation of active kinins, including bradykinin.

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Gone since FY2024

Moreover, we operate in a very competitive and rapidly-changing environment.
Business Overview We are a clinical stage biopharmaceutical company committed to improving the lives of people suffering from severe ischemic disease with two main clinical programs focused on acute ischemic stroke (AIS) and preeclampsia (PE).
Our lead candidate DM199 (rinvecalinase alfa) is the first pharmaceutically active recombinant (synthetic) form of the human tissue kallikrein-1 (rhKLK1) protein to be clinically studied in patients and has been granted Fast Track Designation from the U.S.
We plan to advance DM199 through required clinical trials to create shareholder value by establishing its clinical and commercial potential as a therapy for AIS and PE.
Our lead candidate DM199 is a recombinant form of human tissue kallikrein-1 , which is a synthetic version of the naturally occurring protease enzyme kallikrein-1 and the first and only rhKLK1 undergoing global clinical development studies in both AIS and PE.
Naturally occurring KLK1 (extracted from human urine or porcine pancreas) has been an approved therapeutic agent in Asia for decades in the treatment of AIS and hypertension associated with cardiorenal disease.
DM199 is produced using recombinant DNA technology without the need for extracted human or animal tissue sources and thereby eliminates risk of pathogen transmission.
KLK1 is a serine protease enzyme that plays an important role in the regulation of diverse physiological processes via a molecular mechanism that may enhance microcirculatory blood flow and tissue perfusion by increasing production of nitric oxide (NO), prostacyclin (PGI2) and endothelium-derived hyperpolarizing factor (EDHF).
In preeclampsia, DM199 is intended to lower blood pressure, enhance endothelial health and improve perfusion to maternal organs and the placenta, potentially disease modifying outcomes improving both maternal and perinatal outcomes.
We are developing DM199 to address two major critical unmet needs.
In AIS, up to 80% of AIS patients are not eligible for treatment with currently approved clot-busting (thrombolytic) drugs or catheter-based clot removal (mechanical thrombectomy).
DM199 is intended to enhance collateral blood flow and boost neuronal survival in the ischemic penumbra and inhibit neuronal cell death (apoptosis) while promoting neuronal remodeling and neoangiogenesis and offer a treatment option for patients who have otherwise no therapeutic options.
In PE, there are currently no approved agents in any global market to safely lower maternal blood pressure and/or reduce the risk of fetal growth restriction.
Historically, the major issue is that traditional vasodilators that are commonly used to reduce essential hypertension (eg, beta-blockers, angiotensin converting enzyme inhibitors (ACEi)) can readily cross the placenta and enter into the fetal circulation and cause harm to the developing fetus.
We believe that DM199 is uniquely suited to treat PE since its inherent molecular size (~26 kilodaltons (KD)) is typically too large to cross the blood-placental barrier but may simultaneously reduce blood pressure and enhance microcirculatory perfusion to the maternal organs and placenta.
DM199 has the potential to not only address hypertension of PE but also confer disease modifying outcomes for both maternal and perinatal outcomes including fetal growth restriction.
Our clinical program in AIS centers on our ReMEDy2 clinical trial of DM199 for the treatment of AIS.
The trial excludes patients who received mechanical thrombectomy (MT) or participants with large vessel occlusions in the intracranial carotid artery or the M1 segment for the middle cerebral, vertebral or basilary arteries or those that are otherwise eligible for MT.
As a result of our recent protocol amendment, participants treated with tissue plasminogen activator (tPA) or tenecteplase (TNK), thrombolytic agents intended to dissolve blood clots, are now eligible for participation if they continue to experience a persistent neurological deficit and meet all other trial criteria, including repeat brain imaging to assess any hemorrhagic (bleeding) transformation.
The primary endpoint of the ReMEDy2 trial is physical recovery from stroke as measured by the well-established modified Rankin Scale (mRS) at day 90, specifically recovering to an mRS score of 0-1 (mRS range of 0-6).
We believe that our ReMEDy2 trial has the potential to serve as a pivotal registration study of DM199 in this patient population.
Our clinical development program in PE is a safety, tolerability, and pharmacodynamic, proof-of-concept study in patients with PE and is financed as an investigator-sponsored trial (IST).
This is a Phase 2 single center, open-label, multiple ascending dose (MAD, intravenous plus subcutaneous), dose escalation study being conducted at the Tygerberg Hospital, Cape Town, South Africa.
As announced in November 2024, enrollment commenced in the dose escalation portion of this study.
Up to 90 women with PE, and potentially an additional 30 subjects with fetal growth restriction, may be evaluated.
Part 1A of the PE study is recruiting up to 30 women planned for delivery within 72 hours and Part 2 will recruit up to 90 women in the expectant management setting.
Part 1A of the study is intended to identify a suitable dose for Part 2 of the study and key outcomes from Part 1A are safety (including confirmation that DM199 does not cross the placental barrier), tolerability and identification of a suitable Phase 2 dose.
Two efficacy endpoints being tracked are the change in maternal systolic blood pressure (SBP) after dosing and, for patients with early onset PE, improved baseline uterine artery blood flow.
The results from Part 1A are expected in the second quarter of 2025.
Importantly, human urinary-derived KLK1 has not been shown to increase the risk of severe intracranial hemorrhage.
Similarly, in the use of KLK1 to treat PE, preliminary evidence presented in several China-based studies using KLK1 derived from pig pancreas have shown reductions in maternal blood pressure and improvements in placental perfusion.
We further note that there are numerous regulatory, commercial and clinical drawbacks associated with KLK1 derived from these sources which we believe can be overcome by developing a recombinant version of KLK1 such as DM199.
We believe higher regulatory standards and the potential for impurities, endotoxins and chemical byproducts due to the inherent variability in the isolation and purification process are the primary reasons why KLK1 derived from these sources are not currently available and used in the United States or Europe.
We are not aware of any recombinant version of KLK1 with regulatory approval for human use in any country, nor are we aware of any recombinant version in development, other than our drug candidate, DM199.
The most well-characterized activity of KLK1 is the enzymatic cleavage of low molecular weight kininogen (LMWK) to produce Lys-bradykinin (BK)-like peptides, collectively known as kinins, which activate BK receptors (primarily BK2R since the BK1R is typically only activated in pathological situations).
As illustrated below, activation of BK receptors by kinins sets in motion metabolic pathways which locally produce nitric oxide, prostaglandins (primarily prostacyclin in endothelial cells) and endothelium-derived hyperpolarizing factor.
Increased nitric oxide and prostacyclin work through the cyclic guanosine monophosphate (cGMP) and cyclic nucleotides cyclic adenosine monophosphate (cAMP) pathways, to preferentially relax smooth muscle cells and improve blood flow (through vasodilation), potentially protecting tissues and end-organs from ischemic damage.
DM199, as a protein augmentation therapy, is intended to increase KLK1 levels to more fully activate the KKS driving the local production of NO, PGI2 and EDHF, to promote endothelial health and protect the brain and kidney from damage.
By providing additional supply of the KLK1 protein, DM199 treatment could potentially improve blood flow and reduce inflammation in damaged end-organs, such as the brain and the kidneys, supporting their structural integrity and normal functioning.
We believe DM199 may provide a new treatment with significant benefits over the current standards of care by offering a therapeutic treatment option to a greater number of patients with the potential for fewer side effects.

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