DiaMedica Therapeutics, Inc.

DM199 for African Americans with CKD (APOL1)

A New Treatment for a Multi-Faceted Disease

African Americans have a three to four times greater risk for developing kidney failure than Caucasians. The ACEi drug Captopril® is approved for use in patients with CKD due to Type 1 diabetes and both ACEi and ARBs are widely prescribed to slow the progression of CKD.  Furthermore, the treatment with ACEi has been linked to hyperkalemia (elevated blood potassium levels), which increases the risk for abnormal heart rhythms and sudden death.  In fact, two clinical trials investigating the use of ACEi and ARB combination therapy in kidney disease were stopped prematurely because participants developed hyperkalemia.  The added complication of hyperkalemia results in patients receiving smaller, or suboptimal, doses or patients being untreated because they cannot tolerate the treatment.  Additional side effects with ACEi treatment are angioedema (swelling of skin tissue) and more commonly a persistent cough.

DM199 treatment is intended to directly replenish KLK1 levels, maintaining or potentially restoring kidney function. Current treatment options, especially ACEi drugs, only partially restore kidney function and are associated with high-risk side effects.  ACEi drugs can generate excessive BK where it is not needed, potentially leading to side effects such as cough and angioedema.  DM199 treatment may potentially allow KLK1 to follow its normal physiological processes and release BK when and where it is needed, avoiding these side effects.

We believe that DM199, a protein replacement therapy, has the potential to change the treatment paradigm, promoting better, and possibly restoring, overall function and protecting the kidney from further damage.

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
Phase 1 complete
Phase 2 complete
Phase 2/3 in progress
Cardio-Renal Disease
Undisclosed DM199 (Rinvecalinase alfa) SC
Phase 2 Ready Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 2/3 not started
Inflammatory
Severe Inflammatory Disease DM300 IV
Preclinical Preclinical in progress
Phase 1 not started
Phase 2 not started
Phase 2/3 not started

1.  Due to the heightened risk of African Americans with the APOL1 genetic mutation to progress to end-stage renal disease, participants in this cohort will be tested for the presence of the APOL1 genetic mutation

About Chronic Kidney Disease (CKD)

Chronic Kidney Disease (CKD) is a decline in overall kidney function, characterized by poor blood flow through the kidneys and decreased ability to filter water and waste products out of the blood. Untreated CKD may progress to end stage renal disease (ESRD), in which the kidneys stop functioning entirely, and the patient requires ongoing dialysis or kidney transplantation.

Market Need

  • ~6 million African Americans with CKD
  • Three to four times more likely to suffer kidney failure than Caucasians
  • Exhibit lower KLK1 levels and lower renal blood flow
  • Limited treatment therapies availble 

Mechanism of Action

Potential Benefits of DM199 for CKD

  1. Regulate blood flow (↑ eGFR):

    • Improve micro vascularization blood flow

  2. Improve glomerular function (↓ Albuminuria):

    • Reduce inflammation, oxidative stress and fibrosis
    • Reduce thickening of glomerular basement membrane
    • Improve podocyte health
    • Inhibit mesangial cell proliferation

  3. Regulate epithelial sodium channel (ENaC):

    • Regulate salt & water reabsorption and excretion, in particular salt–sensitive patients
    • Control blood pressure

  4. Increase Tregs (halt autoimmune attack)

    • Halt pathological autoimmune attack on glomerulus

DiaMedica is currently conducting clinical trials of DM199 in non-diabetic, hypertensive African Americans. Patients will receive DM199 by subcutaneous injection. Clinicians will evaluate changes in eGFR (blood flow through the kidney) and albuminuria (renal filtration ability).

Clinical Studies

DiaMedica is currently conducting clinical trials of DM199 in non-diabetic, hypertensive African Americans. Patients will receive DM199 by subcutaneous injection. Clinicians will evaluate changes in eGFR (blood flow through the kidney) and albuminuria (renal filtration ability). DiaMedica also intends to identify subjects who carry the APOL1 gene mutation to assess the gene’s impact on DM199 therapy outcomes.

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