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. African Americans who have the APOL1 gene mutation are at an even higher risk. Currently, there are no cures for CKD and treatment strategies for CKD include the strict control of high blood pressure and high blood sugar.  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

Program Asset Route of Admin Development Stage
Preclinical Phase 1 Phase 2 Phase 3
Kidney Diseases
African Americans with CKD DM199 SC
REDUX Phase 2 Study Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 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

  • ~5.9 million African Americans with CKD
  • 3x – 4x more likely to suffer kidney failure than Caucasians
  • Exhibit lower KLK1 levels and lower renal blood flow
  • APOL1 gene mutation associated with an even higher risk of progressing to ESRD (potential rare disease)
  • One U.S. FDA-approved therapy available recently approved to slow the rate of disease progression.

Mechanism of Action

Potential Benefits of DM199 for CKD

  1. Regulate blood flow:

    • Improve micro vascularization
    • Increases oxygen and nutrients
  2. Improve glomerular function:

    • Reduce inflammation, oxidative stress and fibrosis
    • Prevent or reduce thickening of glomerular basement membrane
    • Inhibit mesangial cell proliferation
  3. Regulate epithelial sodium channel (ENaC):

    • Restore regulation of salt & water reabsorption and excretion
  4. Increase T-regs (CKD autoimmune diseases)

    • Halt pathological autoimmune attack on glomerulus

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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