DM199 for Cardio-Renal Disease

Controlling Blood Pressure and Improving Overall Kidney Function

DM199 (KLK1) is believed to improve overall kidney function via local stimulate the production of nitric oxide and prostaglandins, which help to improve renal blood flow and reduce inflammation.

Pipeline

Program Asset Route of Admin Development Stage
Preclinical Phase 1 Phase 2 Pivotal
Cardio-Renal Disease
Planned to be Disclosed in 2H 2023 DM199 SC
Potentially Phase 2 Ready Preclinical complete
Phase 1 complete
Phase 2 in progress
Pivotal not started

About Cardio-Renal

"Cardio-renal" refers to the interrelated medical fields of cardiology and nephrology.  The term is often used to describe conditions that involve both the heart (cardio) and kidneys (renal) and the complex physiological interactions between the two.

Cardio-renal syndrome, for example, is a condition where dysfunction in either the heart or kidneys can lead to acute or chronic dysfunction of the other.  This can manifest in numerous ways, such as when acute or chronic heart failure leads to decreased kidney function, or when acute or chronic kidney disease leads to heart damage, heart failure or other cardiovascular complications.

The management of cardio-renal disease often requires a multidisciplinary approach, as treatment interventions in one system can significantly impact the other.  The cardio-renal connection is a growing area of medical research in which it is increasingly recognized that maintaining the health of both these vital organs is critical for overall patient health and well-being.

Kidney disease

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.

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 angiotensin converting enzyme inhibitor (ACEi) drug Captopril┬« is approved for use in patients with CKD due to Type 1 diabetes and both ACEi and angiotensin receptor blockers (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 may result in patients receiving smaller, suboptimal doses or patients being untreated because they cannot tolerate the treatment.  Additional potential 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.  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.

Mechanism of Action

Potential Benefits of DM199 for Cardio-Renal

  1. Regulate blood flow:

    • Improve renal blood flow
    • Reduce hemodynamics
  2. Regulate epithelial sodium channel (ENaC):

    • Increase salt excretion and natriuresis
    • Reduce fluid retention and hemodynamic load
    • Control blood pressure, in particular in salt-sensitive patients
  3. Improve glomerular function:

    • Reduce glomeruli hyperfiltration
    • Improve podocyte health and reduce albuminuria
    • Reduce thickening of glomerular basement membrane

Clinical Studies

We are currently evaluating next steps for cardio-renal program.