Pipeline

Program Asset Route of Admin Development Stage
Preclinical Phase 1 Phase 2 Phase 3
Neurological
Acute Ischemic Stroke DM199 IV/SC
REMEDY Phase 2/3 Study Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 3 not started
Kidney Diseases
IgA Nephropathy DM199 SC
REDUX Phase 2 Study Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 3 not started
Diabetic Kidney Disease DM199 SC
REDUX Phase 2 Study Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 3 not started
African Americans with CKD DM199 SC
REDUX Phase 2 Study Preclinical complete
Phase 1 complete
Phase 2 in progress
Phase 3 not started
Other
Additional Recombinant Protein DM300
Preclinical Preclinical in progress
Phase 1 not started
Phase 2 not started
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.

Restoring Healthy Function to Multiple Body Systems

DM199 is a synthetic protein therapy with the potential to treat multiple diseases, including chronic kidney disease (CKD) and acute ischemic stroke (AIS). DM199 is intended to restore levels of the naturally occurring protein KLK1, which acts on interrelated mechanisms in the kidneys and blood vessels to improve circulation and overall function.

How DM199 Stands Out

We believe DM199 may provide new treatment options with significant benefits over the current standards of care. In the treatment of AIS, DM199 is being tested with up to a 24 hour treatment window from the onset of a stroke, potentially providing a treatment option in the United States for the approximately 80% of AIS patients currently receiving only supportive care. In the treatment of CKD, we believe that DM199 has the potential to maintain, or possibly restore kidney function, by both improving blood flow (as measured by eGFR) and reducing albuminuria (as measured by the urinary albumin to creatinine ratio). We are not aware of any approved therapies in the United States or the European Union to address low KLK1 levels. To date, clinical trials have been and/or are being conducted in the United States, Europe and Australia. In these studies, DM199 has consistently demonstrated excellent safety and tolerability with no treatment-related serious adverse events (SAEs).

DM199 also has distinct advantages over existing KLK1 replacement therapies. KLK1, primarily derived from human urine, is widely used in China (marketed under the brand name Kailikang® by Shanghai Pharma) for the treatment of AIS, and we estimate that over 600,000 patients have been treated since its introduction in 2005. We believe that DM199, a synthetic form of KLK1, administered subcutaneously could result in improved efficacy with more stable pharmacokinetics (drug level exposure) while avoiding the potential side effects of Kailikang, specifically the risk of endotoxins, impurities and antibody formation associated with Kailikang given that it is isolated from human urine.  DM199 also addresses potential supply constraints that makes Kailikang difficult and expensive to produce given the limited source of human urine.  We believe these factors make the recombinant protein DM199 a product candidate that is better positioned for regulatory approval worldwide compared to a urine-derived protein since it can meet the rigorous manufacturing standards required by modern regulatory agencies.

Restoring Normal Physiologic Function

Mechanism of Action for Stroke

When given within 24 hours of a stroke’s onset, DM199 promotes microcirculation at the site of the clot and improves neurovascular coupling, or balancing of the blood supply and brain activity. In the weeks following, DM199 promotes vascular integrity and inhibits apoptosis and inflammation, protecting neurons and glia in the affected area.

Mechanism of Action for Kidney Disease

DM199 is designed to improve overall kidney function by acting upon multiple interrelated mechanisms. DM199 aims to improve microvascularization, increasing oxygen and nutrient delivery and to regulate the epithelial sodium channel (ENaC), modulating salt and water retention. It is also expected to improve glomerular function by reducing inflammation, oxidative stress and fibrosis, and preventing thickening of the glomerular wall. Finally, DM199 has also been shown to increase regulatory T cell (Tregs) production in animal model, which suggests that DM199 has the potential to halt pathogenic autoimmune attacks on the glomerulus.

Market Landscape for CKD

Chronic Kidney Disease (CKD)

37 Million

People in the U.S. (15% of U.S. adults) are estimated to have CKD1

16x – 40x

More likely to die from cardiovascular events than reach end-stage renal disease (ESRD)2

23%

Of U.S. Medicare budget spent on kidney treatment ($114 billion)3

1 Centers for Disease Control, 2019 Kidney Disease Fact Sheet
2 National Institute of Health Fact Sheet, 2010
3 USRD, CKD and ESRD (https://www.usrds.org/2018/view/v1_07.aspx)

Acute Ischemic Stroke (AIS)

15 Million

Strokes per year globally (800K in the U.S.)

87%

Are acute ischemic strokes (AIS)

~90%

Of AIS patients have no direct treatment options

Kidney Diseases

IgA nephropathy (IgAN), is a serious, progressive autoimmune disease that results in chronic inflammation of the kidney. Up to 50% of those diagnosed with IgAN will progress to end-stage renal disease (ESRD). IgAN is the most common cause of glomerulonephritis. Glomerulonephritis refers to one of several kidney diseases characterized by inflammation of either the glomeruli or the small blood vessels in the kidneys impairing the kidney’s ability to filter waste and excess water from the blood. Glomerulonephritis is the largest disease-related cause of end-stage renal disease (ESRD) after diabetes and is responsible for 25-30% of all annual ESRD cases.

TREATING IgAN

Chronic Kidney Disease (CKD), the progressive loss of kidney function, disproportionally impacts African Americans. Due in large part to higher rates of diabetes and hypertension (high blood pressure), African Americans are three to four times more likely to suffer from CKD than Caucasians. One of the most serious consequences of untreated CKD is end stage renal disease (ESRD), where the kidneys have ceased to function and the individual requires continuous on-going dialysis or kidney transplantation. Kidney disease is reaching epidemic proportions in the United States. It is estimated that more than 7 million African Americans are afflicted with this potentially devastating condition.

Treating CKD

Diabetic kidney disease (DKD) is a type of kidney disease caused by diabetes. Diabetes is the leading cause of kidney disease – approximately 1 out of 3 adults with diabetes has kidney disease1. DKD is characterized by a decline in kidney function, potentially leading to end-stage renal disease (ESRD).

1. Centers for Disease Control and Prevention. Chronic Kidney Disease in the United States, 2019. Atlanta, GA: US Department of Health and Human Services. Centers for Disease Control and Prevention; 2019.

Treating DKD

Neurological Diseases

Stroke is characterized by the rapidly developing loss of brain function due to a blockage of blood flow in the brain.  As a result, the affected area of the brain becomes inactive and eventually dies. According to the U.S. Center for Disease Control and Prevention (CDC), about 87% of strokes are ischemic in nature.  According to the CDC, worldwide, stroke is an important cause of adult disability and the second leading cause of death in developed countries.

Treating AIS