Our pipeline is focused on serious diseases of high unmet need where the latest discoveries in microRNA (miRNA) biology are challenging traditional drug development paradigms and creating opportunities for novel therapeutic approaches. Our team of researchers and leading scientific collaborators understand the unique needs of miRNA-based therapeutics development: identifying valid, ‘druggable’ targets and applying pharmacology and translational biology to optimize therapies with the greatest chance of clinical success.
INDICATION
miR TARGET
PARTNER
LEAD OPTIMIZATION
PRE-CLINICAL
CLINICAL
Heart Failure
208
Servier
Pre-Clinical 5
Affecting over 5 million patients in the US alone, heart failure develops as a consequence of injury to the heart caused by atherosclerosis, heart attack, high blood pressure, genetic defects or viral infection. The failing heart cannot pump (or fill) properly to supply adequate blood to the body, resulting in diminished quality of life and frequent hospitalization. The five-year mortality rate for heart failure (48-74%) exceeds that of many common cancers and has stubbornly remained in this range for decades, highlighting the urgent need for innovative therapeutic approaches.
miRagen’s lead heart failure progam is focused on miR-208, a heart-specific miRNA. Inhibition of this miRNA protects the stressed heart from maladaptive changes and preserves cardiac function, leading the way to novel miR-208-directed therapies that may offer new hope for patients suffering from this devastating condition.
Post-Myocardial Infarction Remodeling
15/195
Servier
Pre-Clinical 4
A myocardial infarction (MI) or “heart attack” occurs when coronary arteries become blocked by a blood clot or atherosclerotic plaque, reducing the supply of oxygenated blood to the heart and causing the death of cardiac muscle cells. In the wake of an MI, progressive changes in heart structure (known as cardiac remodeling) occur that result in functional decline.
miRagen’s lead program in post-MI remodeling targets the miR-15/195 family. Inhibitors of this miRNA family reduce heart muscle cell death and promote heart muscle cell regeneration following MI, resulting in improved cardiac function.
Vascular Disease
145
Pre-Clinical 4
In an adaptive response to stress (injury or high blood pressure), the body’s muscular blood vessels can undergo changes in size, composition and reactivity. Over time, however, this vascular remodeling is a significant factor contributing to the development of many cardiovascular diseases.
Therapeutic inhibition of miR-145, a key regulator of vascular smooth muscle cells, reduces pathological vascular remodeling and lowers blood pressure. miRagen’s miR-145 preclinical development program is focused on novel applications in hypertension and other vascular diseases.
Myeloproliferative Disease
451
Pre-Clinical 3
Myeloproliferative disorders are rare cancers characterized by overproduction of blood cells, placing patients at risk of blood clots and other life-threatening complications.
Inhibition of miR-451, a miRNA which regulates erythropoiesis, effectively reduces red blood cell production and represents a novel therapeutic approach to the treatment of the myeloproliferative disorder, polycythemia vera.
Pathological Fibrosis
29
Pre-Clinical 3
Tissues and organs in the body respond to injury through a wound-healing reponse involving formation of fibrous scar tissue, characterized by deposition of extracellular matrix proteins like collagen and elastin. In the setting of chronic stress, however, progessive accumulation of fibrotic tissue impairs the function of vital organs like the heart, lungs, liver and kidney and is a major (and largely untreatable) contributor to morbidity and mortality.
Discoveries by miRagen researchers revealed that miR-29 is a powerful regulator of extracellular matrix production and is an attractive therapeutic target for the treatment of pathological fibrosis and wound healing indications.
Cardiometabolic Disease
208
Pre-Clinical 5
Cardiometabolic syndrome is a combination of medical disorders including obesity, dyslipidemia, high blood pressure and insulin resistance. Affecting over a third of the US population, cardiometabolic syndrome significantly increases the risk of developing diabetes and cardiovascular disease, which remain the leading causes of death worldwide.
miRagen’s lead program in cardiometabolic disease is developing inhibitors of miR-208, a cardiac miRNA that plays a previously unanticipated and highly novel role in metabolic control. Therapeutic inhibition of miR-208 protects against obesity and other aspects of cardiometabolic disease.
Peripheral Arterial Disease
92
Pre-Clinical 2
Affecting approximately 8 million Americans, peripheral artery disease (PAD) is a painful and debilitating condition of impaired blood flow to the limbs (particularly the legs) resulting from build-up of atherosclerotic plaque in blood vessels. Patients suffering from PAD are at increased risk of limb loss, heart attack and stroke, but current therapeutic options for this condition remain limited.
miRagen’s lead progam in PAD targets miR-92a, a miRNA linked to the regulation of blood vessel growth. In preclinical models of PAD and myocardial infarction (where blood supply to limbs or the heart is compromised), therapeutic inhibition of miR-92a enhances blood vessel growth and improves functional recovery of damaged tissue.
Cardiometabolic Disease
378
Lead Optimization 3
Cardiometabolic syndrome is a combination of medical disorders including obesity, dyslipidemia, high plood pressure and insulin resistance. Affecting over a third of the US population, cardiometabolic syndrome significantly increases the risk of developing diabetes and cardiovascular disease, which remain the leading causes of death.
miR-378 has been shown to contribute to the development of obesity and metabolic syndrome. Current preclinical work is focused on evaluating therapeutic approaches to miR-378 inihibition in the setting of metabolic stress.
Neuromuscular Disease
206
Lead Optimization 2
Neuromuscular diseases such as amyotrophic lateral sclerosis (ALS; Lou Gherig’s disease) or Duchenne muscular dystrophy (DMD) are characterized by the progressive degeneration of neuromuscular synapses (essential structures which faciltate communication between motor nerves and muscle), leading to muscle atrophy and eventual loss of motor function.
In preclinical models of ALS and DMD, the skeletal muscle-specific miRNA miR-206 plays a crucial role in supporting regeneration of neuromuscular synapses and skeletal muscle, and represents a promising new therapeutic target for these diseases of high unmet need.