EPIGEN BIOSCIENCES

Small Molecule Drug Discovery and Development

Epigen is a drug discovery and development company enabling new therapeutic programs and product opportunities with strong intellectual property (IP) to be advanced into clinical development.

LPA1R ANTAGONIST

Diabetic Kidney Disease, 
Other Indications Non-Alcoholic Steatoheptatits, Idiopathic Pulmonary Fibrosis

Renal fibrosis is the final common pathway for virtually every type of chronic kidney disease (CKD) that is responsible for significant mortality. This disease places an enormous burden on our healthcare system, as expenditure for CKD patients currently accounts for more than a quarter of Medicare spending which is only expected to rise. In 2020, approximately 143,000 new patients are projected to start renal replacement therapy in the United States; approximately 786,000 patients with ESRD are projected to be treated that year at an annual cost of $54 billion to the Medicare program.

Non-alcoholic steatohepatitis (NASH), a severe type of non-alcoholic fatty liver disease (NAFLD). NAFLD is the most common liver disease and is associated with obesity and type-2 diabetes. There are no effective treatments available for NASH.

​

Idiopathic pulmonary fibrosis (IPF) is a type of lung disease that results in scarring (fibrosis) of the lungs for an unknown reason. Over time, the scarring gets worse and it becomes hard to take in a deep breath and the lungs cannot take in enough oxygen.

​

SIGMA1R LIGAND

Alzheimer's Disease, Other Indications ALS, Diabetic Retinopathy, Rett Syndrome

Alzheimer's disease is a neurodegenerative disease of the brain which leads to loss of memory and cognitive function. With aging world population, number of patients suffering from Alzheimer’s disease is increasing rapidly. Large unmet need owing to lack of effective, disease-modifying drugs.

Diabetic retinopathy (DR) is a leading cause of blindness, and is characterized by loss of neurons and disruption of retinal vasculature in the retina. Between 40 to 45 percent of Americans diagnosed with diabetes have some stage of diabetic retinopathy. Patients with diabetes lose color and contrast sensitivity within 2 years of the retinopathy onset. Focal ERG (electroretinogram) analysis, which detects electrical responses of ganglion cells, reveals dysfunction of these cells early in diabetes.  Pharmacologic treatment for the neuronal and vascular manifestations of DR are severely limited, except some injectable treatments such as Lucentis and Eyelea, thus there is a high medical need for new agents to address DR.

​

Rett syndrome is a rare non-inherited genetic postnatal neurological disorder that occurs almost exclusively in girls and leads to severe impairments, affecting nearly every aspect of the child’s life: their ability to speak, walk, eat, and even breathe easily. The hallmark of Rett syndrome is near constant repetitive hand movements while awake. Cognitive assessment in children with Rett syndrome is complicated, but we know that they understand far more than they can communicate to us, evidenced by their bright and attentive eyes, and their ability to express a wide spectrum of moods and emotions. 

P70 S6 KINASE INHIBITOR

Fragile X Syndrome

Fragile X syndrome (FXS) is the most common inheritable form of cognitive impairment and the leading known genetic cause of autism. FXS is caused by the loss of expression of the fragile X mental retardation protein (FMRP). A major challenge for FXS research is to develop treatment strategies that improve the intellectual capabilities of patients. Dysregulated protein synthesis is widely accepted as a core molecular abnormality associated with FXS. Because neuronal protein synthesis is critical for learning and memory, altered synaptic translation is considered a major contributor to the intellectual deficits seen in FXS. Currently available pharmacological intervention strategies for FXS primarily treat behavioral problems and have focused largely on targets upstream of translational control to normalize FXS-related phenotypes. We have identified a specific target that is a common downstream effector of both mTORC1 and ERK signaling and plays a direct role in regulating translation. Genetic deletion of the target in an animal model of FXS corrected exaggerated protein synthesis and other biochemical, neuroanatomical and behavioral abnormalities associated with FXS. These results suggest a strategy for developing a disease modifying therapeutic for FXS. By using a rational design approach that combines structural protein information and optimal ADME properties, we have discovered a novel series of potent inhibitors. Epigen has developed specific and drug-like small molecule inhibitors to this target. We have teamed up with Dr. Alysson Muotri's laboratories at UCSD to propose a novel discovery paradigm for effective drug candidate compounds for FXS by using newly developed cerebral organoids, or “mini-brains” to model the disease in 3D in the laboratory.

PAM-II

Stroke, TBI

Stroke is a major cause of death and disabilities in the United States but substantial investments in developing anti-stroke medicine have struggled to produce clinically-efficacious therapies. Our optimism for PAM-II-based therapies in stroke stems from the potent therapeutic effects of a7 nAChR activation associated with ubiquitous a7 nAChR expression in neuronal and immune tissues. PAM-IIs appear to augment multiple endogenous anti-stroke therapeutic pathways complimentary to reperfusion and thus, beyond classical neuroprotection. This concept is novel and substantively different from strategies used in the past. Furthermore, the anticipated clinical utility of PAMIIs is likely to extend beyond stroke to certain neurodegenerative and psychiatric disorders linked to cognitive decline and attention deficits (e.g., dementias, schizophrenia) because these conditions are associated with decreased cholinergic tone and a decrease, but not disappearance, of functional a7 nAChRs. Thus, PAMIIs are expected to improve cognitive function and attention by increasing cholinergic tone via potentiating a7 activity. In this regard, PAMII-based treatments are expected to benefit stroke patients via multiple mechanisms and routes of action.