Endsulin
Revolutionary Genetic Therapy for Type-1 Diabetes

Endsulin, a preclinical gene therapy company, is leading a pioneering effort to revolutionize type-1 diabetes (T1D) treatment. The company’s ethos, encapsulated in its name – a call to end insulin dependency, underscores a bold ambition. Harnessing cutting-edge genetic therapy, exclusively licensed from the University of Wisconsin Alumni Research Foundation, Endsulin is determined to liberate individuals with T1D from the stringent daily grind of insulin injections.

T1D is an autoimmune disorder whereby the immune system destroys insulin-producing beta cells in the pancreas. The disorder effects roughly 1.6 million people in the United States alone, with over 50,000 new diagnoses each year. It is a leading cause of cardiovascular disease, kidney failure and blindness. Living with T1D often requires patients to continuously monitor glucose levels and undergo multiple insulin injections throughout the day.

Endsulin has pioneered a one-time viral vector liver targeted gene therapy. The therapy is glucose sensing and regulating via well characterized pathways in hepatocyte cells of the liver.

The liver-focused delivery system holds great promise for many reasons. “One of the advantages is that hepatocyte cells are the only other human cells apart from pancreatic beta cells that possess glucose regulating elements.

Moreover, hepatic cells lack specific proteins on their outer layer known to trigger an immune response. In our studies conducted to date utilizing a low dose AAV delivery to the liver exhibits low toxicity, and has shown low potential to trigger an auto-immune response, highlighting the exciting potential of this approach,” says Thomas Dee, chairperson and CEO at Endsulin.

The therapy is conveniently administered intravenously directly to the liver requiring no surgical intervention. Its effects manifest within a few days of treatment, and early studies suggest the potential for long term durability in maintenance of euglycemia. “We believe our approach provides multiple advantages over other techniques being studied, as only one gene is required to express, multiple surgical procedures are avoided, and there is no need for chronic immunosuppressants,” says Dee.

Endsulin’s next goal is to master manufacturing the therapeutic construct consistently, efficiently, and effectively. While many manufacturers have made significant progress in enhancing the upstream production process, which involves the generation of the viral vector, the downstream process frequently poses challenges, presenting a complex hurdle for many companies in this industry.

To address these challenges, the company has dedicated considerable resources to advancing downstream analytics. A notable progress in this regard is the employment of digital droplet PCR (ddPCR). This technique allows for the precise quantification of specific sequences in a DNA sample, which aids in mitigating the presence of empty capsids—viral shells without the therapeutic gene, its presence can affect the efficacy of the therapy.

Having secured a license from the U.S Food and Drug Administration’s Center for Veterinary Medicine, Endsulin is poised to commence studies targeting naturally diabetic canines. These studies will further inform the dosing and durability to support expansion of testing in humans, redefining its fight against diabetes and heralding a new era of therapeutic possibilities.