Encoded Therapeutics Raises $104 Million to Advance Gene Therapy Program

Rare Daily Staff

Photo: Kartik Ramamoorthi, co-founder and CEO Encoded

Encoded Therapeutics, creating new opportunities for gene therapy by addressing limitations of current approaches, raised $104 million in a series C venture financing.

New investors Menlo Ventures, RTW Investments, Boxer Capital of Tavistock Group, and Alexandria Venture Investments joined existing shareholders Venrock, ARCH Venture Partners, Matrix Capital Management, Illumina Ventures, and Altitude Life Science Ventures in Encoded’s series C financing round.

The company said its precision gene therapy platform has the potential to enable the development of gene therapies with greater cell-type selectivity, increased potency, and the ability to modulate the expression of endogenous genes.

“Our mission is to develop and commercialize life-changing therapeutics for severe genetic disorders that are not addressable with existing gene therapy approaches,” said Encoded co-founder and CEO Kartik Ramamoorthi.

Rather than using a viral vector to deliver a working gene into a patient’s cells, Encoded uses genomics and computational technologies to identify and optimize DNA sequences in the human genome, known as regulatory elements, to control gene expression. These regulatory elements are packaged into gene therapy viral vectors to precisely recapitulate natural patterns of gene expression, thus addressing key limitations with existing approaches. This gene regulation platform creates opportunities to advance gene therapies for previously untreatable disorders.

Encoded is focused on four core areas of research: neurocircuitry disorders, liver and metabolic disease, neurodegeneration, and cardiovascular disease. Initial programs use clinically-validated adeno-associated viral vectors (AAV), and offer the potential to address disorders outside the reach of current gene therapy technology or significantly improve the benefits of gene therapy in established targets.

So far, Encoded’s technology has only been tested in animal models. It plans to use the funds just raised to advance its lead program in Dravet Syndrome and its preclinical pipeline, as well as to leverage its platform to develop new therapeutics to treat severe genetic disorders.

Dravet syndrome is a severe genetic disorder that occurs in approximately 1 in 16,000 births worldwide. The disorder is characterized by uncontrolled seizures, ataxia, significant developmental delays and an increased risk of early mortality due to sudden unexpected death in epilepsy. The majority of Dravet syndrome cases are caused by loss-of-function mutations in the SCN1A gene. Current treatments reduce seizures but do not address the underlying cause of the disorder—SCN1A haploinsufficiency.

A gene therapy approach has the potential to impact the full spectrum of the disorder by targeting the underlying mechanism, yet Dravet syndrome is an exceptionally challenging target because the SCN1A gene exceeds the packaging capacity of AAV and targeting of a specific neuronal cell type, GABAergic inhibitory interneurons, is required. Encoded has designed an AAV therapeutic that targets the relevant cell type and upregulates endogenous SCN1A expression. Preclinical data demonstrating an ability to achieve both cell-selective targeting and upregulation was presented at the 22^nd Annual Meeting of the American Society of Gene & Cell Therapy in Washington, D.C. in May.

These data demonstrated that a single dose of Encoded’s gene therapy is capable of up-regulating SCN1A expression in GABAergic inhibitory interneurons. Dravet mice treated with Encoded’s gene therapy exhibited a significant improvement in sensitivity to hyperthermic seizures. When observed for sudden unexpected death in epilepsy over a 10 month period, gene therapy-treated Dravet mice were indistinguishable from wild-type mice, whereas control-treated Dravet mice experienced approximately 50 percent mortality in that time.

Another preclinical biotech, Stoke Therapeutics is using a different approach to address gene therapy’s limitations by regulating the messenger RNA to make more of protein lacking in Dravet syndrome patients. It recently raised $142 million in an IPO to advance its lead candidate for the disorder into human trials.