Encoded Therapeutics Raises $135 Million, Gets Rare Pediatric Disease Designation for Dravet Gene Therapy

Rare Daily Staff

Encoded Therapeutics has raised $135 million in an oversubscribed series D financing and said that the U.S. Food and Drug Administration granted the company Orphan Drug designation and Rare Pediatric Disease designation for its lead asset ETX101 for the treatment of SCN1A+ Dravet syndrome.

GV led the financing with participation from Matrix Capital Management, ARCH Venture Partners, Illumina Ventures, RTW Investments, Boxer Capital, Nolan Capital, HBM Genomics, Menlo Ventures, Meritech Capital, Farallon Capital Management, SoftBank Vision Fund 21, and additional unnamed investors.

Proceeds from the new funding will be used to conduct clinical trial activities including a natural history study to better understand the progression of SCN1A+ Dravet Syndrome as well as first-in-human trials for ETX101. Additionally, the funds will support progression of the company’s pipeline of gene therapies being evaluated for additional pediatric CNS disorders.

“We are grateful to our investors for supporting our vision to transform patients’ lives with cell type-selective genetic medicines,” said Encoded co-founder and CEO Kartik Ramamoorthi.

Encoded says 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.

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.

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 up-regulates endogenous SCN1A expression. In preclinical data, Encoded has demonstrated that a single dose of its gene therapy is capable of up-regulating SCN1A expression in GABAergic inhibitory interneurons.

Orphan Disease and Rare Pediatric Disease designations offer incentives for the development of therapeutics for underserved populations.

The FDA grants orphan designation to drugs intended for the treatment of rare diseases that affect fewer than 200,000 people in the United States, which affords certain benefits, including tax credits for qualified clinical testing, waiver or partial payment of FDA application fees and seven years of market exclusivity, if approved.

The FDA grants Rare Pediatric Disease designation for serious or life-threatening diseases with manifestations in individuals aged from birth to 18 years, including access to the FDA’s expedited review and approval process. The designation makes ETX101 eligible for a Rare Pediatric Disease Priority Review voucher upon approval of the therapy by the FDA.

The vouchers can be used to reduce the time of an FDA new drug approval review to six months from ten months. The vouchers are potentially lucrative because they are transferable. Most recently, Sarepta sold its priority review voucher to Vifor Pharma $111 million in February 2020.

Photo: Encoded co-founder and CEO Kartik Ramamoorthi

Editor’s note: This story was updated to correct the most recent sales of a priority review voucher.