Encoded Therapeutics bags $104M to propel 'precision gene therapy' for Dravet syndrome

Encoded Therapeutics reeled in $104 million in series C cash to bankroll the development of its lead program: a precision gene therapy for Dravet syndrome, a rare form of epilepsy. The Bay Area biotech will also use the funds to push its preclinical programs and come up with new treatments for severe genetic disorders. 

The company’s work is based on a platform designed to overcome hurdles it has identified in the gene therapy space. Gene therapies tend to work in one of three ways: They deliver a healthy copy of a faulty gene, introduce a new gene into the body or “knock out” a defective gene. But they can run into problems with cell selectivity, potency and the ability to control endogenous genes, Encoded CEO Karthik Ramamoorthi, Ph.D., told FierceBiotech. 

“We’ve developed a series of technologies that are both computational and genomics- or sequencing-based that allow us to screen for and identify sequences in vivo that control where and when genes are able to be expressed,” Ramamoorthi said. “We take these sequences and place them in gene therapies—such as adeno-associated viruses (AAVs)—that allow us to control where the adeno-associated viruses are able to express the payload.” 

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Consider Duchenne muscular dystrophy, in which delivering a working copy of the dystrophin gene is an attractive way to remedy the low levels or lack of dystrophin protein that causes the disease. But the gene is too big to fit into the delivery vector, so companies like Sarepta Therapeutics are getting around this by using a truncated version of the gene. Encoded’s technology lets it take a different approach: Instead of figuring out how to package a large gene into the viral vector, it can load the virus with a different genetic sequence that can change the expression of the gene in the body, Ramamoorthi said. 

“The genome has billions of sequences that contribute to precise gene control, but it’s very difficult to build that type of selectivity of precision in a small viral vector. The screening technology looks broadly across thousands or tens of thousands of unique regulatory elements, we pick out ones that contribute to gene control and build them in different iterations to create an optimized gene therapy,” Encoded Chief Scientific Officer Stephanie Tagliatela said.       . 

Encoded’s platform can also target specific cell types and create stronger therapies. A more potent treatment would improve a patient’s ability to make the product—dystrophin protein, for example—and so would require lower doses and boost safety. 

Despite an increasingly crowded field, Encoded’s first target is Dravet syndrome. GW Pharmaceuticals' cannabis-based Epidiolex earned the FDA nod for Dravet and Lennox-Gastaut syndromes last June, and BioCodex’s Diacomit scored approval as an add-on drug for Dravet two months later. Numerous companies have prospects in development, from Supernus and Stoke Therapeutics to Zogenix and tandem Takeda and Ovid Therapeutics

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“The products in development or that have been recently approved really only address one aspect of the disease,” Tagliatela said. “Dravet is a severe pediatric genetic disorder and one of the manifestations of that disorder are very intractable seizures. … But there is a whole other constellation of symptoms patients suffer from that aren’t addressed by the standard of care today.” 

With its precision gene therapy, Encoded aims to solve gait problems, ataxia (impaired coordination) and developmental delays. It is designed to remedy mutations in the SCN1A gene—the cause of the majority of Dravet cases—by boosting endogenous expression of SCN1A in a specific cell type in the brain. 

Encoded presented preclinical data on its Dravet program last month at the annual meeting of the American Society of Gene and Cell Therapy. The treatment upregulated SCN1A expression in a specific type of inhibitory interneurons. Encoded aims to bring the treatment into clinical trials in early 2021, Ramamoorthi said. 

The company kept its other pipeline hopefuls under wraps and will disclose them as they mature. 

“The vision for the company is to drive gene therapy into new areas. Over the course of this year, we will be moving the Dravet program forward while advancing preclinical programs in liver, metabolic and cardiovascular disease,” Ramamoorthi said. “Our goal for this year is to drive the company to become a leader in the space.” 

The series C came from a marquee group of investors including Encoded backers Venrock, Arch Venture Partners, Matrix Capital Management, Illumina Ventures and Altitude Life Science Ventures as well as newcomers Menlo Ventures, RTW Investments, Boxer Capital and Alexandria Venture Investments.