Stoke Therapeutics Preps IPO to Bring Dravet Syndrome Drug to Clinic

Xconomy Boston — 

After Stoke Therapeutics closed $90 million in financing last fall, CEO Ed Kaye signaled his biotech would seek more cash through an IPO soon. The preclinical-stage biotech is now officially on a path to the public markets.

In paperwork filed late Thursday with the SEC, Bedford, MA-based Stoke set a preliminary $86 million target for its IPO, which will fund its research on drugs to treat rare genetic diseases. The company has applied for a Nasdaq listing under the stock symbol “STOK.”

Stoke is developing treatments for diseases in which a genetic mutation leads to a protein deficiency. The company says it is focusing on autosomal dominant diseases, which are disorders in which only one copy of the gene needs to be mutated for the disease to develop.

The biotech’s drugs are part of a class of therapies called antisense oligonucleotides (ASOs), which are strands of synthetic RNA. These drugs are designed to target messenger RNA, the molecules that carry the genetic blueprints instructing cells how to make proteins. By regulating mRNA, Stoke says its drugs could address the underlying cause of a genetic disease rather than treating its symptoms.

Companies have used this approach to treat such diseases before. ASO drugs have reached the market from Sarepta Therapeutics (NASDAQ: SRPT) for Duchenne muscular dystrophy and from Biogen (NASDAQ: BIIB) for spinal muscular atrophy. But Stoke contends that the approaches of those drugs are specific to the diseases they treat, and don’t represent a way to generally get cells to produce more of a deficient protein.

Stoke says in the filng that its proprietary technology can design ASOs so that they coax cells to produce more of the mRNA needed to instruct cells to make a deficient protein, “thereby restoring the target protein to near normal levels.” The company adds that its technology is not dependent on a particular genetic mutation, which means that a single Stoke drug could address multiple diseases. Stoke says it has identified approximately 2,900 single-gene diseases that it could potentially treat.

Stoke’s most advanced drug, STK-001, is being developed to treat Dravet syndrome, a severe form of epilepsy that leads to frequent and prolonged seizures. The disorder affects one in every 15,700 births, according to an estimate from the nonprofit Dravet Syndrome Foundation. So far the FDA has approved one Dravet treatment, a syrup from GW Pharmaceuticals called cannabidiol (Epidiolex). FDA review of an experimental Dravet therapy from Zogenix (NASDAQ: ZGNX) is on hold after the regulator last month flagged deficiencies in the company’s submission. Those drugs were developed to reduce the number of seizures patients experience, not to boost the levels of a deficient protein.

STK-001 is still preclinical. Stoke says in the filing that it plans to submit the paperwork to proceed to human testing by early 2020. If the company starts a Phase 1/2 study in children and teens with Dravet syndrome in the first half of next year, Stoke estimates preliminary data from the study would be available in 2021.

With the IPO cash, Stoke says it aims to take its lead drug to the start of Phase 3 testing, and continue research on others in its pipeline. Stoke says it expects to select its next drug candidate by the first half of next year. Its preclinical programs are being studied for protein deficiencies that affect the central nervous system, eye, kidney, and liver.

While Stoke says its technology could go further than currently available ASOs, the company is following a path blazed by previous drugs in the class. The biotech is using ASO chemistry similar to what was used for Spinraza, which it says should minimize safety risks. Stoke already has a lot of ASO know-how on board. The inventor of Spinraza, Cold Spring Harbor Laboratory scientist Adrian Krainer, is a Stoke co-founder. Kaye was formerly the chief medical officer, and later, CEO, at Sarepta.

Since its founding in 2014, Stoke has raised about $134 million, according to its filing. That sum includes the $90 million Series B round of funding that closed in October. Stoke’s largest shareholder is Apple Tree Partners with a 65.3 percent stake.

Photo by Flickr user Marco Verch via a Creative Commons license