Taysha Gene Therapies gears up to approach regulators with a new candidate for a debilitating neurodegenerative disease
After launching early last year, Taysha Gene Therapies quickly went about checking off key milestones. Within five months, it pulled in a hefty Series B round and made the jump to Nasdaq. And now, it has a late-stage candidate that CEO RA Session II says is just about ready for regulators.
The Dallas-based biotech on Monday unveiled a deal for global rights to TSHA-120 — a gene therapy discovered in the lab of UT Southwestern’s Steven Gray to treat a debilitating neurodegenerative disease called giant axonal neuropathy (GAN). It’s the first gene therapy to be administered in humans intrathecally (into the spinal canal), according to Session, who’s currently lining up an end-of-phase meeting with the FDA.
“It basically, for us, validates the scientific approach that we currently use on the rest of the portfolio,” Session said.
The AveXis and BridgeBio veteran founded Taysha back in January 2020 with the help of former AveXis CEO Sean Nolan. At the time, they wanted to take what they learned building the first-ever gene therapy for spinal muscular atrophy and scale the process. The company launched in April with $30 million in Series A funding and a pipeline of gene therapies from UT Southwestern, which Session has called an “under-recognized gem.”
“RA and I chatted frequently during our early financings,” Prasad said. “We just realized things were going so well after the Series B, we just turned around and said, ‘Let’s go public.’”
TSHA-120 is now Taysha’s 26th program. So far, 14 patients have been dosed with the AAV9 candidate in an open-label dose-escalation study launched in 2015 by the NIH and the patient advocacy group Hannah’s Hope. Researchers observed a halt in disease progression at the second-highest dose level one year post-treatment, and six patients have shown dose-dependent improvements for more than three years, according to Taysha.
The biotech has roughly 6 months of data on the highest dose cohort, and expects to read out more data later this year.
“If we continue to see that dose improvement, who knows what we would expect,” Session said.
GAN is a rare autosomal recessive disease of the central and peripheral nervous systems caused by mutations in the gene coding for gigaxonin. Children with GAN usually show symptoms before the age of five, including progressive scoliosis, contractures, and atrophy of the spinal cord. Some patients lose their ability to walk, and end up in a wheelchair. And too often, patients die in their late teens or early 20s.
There’s currently no treatment for GAN, and an estimated 2,400 patients in the US and Europe.
“When you think about brain diseases and diseases of the central nervous system and the peripheral nervous system, and in fact, philosophically, for any drug approach — you should really target the organ that’s malfunctioning, to try and limit any kind of off-target toxicity,” Prasad said.
That’s why Taysha is dosing the candidate intrathecally, he said. The process also allows them to start on the right side of the blood-brain barrier.
“The biodistribution of AAV9 from an IV perspective, only 1% to 3% of the drug actually crosses into the blood-brain barrier,” Session said. “And so as Suyash said, we could deliver … a lower total dose, but put the drug exactly where it needs to be.”
Taysha is giving Hannah’s Hope $5.5 million upfront, plus up to $19.3 million in milestones. The advocacy group stands to make low single-digit royalties on net sales.
“With the data that we have in-house today, we’re extremely excited about what the possible regulatory pathway could look like,” Session said. “With that being said we need to have the conversations with the regulators.”
He plans on discussing with regulators in the US, Europe and Japan “as soon as possible.”
Update: Hannah’s Hope is eligible for up to $19.3 million in milestones