Some former executives and investors behind the second gene therapy to win FDA approval are teaming up again. Their new company, Taysha Gene Therapies, is launching with $30 million in the bank and a plan to bring its first central nervous system (CNS) disorder program into human testing later this year.
Taysha is focusing on monogenic CNS diseases, which are caused by a single mutation in a single gene, says president and CEO RA Session II. The Dallas-based startup is developing treatments for rare genetic diseases as well as conditions that affect larger segments of the population, such as epilepsy and neurodegenerative disorders.
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“As long as it’s a monogenic CNS disease, we’re going to go after it,” Session says.
Taysha has a pipeline of 15 gene therapies, and an option to add four more. The experimental treatments come from the University of Texas Southwestern (UTSW) Medical Center, which has a gene therapy program led by Steven Gray and Berge Minassian. Session, a former pharmaceutical industry executive who is currently an entrepreneur in residence at UTSW, says university administrators asked him to come up with ideas for funding the gene therapy research. Some entities were interested in taking on individual assets, but Sessions concluded that the best way to fund the entire portfolio was to create one company.
Rare diseases represent an unmet medical need, but even when the biology is clear a therapy’s commercial prospects can be murky. Drugs for chronic conditions can take several years to reach peak sales, but that peak then continues for years as more patients use a product, Session says. In rare diseases, this “time to peak” is typically achieved in the first year to 18 months of sales. Afterward, revenue falls because a rare disease by definition does not affect a big pool of potential new patients. Session says that in order to be financially sustainable, a drug company needs to constantly launch new products, and the UTSW assets give Taysha the opportunity to do just that.
It helps that Taysha is not starting from scratch. Session is a former business development executive for AveXis, a gene therapy developer that got its start in Dallas. Novartis (NYSE: NVS) acquired AveXis in 2018, and made the company its gene therapy division. Last year, AveXis’s Zolgensma won FDA approval for spinal muscular atrophy—the second gene therapy to receive the regulator’s nod.
Gene therapy uses an engineered virus to deliver a functioning gene that replaces a defective one. Taysha’s gene therapies will be delivered by adeno-associated virus 9 (AAV9), a virus that can cross the blood-brain barrier. It’s the same virus used for Zolgensma and Session says AveXis’s work shows that the virus can be given to patients safely and effectively. Also, experience with the viral technology gives the company a leg up on knowing how to manufacture any therapies it produces quickly and at scale, he adds.
The seed financing announced Wednesday will fund Taysha’s early work. PBM Capital, the first investor in AveXis, and Nolan Capital, the investment fund of former AveXis CEO Sean Nolan, co-led the round.
Taysha’s lead program is TGTX-101, an experimental gene replacement therapy for GM2-gangliosidosis, a rare, inherited enzyme disorder that leads to the destruction of neurons in the brain and spinal cord. Session says this program is expected to begin clinical testing later this year. The company aims to ask the FDA for permission to start clinical trials for three additional gene therapies by the end of next year. Those programs include the mitochondrial disorder SURF1 deficiency; a form of epilepsy caused by a mutation to the SLC6A1 gene; and Rett syndrome, a neurological disorder caused by a genetic mutation.
In addition to advancing new gene therapies, Taysha is also developing new gene therapy technologies. Session says some of the research focuses on new capsids, the protein shells that enclose a virus. These “next-generation capsids” could potentially get a gene therapy to different cells in the body more efficiently and effectively, which could lead to therapies that require a lower dose, ultimately improving safety, he says.
Taysha is also developing technology for redosing a gene therapy. While these therapies are meant to be long-lasting, their durability over the course of a patient’s lifetime is still unknown, Session says. Redosing with the same therapy isn’t possible because patients develop antibodies to the virus. Taysha is developing a way to redose via a new route of administration—the vagus nerve. Session declined to elaborate, saying only that “it’s early but it’s interesting. It’s an issue the sector has been grasping at and trying to solve.”
AveXis is still developing new gene therapies. A company executive told Xconomy earlier this year that an application to start human tests of a Rett syndrome therapy is expected to be ready by mid-2020. A number of companies on are on AveXis’s heels, some of them focused in particular on the central nervous system and the brain. The CNS gene therapies at Passage Bio (NASDAQ: PASG) are from the University of Pennsylvania. New York-based Neurogene is also focused on rare monogenic neurological diseases. Prevail Therapeutics of New York and Voyager Therapeutics (NASDAQ: VYGR) are developing gene therapies for Parkinson’s disease.
Taysha will develop its programs in partnership with UTSW. The university is handling discovery and preclinical research, as well as the studies leading up to an application to start clinical trials. UTSW will also handle manufacturing for clinical trials. Taysha will take the lead on clinical testing and regulatory work. If any of the gene therapies win regulatory approval, the company will take over manufacturing and handle commercialization.