Taysha Gene Therapies Inc., a new Dallas-based company reuniting former executives of Avexis Inc. and its funders, has launched with a $30 million seed financing intended to advance a pipeline of 15 new AAV-based candidates. Its team expects to file four INDs by the end of 2021, starting with one for GM2-gangliosidosis that could move to the clinic later this year. Programs targeting SURF1 deficiency, SLC6A1 genetic epilepsy and Rett syndrome will follow. PBM Capital, the first institutional investor in Avexis, and Nolan Capital, the investment fund of former Avexis CEO Sean Nolan, co-led the round. Nolan joined as board chair.

The company is partnering with the University of Texas Southwestern's gene therapy program and department of pediatrics, which will run discovery and preclinical research, lead IND-enabling studies and provide clinical manufacturing. The university is also an equity owner in the company, with a seat on its board. Members of Taysha's team will lead clinical development, regulatory strategy and commercial manufacturing and marketing.

The startup's most advanced asset, TGTX-101 for GM2, is currently in potency testing ahead of a pending CTA filing in Canada, where an initial trial will be run at Kingston, Ontario-based Queen's University, a collaborator with UT Southwestern scientist Steve Gray on its development.

The overall portfolio has three broad themes: neurodegenerative disorders, neurodevelopmental diseases and genetic forms of epilepsy. But it also has an overarching strategy built into it, owing to a key contrast between small-molecule and gene therapy commercial life cycles, Taysha's president, CEO and founder, RA Session II told BioWorld.

While small-molecule sales typically ramp up to their peak over five years or so before plateauing and declining from generic competition, Session said that gene therapies require more of a portfolio approach. "You have to constantly be launching new programs," he said, describing a commercial cycle geared toward sustainability. Whether such a strategy will be sustainable for patients, who faced list pricing of $2.1 million for Avexis' first commercial medicine, Zolgensma (onasemnogene abeparvovec), remains to be seen. Though, as with other medicines, time, competition, insurance and patient support programs will likely moderate eventual out-of-pocket costs, should Taysha's therapies make it to market.

"With the first program launching, you'll treat the prevalent population relatively quickly. As you're ramping down to start treating the incidence population, your next program is now launching and hopefully getting commercial approval" as part of a repeating cycle, he said.

All of the programs in Taysha's portfolio are built with an adeno-associated virus serotype 9 vector (AAV9) the commercially proven vector used in the Avexis-developed spinal muscular atrophy therapy Zolgensma. "We know that it works," Session said. For that reason, at Taysha, the focus is on diversifying the payloads the capsid carries. In the company's lead program, that means deploying a gene replacement construct. In other cases, gene knockdown with mRNA or other approaches will be called for. In addition to the 15 candidates already in its portfolio, the company has options on an additional four programs.

Texas roots

Session, a Dallas native, has built significant experience in the gene therapy space during a critical time for the field, logging two substantial stints at PTC Therapeutics Inc., where he first helped launch Translarna (ataluren) and later worked on the company's 2013 IPO, as well as corporate and commercial development. Next, at Avexis, he led corporate strategy and business development, ultimately playing a role in the company's $8.7 billion sale to Novartis AG .

In the midst of that adventure, Session spent three years helping build up UT Southwestern spinout Reata Pharmaceutical Inc., where he forged ties to the school that ultimately led to the creation of Taysha in partnership with Steve Gray, director of the school's Viral Vector Core, and Claire Aldridge, associate vice president of commercialization and business development at the school's medical center. Gray, a prolific contributor to gene therapy programs, according to Session, will advise the company, while Aldridge joined its board. Berge Minassian, a UT Southwestern professor and its division chief of child neurology, is the company's chief medical advisor.

Funding for Taysha came quickly, flowing fast from Session's early outreach to his former mentor and colleague Nolan for advice, and early Avexis investor Paul Manning, chairman and CEO of PMB Capital. Session's goal with the new funds, he said, is to "create value early on, then ultimately go back out to investors at a higher valuation," probably later this year.

Taysha, a name suggested by Session's 8-year-old daughter, comes from the lexicon of the Caddo Native American tribe of East Texas, meaning "ally" or "friend." Transformed over time, it became the state's name. "We strive to be an ally to the patients, KOLs and clinicians we serve, and a friend to all in the biotech sector and the community," Sessions said. Furthermore, the company will always be headquartered in Dallas, he pledged. "I think the name really catalyzes all of that," he said.

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