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DALLAS–(BUSINESS WIRE)–Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric gene therapy company focused on the development and commercialization of AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (SNC) in rare and important patient populations, today announced that it has obtained an exclusive option from UT Southwestern (UTSW) to license the worldwide rights to a clinical-stage AAV9 gene therapy replacement program for the treatment of CLN7 disease. The company has also entered into a research collaboration with UTSW to develop a next-generation construct for the treatment of CLN7 disease, which is expected to improve potency, safety profile, packaging efficiency and manufacturability compared to first-generation construction. Completion of the next-generation build design is expected by year-end 2021, with commercial-grade GMP hardware expected in 2022.

The first-generation construct of the CLN7 program was developed in the laboratory of Steven Gray, Ph.D., associate professor at UT Southwestern Medical Center and chief scientific advisor to Taysha, with financial support from Mila’s Miracle and Batten Hope, the leading CLN7 patient advocacy groups. The CLN7 program is currently undergoing a Phase 1 proof-of-concept clinical trial being conducted by UTSW, and Taysha expects the availability of preliminary clinical data on the safety and efficacy of proof of concept in humans from the first-generation construct by the end of 2021. Taysha intends to initiate a planned pivotal trial using a next-generation construct in 2022, with reference to clinical data from human proof of concept generated from the first generation construct.

Additionally, Taysha provided a grant to Batten Hope to support patient outreach, disease education and newborn screening initiatives.

CLN7 disease is a rare, fatal and rapidly progressive neurodegenerative disease that is a form of Batten disease. CLN7 is caused by autosomal recessive mutations in MFSD8 gene responsible for lysosomal dysfunction. The disease begins around the age of two to five, with death often occurring in the early teens. Patients experience progressive loss of nerve cells in parts of the brain and typically experience seizures, vision loss, speech impairment, and mental and motor regression. Currently, there are no approved therapies to treat CLN7 disease, which affects approximately 4,000 patients worldwide.

Preclinical data in rodents supported the advancement of the first-generation construct into a Phase 1 proof-of-concept clinical study in patients with CLN7 disease. In one live efficacy study, intrathecal (IT) administration of the first generation construct to MFSD8 knockout mice with high or low doses resulted in clear effects on age and dose with early intervention and dose high yielding the best therapeutic benefits. A high dose of IT of the first generation construct in younger knockout mice resulted in: 1) widespread expression of MFSD8 mRNA in all tissues tested; 2) almost complete normalization of impaired free-field and rotarod performance 6 and 9 months after injection; 3) a more than doubled median life expectancy (16.82 months versus 7.77 months in untreated knockout mice); and 4) maintaining a healthy body weight for an extended period. Toxicology studies in wild-type rodents have demonstrated the safety and tolerability of computer delivery of the first generation construct. These preclinical data will be presented by Xin Chen, Ph.D., assistant professor, Department of Pediatrics at UT Southwestern, in an oral presentation on the 17and Annual International Congress on Neuronal Ceroid Lipofuscinosis on October 8, 2021.

“The CLN7 program is a strategic addition to our gene therapy pipeline focused on monogenic CNS diseases. Encouraging preclinical data generated in relevant rodent models suggests that the first generation construct has the potential to reduce overall disease pathology, preserve motor function and ultimately prolong survival,” said RA Session II, President , founder and CEO of Taysha. “The first-generation construct is currently undergoing a Phase 1 proof-of-concept clinical trial with two patients treated to date, and we look forward to the availability of preliminary data by the end of the year. . With human proof-of-concept clinical data at baseline, we plan to advance a next-generation construct in a pivotal trial scheduled for 2022, which is expected to improve potency, safety, packaging efficiency, and manufacturability by compared to the first generation construction. Above all, we are also pleased to announce our grant to Batten Hope, the leading non-profit patient advocacy organization for CLN7 disease, to support patient awareness, disease education and newborn screening initiatives. We believe that a gene therapy approach has the potential to address a significant unmet need in approximately 4,000 patients worldwide.

Gina Hann, Founder, President and Treasurer of Batten Hope, added, “Our mission is to support families with children suffering from terminal and rapidly progressive neurodegenerative diseases like CLN7. We are honored to receive Taysha’s support to raise awareness, increase newborn screening, and help patients access potentially transformative treatments that offer hope and therapeutic progress for conditions with significant unmet need.

UTSW is currently enrolling patients in an investigator-sponsored dose-escalation open-label, proof-of-concept clinical trial at Dallas Children’s Hospital for intravenously administered AAV9 gene replacement therapy. intrathecal for the treatment of childhood CLN7 disease. The primary endpoint of the trial is safety and tolerability based on the incidence and severity of treatment-related serious adverse events. Secondary efficacy endpoints include global clinical impression, neuropsychological, ataxia and motor function assessments and quality of life. The rationale for the design and a discussion of the outcome measures of this clinical trial will be presented in poster format at the next 17and Annual International Congress on Neuronal Ceroid Lipofuscinosis. To date, one patient has been dosed at 5×1014 vg total and a second patient received a dose of 1×1015 total vg measured by qPCR method. UTSW continues to enroll patients in this 1×10 Phase 1 study15 vg total and plans to dose additional patients in the short term. Preliminary safety and efficacy data are expected by the end of 2021.

With the addition of the CLN7 program, Taysha expects to have five clinical-stage programs by the end of the year. As such, the TSHA-104 program for the treatment of SURF1-associated Leigh Syndrome will be transferred to company collaborators at UTSW to complete studies enabling IND, followed by a planned clinical trial. initiated by the investigator by the end of 2022. Taysha will continue to support the SURF1 natural history study in partnership with UTSW.

Financial terms of the agreements were not disclosed.

Webcast Information

Taysha management will host a webcast today at 8:00 a.m. ET / 7:00 a.m. CT to discuss today’s news. To participate, please access the following link: http://lifesci.rampard.com/WebcastingAppv5/Events/eventsDispatcher.jsp?Y2lk=MTQ1MQ==. The live webcast and replay can also be accessed by visiting Taysha’s website at https://ir.tayshagtx.com/news-events/events-presentations. An archived version of the webcast will be available on the website for 60 days.

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a particular focus on the development of curative drugs, we aim to rapidly translate our treatments from bench to bedside. We have combined our team’s proven experience in gene therapy drug development and commercialization with the world-class UT Southwestern gene therapy program to build an extensive AAV gene therapy pipeline focused on rare and large-scale indications. . Together, we are leveraging our fully integrated platform – a powerhouse for potential new treatments – to dramatically improve the lives of patients. More information is available at www.tayshagtx.com.

Forward-looking statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as “anticipates”, “believes”, “expects”, “intends”, “projects and “future” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements regarding the potential of our product candidates, as well as the CLN7 program, to positively impact quality of life and alter disease course in the patients we seek to treat, our expectations regarding the benefits of a next-generation construct for CLN7, our research, development, and regulatory plans for our product candidates, the potential for these product candidates to receive regulatory approval from the FDA or foreign regulators equivalents, and whether, if approved, these product candidates will be successfully distributed and commercialized and the potential market opportunities for these product candidates. Forward-looking statements are based on management’s current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements are not guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks relating to our business are described in detail in our filings with the Securities and Exchange Commission (“SEC”), including our Annual Report on Form 10-K for the fiscal year ended December 31, 2020, and our report quarterly on Form 10-Q for the quarter ended June 30, 2021, both available on the SEC’s website at www.sec.gov. Additional information will be made available in other documents filed from time to time with the SEC. These risks may be amplified by the impacts of the COVID-19 pandemic. These forward-looking statements speak only as of the date hereof, and we assume no obligation to update these statements except as required by law.