DALLAS – (COMMERCIAL THREAD) – Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centered, pivotal gene therapy company focused on the development and commercialization of AAV-based gene therapies for the treatment of disease monogenic central nervous system (CNS) in rare and large patient populations, today announced the initiation of clinical development of TSHA-118 for the treatment of CLN1 disease as part of a clinical trial application ( CTA) recently approved. Queen’s University in Ontario, Canada was chosen as the initial clinical site under the leadership of Dr. Jagdeep Wahlia. There is also an open investigational new drug (IND) application in the United States for TSHA-118 in CLN1 disease.
“CLN1 disease is caused by mutations in the CLN1 gene, which encodes the soluble lysosomal enzyme palmitoyl-protein thioesterase-1, or PPT1, â€said Suyash Prasad, MBBS, M.SC., MRCP, MRCPCH, FFPM, Chief Medical Officer and Head of Research and Development by Taysha. “Presentation of a function CLN1 gene with TSHA-118 treatment offers a potentially effective therapeutic approach that addresses the root cause of the disease. In preclinical models of CLN1, TSHA-118 significantly prolonged survival and improved behavior. We are strongly encouraged by the therapeutic potential of TSHA-118 and expect PPT1 activity of 5% or greater to normalize survival and significantly improve clinical phenotype based on natural history data.
TSHA-118 is a self-complementary AAV9 gene replacement therapy designed to express a CLN1 transgene optimized for human codons for the treatment of CLN1 disease. The global trial is a phase 1/2, open-label, single-arm trial evaluating TSHA-118 for the treatment of CLN1 disease using commercial grade materials. The initial clinical site is Queen’s University under the direction of the Principal Investigator, Jagdeep S. Walia, MBBS, FRCPC, FCCMG, Clinical Geneticist and Chief Associate Professor, Division of Medical Genetics (Department of Pediatrics) at Queen’s, and Director of the research (Department of Pediatrics) at the Kingston Health Sciences Center. Preliminary data on clinical safety and PPT1 enzyme activity in serum and CSF is expected in the first half of 2022. TSHA-118 has received orphan drug designation, rare pediatric disease designation, and rapid route designation. of the United States Food and Drug Administration and orphan drug designation from the European Commission for the treatment of CLN1 disease.
“Currently, there is no approved treatment for this severe and rapidly progressive lysosomal overload neurodegenerative disease,†said RA Session II, President, Founder and CEO of Taysha. “The initiation of clinical development is a formative moment and, based on its compelling profile and the promising preclinical data generated to date, we believe that TSHA-118 offers the potential for a disease-modifying therapeutic approach for patients. patients affected by this disease. We look forward to working in collaboration with Queen’s University and await the availability of preliminary data on clinical safety and PPT1 enzyme activity during the first semester of 2022. ”
Encouraging preclinical data demonstrated that intrathecal treatment with TSHA-118 significantly prolonged survival in CLN1 knockout mice and improved behavior. Mice treated with TSHA-118 showed persistent supraphysiologic levels of active PPT1 and sustained preservation of motor function. In CLN1 knockout mice, TSHA-118 was safe and well tolerated with no associated adverse effects, suggesting a wide therapeutic window for clinical dosing.
Two ongoing natural history studies include an observational study in Hamburg to assess the natural history of CLN1 and other CLN diseases as part of the international DEM-CHILD database, as well as a retrospective study and prospective combined at the University of Rochester to characterize the age-at onset of major symptoms and the relationship between age and severity. Disease severity and different forms of CLN1 disease have been shown to correlate with the enzymatic activity of PPT1. Adult patients have 5% to 8% PPT1 enzyme activity and late symptoms, indicating that an increase in PPT1 activity from 0.1% to 5% with therapeutic approaches has the potential to modify disease. .
About CLN1 disease
CLN1 disease, also known as infantile neuronal ceroid lipofuscinosis or infantile Batten disease, is a lysosomal overload disorder that is a progressive and fatal neurodegenerative disease with an onset of childhood affecting approximately 1 in 138,000 live births in the world. The estimated prevalence of CLN1 disease is 1,000 patients in the United States and the European Union. CLN1 disease is caused by loss-of-function mutations in the CLN1 gene which encodes the palmitoyl-protein thioesterase-1, or PPT1, enzyme involved in the breakdown of lipid-modified proteins. Loss-of-function mutations in the CLN1 gene cause a build-up of lipid-modified proteins which ultimately leads to neuronal cell dysfunction and death. CLN1 typically manifests within the first year of life with progressive visual impairment, motor and cognitive decline, seizures, and ultimately premature death. Some patients have late, juvenile, or adult CLN1 disease and develop symptoms later in childhood or adulthood. There are no approved disease-modifying therapies for the treatment of CLN1 disease.
About Taysha gene therapies
Taysha Gene Therapies (Nasdaq: TSHA) is dedicated to eradicating monogenic CNS disease. By focusing singularly on the development of curative drugs, we aim to rapidly translate our treatments from the laboratory to the bedside. We have combined our team’s proven track record in gene therapy drug development and commercialization with UT Southwestern’s world-class gene therapy program to create an extensive AAV gene therapy pipeline focused on rare and rare indications. at large market. Together, we are leveraging our fully integrated platform, an engine for potential new treatments, with the goal of dramatically improving 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 “anticipatesâ€, “believesâ€, “expectsâ€, “intendsâ€, “plans†“,” Plans “and” “future” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include statements regarding the potential of our product candidates, including our preclinical product candidates, to positively impact quality of life and to alter the course of disease in the patients we seek to treat, our research, development and regulatory plans for our product candidates, whether these product candidates will receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed, the potential market opportunity for these product candidates and the growth of our business plans. 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. Therefore, these forward-looking statements are not guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. The risks relating to our business are described in detail in our filings with the Securities and Exchange Commission (“SECâ€), including our Annual Report on Form 10-K for the year ended December 31, 2020 and our Quarterly Report. on Form 10-Q for the quarter ended September 30, 2021, both available on the SEC’s website at www.sec.gov. Additional information will be made available in other documents that we file from time to time with the SEC. These risks may be magnified by the impacts of the COVID-19 pandemic. These forward-looking statements speak only as of the date hereof, and we disclaim any obligation to update such statements, except as required by law.
