Taysha Gene Therapies Announces Publication of Natural History Data for TSHA-120 in Giant Axonal Neuropathy in the Journal, Brain

Largest cohort of genetically confirmed patients with GAN, including patients with the classic (early-onset) and milder (late-onset) forms of GAN

Largest cross-sectional analysis highlighted clinical differences in patients with early-onset GAN versus late-onset GAN based on MFM32 performance as well as other functional motor scales and disease markers

Robust assessment across clinical outcomes for GAN, including motor, sensory, respiratory, neurophysiologic, MRI and biopsy data

First clinical study to evaluate a cohort of individuals with GAN for autonomic impairment

On track to report clinical data for TSHA-120 from the 3.5x10¹⁴ total vg dose cohort in the second half of 2021

Planning to engage with major regulatory agencies to discuss the approval pathway and expect to provide a regulatory update by year-end 2021

Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric, pivotal-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS) in both rare and large patient populations, today announced the publication of new analyses of natural history data for TSHA-120 in giant axonal neuropathy, or GAN. The data were published online and will be included in the June edition of Brain, a highly esteemed neurological science peer-reviewed journal.

GAN is a progressive neurodegenerative disease that affects both the central and peripheral nervous systems. The disease is caused by loss-of-function mutations in the gene coding for gigaxonin, which results in dysregulation of intermediate filament turnover, an important structural component of the cell. Although no symptoms are present in the first few months of life, many children with GAN do show early symptoms and features before the age of five, including unsteady gait, frequent falls, and motor weakness. Symptoms worsen over time and children develop scoliosis, contractures, atrophy of the spinal cord and abnormalities of the white matter in the brain. Currently, there are no approved treatments for GAN, which results in death for patients in their late teens or early twenties.

In this natural history study, 45 patients, age 3 years to 21 years old, with genetically confirmed GAN were enrolled at NIH and evaluated at their first enrollment visit. The objective of the cross-sectional analysis was to identify genetic variants, explore correlations between genotype and phenotype, identify reliable markers of disease severity and assess how these markers correlate with ambulatory function and the impact of the early- and late-onset phenotypes on these markers.

The two sub cohorts of GAN patients in the study included thirty-five patients with early-onset GAN and 10 patients with late-onset GAN. In the early-onset cohort, the mean age of onset of gait or motor impairment was 2.3 years old whereas the mean age of onset of symptoms in the late-onset cohort was 5.4 years old. Motor Function Measure 32 (MFM32), a validated and well-known scale to measure strength and motor function had the strongest correlation across outcome measures and age in patients with GAN. Patients with late-onset GAN had better functional performance compared to similarly aged patients with early-onset GAN. Ambulatory ability between the two phenotypes also differed. Disease progression in early-onset GAN patients occurred in a uniform and homogenous manner. Autonomic manifestations of the disease did not correlate with age or motor function.

“The recent publication in Brain serves as the baseline data for a longitudinal natural history assessment and adds important context to results from three dose cohorts in the ongoing clinical GAN trial,” said Suyash Prasad, MBBS, M.Sc., MRCP, MRCPCH, FFPM, Chief Medical Officer and Head of Research and Development of Taysha. “These results also confirm our findings that there is a clinical difference between early-onset GAN, a relentlessly progressive and fatal neuropathy, and late-onset GAN, which has significant disease morbidity, and underscores the importance for GAN to be included in genetic screens for hereditary neuropathies. The estimated prevalence for GAN is 2,400 patients but the GAN population may be larger than previously appreciated. We view genetic testing as an important aspect of patient identification and look forward to leveraging our key collaborations with companies to increase patient diagnostic efforts and allow for earlier intervention. Of note, data from today’s publication provide further support and confidence in the overall clinical program design for TSHA-120 which include this ongoing, prospective, natural history and outcomes assessment study, and an interventional dose selection safety and efficacy study. Building on the previously presented and favorable interventional study data, we remain on track to report clinical data from the highest dose cohort in the interventional clinical trial for TSHA-120 in the second half of this year. We look forward to engaging with major regulatory agencies to discuss the approval pathway for TSHA-120 and to provide a regulatory update by year-end.”

About Taysha Gene Therapies

Taysha Gene Therapies (Nasdaq: TSHA) is on a mission to eradicate monogenic CNS disease. With a singular focus on developing curative medicines, 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 both rare and large-market indications. Together, we leverage our fully integrated platform—an engine for potential new cures—with a goal of dramatically improving patients’ lives. More information is available at www.tayshagtx.com.

Forward-Looking Statements

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