Efficacy data for high dose cohort demonstrated clinically meaningful and statistically significant improvement in MFM32 by Year 1 compared to natural history (n=3)
Long-term durability data across all therapeutic dose cohorts demonstrated a 10-point improvement in mean change in MFM32 by Year 3 compared to estimated natural history decline of 24 points (n=5)
Biopsy data in five of six patient samples analyzed to date confirmed active regeneration of nerve fibers following treatment with TSHA-120 (n=6)
TSHA-120 was safe and well-tolerated supported by 53 patient-years of clinical data
DALLAS, TX, USA I January 31, 2022 I 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 reported positive clinical efficacy and safety data for the high dose cohort of 3.5×1014 total vg, as well as long-term durability data across all therapeutic doses of TSHA-120 in giant axonal neuropathy (GAN).
“The totality of data generated by TSHA-120 to date support our plans to engage with major regulatory agencies in order to discuss pathways for registration and we look forward to providing a regulatory update later this year,” noted RA Session II, President, Founder and CEO of Taysha. “In the interim, we are finalizing our commercial strategy with a focus on patient identification, disease awareness and payor engagement for the estimated 5,000 affected patients in addressable markets.”
Key Clinical Data Support Durable, Clinically Meaningful and Statistically Significant Slowing of Disease Progression Across All Therapeutic Cohorts (1.2×1014 total vg, 1.8×1014 total vg and 3.5×1014 total vg)
- High Dose Cohort Data (3.5×1014 total vg) by Year 1: 5-point improvement in the change in rate of decline in MFM32 score for the high dose cohort compared to natural history decline of 8 points by Year 1 (n=3, p = 0.04)
- Analysis of All Therapeutic Dose Cohorts by Year 1: 7-point improvement in the change in rate of decline in MFM32 score across all therapeutic dose cohorts compared to natural history decline of 8 points by Year 1 (n=12, p<0.001)
- Analysis of All Therapeutic Dose Cohorts over 3 Years: 10-point improvement in the mean change from baseline in MFM32 score across all therapeutic dose cohorts compared to estimated natural history decline of 24 points by Year 3 (n=5, statistical analysis not performed)
- Disease Stabilization Demonstrated in the Single Patient to Reach Year 5 Visit: 26-point improvement in the change from baseline in MFM32 score for the single patient treated with TSHA-120 compared to estimated natural history by Year 5 (n=1, statistical analysis not performed)
- Bayesian Analysis: Confirmed 97% probability of clinically meaningful slowing of 50% or more in disease progression across all therapeutic dose cohorts
Secondary Endpoints for Pathologic, Physiologic and Clinical Markers Demonstrate Preservation of Visual Acuity, Stabilization of Retinal Nerve Fiber Layer Thickness and Regeneration of Nerve Fibers
- Biopsies obtained pre- and post-gene transfer in five of six patient samples analyzed confirmed active regeneration of axons with increased number of regenerative nerve clusters (n=6; remaining samples being analyzed)
- Preservation of visual acuity across all therapeutic doses compared to progressive loss of visual acuity observed in natural history (n=12)
- Stabilization of retinal nerve fiber layer (RNFL) thickness and prevention of axonal nerve degeneration compared to diffuse thinning of RNFL observed in natural history (n=12)
Key Long-Term Safety and Tolerability Findings
- 53 patient-years of clinical data support favorable safety and tolerability profile
Suyash Prasad, MBBS, M.Sc., MRCP, MRCPCH, FFPM, Chief Medical Officer and Head of Research and Development at Taysha added, “These results are consistent, clinically meaningful and statistically significant. Notably, analysis across all therapeutic dose cohorts confirms the sustained long-term durability of effect for TSHA-120-treated patients. These data also provide new evidence of TSHA-120’s ability to regenerate nerve fibers, demonstrating an improvement in disease pathology, and to preserve visual acuity, which should significantly benefit patients’ and families’ quality-of-life.”
TSHA-120 is an intrathecally dosed AAV9 gene replacement therapy delivering the gene gigaxonin for the treatment of GAN. TSHA-120 is currently being evaluated in an ongoing clinical trial conducted by the National Institute of Neurological Disorders and Stroke (NINDS) division of the National Institutes of Health (NIH) under the leadership of principal investigator, Carsten Bönneman, M.D. Taysha has partnered with GeneDx to support inclusion of the genetic marker for GAN in the GeneDx hereditary neuropathy panel at no cost to individuals at risk for or suspected of having GAN, and with the Hereditary Neuropathy Foundation and Charcot-Marie-Tooth Association Centers of Excellence to increase GAN disease awareness and access to testing.
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. Children with GAN present before the age of five with symptoms including unsteady gait, frequent falls, motor weakness. Currently, there are no approved treatments for GAN, which results in death for patients in their late teens or early twenties.
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.
SOURCE: Taysha Gene Therapies
Post Views: 43
Efficacy data for high dose cohort demonstrated clinically meaningful and statistically significant improvement in MFM32 by Year 1 compared to natural history (n=3)
Long-term durability data across all therapeutic dose cohorts demonstrated a 10-point improvement in mean change in MFM32 by Year 3 compared to estimated natural history decline of 24 points (n=5)
Biopsy data in five of six patient samples analyzed to date confirmed active regeneration of nerve fibers following treatment with TSHA-120 (n=6)
TSHA-120 was safe and well-tolerated supported by 53 patient-years of clinical data
DALLAS, TX, USA I January 31, 2022 I 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 reported positive clinical efficacy and safety data for the high dose cohort of 3.5×1014 total vg, as well as long-term durability data across all therapeutic doses of TSHA-120 in giant axonal neuropathy (GAN).
“The totality of data generated by TSHA-120 to date support our plans to engage with major regulatory agencies in order to discuss pathways for registration and we look forward to providing a regulatory update later this year,” noted RA Session II, President, Founder and CEO of Taysha. “In the interim, we are finalizing our commercial strategy with a focus on patient identification, disease awareness and payor engagement for the estimated 5,000 affected patients in addressable markets.”
Key Clinical Data Support Durable, Clinically Meaningful and Statistically Significant Slowing of Disease Progression Across All Therapeutic Cohorts (1.2×1014 total vg, 1.8×1014 total vg and 3.5×1014 total vg)
- High Dose Cohort Data (3.5×1014 total vg) by Year 1: 5-point improvement in the change in rate of decline in MFM32 score for the high dose cohort compared to natural history decline of 8 points by Year 1 (n=3, p = 0.04)
- Analysis of All Therapeutic Dose Cohorts by Year 1: 7-point improvement in the change in rate of decline in MFM32 score across all therapeutic dose cohorts compared to natural history decline of 8 points by Year 1 (n=12, p<0.001)
- Analysis of All Therapeutic Dose Cohorts over 3 Years: 10-point improvement in the mean change from baseline in MFM32 score across all therapeutic dose cohorts compared to estimated natural history decline of 24 points by Year 3 (n=5, statistical analysis not performed)
- Disease Stabilization Demonstrated in the Single Patient to Reach Year 5 Visit: 26-point improvement in the change from baseline in MFM32 score for the single patient treated with TSHA-120 compared to estimated natural history by Year 5 (n=1, statistical analysis not performed)
- Bayesian Analysis: Confirmed 97% probability of clinically meaningful slowing of 50% or more in disease progression across all therapeutic dose cohorts
Secondary Endpoints for Pathologic, Physiologic and Clinical Markers Demonstrate Preservation of Visual Acuity, Stabilization of Retinal Nerve Fiber Layer Thickness and Regeneration of Nerve Fibers
- Biopsies obtained pre- and post-gene transfer in five of six patient samples analyzed confirmed active regeneration of axons with increased number of regenerative nerve clusters (n=6; remaining samples being analyzed)
- Preservation of visual acuity across all therapeutic doses compared to progressive loss of visual acuity observed in natural history (n=12)
- Stabilization of retinal nerve fiber layer (RNFL) thickness and prevention of axonal nerve degeneration compared to diffuse thinning of RNFL observed in natural history (n=12)
Key Long-Term Safety and Tolerability Findings
- 53 patient-years of clinical data support favorable safety and tolerability profile
Suyash Prasad, MBBS, M.Sc., MRCP, MRCPCH, FFPM, Chief Medical Officer and Head of Research and Development at Taysha added, “These results are consistent, clinically meaningful and statistically significant. Notably, analysis across all therapeutic dose cohorts confirms the sustained long-term durability of effect for TSHA-120-treated patients. These data also provide new evidence of TSHA-120’s ability to regenerate nerve fibers, demonstrating an improvement in disease pathology, and to preserve visual acuity, which should significantly benefit patients’ and families’ quality-of-life.”
TSHA-120 is an intrathecally dosed AAV9 gene replacement therapy delivering the gene gigaxonin for the treatment of GAN. TSHA-120 is currently being evaluated in an ongoing clinical trial conducted by the National Institute of Neurological Disorders and Stroke (NINDS) division of the National Institutes of Health (NIH) under the leadership of principal investigator, Carsten Bönneman, M.D. Taysha has partnered with GeneDx to support inclusion of the genetic marker for GAN in the GeneDx hereditary neuropathy panel at no cost to individuals at risk for or suspected of having GAN, and with the Hereditary Neuropathy Foundation and Charcot-Marie-Tooth Association Centers of Excellence to increase GAN disease awareness and access to testing.
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. Children with GAN present before the age of five with symptoms including unsteady gait, frequent falls, motor weakness. Currently, there are no approved treatments for GAN, which results in death for patients in their late teens or early twenties.
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.
SOURCE: Taysha Gene Therapies
Post Views: 43
