Durable improvements across consistent clinical domains in both adult and pediatric patients, including motor skills, communication/socialization, autonomic function, seizures, and an encouraging safety profile seen across adult (up to 52 weeks) and pediatric (up to 22 weeks) patients with different genetic mutation severity
Longer-term data from both adult patients showed sustained and new improvements across multiple efficacy measures and clinical domains following the completion of steroid taper (patient one: sat unassisted for first time in over a decade, normalized sleep, stabilized seizures; patient two: improved hand stereotypies and breathing, seizure-free for 8.5 months at 25% lower anti-seizure medication)
Initial data from first two pediatric patients showed improvements across multiple efficacy measures and clinical domains, with early evidence of developmental gains (patient one: improved hand function, grasp and gross motor coordination, gained visual reception and receptive language skills; patient two: gained ability to stand up from chair and walk up a stair, increase in seizure-free days)
IDMC approved Company’s request for early advancement to cohort two (high dose) in the REVEAL pediatric trial; dosing expected in Q3 2024 following IDMC review of initial safety data from the first high dose patient in the adolescent and adult trial
Company will host webcast today at
“We are highly encouraged by the safety profile and broad clinical response observed across multiple domains in both the adult and pediatric patients with different genetic mutation severity treated with the low dose of TSHA-102,” said
REVEAL Phase 1/2 Adolescent and Adult Trial (
- Completed dosing in cohort one (low dose, n=2) of 5.7x1014 total vg
- Dosed first patient in cohort two (high dose, n=3) of 1x1015 total vg in the second quarter of 2024
- Initial available safety and efficacy data from cohort two expected in the second half of 2024
Longer-term data from the first adult patient (20 years old; large MECP2 deletion; associated with severe phenotype) and second adult patient (21 years old; missense MECP2 mutation; associated with milder phenotype) with late motor deterioration, stage four Rett syndrome dosed with TSHA-102 in the low dose cohort:
- Generally well-tolerated with no serious adverse events (SAEs) related to TSHA-102 or dose-limiting toxicities (DLTs) as of 52-week assessment post-treatment for patient one and 36-week assessment post-treatment for patient two
- Sustained and new improvements observed across multiple clinical domains relative to baseline, as of 52-weeks post-treatment for patient one, based on clinical observations reported by the Principal Investigator (PI), including:
- Motor skills: improved hand function and gained ability to sit unassisted for first time in over a decade and move legs (patient one), and improved hand stereotypies for the first time since regression at age three and improved posture and stability (patient two)
- Communication/Socialization: improved social interest, vocalization and ability to use eye-gaze driven communication device (patient one), and improved social interest with increased response to spoken words and eye contact (patient two)
- Autonomic function: improved breathing patterns, normalized sleep quality/duration for first time in 20 years and improved circulation (patient one), and improved breathing patterns and circulation (patient two)
- Seizures: stable seizure events (patient one), and significantly reduced seizure events (patient two)
- Seizure Diary and caregiver reports:
- Patient one at week 52 post-treatment: stable seizure events at lower levels of anti-seizure medication relative to baseline
- Patient two at week 36 post-treatment: significantly reduced seizure events at 25% lower levels of anti-seizure medication relative to baseline (2-4 seizures per week), with 8.5 months reported seizure-free
- Clinical improvements seen across multiple efficacy measurements relative to baseline include:
- Patient one at week 52 post-treatment: Sustained improvement in Clinical Global Impression–Improvement (CGI-I), Clinical Global Impression–Severity (CGI-S) and Seizure Diaries, with new improvement in Revised Motor Behavior Assessment (R-MBA), Parental Global Impressions–Improvement (PGI-I) and Rett Syndrome Behavior Questionnaire (RSBQ) following completion of steroid and sirolimus taper
- Patient two at week 25 post-treatment: Sustained improvement in CGI-I and PGI-I, with new improvement in R-MBA and Seizure Diaries following completion of steroid taper
REVEAL Phase 1/2 Pediatric Trial (
- Completed dosing in cohort one (low dose, n=2) of 5.7x1014 total vg
- Received IDMC approval of Company’s request to advance early to cohort two (high dose, n=3) evaluating 1x1015 total vg, with dosing to occur following IDMC review of the 42-day safety data from the first high dose patient in the adolescent and adult trial
- Dosing of first pediatric patient in cohort two expected in the third quarter of 2024
- Initial available safety and efficacy data from cohort two expected in the second half of 2024
Initial results from the first pediatric patient (6 years old; MECP2 deletion; associated with moderate phenotype) and second pediatric patient (7 years old; missense MECP2 mutation; associated with milder phenotype) with pseudo stationary symptoms, stage three Rett syndrome dosed with TSHA-102 in the low dose cohort:
- Generally well-tolerated with no SAEs related to TSHA-102 or DLTs as of 22-week assessment post-treatment for patient one and 11-week assessment post-treatment for patient two; there were two SAEs reported in the second pediatric patient that were not deemed treatment-related (both were related to underlying disease and one was also attributed to immunosuppression) and have resolved
- Significant challenges with AEs dues to immunosuppressive regimen
- Initial improvements observed across multiple clinical domains relative to baseline as of 12-weeks post-treatment for patient one and 8-weeks post-treatment for patient two, based on clinical observations reported by the PI:
- Motor skills: improved hand function with the ability to hold an object for three minutes vs up to 12 seconds at baseline, improved truncal stability and balance with the gained ability to move her leg on her own to better take a step with assistance and sit unassisted for a longer duration, and improved swallowing and oral intake relative to gastrostomy tube feeding (patient one), and improved hand function and gait, speed and stability when walking with some new skills gained, including standing up from a chair and walking up a stair (patient two)
- Communication/Socialization: improved communication and ability to use eye-gaze driven communication device and gained visual reception and receptive language skills (patient one), and improved social interest and eye contact (patient two)
- Autonomic function: reduced breath holding (patient one), and improved breathing patterns (patient two)
- Seizures: stable seizure events (patient one), and increase in days reported seizure-free since dosing (patient two)
- Seizure Diary and caregiver reports:
- Patient one at 22-weeks post-treatment: stable seizure events relative to baseline
- Patient two at 11-weeks post-treatment: increase in days reported seizure-free since dosing relative to baseline (2-4 seizures daily), although a new anti-seizure medication was added to patient two’s regimen at week four, which she has maintained through week 11 post-treatment
- Clinical improvements seen across multiple efficacy measurements relative to baseline include:
- Patient one at 12-weeks post-treatment: CGI-I, PGI-I, R-MBA, Adapted
Mullen Scales of Early Learning (MSEL-A) and Seizure Diaries - Patient two at 8-weeks post-treatment: CGI-I, PGI-I, RSBQ, R-MBA and Seizure Diaries
- Patient one at 12-weeks post-treatment: CGI-I, PGI-I, R-MBA, Adapted
Presentation with additional details and accompanying figures are available through Taysha’s website here.
Conference Call and Webcast Information
Taysha management will hold a conference call and webcast today at
2024 IRSF Rett Syndrome Scientific Meeting Presentation Details
These data will also be presented by
About TSHA-102
TSHA-102 is a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy in clinical evaluation for Rett syndrome. Designed as a one-time lumbar intrathecal treatment, TSHA-102 aims to address the genetic root cause of the disease by delivering a functional form of MECP2 to cells in the CNS. TSHA-102 utilizes a novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression. TSHA-102 has received Regenerative Medicine Advanced Therapy, Fast Track and Orphan Drug and Rare Pediatric Disease designations from the FDA, Orphan Drug designation from the
About Rett Syndrome
Rett syndrome is a rare neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene encoding methyl CpG-binding protein 2 (MeCP2), which is essential for regulating neuronal and synaptic function in the brain. The disorder is characterized by loss of communication and hand function, slowing and/or regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy. Rett syndrome progression is divided into four key stages, beginning with early onset stagnation at 6 to 18 months of age followed by rapid regression, plateau and late motor deterioration. Rett syndrome primarily occurs in females and is one of the most common genetic causes of severe intellectual disability. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease. Rett syndrome caused by a pathogenic/likely pathogenic MECP2 mutation is estimated to affect between 15,000 and 20,000 patients in the U.S., EU, and U.K.
About
Taysha Gene Therapies (Nasdaq: TSHA) is a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. Its lead clinical program TSHA-102 is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the genetic root cause of the disease. With a singular focus on developing transformative medicines, Taysha aims to address severe unmet medical needs and dramatically improve the lives of patients and their caregivers. The Company’s management team has proven experience in gene therapy development and commercialization. Taysha leverages this experience, its manufacturing process and a clinically and commercially proven AAV9 capsid in an effort to rapidly translate treatments from bench to bedside. For more information, please visit 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,” “plans,” and “future” or similar expressions are intended to identify forward-looking statements. Forward-looking statements include, but are not limited to, statements concerning the potential of TSHA-102 and Taysha’s other product candidates, to positively impact quality of life and alter the course of disease in the patients Taysha seeks to treat, its research, development and regulatory plans for its product candidates, including the anticipated timelines for reporting data for the TSHA-102 REVEAL trials and the trial design of the TSHA-102 REVEAL trials, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed and the potential market opportunity for Taysha’s 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 do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding Taysha’s business are described in detail in its
Company Contact:
Director, Head of Corporate Communications, and Investor Relations
hcollins@tayshagtx.com
Media Contact:
Inizio Evoke
Carolyn.hawley@inizioevoke.com
Source: Taysha Gene Therapies, Inc.