High dose TSHA-102 was generally well tolerated with no SAEs or DLTs in two adolescent/adult patients and one pediatric patient as of data cutoff; IDMC approved continued enrollment in cohort two (high dose) across both REVEAL trials; eight patients dosed to date (low dose=4, high dose=4)
Advanced discussions with the FDA on trial design, endpoints and potential use of established natural history dataset for Part B of REVEAL trials, and aligned on a meeting cadence to expedite the development plan for TSHA-102 following initial RMAT Type B meeting
FDA approved use of pivotal TSHA-102 product in REVEAL trials based on successful demonstration of analytical comparability; Company released pivotal product manufactured with the final commercial manufacturing process following Type D CMC meeting
Clinical data from cohort two (high dose) and cohort one (low dose) of both REVEAL trials expected in H1 2025
Conference call and live webcast today at 4:30 PM Eastern Time
“We are pleased with the progress made with the FDA on further elucidating the potential regulatory pathway for TSHA-102 as we advanced discussions on the trial design, endpoints and potential use of an established natural history dataset for Part B of our REVEAL trials. Additionally, we aligned on a meeting cadence to expedite the development plan for TSHA-102,” said
Recent Corporate and TSHA-102 Program Highlights
- Completed Regenerative Medicine Advanced Therapy (RMAT) Type B Meeting. Advanced discussions on regulatory pathway for TSHA-102 following initial RMAT Type B multidisciplinary meeting with the
United States (U.S.) Food and Drug Administration (FDA)- Advanced discussions with the FDA on trial design, endpoints and potential use of an established natural history dataset for Part B of the REVEAL Phase 1/2 trials
- Based on FDA feedback from ongoing discussions, the Company intends to focus on objective measures that clinically capture functional gains; the Rett Syndrome Behavior Questionnaire (RSBQ) will not be included as a primary or secondary endpoint in Part B of the REVEAL trials
- Aligned with the FDA on the Company’s proposed meeting cadence to expedite the development and review of TSHA-102 and on the adequacy of the nonclinical data package submitted to date to support Biologics License Application submission
- Reached FDA Alignment on Commercial Manufacturing Process. Completed Type D Chemistry Manufacturing and Controls (CMC) meeting with the FDA regarding TSHA-102
- The FDA approved use of the pivotal product in the REVEAL trials based on the successful demonstration of analytical comparability between the clinical product and the product derived from the final commercial manufacturing process
- The Company released the pivotal product manufactured with the final commercial manufacturing process for use in Part B of the REVEAL Phase 1/2 trials
- The FDA endorsed the intended commercial manufacturing process, proposed analytical methods, and corresponding qualification and validation plans, including mechanism of action potency release assays
- High Dose of TSHA-102 was Generally Well Tolerated. TSHA-102 was generally well tolerated with no serious adverse events (SAEs) or dose-limiting toxicities (DLTs) in the first two adolescent/adult patients as of 20 and nine weeks, respectively, and in the first pediatric patient as of six weeks
- Continued Enrollment in High Dose Cohorts. Received Independent Data Monitoring Committee (IDMC) approval to continue with enrollment in cohort two (high dose, 1x1015 total vector genomes (vg)) across both REVEAL Phase 1/2 trials, following review of available clinical data from the first two adolescent/adult patients and the first pediatric patient treated with the high dose of TSHA-102
- Dosed the third adolescent/adult patient in cohort two and enrolled the second pediatric patient in cohort two, with dosing scheduled for the current quarter
- Presented Positive Previously Disclosed Clinical Data on Low Dose TSHA-102. Clinical data from cohort one (low dose, 5.7x1014 total vg) in both the ongoing REVEAL Phase 1/2 adolescent/adult trial and the REVEAL Phase 1/2 pediatric trial were presented during an oral presentation at the 9th
World Rett Syndrome Congress inOctober 2024 - Adolescent/Adult Trial (n=2):
- Generally well tolerated with no SAEs related to TSHA-102 or DLTs as of 52 and 36 weeks for patient one and two, respectively
- Early and consistent clinical improvements and functional gains demonstrated across multiple clinical domains (fine and gross motor skills, communication/socialization, autonomic function and seizure events) as early as four weeks post-treatment, with sustained and new improvements through 52- and 25-weeks post-treatment for patient one and two, respectively, based on clinician and caregiver assessments and video evidence
- Pediatric Trial (n=2):
- Generally well tolerated with no SAEs related to TSHA-102 or DLTs as of 22 and 11 weeks for patient one and two, respectively
- Early and consistent clinical improvements and functional gains demonstrated across multiple clinical domains (fine and gross motor skills, communication/socialization, autonomic function and seizure events) as early as four weeks post-treatment, with sustained and new improvements through 12- and eight-weeks post-treatment for patient one and two, respectively, based on clinician and caregiver assessments and video evidence
- Adolescent/Adult Trial (n=2):
- Presented Biodistribution Data Further Supporting the Clinical Potential of Intrathecal Delivery. Data from an analysis of 28 non-human primates (NHP) across five studies evaluating AAV9 gene therapy delivery were presented during a poster presentation at the 31st Annual
Congress of theEuropean Society of Gene & Cell Therapy inOctober 2024 - Both intrathecal and intra-cisterna magna administration showed comparable, consistent and widespread biodistribution of AAV9 vector throughout the brain and spinal cord regions in NHPs
- Findings reaffirm the clinical potential of intrathecal administration as an effective, safe and minimally invasive delivery approach for broad targeting of the CNS that has potential for outpatient delivery in both children and adults
Anticipated Milestones
REVEAL Adolescent and Adult Trial
- Safety and efficacy data in cohort two (high dose; n=3) and an update on safety and efficacy data in cohort one (low dose; n=2) expected in the first half of 2025
REVEAL Pediatric Trial
- Safety and efficacy data in cohort two (high dose; n=3) and an update on safety and efficacy data in cohort one (high dose; n=2) expected in the first half of 2025
Third Quarter 2024 Financial Highlights
Research and Development Expenses: Research and development expenses were
General and Administrative Expenses: General and administrative expenses were
Net loss: Net loss for the three months ended
Cash and cash equivalents: As of
Conference Call and Webcast Information
Taysha management will hold a conference call and webcast today at 4:30 p.m. ET to review its financial and operating results and provide a corporate update. The dial-in number for the conference call is 877-407-0792 (
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 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
About
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 statements concerning the potential of TSHA-102, including the reproducibility and durability of any favorable results initially seen in patients dosed to date in clinical trials, including with respect to functional milestones, and our other product candidates to positively impact quality of life and alter the course of disease in the patients we seek to treat, our research, development and regulatory plans for our product candidates, including the timing of initiating additional trials and reporting data from our clinical trials, the potential for these product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, the clinical potential of intrathecal administration and our current cash resources supporting our planned operating expenses and capital requirements into the fourth quarter of 2026. 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 our business are described in detail in our
Condensed Consolidated Statements of Operations (in thousands, except share and per share data) |
||||||||||||||||||||||||
| For the Three Months Ended |
For the Nine Months Ended |
|||||||||||||||||||||||
| 2024 | 2023 | 2024 | 2023 | |||||||||||||||||||||
| Revenue | $ | 1,788 | $ | 4,746 | $ | 6,311 | $ | 11,847 | ||||||||||||||||
| Operating expenses: | ||||||||||||||||||||||||
| Research and development | 14,946 | 11,791 | 50,676 | 44,096 | ||||||||||||||||||||
| General and administrative | 7,902 | 8,589 | 22,324 | 23,328 | ||||||||||||||||||||
| Impairment of long-lived assets | 4,838 | 616 | 4,838 | 616 | ||||||||||||||||||||
| Total operating expenses | 27,686 | 20,996 | 77,838 | 68,040 | ||||||||||||||||||||
| Loss from operations | (25,898 | ) | (16,250 | ) | (71,527 | ) | (56,193 | ) | ||||||||||||||||
| Other income (expense): | ||||||||||||||||||||||||
| Change in fair value of warrant liability | 75 | (100,456 | ) | (67 | ) | (100,456 | ) | |||||||||||||||||
| Change in fair value of term loan | (1,703 | ) | - | (4,035 | ) | - | ||||||||||||||||||
| Interest income | 2,107 | 1,109 | 5,240 | 1,651 | ||||||||||||||||||||
| Interest expense | (24 | ) | (1,471 | ) | (80 | ) | (4,285 | ) | ||||||||||||||||
| Other expense | (81 | ) | (19 | ) | (44 | ) | (24 | ) | ||||||||||||||||
| Total other income (expense), net | 374 | (100,837 | ) | 1,014 | (103,114 | ) | ||||||||||||||||||
| Net loss | $ | (25,524 | ) | $ | (117,087 | ) | $ | (70,513 | ) | $ | (159,307 | ) | ||||||||||||
| Net loss per common share, basic and diluted | $ | (0.10 | ) | $ | (0.93 | ) | $ | (0.29 | ) | $ | (1.88 | ) | ||||||||||||
| Weighted average common shares outstanding, basic and diluted | 267,824,045 | 125,700,799 | 244,052,057 | 84,630,796 | ||||||||||||||||||||
Condensed Consolidated Balance Sheet Data (in thousands, except share and per share data) |
||||||||
2024 |
2023 |
|||||||
| ASSETS | ||||||||
| Current assets: | ||||||||
| Cash and cash equivalents | $ | 157,688 | $ | 143,940 | ||||
| Restricted cash | 449 | 449 | ||||||
| Prepaid expenses and other current assets | 3,418 | 3,479 | ||||||
| Assets held for sale | - | 2,000 | ||||||
| Total current assets | 161,555 | 149,868 | ||||||
| Restricted cash | 2,151 | 2,151 | ||||||
| Property, plant and equipment, net | 7,613 | 10,826 | ||||||
| Operating lease right-of-use assets | 8,678 | 9,582 | ||||||
| Other non-current assets | 220 | 304 | ||||||
| Total assets | $ | 180,217 | $ | 172,731 | ||||
| LIABILITIES AND STOCKHOLDERS' EQUITY | ||||||||
| Current liabilities: | ||||||||
| Accounts payable | $ | 4,932 | $ | 6,366 | ||||
| Accrued expenses and other current liabilities | 12,608 | 12,284 | ||||||
| Deferred revenue | 11,795 | 18,106 | ||||||
| Total current liabilities | 29,335 | 36,756 | ||||||
| Term loan, net | 42,971 | 40,508 | ||||||
| Operating lease liability, net of current portion | 17,751 | 18,953 | ||||||
| Other non-current liabilities | 1,363 | 1,577 | ||||||
| Total liabilities | 91,420 | 97,794 | ||||||
| Stockholders' equity | ||||||||
| Preferred stock, |
- | - | ||||||
| Common stock, |
2 | 2 | ||||||
| Additional paid-in capital | 674,643 | 587,942 | ||||||
| Accumulated other comprehensive income | (2,328 | ) | - | |||||
| Accumulated deficit | (583,520 | ) | (513,007 | ) | ||||
| Total stockholders’ equity | 88,797 | 74,937 | ||||||
| Total liabilities and stockholders' equity | $ | 180,217 | $ | 172,731 | ||||
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.