Data from first adult patient dosed in REVEAL Phase 1/2 trial showed TSHA-102 was well-tolerated with no treatment-emergent serious adverse events (SAEs) as of six-week assessment and improvement in key efficacy measures, including Clinical Global Impression – Improvement (CGI-I), Clinical Global Impression – Severity (CGI-S) and Rett Syndrome Behavior Questionnaire (RSBQ), four weeks post-treatment
Principal Investigator (PI) observed clinical improvement in multiple domains, including autonomic function (sleep and breathing), vocalization, as well as gross motor skills (gained ability to sit unassisted for three minutes) and fine motor skills (gained ability to hold objects), supported by initial clinical data and video evidence
Clinical Trial Application (CTA) submitted to the
Private placement financing (“PIPE”) is expected to result in gross proceeds of approximately $150 million from new and existing investors and, net proceeds from PIPE, along with existing cash and cash equivalents, extends cash runway into the third quarter of 2025
Conference call and live webcast today at 8:30 AM Eastern Time
“We are pleased with the progress we have made this quarter in the clinical evaluation of our two lead investigational programs. For TSHA-102 in Rett syndrome, we believe the initial safety profile and significant clinical improvements seen in the first adult patient with severe disease four weeks post-treatment reinforces the transformative potential of our gene therapy to address the root cause of Rett syndrome. Importantly, these early data indicate that the miRNA-Responsive Auto-Regulatory Element (miRARE) technology is mediating MECP2 expression in the CNS on a cell-by-cell basis, supporting the regulatory control of miRARE. We are highly encouraged by the initial data for TSHA-102 and are focused on continuing to explore its therapeutic potential, with the dosing of the second patient expected in the third quarter. We also received FDA clearance to initiate clinical development of TSHA-102 in pediatric patients in the
Dr.
Rett syndrome is a rare neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. The disorder is characterized by intellectual disabilities, loss of communication, seizures, slowing and/or regression of development, motor and respiratory impairment, and shortened life expectancy. Rett syndrome caused by a pathogenic/likely pathogenic MECP2 mutation is estimated to affect between 15,000 and 20,000 patients in the
Recent Corporate Highlights
- Private placement led by new investor,
RA Capital Management , with participation from a large institutional investor,PBM Capital ,RTW Investments, LP ,Venrock Healthcare Capital Partners , TCGX,Acuta Capital Partners ,Kynam Capital Management, LP ,Octagon Capital ,Invus , GordonMD®Global Investments LP , andB Group Capital - Cash runway expected to fund operational plans into the third quarter of 2025
- Net proceeds to primarily fund clinical development of TSHA-102 in Rett syndrome and provide support for program activities for TSHA-120 in GAN, working capital, and other general corporate purposes
Recent Clinical Highlights
TSHA-102 in Rett syndrome: a self-complementary intrathecally delivered AAV9 gene transfer therapy in clinical evaluation for Rett syndrome, a rare genetic neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene. TSHA-102 utilizes a novel miRARE platform designed to mediate levels of MECP2 in the CNS on a cell-by-cell basis without risk of overexpression. TSHA-102 has received Orphan Drug and Rare Pediatric Disease designations from the FDA and has been granted Orphan Drug designation from the
TSHA-102 is being evaluated in the REVEAL Phase 1/2 trial, a first-in-human, open-label, randomized, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102 in adult females with Rett syndrome due to MECP2 loss-of-function mutation. Primary efficacy endpoints are patient assessments by clinicians using the Clinical Global Impressions Scale – Improvement (CGI-I), Rett Syndrome Hand Function Scale, and Revised Motor Behavior Assessment (R-MBA). Secondary endpoints include patient assessments by clinicians and caregivers using the Clinical Global Impressions Scale – Severity (CGI-S), the Rett Syndrome Behavior Questionnaire (RSBQ) and other clinical assessment scales.
Results from the first adult patient dosed in cohort one (low dose) with TSHA-102 in the REVEAL Phase 1/2 trial:
- Well-tolerated safety profile with no treatment-emergent SAEs as of six-week assessment post-treatment
- The following were demonstrated in key efficacy measures four weeks post-treatment:
- Clinical Global Impressions – Improvement (CGI-I) scale adapted to Rett syndrome, a clinician-reported assessment of overall improvement using a seven-point scale (one=“very much improved” and seven=“very much worse”), demonstrated a score of two indicating “much improved”
- Clinical Global Impressions – Severity (CGI-S) scale, a clinician-reported assessment of overall severity of a patient’s illness using a seven-point scale, demonstrated a one-point improvement from the baseline score of six (“severely ill”) to a score of five (“markedly ill”)
- Rett Syndrome Behavior Questionnaire (RSBQ), a 45-item questionnaire to assess Rett syndrome characteristics, demonstrated a total score improvement of 23 points from the baseline score of 52 to a score of 29
- Seizure diary demonstrated no quantifiable seizure events through week five post-treatment
- No marked changes observed four weeks post-treatment in the Revised Motor Behavior Assessment (R-MBA), a 24-question clinician-reported scale measuring disease behaviors of Rett syndrome
- Initial efficacy data and clinical observations supported by video evidence from PI six-weeks post-treatment indicate clinical improvements in multiple domains, including:
- Autonomic function with improvements in breathing patterns and sleep quality/duration, including the normalization of night-time behavior
- Vocalization with increased social interest
- Gross motor skills with the gained ability to sit unassisted for three minutes
- Fine motor skills and hand function with the gained ability to hold an object, unclasp her hands and use her fingers to touch a screen
- Further updates on available clinical data expected quarterly
- Dosing of second patient cleared by the Independent Data Monitoring Committee (IDMC) and expected in Q3 2023, with continued dosing of adult patients in second half of 2023
U.S. FDA cleared the IND application for TSHA-102 in pediatric patients with Rett syndrome- CTA submitted to
U.K. MHRA for TSHA-102 in pediatric patients with Rett syndrome
TSHA-120 for giant axonal neuropathy (GAN): a self-complementary intrathecally delivered AAV9 gene therapy in clinical evaluation for GAN, an ultra-rare inherited genetic neurodegenerative disorder with no approved treatments. TSHA-120 has received Orphan Drug and Rare Pediatric Disease designations from the FDA and has been granted Orphan Drug designation from the
- At R&D Day in
June 2023 , Taysha provided an overview of new comprehensive data analysis and development of disease progression model (DPM), which the Company believes has the potential to address FDA feedback regarding the heterogeneity of GAN and effort-dependent nature of MFM32 as the primary endpoint in an unblinded study - New comprehensive data analysis utilizing the DPM submitted as meeting request to the FDA; feedback for a potential regulatory pathway for TSHA-120 expected in Q3 2023
- FDA feedback on CMC module 3 amendment concluded that the analytical data is sufficient to support the comparability of pivotal lot and release for use in clinical studies
Second Quarter 2023 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 8:30 a.m. ET to review its financial and operating results and to provide a corporate update. The dial-in number for the conference call is 877-407-0792 (
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 our product candidates, including the reproducibility and durability of any favorable results initially seen in our first patient dosed in the REVEAL trial and including our preclinical 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, 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, the potential market opportunity for these product candidates, our corporate growth plans, statements associated with the timing, size and completion of the Private Placement, the forecast of our cash runway and the Company’s expectations regarding funding, operating and working capital expenditures. 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
Balance Sheet Data
(in thousands, except share and per share data)
(Unaudited)
| ASSETS | ||||||
| Current assets: | ||||||
| Cash and cash equivalents | $ | 45,083 | $ | 87,880 | ||
| Prepaid expenses and other current liabilities | 9,032 | 8,537 | ||||
| Total current assets | 54,115 | 96,417 | ||||
| Restricted cash | 2,637 | 2,637 | ||||
| Property, plant and equipment, net | 14,139 | 14,963 | ||||
| Operating lease right-of-use assets | 10,348 | 10,943 | ||||
| Other non-current assets | 304 | 1,316 | ||||
| Total assets | $ | 81,543 | $ | 126,276 | ||
| LIABILITIES AND STOCKHOLDERS' (DEFICIT) EQUITY | ||||||
| Current liabilities: | ||||||
| Accounts payable | $ | 10,766 | $ | 10,946 | ||
| Accrued expenses and other current liabilities | 19,631 | 18,287 | ||||
| Deferred revenue | 26,909 | 33,557 | ||||
| Total current liabilities | 50,641 | 62,790 | ||||
| Deferred revenue, net of current portion | 6,212 | |||||
| Term loan, net | 38,354 | 37,967 | ||||
| Operating lease liability, net of current portion | 19,528 | 20,440 | ||||
| Other non-current liabilities | 3,922 | 4,130 | ||||
| Total liabilities | 118,657 | 125,327 | ||||
| Stockholders' (deficit) equity | ||||||
| Preferred stock, |
- | - | ||||
| Common stock, |
1 | 1 | ||||
| Additional paid-in capital | 406,546 | 402,389 | ||||
| Accumulated deficit | (443,661 | ) | (401,441 | ) | ||
| Total stockholders’ (deficit) equity | (37,114 | ) | 949 | |||
| Total liabilities and stockholders' (deficit) equity | $ | 81,543 | $ | 126,276 | ||
Condensed Consolidated Statements of Operations
(in thousands, except share and per share data)
(Unaudited)
| For the three months ended |
For the three months ended |
For the six months ended |
For the six months ended |
|||||||||
| Revenue: | ||||||||||||
| Service Revenue | $ | 2,395 | $ | - | $ | 7,101 | $ | - | ||||
| Operating expenses: | ||||||||||||
| Research and development | 19,791 | 23,506 | 32,305 | 61,688 | ||||||||
| General and administrative | 5,988 | 9,867 | 14,739 | 21,336 | ||||||||
| Total operating expenses | 25,779 | 33,373 | 47,044 | 83,024 | ||||||||
| Loss from operations | (23,384 | ) | (33,373 | ) | (39,943 | ) | (83,024 | ) | ||||
| Other income (expense): | ||||||||||||
| Interest Income | 223 | 27 | 542 | 41 | ||||||||
| Interest expense | (1,440 | ) | (743 | ) | (2,814 | ) | (1,415 | ) | ||||
| Other expense | 3 | (3 | ) | (5 | ) | (11 | ) | |||||
| Total other income (expense) | (1,214 | ) | (719 | ) | (2,277 | ) | (1,385 | ) | ||||
| Net loss | $ | (24,598 | ) | $ | (34,092 | ) | $ | (42,220 | ) | $ | (84,409 | ) |
| Net loss per common share, basic and diluted | $ | (0.38 | ) | $ | (0.85 | ) | $ | (0.66 | ) | $ | (2.16 | ) |
| Weighted average common shares outstanding, basic and diluted | 64,244,531 | 40,142,403 | 63,755,435 | 39,163,996 | ||||||||
Company Contact:
Director, Head of Corporate Communications
hcollins@tayshagtx.com
Media Contact:
carolyn.hawley@canalecomm.com
Source: Taysha Gene Therapies, Inc.