Taysha Gene Therapies(US:TSHA)2024-11-13 21:38Clinical Development - TSHA-102 is in clinical development for Rett syndrome, with the first two adult patients dosed in 2023 and cohort 1 (low dose) considered complete[162]. - The Independent Data Monitoring Committee approved early dose escalation to cohort 2 (high dose) in the adolescent and adult trial, with the first patient dosed in Q2 2024[162]. - TSHA-102 was generally well tolerated, with no serious adverse events reported as of the 20-week assessment in cohort 2[162]. - TSHA-102 has received orphan drug designation and Fast Track Designation from the FDA for the treatment of Rett syndrome[165]. - The FDA granted Regenerative Medicine Advanced Therapy designation for TSHA-102, aimed at expediting development and review processes[165]. - The first adult patient in cohort 1 demonstrated sustained improvements in motor function and communication, with the ability to sit unassisted and increased vocalizations by week 52 post-treatment[181]. - The second adult patient showed a 25% reduction in seizure frequency at week 25 post-treatment, with a significant improvement in overall seizure control[184]. - The first adult patient reported a 35-point improvement in the Rett Syndrome Behavior Questionnaire (RSBQ) total score at week 52 compared to baseline[186]. - The first adult patient also exhibited a 17-point improvement in the Revised Motor Behavior Assessment (R-MBA) total score at week 52, indicating enhanced motor and functional skills[187]. - The first pediatric patient in cohort 1 was dosed in December 2023, with ongoing trials expanding into the UK and Canada[174]. - The maximum tolerated dose (MTD) established in Part A of the trials will guide the dose expansion in Part B, focusing on efficacy endpoints and study duration[178]. - The company expects to report safety and efficacy data from cohort 2 of both the adolescent and adult trial and the pediatric trial in the first half of 2025[162][164]. - The first pediatric patient improved her ability to hold an object for up to three minutes at week 12, compared to 12 seconds at baseline[205]. - The first pediatric patient experienced a seven-point increase in RSBQ Total Score at week 12 compared to baseline[208]. - The first pediatric patient showed improvements in multiple clinical domains, including fine and gross motor skills, and communication abilities[205]. - The second pediatric patient exhibited improvements in fine and gross motor skills, including the ability to stand up from a chair and walk up stairs[207]. - The first pediatric patient demonstrated an improvement in age equivalence scores across multiple domains in the MSEL-A assessment at week 12[214]. - The second pediatric patient demonstrated a 13-point improvement in RSBQ Total Score at week eight post-TSHA-102 administration compared to week four[221]. - The second pediatric patient had an increase in days reported seizure-free post-treatment, with a reduction in seizure frequency observed two weeks post-TSHA-102[224]. Financial Performance - The company has raised an aggregate of $671.0 million from various funding sources, including an IPO and follow-on offerings, to support operations[166]. - Net losses for the nine months ended September 30, 2024, were $70.5 million, compared to $159.3 million for the same period in 2023[168]. - As of September 30, 2024, the accumulated deficit was $583.5 million, with expectations of continued significant operating losses[169]. - Revenue for the three months ended September 30, 2024, was $1.8 million, a decrease of 62.4% from $4.7 million for the same period in 2023[277]. - Revenue for the nine months ended September 30, 2024, was $6.3 million, down from $11.8 million in 2023, a decline of 46.2%[287]. - Research and development expenses increased to $14.9 million for the three months ended September 30, 2024, up from $11.8 million in 2023, representing a 26.5% increase[279]. - Research and development expenses for the nine months ended September 30, 2024, totaled $50.7 million, an increase of 15.5% from $44.1 million in 2023[288]. - General and administrative expenses decreased to $7.9 million for the three months ended September 30, 2024, from $8.6 million in 2023, a reduction of 8.2%[280]. - General and administrative expenses for the nine months ended September 30, 2024, were $22.3 million, a decrease of 4.3% from $23.3 million in 2023[289]. - A non-cash impairment charge of $4.8 million was recorded for the three months ended September 30, 2024, compared to $0.6 million in the same period of 2023[281]. - Net loss for the three months ended September 30, 2024, was $25.5 million, significantly improved from a net loss of $117.1 million in 2023[277]. - A non-cash impairment charge of $4.8 million was recorded for the nine months ended September 30, 2024, compared to $0.6 million in the same period of 2023[290]. - Interest income increased to $2.1 million for the three months ended September 30, 2024, compared to $1.1 million in 2023, a growth of 90.9%[284]. - Interest income increased to $5.2 million for the nine months ended September 30, 2024, up from $1.7 million in the same period of 2023, primarily due to dividends from a money market fund[293]. - Interest expense significantly decreased to $0.1 million for the nine months ended September 30, 2024, from $4.3 million in the same period of 2023, a reduction of approximately $4.2 million[294]. - The company experienced a net change in cash, cash equivalents, and restricted cash of $13.7 million for the nine months ended September 30, 2024, down from $76.4 million in 2023[310]. - For the nine months ended September 30, 2024, the net cash used in operating activities was $62.9 million, compared to $56.9 million for the same period in 2023[310][311][312]. - Cash provided by financing activities for the nine months ended September 30, 2024, was $77.0 million, a decrease from $140.6 million in the same period of 2023[310][314]. - Investing activities used $0.4 million in cash for the nine months ended September 30, 2024, compared to $7.3 million in the same period of 2023[310][313]. - The company has not recognized any revenue from product sales to date and does not expect to generate revenue from product sales in the foreseeable future[269]. Strategic Initiatives - The company has deprioritized certain clinical-stage programs and is seeking external strategic options for further development[170]. - The company entered into a research, collaboration, and license agreement with UT Southwestern, obtaining exclusive, worldwide, royalty-free licenses for certain patent rights and know-how[250]. - The company issued 2,179,000 shares of common stock to UT Southwestern and has no future milestone or royalty obligations under the UT Southwestern Agreement, except for patent maintenance costs[252]. - The company paid a one-time upfront license fee of $3.0 million to Abeona for the CLN1 Agreement and is obligated to pay up to $26.0 million in regulatory-related milestones and up to $30.0 million in sales-related milestones per licensed product[256]. - The company recognized a $3.0 million regulatory milestone payment in December 2021 related to the Abeona CLN1 Agreement following the approval of its CTA filing for TSHA-118[257]. - The company paid a one-time upfront license fee of $3.0 million to Abeona for the Rett Agreement and is obligated to pay up to $26.5 million in regulatory-related milestones and up to $30.0 million in sales-related milestones per licensed product[261]. - The company recognized a $3.5 million milestone payment in August 2023 related to the Rett Agreement after dosing the first patient with TSHA-102 in a clinical trial[262]. - The company recognized revenue from the Astellas Transactions for the nine months ended September 30, 2024, as research and development activities related to the Rett program were performed[268]. Future Outlook - The company anticipates needing substantial additional funding for ongoing operations and research and development, particularly for Rett clinical trials[304]. - The company expects existing cash and cash equivalents to fund operations into the fourth quarter of 2026, but will require additional capital for research, manufacturing, and commercialization activities[306]. - The company may need to rely on additional financing to achieve its business objectives, which may not be available on acceptable terms[309]. - The company is classified as a smaller reporting company, with a market value of shares held by non-affiliates below $700 million[321]. - The company may continue to take advantage of reduced disclosure requirements as an emerging growth company until it no longer qualifies[320].