DALLAS, June 07, 2024 (GLOBE NEWSWIRE) -- Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a clinicalstage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system (CNS), today announced that, on June 3, 2024, the Compensation Committee of Taysha's Board of Directors granted three new employees, in the aggregate, options to purchase 360,000 shares of the Company's common stock in connection with their employment. The ...

Financial Data and Key Metrics Changes - The net loss for the three months ended March 31, 2024, was $24.1 million or $0.10 per share, compared to a net loss of $17.6 million or $0.28 per share for the same period in 2023, indicating an increase in losses [90] - Research and development expenses were $20.7 million for the three months ended March 31, 2024, compared to $12.5 million for the same period in 2023, reflecting increased clinical trial activities [108] - As of March 31, 2024, the company had $124 million in cash and cash equivalents, which is expected to support planned operating expenses and capital requirements into 2026 [110] Business Line Data and Key Metrics Changes - The company is focused on the TSHA-102 program, which is in clinical evaluation for the treatment of Rett Syndrome, with ongoing Phase I/II REVEAL trials for both adolescent/adult and pediatric populations [21][24] - Encouraging longer-term data was reported for the first two adult patients treated in the low-dose cohort, showing sustained improvements across key efficacy measures [26][28] - The second pediatric patient has been dosed in the low-dose cohort, with initial data expected to be reported in mid-2024 [29][86] Market Data and Key Metrics Changes - Rett Syndrome affects an estimated 15,000 to 20,000 patients in the United States, European Union, and the United Kingdom, with no approved disease-modifying therapies currently available [42] - The company received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA, which facilitates closer collaboration and expedited development processes [31][70] Company Strategy and Development Direction - The company aims to generate critical longer-term clinical data across a broad range of ages and stages of patients with Rett Syndrome, guiding the next phase of studies [22][51] - The strategy includes expanding clinical trials into pediatric populations and evaluating the high dose of TSHA-102 across different age groups [51][62] - The company is committed to working closely with the FDA and other regulatory agencies to advance the TSHA-102 program [51] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the therapeutic potential of TSHA-102, highlighting the sustained improvements observed in adult patients and the potential for similar outcomes in pediatric patients [41][82] - The management acknowledged the high unmet medical need in Rett Syndrome and the importance of their gene therapy approach in addressing this challenge [42][70] - Future updates are anticipated, including initial clinical data from the pediatric trial and further insights from the completed low-dose cohort of the adolescent and adult trial [71][92] Other Important Information - The company is currently enrolling patients in both the adolescent/adult and pediatric trials, with a focus on diverse genetic backgrounds to evaluate the clinical impact of TSHA-102 [63][69] - The independent data monitoring committee approved the request to proceed to an early dose escalation in the adolescent and adult trial [25] Q&A Session Summary Question: What are the expectations for younger patients in the trial? - Management indicated that while the pediatric population is heterogeneous, they expect to see consistent clinical impacts across multiple domains similar to adult patients, with a focus on gross and fine motor function, socialization, and seizure improvement [95][113] Question: Can you comment on the RMAT designation and the data provided to the FDA? - The RMAT designation was granted based on data from two adult patients and one pediatric patient, indicating significant clinical impact and unmet medical needs [115][119] Question: How is Astellas involved in data sharing? - The company provides quarterly updates to Astellas, and they are involved in regulatory interactions, ensuring transparency regarding data generation and strategic aspects of the program [120] Question: When can we expect initial pediatric data? - Initial pediatric data is expected to be presented at the Rett conference on June 19, with plans for a webcast for investors [125] Question: What are the advantages of intrathecal administration compared to competitors? - Management highlighted that preclinical and clinical data support the effectiveness of TSHA-102 via intrathecal administration, showing significant impacts on various clinical domains [130]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended March 31, 2024 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ___________ Commission File Number: 001-39536 Taysha Gene Therapies, Inc. (Exact Name of Registrant as Specified in its Charter) | Delaware | 84- ...

Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q4 2023 Earnings Conference Call March 19, 2024 4:30 PM ET Company Participants Hayleigh Collins - Director, Head of Corporate Communications and Investor Relations Sean Nolan - Chief Executive Officer Sukumar Nagendran - President and Head of Research and Development Kamran Alam - Chief Financial Officer Conference Call Participants Whitney Ijem - Canaccord Elizabeth Webster - Goldman Sachs Kristen Kluska - Cantor Fitzgerald Gil Blum - Needham & Company Mehdi Gouda ...

FORWARD LOOKING STATEMENTS This presentation is intended to be viewed by investors in the U.S. only 2 TSHA-102: Lead Clinical Program in Rett Syndrome • Clinically and commercially proven AAV9 capsid with clinical activity and tolerability across multiple CNS indications • Intrathecal delivery in an outpatient setting targets key CNS regions and minimizes viral load, potentially reducing risk of systemic inflammatory response • Self-complementary technology facilitates more rapid transgene expression Proven ...

Exhibit 99.1 Initial data from cohort one (low dose, 5.7x1014 total vg) in REVEAL pediatric trial expected mid-2024; initial data from cohort two (high dose, 1x1015 total vg) in both trials (adolescent/adult and pediatric) expected in 2H 2024 Conference call and live webcast today at 4:30 PM Eastern Time Dallas – March 19, 2024 – Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (Taysha or the Company), a clinical-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the ...

PART I [Business](index=6&type=section&id=Item%201.%20Business) Taysha Gene Therapies is a clinical-stage biotech company focused on AAV-based gene therapies for severe monogenic CNS diseases, prioritizing its lead program TSHA-102 for Rett syndrome [Overview](index=6&type=section&id=Overview) Taysha is a clinical-stage biotech company focused on AAV-based gene therapies for severe monogenic CNS diseases, with TSHA-102 for Rett syndrome as its lead program - The company's primary focus is on advancing AAV-based gene therapies for severe monogenic diseases of the central nervous system (CNS)[17](index=17&type=chunk) - The lead clinical program, TSHA-102, is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies addressing the genetic root cause[17](index=17&type=chunk) - Following strategic pipeline prioritization, the company discontinued the development of its TSHA-120 program for giant axonal neuropathy (GAN) in September 2023[17](index=17&type=chunk) - TSHA-102 is being evaluated in two REVEAL Phase 1/2 trials: one for adolescents and adults, and another for pediatric patients, with the first patients in both trials dosed in 2023[18](index=18&type=chunk)[19](index=19&type=chunk) [Our Pipeline](index=7&type=section&id=Our%20Pipeline) The company's pipeline focuses on TSHA-102 for Rett Syndrome in Phase 1/2 trials, while other programs are deprioritized for external strategic options Development Stage of Rett Syndrome Program | Program | Indication | Preclinical | Phase 1/2 | Phase 3 | | :--- | :--- | :--- | :--- | :--- | | TSHA-102 | Rett Syndrome | | ✓ | | - The company has deprioritized company-sponsored evaluation of TSHA-120 (GAN), TSHA-105 (SLC13A5), TSHA-118 (CLN1), and TSHA-121 (CLN7), and is seeking external strategic options to enable their further development[22](index=22&type=chunk) [TSHA-102 for Rett Syndrome](index=7&type=section&id=TSHA-102%20for%20Rett%20Syndrome) TSHA-102 is an AAV9 gene therapy for Rett syndrome using miRARE technology, with Phase 1/2 trials showing a well-tolerated safety profile and clinical improvements - TSHA-102 utilizes a novel miRNA-Responsive Auto-Regulatory Element (miRARE) to mediate MeCP2 levels and prevent overexpression, a key risk in Rett syndrome gene therapy[24](index=24&type=chunk) - The first adult patient (Stage IV, severe phenotype) showed sustained improvements in motor function (sitting unassisted), hand function, communication (using eye-driven device), and autonomic function (normalized sleep) at 35 weeks post-treatment[31](index=31&type=chunk)[32](index=32&type=chunk) - The second adult patient (Stage IV, milder phenotype) showed sustained improvements in motor function (improved hand stereotypies), social skills, and autonomic function at 19 weeks post-treatment, with a significant reduction in seizure frequency, being seizure-free for 17 weeks[33](index=33&type=chunk)[34](index=34&type=chunk) Efficacy Data Summary for First Adult Patient (Low Dose) | Metric | Baseline | Post-Treatment (Week 25) | Change/Observation | | :--- | :--- | :--- | :--- | | **CGI-S** | 6 (Severely ill) | 5 (Markedly ill) | Clinically significant improvement | | **CGI-I** | N/A | 2 (Much improved) | Sustained improvement | | **RSBQ Total Score** | - | - | 30-point improvement | | **RSHFS (Dominant Hand)** | Hold 1 object | Hold 2 objects | Improvement in function | | **RSHFS (Non-Dominant Hand)** | No active grasping | Assisted to grasp 1 object | Gained basic grasping ability | [License Agreements](index=21&type=section&id=License%20Agreements) The company's pipeline relies on key license agreements with UT Southwestern and Abeona Therapeutics, including an option agreement with Astellas - Entered into a research, collaboration, and license agreement with UT Southwestern, obtaining an exclusive, worldwide, royalty-free license for certain patent rights in exchange for **2,179,000 shares** of common stock[86](index=86&type=chunk)[87](index=87&type=chunk)[88](index=88&type=chunk) - Licensed TSHA-118 for CLN1 disease from Abeona Therapeutics, involving a **$3.0 million** upfront fee, up to **$56.0 million** in potential milestones, and high single-digit royalties[90](index=90&type=chunk)[92](index=92&type=chunk) - Licensed TSHA-102 for Rett syndrome from Abeona Therapeutics, involving a **$3.0 million** upfront fee, up to **$56.5 million** in potential milestones, and high single-digit royalties, with a **$3.5 million** milestone triggered and paid in 2023 upon dosing the first patient[95](index=95&type=chunk)[97](index=97&type=chunk)[98](index=98&type=chunk) - Granted Astellas an exclusive option for TSHA-102 (Rett syndrome) and TSHA-120 (GAN), though Astellas later elected not to exercise the GAN option[101](index=101&type=chunk)[102](index=102&type=chunk)[103](index=103&type=chunk) [Intellectual Property](index=25&type=section&id=Intellectual%20Property) Taysha's intellectual property portfolio, as of February 27, 2024, consists of in-licensed patents and applications protecting its product candidates until 2038-2041 - As of February 27, 2024, the company in-licenses **five U.S. patents**, **six foreign patents**, and has **16 pending U.S. utility patent applications** and **68 pending foreign patent applications**[106](index=106&type=chunk) - For TSHA-102 (Rett Syndrome), the company in-licenses multiple patent families with patents, if issued, expected to expire between **2038 and 2041**[107](index=107&type=chunk)[108](index=108&type=chunk)[109](index=109&type=chunk) - For the deprioritized TSHA-120 (GAN) program, in-licensed patents, if issued, are expected to expire in **2041**[110](index=110&type=chunk) [Government Regulation](index=29&type=section&id=Government%20Regulation) The company's gene therapies are subject to extensive regulation by the FDA and international authorities, involving multi-phase clinical trials, expedited programs, and post-approval compliance - Biological products are regulated under the Food, Drug, and Cosmetic Act (FDCA) and the Public Health Service Act (PHSA), requiring a multi-step approval process including preclinical studies, an effective IND, and adequate and well-controlled clinical trials before submitting a BLA[126](index=126&type=chunk)[127](index=127&type=chunk) - The FDA offers expedited programs for serious conditions, including Fast Track, Breakthrough Therapy, and Regenerative Medicine Advanced Therapy (RMAT) designations, which can accelerate development and review[141](index=141&type=chunk)[142](index=142&type=chunk)[143](index=143&type=chunk) - The company may seek Orphan Drug Designation for products treating rare diseases (affecting less than **200,000 people** in the U.S.), which provides incentives like market exclusivity for **seven years** upon approval[148](index=148&type=chunk)[149](index=149&type=chunk) - In the EU, medicinal products require a Marketing Authorization (MA) granted through a centralized, decentralized, or national procedure, with Advanced Therapy Medicinal Products (ATMPs) like gene therapies requiring the centralized procedure managed by the EMA[166](index=166&type=chunk)[167](index=167&type=chunk)[176](index=176&type=chunk) [Human Capital Resources](index=55&type=section&id=Human%20Capital%20Resources) Taysha's human capital strategy focuses on recruiting and retaining employees through a value-based culture, with **52 full-time employees** as of December 31, 2023 - As of December 31, 2023, the company had **52 full-time employees**, all located in the United States[213](index=213&type=chunk) - The company's human capital objectives include identifying, recruiting, retaining, and incentivizing employees, utilizing equity incentive plans to attract and motivate personnel[212](index=212&type=chunk) [Risk Factors](index=57&type=section&id=Item%201A.%20Risk%20Factors) The company faces substantial financial, development, regulatory, manufacturing, commercialization, and intellectual property risks, requiring significant additional funding and careful navigation of complex regulations - **Financial Risks:** The company has a history of significant losses (**$111.6 million** in 2023) and expects to incur more, requiring substantial additional funding to continue operations and potentially curtailing plans if capital cannot be raised[219](index=219&type=chunk)[220](index=220&type=chunk)[227](index=227&type=chunk) - **Development & Regulatory Risks:** All product candidates are in early development stages, and the novelty of gene therapy creates a complex, unpredictable, and lengthy regulatory approval process, with early trial success not guaranteeing later stages[219](index=219&type=chunk)[243](index=243&type=chunk)[248](index=248&type=chunk) - **Manufacturing & Reliance on Third Parties:** Gene therapies are complex and difficult to manufacture, with the company relying on third-party CMOs, where any production issues could cause significant delays, and the collaboration with UT Southwestern is critical for the entire preclinical pipeline[219](index=219&type=chunk)[307](index=307&type=chunk)[345](index=345&type=chunk) - **Commercialization Risks:** Even if approved, products may not achieve market acceptance, and the company faces significant competition from other biotech firms, including those with approved or late-stage candidates for Rett syndrome, with securing adequate reimbursement from payors being a major uncertainty[318](index=318&type=chunk)[328](index=328&type=chunk)[335](index=335&type=chunk) - **Intellectual Property Risks:** The company's success depends on its ability to obtain and protect intellectual property rights for its product candidates, facing risks of patent infringement claims and challenges to its licensed patents[219](index=219&type=chunk)[358](index=358&type=chunk)[376](index=376&type=chunk) [Unresolved Staff Comments](index=152&type=section&id=Item%201B.%20Unresolved%20Staff%20Comments) The company reports no unresolved staff comments from the SEC - None[492](index=492&type=chunk) [Cybersecurity](index=152&type=section&id=Item%201C.%20Cybersecurity) The company manages cybersecurity risks through an information security program overseen by the VP of Engineering and Operations and the Audit Committee - The company's information technology team, led by the VP of Engineering and Operations, identifies, assesses, and manages cybersecurity threats[494](index=494&type=chunk) - The Board of Directors' Audit Committee is responsible for overseeing the cybersecurity risk management processes[500](index=500&type=chunk) - The company utilizes a vendor management process to manage cybersecurity risks associated with third-party providers like CROs and CMOs[498](index=498&type=chunk) [Properties](index=154&type=section&id=Item%202.%20Properties) The company leases administrative, manufacturing, and laboratory facilities in Texas and North Carolina, deemed suitable for current operations - Leases administrative space in Dallas, TX (approx. **33,000 sq ft**)[504](index=504&type=chunk) - Leases a manufacturing facility in Durham, NC (approx. **187,500 sq ft**)[504](index=504&type=chunk) - Leases laboratory space in Research Triangle Park, NC (approx. **13,000 sq ft**)[504](index=504&type=chunk) [Legal Proceedings](index=154&type=section&id=Item%203.%20Legal%20Proceedings) In January 2024, the company was named a nominal defendant in a stockholder derivative lawsuit alleging breach of fiduciary duty related to a 2023 private placement - In January 2024, the company was named a nominal defendant in a putative stockholder derivative action related to the August 2023 Private Placement[506](index=506&type=chunk) - The complaint asserts claims for breach of fiduciary duty and unjust enrichment against certain current and former directors[506](index=506&type=chunk) - The company has not recorded a liability for this lawsuit as the outcome is not currently probable or estimable[506](index=506&type=chunk) [Mine Safety Disclosures](index=154&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is not applicable to the company - Not applicable[508](index=508&type=chunk) PART II [Market for Registrant's Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities](index=155&type=section&id=Item%205.%20Market%20for%20Registrant%27s%20Common%20Equity%2C%20Related%20Stockholder%20Matters%20and%20Issuer%20Purchases%20of%20Equity%20Securities) The company's common stock trades on Nasdaq under "TSHA", with **40 holders of record** as of March 19, 2024, and no history of cash dividends or share repurchases - Common stock is listed on The Nasdaq Global Market under the symbol "TSHA"[511](index=511&type=chunk) - As of March 19, 2024, there were **40 holders of record** of the common stock[511](index=511&type=chunk) - The company has never paid cash dividends and does not intend to in the foreseeable future[512](index=512&type=chunk) [Reserved](index=155&type=section&id=Item%206.%20%5BReserved%5D) This item is reserved [Management's Discussion and Analysis of Financial Condition and Results of Operations](index=156&type=section&id=Item%207.%20Management%27s%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) This section details the company's financial performance and liquidity, showing a reduced net loss in 2023 and cash to fund operations into 2026 [Results of Operations](index=165&type=section&id=Results%20of%20Operations) In 2023, revenue increased to **$15.5 million** while operating expenses decreased, leading to a reduced net loss compared to 2022 Results of Operations Summary (in thousands) | | For the Year Ended December 31, | | :--- | :--- | :--- | | | **2023** | **2022** | | **Revenue** | $15,451 | $2,502 | | **Research and development** | $56,778 | $91,169 | | **General and administrative** | $30,047 | $37,360 | | **Impairment of long-lived assets** | $1,065 | $36,420 | | **Total operating expenses** | $87,890 | $164,949 | | **Loss from operations** | $(72,439) | $(162,447) | | **Net loss** | $(111,566) | $(166,014) | - Revenue increased to **$15.5 million** in 2023 from **$2.5 million** in 2022, derived entirely from the Astellas Transactions, including **$13.2 million** from Rett syndrome R&D activities and **$2.3 million** from the expiration of the GAN Option[550](index=550&type=chunk) - Research and development expenses decreased by **$34.4 million** year-over-year, primarily due to a **$21.7 million** reduction in compensation expense from lower headcount and a **$24.6 million** decrease in manufacturing and consulting fees, partially offset by an **$11.9 million** increase in Rett clinical trial expenses[551](index=551&type=chunk) - General and administrative expenses decreased by **$7.4 million** year-over-year, mainly due to a **$10.9 million** reduction in compensation expenses from lower headcount[552](index=552&type=chunk) [Liquidity and Capital Resources](index=167&type=section&id=Liquidity%20and%20Capital%20Resources) As of December 31, 2023, the company had **$143.9 million** in cash, expected to fund operations into 2026, bolstered by a **$140.3 million** private placement and a new **$40.0 million** term loan - As of December 31, 2023, the company had cash and cash equivalents of **$143.9 million**[559](index=559&type=chunk) - The company believes its existing cash and cash equivalents will fund operating expenses and capital requirements into **2026**[573](index=573&type=chunk) - In August 2023, the company raised **$140.3 million** in net proceeds from a private placement[570](index=570&type=chunk) - In November 2023, the company entered into a new **$40.0 million** term loan agreement with Trinity Capital and used the proceeds to terminate and repay its previous loan with Silicon Valley Bank[561](index=561&type=chunk)[563](index=563&type=chunk) Summary of Cash Flows (in thousands) | | For the Year Ended December 31, | | :--- | :--- | :--- | | | **2023** | **2022** | | **Net cash used in operating activities** | $(73,018) | $(88,390) | | **Net cash used in investing activities** | $(7,352) | $(24,930) | | **Net cash provided by financing activities** | $136,393 | $52,097 | | **Net change in cash, cash equivalents and restricted cash** | $56,023 | $(61,223) | [Critical Accounting Policies and Significant Judgments and Estimates](index=175&type=section&id=Critical%20Accounting%20Policies%20and%20Significant%20Judgments%20and%20Estimates) The company's critical accounting policies involve significant judgments and estimates, particularly in revenue recognition, stock-based compensation, and fair value measurement of debt - **Revenue Recognition (Astellas):** The company identified three performance obligations in the Astellas Option Agreement and allocated the **$36.1 million** transaction price based on estimated standalone selling prices, using a probability-weighted expected return method for the options[593](index=593&type=chunk)[594](index=594&type=chunk) - **Stock-Based Compensation:** Fair value of stock options is estimated using the Black-Scholes model, which requires assumptions for expected term, volatility, and risk-free interest rate[588](index=588&type=chunk) - **Fair Value Option:** The company elected the fair value option for its Trinity Term Loan, meaning the liability is remeasured at fair value each reporting period, with changes recorded in the statement of operations[597](index=597&type=chunk) - **Research and Development Costs:** The company records accruals for estimated ongoing research costs, analyzing the progress of studies, invoices received, and contracted costs to evaluate the adequacy of liabilities[585](index=585&type=chunk) [Quantitative and Qualitative Disclosures About Market Risk](index=179&type=section&id=Item%207A.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a smaller reporting company, Taysha is not required to provide information for this item - The company is a smaller reporting company and is not required to provide the information under this item[603](index=603&type=chunk) [Financial Statements and Supplementary Data](index=180&type=section&id=Item%208.%20Financial%20Statements%20and%20Supplementary%20Data) This section presents the company's audited consolidated financial statements for 2023 and 2022, including balance sheets, statements of operations, equity, and cash flows, with an unqualified opinion from Deloitte & Touche LLP Consolidated Balance Sheet Data (in thousands) | | Dec 31, 2023 | Dec 31, 2022 | | :--- | :--- | :--- | | **Cash and cash equivalents** | $143,940 | $87,880 | | **Total assets** | $172,731 | $126,276 | | **Total current liabilities** | $36,756 | $62,790 | | **Total liabilities** | $97,794 | $125,327 | | **Total stockholders' equity** | $74,937 | $949 | Consolidated Statement of Operations Data (in thousands) | | Year Ended Dec 31, 2023 | Year Ended Dec 31, 2022 | | :--- | :--- | :--- | | **Revenue** | $15,451 | $2,502 | | **Total operating expenses** | $87,890 | $164,949 | | **Loss from operations** | $(72,439) | $(162,447) | | **Net loss** | $(111,566) | $(166,014) | | **Net loss per common share** | $(0.96) | $(3.78) | [Changes in and Disagreements With Accountants on Accounting and Financial Disclosure](index=235&type=section&id=Item%209.%20Changes%20in%20and%20Disagreements%20With%20Accountants%20on%20Accounting%20and%20Financial%20Disclosure) The company reports no changes in or disagreements with its accountants on accounting and financial disclosure - None[826](index=826&type=chunk) [Controls and Procedures](index=235&type=section&id=Item%209A.%20Controls%20and%20Procedures) Management concluded that the company's disclosure controls and internal control over financial reporting were effective as of December 31, 2023, with no material changes - Management concluded that as of December 31, 2023, the company's disclosure controls and procedures were effective[828](index=828&type=chunk) - Management concluded that as of December 31, 2023, the company's internal control over financial reporting was effective[829](index=829&type=chunk) - No material changes in internal control over financial reporting occurred during the quarter ended December 31, 2023[831](index=831&type=chunk) [Other Information](index=235&type=section&id=Item%209B.%20Other%20Information) The company reports no other information for this item - None[833](index=833&type=chunk) [Disclosure Regarding Foreign Jurisdictions that Prevent Inspections](index=235&type=section&id=Item%209C.%20Disclosure%20Regarding%20Foreign%20Jurisdictions%20that%20Prevent%20Inspections) This item is not applicable to the company - Not applicable[834](index=834&type=chunk) PART III [Directors, Executive Officers and Corporate Governance](index=237&type=section&id=Item%2010.%20Directors%2C%20Executive%20Officers%20and%20Corporate%20Governance) Information on directors, executive officers, and corporate governance is incorporated by reference from the 2024 proxy statement - The information required by this item is incorporated by reference from the company's definitive Proxy Statement for the 2024 Annual Meeting of Stockholders[837](index=837&type=chunk) [Executive Compensation](index=237&type=section&id=Item%2011.%20Executive%20Compensation) Information on executive and director compensation is incorporated by reference from the 2024 proxy statement - The information required by this item is incorporated by reference from the company's definitive Proxy Statement for the 2024 Annual Meeting of Stockholders[839](index=839&type=chunk) [Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters](index=237&type=section&id=Item%2012.%20Security%20Ownership%20of%20Certain%20Beneficial%20Owners%20and%20Management%20and%20Related%20Stockholder%20Matters) Information on security ownership of beneficial owners, management, and related matters is incorporated by reference from the 2024 proxy statement - The information required by this item is incorporated by reference from the company's definitive Proxy Statement for the 2024 Annual Meeting of Stockholders[840](index=840&type=chunk) [Certain Relationships and Related Transactions, and Director Independence](index=237&type=section&id=Item%2013.%20Certain%20Relationships%20and%20Related%20Transactions%2C%20and%20Director%20Independence) Information on certain relationships, related transactions, and director independence is incorporated by reference from the 2024 proxy statement - The information required by this item is incorporated by reference from the company's definitive Proxy Statement for the 2024 Annual Meeting of Stockholders[841](index=841&type=chunk) [Principal Accounting Fees and Services](index=237&type=section&id=Item%2014.%20Principal%20Accounting%20Fees%20and%20Services) Information on principal accounting fees and services is incorporated by reference from the 2024 proxy statement - The information required by this item is incorporated by reference from the company's definitive Proxy Statement for the 2024 Annual Meeting of Stockholders[842](index=842&type=chunk) PART IV [Exhibits and Financial Statement Schedules](index=238&type=section&id=Item%2015.%20Exhibits%20and%20Financial%20Statement%20Schedules) This section lists the financial statements and exhibits included in the Annual Report on Form 10-K, with all financial statement schedules omitted - The report includes the company's consolidated financial statements[845](index=845&type=chunk) - All financial statement schedules have been omitted as they are not required or applicable[846](index=846&type=chunk) [Form 10-K Summary](index=242&type=section&id=Item%2016.%20Form%2010-K%20Summary) This item is not applicable to the company - Not applicable[854](index=854&type=chunk)

Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q3 2023 Results Conference Call November 14, 2023 4:30 PM ET Company Participants Hayleigh Collins - Director and Head of Corporate Communications Sean Nolan - Chief Executive Officer Sukumar Nagendran - President and Head of Research and Development Kamran Alam - Chief Financial Officer Conference Call Participants Whitney Ijem - Canaccord Genuity Kristen Kluska - Cantor Fitzgerald Salveen Richter - Goldman Sachs Gil Blum - Needham & Co Yanan Zhu - Wells Fargo Secu ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the quarterly period ended September 30, 2023 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the transition period from ___________ to ___________ Commission File Number: 001-39536 Taysha Gene Therapies, Inc. Indicate by check mark whether the registrant has submitted electro ...

Financial Performance - The company reported a net loss of $42.2 million for the six months ended June 30, 2023, compared to a net loss of $84.4 million for the same period in 2022, with an accumulated deficit of $443.7 million as of June 30, 2023[152]. - Net loss for the three months ended June 30, 2023, was $24.6 million, an improvement from a net loss of $34.1 million in the same period of 2022[308]. - Total revenue for the six months ended June 30, 2023, was $7.1 million, attributed to Rett research and development activities[315]. - Revenue for the three months ended June 30, 2023, was $2.4 million, compared to $0 in the same period of 2022[308]. - Research and development expenses for the six months ended June 30, 2023, were $32.3 million, significantly lower than $61.7 million in 2022, a decrease of approximately 47.5%[316]. - General and administrative expenses for the six months ended June 30, 2023, were $14.7 million, down from $21.3 million in 2022, a reduction of about 30.9%[317]. - Research and development expenses decreased to $19.8 million for the three months ended June 30, 2023, down from $23.5 million in 2022, a reduction of approximately 15.7%[310]. - General and administrative expenses were $6.0 million for the three months ended June 30, 2023, compared to $9.9 million in 2022, reflecting a decrease of about 39.4%[311]. - The company has incurred operating losses since inception and expects to continue incurring significant losses for the foreseeable future[296]. Funding and Capital Management - The company has raised an aggregate of $439.0 million in gross proceeds from its initial public offering and follow-on offerings, primarily funding operations through equity sales and a Term Loan Agreement[150]. - As of June 30, 2023, the company had cash and cash equivalents of $45.1 million, funded primarily through equity financings totaling $439.0 million[319]. - The company believes existing cash and cash equivalents, along with anticipated net proceeds from the August 2023 Private Placement, will fund operations into Q3 2025, but additional capital will be required for R&D, manufacturing, and working capital[331]. - The August 2023 Private Placement is expected to generate approximately $150 million in gross proceeds[328]. - The company anticipates further reductions in spending in 2023 compared to 2022 levels due to strategic pipeline prioritization initiatives[329]. - The company is required to regain compliance with the minimum Market Value of Listed Securities of $50,000,000 by January 30, 2024, or face potential delisting[298]. - The company received a Nasdaq notice on April 25, 2023, indicating that the closing bid price for its common stock was below $1.00 for 30 consecutive business days[297]. Research and Development Activities - TSHA-120, a gene therapy for giant axonal neuropathy, has shown clinically meaningful slowing of disease progression in a Phase 1/2 clinical trial, with a pivotal lot release completed in Q4 2022[147]. - TSHA-102, targeting Rett syndrome, has been dosed in adult patients in a Phase 1/2 clinical trial, with no serious adverse events reported as of the six-week assessment[149]. - The company has paused substantially all other R&D activities to increase operational efficiency, focusing on GAN and Rett syndrome[146]. - The company is focused on advancing clinical development for its product candidates while scaling up clinical and regulatory capabilities[153]. - The company is evaluating alternative study designs for TSHA-120 due to the ultra-rare nature of GAN, with regulatory flexibility acknowledged by the FDA[148]. - The company plans to continue reporting quarterly updates on available clinical data from ongoing studies[149]. - The REVEAL Phase 1/2 clinical trial is evaluating TSHA-102 in up to 18 adult female patients with Rett syndrome, with the first patient dosed in the first half of 2023[178]. - The ongoing Phase 1/2 clinical trial of TSHA-120 has intrathecally dosed 14 patients, with 12 patients having up to three years of long-term follow-up data[217]. - The company has deprioritized the evaluation of preclinical product candidates TSHA-105, TSHA-118, and TSHA-121, but may reconsider them in the future as part of pipeline expansion plans[251]. Clinical Trial Results - The FDA acknowledged MFM32 as an acceptable endpoint for TSHA-120 and recommended additional patient dosing in a double-blind, placebo-controlled design[148]. - TSHA-102 demonstrated significant survival improvement in neonatal KO Rett mice, with 47% surviving to 36 weeks compared to a maximum of 13.3 weeks for vehicle-treated controls[170]. - A one-time intrathecal injection of TSHA-102 significantly increased survival across all dose levels in the MECP2 KO mouse model, with improved body weight, motor function, and respiratory assessments[166]. - In a pharmacology study, TSHA-102 at a dose of 8.8x10^10 vg/mouse resulted in near normalization of survival and significant behavioral improvements as measured by the Bird Score[170]. - TSHA-102 showed a well-tolerated safety profile with no treatment-emergent serious adverse events reported as of six weeks post-treatment[180]. - Significant clinical improvement was observed in autonomic function, vocalization, and motor skills, including the ability to sit unassisted for three minutes for the first time in over a decade[183]. - In the REVEAL trial, the first patient dosed showed improvement in key efficacy endpoints four weeks post-TSHA-102 administration[185]. - The RSBQ Total Score showed significant clinical improvement four weeks post-TSHA-102 administration[186]. - No quantifiable seizure events were reported post-TSHA-102 administration through day 35[191]. - At one year post-gene transfer, a statistically significant slowing of disease progression was observed with TSHA-120 at the highest dose, with a 5-point improvement in the MFM32 score compared to an 8-point decline in natural history[218]. - The change in the rate of decline in the MFM32 score for all therapeutic doses combined showed a 5.20% point reduction compared to the pre-gene transfer rate of decline[221]. - There was a 99.9% probability of any slowing of disease progression and a 79.4% probability of clinically meaningful slowing of 50% or more following treatment with TSHA-120 compared to natural history data[223]. - TSHA-120 treatment showed a 7% treatment effect size in MFM32 with an 81% probability of slowing disease progression[231]. - The estimated treatment effect sizes for mFARS and FARS were 31% and 29% respectively, with a 99% probability of slowing deterioration in ataxic motor function[232]. - The DPM indicated a 100% probability of measurable improvement in nerve response with ulnar SNAP and median SNAP amplitude, with estimated treatment effects of 189% and 152% respectively[239]. - TSHA-120 demonstrated a favorable deviation in disease progression across multiple clinical performance and biological endpoints compared to the DPM[229]. - Safety data indicated no significant acute or subacute inflammation or dose-limiting toxicity associated with TSHA-120 treatment[245]. - The pivotal lot of TSHA-120, released in November 2022, yielded over 50 patient doses at the highest dose cohort of 1.0x10^14 vg by ddPCR[249]. Regulatory Designations - The company received orphan drug designation and rare pediatric disease designation from the FDA for TSHA-102 for the treatment of Rett syndrome[181]. - TSHA-120 for Giant Axonal Neuropathy (GAN) has received orphan drug designation and rare pediatric disease designation from the FDA[199]. - The company has received orphan drug designation for both TSHA-105 and TSHA-118 from the FDA, indicating the potential for significant market opportunities[260][257]. - TSHA-118 has received orphan drug designation and fast track designation from the FDA, with clinical trial material ready for use[257]. Operational Challenges - The company faces numerous risks and uncertainties in estimating future operating capital requirements, which depend on various factors including clinical trial progress and regulatory reviews[332]. - 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[300]. - A non-cash impairment charge was recorded in November 2022 related to the decision not to continue building a manufacturing facility in North Carolina[306]. - The company has no off-balance sheet arrangements during the periods presented[339]. - The company has elected to delay the adoption of certain accounting standards under the JOBS Act, allowing it to comply with new or revised accounting standards at a later date[342].