UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2021 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 84-3199512 ( ...

PART I. FINANCIAL INFORMATION [Item 1. Condensed Consolidated Financial Statements (Unaudited)](index=3&type=section&id=Item%201.%20Condensed%20Consolidated%20Financial%20Statements%20(Unaudited)) This section presents the unaudited condensed consolidated financial statements for Taysha Gene Therapies, Inc. as of September 30, 2021, reflecting a significant increase in operating losses and cash used in operations driven by escalated research and development activities [Condensed Consolidated Balance Sheets](index=3&type=section&id=Balance%20Sheets) As of September 30, 2021, the company's total assets were $241.0 million, a decrease from $258.9 million at year-end 2020, mainly due to a reduction in cash and cash equivalents, while total liabilities increased substantially to $100.6 million from $7.6 million, primarily driven by a new term loan and a build-to-suit lease liability, consequently decreasing total stockholders' equity to $140.4 million from $251.3 million Condensed Consolidated Balance Sheet Highlights (in thousands) | | September 30, 2021 | December 31, 2020 | | :--- | :--- | :--- | | **Assets** | | | | Cash and cash equivalents | $188,785 | $251,253 | | Total current assets | $197,170 | $257,879 | | Total assets | $241,042 | $258,881 | | **Liabilities & Stockholders' Equity** | | | | Total current liabilities | $43,214 | $7,129 | | Build-to-suit lease liability | $26,607 | $— | | Term loan | $27,812 | $— | | Total liabilities | $100,648 | $7,579 | | Total stockholders' equity | $140,394 | $251,302 | | Total liabilities and stockholders' equity | $241,042 | $258,881 | [Condensed Consolidated Statements of Operations](index=4&type=section&id=Statements%20of%20Operations) For the three months ended September 30, 2021, the company reported a net loss of $51.2 million, compared to a $15.0 million loss in the same period of 2020, with the nine-month net loss significantly increasing to $124.1 million from $41.7 million year-over-year, primarily due to a substantial rise in research and development expenses to $94.0 million from $19.6 million Operating Results (in thousands, except per share data) | | For the Three Months Ended Sep 30, | For the Nine Months Ended Sep 30, | | :--- | :--- | :--- | | | **2021** | **2020** | **2021** | **2020** | | Research and development | $39,528 | $11,057 | $94,025 | $19,633 | | General and administrative | $11,153 | $3,984 | $29,518 | $5,002 | | **Loss from operations** | **$(50,681)** | **$(15,041)** | **$(123,543)** | **$(24,635)** | | **Net loss** | **$(51,187)** | **$(15,042)** | **$(124,137)** | **$(41,693)** | | Net loss per common share | $(1.35) | $(1.28) | $(3.31) | $(3.73) | [Condensed Consolidated Statements of Convertible Preferred Stock and Stockholders' Equity (Deficit)](index=5&type=section&id=Statements%20of%20Convertible%20Preferred%20Stock%20and%20Stockholders'%20Equity%20(Deficit)) These statements detail the changes in stockholders' equity, showing a decrease from $251.3 million to $140.4 million for the nine months ended September 30, 2021, primarily driven by a net loss of $124.1 million, partially offset by $13.2 million in stock-based compensation Changes in Stockholders' Equity for the Nine Months Ended Sep 30, 2021 (in thousands) | Description | Amount | | :--- | :--- | | Balance as of December 31, 2020 | $251,302 | | Stock-based compensation | $13,229 | | Net loss | $(124,137) | | **Balance as of September 30, 2021** | **$140,394** | [Condensed Consolidated Statements of Cash Flows](index=7&type=section&id=Statements%20of%20Cash%20Flows) For the nine months ended September 30, 2021, net cash used in operating activities significantly increased to $76.8 million from $10.9 million in the prior-year period, with net cash used in investing activities at $13.0 million, while financing activities provided $30.0 million from a new term loan, resulting in an overall decrease of $59.8 million in cash, cash equivalents, and restricted cash Summary of Cash Flows for the Nine Months Ended Sep 30 (in thousands) | | 2021 | 2020 | | :--- | :--- | :--- | | Net cash used in operating activities | $(76,784) | $(10,881) | | Net cash used in investing activities | $(13,034) | $(3,031) | | Net cash provided by financing activities | $29,978 | $292,546 | | **Net (decrease) increase in cash** | **$(59,840)** | **$278,634** | [Notes to Financial Statements](index=8&type=section&id=Notes%20to%20Financial%20Statements) The notes provide detailed explanations of the company's financial status and operations, including its liquidity position, significant transactions like a new term loan and acquisition of TSHA-120 rights, and a subsequent 'at the market' offering agreement - The company had cash and cash equivalents of **$188.8 million** as of September 30, 2021, which management believes is sufficient to fund planned operations for at least the next twelve months[35](index=35&type=chunk) - In August 2021, the company entered into a Loan and Security Agreement with Silicon Valley Bank for a term loan facility of up to **$100.0 million**, and drew **$30.0 million** on the closing date[49](index=49&type=chunk) - In March 2021, the company acquired exclusive worldwide rights to **TSHA-120** for the treatment of Giant Axonal Neuropathy (GAN) from Hannah's Hope Fund for an upfront payment of **$5.5 million**[71](index=71&type=chunk)[72](index=72&type=chunk) - In October 2021, the company entered into a Sales Agreement for an 'at the market' offering to sell up to **$150.0 million** of its common stock[112](index=112&type=chunk) [Item 2. Management's Discussion and Analysis of Financial Condition and Results of Operations](index=22&type=section&id=Item%202.%20Management's%20Discussion%20and%20Analysis%20of%20Financial%20Condition%20and%20Results%20of%20Operations) Management discusses the company's financial condition, results of operations, and business outlook, highlighting the advancement of a portfolio of 27 gene therapy candidates for CNS diseases, significant increases in operating losses to $124.1 million due to higher R&D and G&A expenses, and the belief that existing cash and term loan access will fund operations into the second half of 2023 [Overview and Recent Developments](index=22&type=section&id=Overview%20and%20Recent%20Developments) Taysha, a patient-centric gene therapy company focused on CNS diseases, is advancing a portfolio of 27 product candidates, recently acquiring exclusive worldwide rights to **TSHA-120** for GAN and securing a term loan agreement for up to **$100 million**, drawing an initial **$30 million** to bolster its financial position, while expecting continued significant operating losses as it advances its pipeline - The company is advancing a deep portfolio of **27 gene therapy product candidates** for monogenic CNS diseases, with options to acquire four additional programs[117](index=117&type=chunk)[123](index=123&type=chunk) - In April 2021, the company acquired exclusive worldwide rights to **TSHA-120**, a clinical-stage AAV9 gene therapy for giant axonal neuropathy (GAN)[117](index=117&type=chunk) - In August 2021, the company entered into a term loan agreement for up to **$100 million** and drew an initial **$30 million**[120](index=120&type=chunk) [Our Pipeline](index=24&type=section&id=Our%20Pipeline) The company's pipeline targets a broad range of neurological indications, with detailed updates on key programs including **TSHA-120** for GAN showing dose-dependent slowing of disease progression, **TSHA-102** for Rett Syndrome demonstrating regulated gene expression and improved safety in preclinical models, and other programs like **TSHA-101** and **TSHA-118** advancing with expected clinical data - **TSHA-120** (GAN): Phase 1/2 trial data showed a **statistically significant improvement** versus historical controls, with the **1.8x10¹⁴ vg dose halting disease progression**, and a Bayesian analysis confirmed these findings[144](index=144&type=chunk)[148](index=148&type=chunk)[149](index=149&type=chunk) - **TSHA-102** (Rett Syndrome): Preclinical data published in 'Brain' showed the **miRARE platform extended knockout survival by 56%** and **attenuated behavioral side effects** compared to unregulated constructs, with an **IND/CTA submission is planned for November 2021**[175](index=175&type=chunk)[176](index=176&type=chunk)[177](index=177&type=chunk) - **TSHA-101** (GM2 Gangliosidosis): A **Phase 1/2 trial is ongoing** in Canada, with **preliminary clinical safety and HEX A enzyme activity data expected in December 2021**[117](index=117&type=chunk)[166](index=166&type=chunk) - **TSHA-118** (CLN1 Disease): The company plans to **initiate a Phase 1/2 clinical trial by year-end 2021** and expects **preliminary clinical data in the first half of 2022**[117](index=117&type=chunk)[173](index=173&type=chunk) [Results of Operations](index=45&type=section&id=Results%20of%20Operations) This section provides a comparative analysis of the company's financial performance, showing that for the nine-month period, R&D expenses increased by **$74.4 million** to $94.0 million due to higher manufacturing costs, employee compensation, and third-party research expenses, while G&A expenses increased by **$24.5 million** to $29.5 million, primarily from increased compensation and professional fees Comparison of Operating Expenses (in thousands) | | For the Nine Months Ended Sep 30, | | :--- | :--- | | | **2021** | **2020** | | Research and development | $94,025 | $19,633 | | General and administrative | $29,518 | $5,002 | | **Total operating expenses** | **$123,543** | **$24,635** | - The **$74.4 million increase** in nine-month R&D expenses was primarily due to a **$29.7 million increase** in manufacturing and raw material costs, a **$24.4 million increase** in employee compensation, and a **$20.3 million increase** in third-party R&D consulting fees[219](index=219&type=chunk) - The **$24.5 million increase** in nine-month G&A expenses was mainly attributable to a **$13.2 million increase** in compensation (including **$6.2 million in stock-based compensation**) and an **$11.3 million increase** in professional fees[220](index=220&type=chunk) [Liquidity and Capital Resources](index=47&type=section&id=Liquidity%20and%20Capital%20Resources) The company has historically funded operations through equity and debt, holding **$191.4 million** in cash, cash equivalents, and restricted cash as of September 30, 2021, and believes existing cash combined with full access to its term loan facility will fund operations **into the second half of 2023**, though **substantial** additional funding will be required for future development and commercialization - As of September 30, 2021, the company had cash, cash equivalents, and restricted cash of **$191.4 million**[225](index=225&type=chunk) - The company believes its existing cash and cash equivalents, along with full access to the term loan facility, will fund operations **into the second half of 2023**[228](index=228&type=chunk) - Future funding requirements are **substantial** and depend on the progress of clinical trials, manufacturing scale-up, and potential commercialization activities[227](index=227&type=chunk)[228](index=228&type=chunk) [Item 3. Quantitative and Qualitative Disclosures About Market Risk](index=50&type=section&id=Item%203.%20Quantitative%20and%20Qualitative%20Disclosures%20About%20Market%20Risk) As a **smaller reporting company**, Taysha Gene Therapies is **not required to provide the information** requested under this item - The company is a **smaller reporting company** as defined by Rule 12b-2 of the Exchange Act and is **not required to provide the information** under this Item[242](index=242&type=chunk) [Item 4. Controls and Procedures](index=50&type=section&id=Item%204.%20Controls%20and%20Procedures) Management, with the participation of the CEO and CFO, evaluated the company's disclosure controls and procedures and concluded that as of September 30, 2021, these controls were **effective**, with **no material changes** in internal control over financial reporting during the quarter - The Chief Executive Officer and Chief Financial Officer concluded that as of September 30, 2021, the company's disclosure controls and procedures were **effective**[243](index=243&type=chunk) - There were **no changes in internal control over financial reporting** during the quarter that materially affected, or are reasonably likely to materially affect, internal controls[244](index=244&type=chunk) PART II. OTHER INFORMATION [Item 1. Legal Proceedings](index=52&type=section&id=Item%201.%20Legal%20Proceedings) The company states that it is **not currently subject to any material legal proceedings** - The company is **not currently a party to any legal proceedings that are likely to have a material adverse effect on its business**[248](index=248&type=chunk) [Item 1A. Risk Factors](index=52&type=section&id=Item%201A.%20Risk%20Factors) This section updates previously disclosed risk factors, highlighting a new risk concerning indebtedness from the August 2021 Term Loan Agreement, which contains **restrictive covenants** that could **limit operational flexibility**, and a breach could result in an **event of default** and **acceleration of debt repayment** - The Term Loan Agreement entered into on August 12, 2021, contains various **covenants that limit the company's ability** to, among other things, incur debt, merge, dispose of assets, make investments, and pay dividends[250](index=250&type=chunk)[253](index=253&type=chunk) - A breach of these covenants could result in an **event of default**, allowing lenders to declare all outstanding amounts immediately due and payable[251](index=251&type=chunk) - The ability to draw down an **additional $60.0 million** under the term loan is **subject to meeting specified conditions** or obtaining lender approval, which may not be achieved[252](index=252&type=chunk) [Item 2. Unregistered Sales of Equity Securities and Use of Proceeds](index=53&type=section&id=Item%202.%20Unregistered%20Sales%20of%20Equity%20Securities%20and%20Use%20of%20Proceeds) The company reports **no unregistered sales** of equity securities during the period and confirms there has been **no material change in the planned use of proceeds** from its Initial Public Offering - There were **no recent sales of unregistered equity securities**[255](index=255&type=chunk) - There has been **no material change in the planned use of proceeds** from the company's initial public offering[257](index=257&type=chunk) [Item 3. Defaults Upon Senior Securities](index=53&type=section&id=Item%203.%20Defaults%20Upon%20Senior%20Securities) This item is **not applicable** to the company - **Not applicable**[259](index=259&type=chunk) [Item 4. Mine Safety Disclosures](index=53&type=section&id=Item%204.%20Mine%20Safety%20Disclosures) This item is **not applicable** to the company - **Not applicable**[260](index=260&type=chunk) [Item 5. Other Information](index=53&type=section&id=Item%205.%20Other%20Information) The company reports **no information** for this item - **None**[261](index=261&type=chunk) [Item 6. Exhibits](index=54&type=section&id=Item%206.%20Exhibits) This section lists the exhibits filed with the quarterly report, which include the company's Amended and Restated Certificate of Incorporation and Bylaws, the Loan and Security Agreement dated August 12, 2021, and certifications by the Principal Executive Officer and Principal Financial Officer - The exhibits list includes **key corporate documents and the Loan and Security Agreement** from August 12, 2021[264](index=264&type=chunk)

Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q3 2021 Earnings Conference Call November 10, 2021 8:00 AM ET Company Participants Kimberly Lee - SVP, Corporate Communications & IR RA Session II - President, CEO & Founder Suyash Prasad - CMO & Head, R&D Kamran Alam - CFO Conference Call Participants Joon Lee - Truist Securities Gil Blum - Needham and Company Laura Chico - Wedbush Securities Elizabeth Webster - Goldman Sachs Mike Ulz - Morgan Stanley Kevin DeGeeter - Oppenheimer Yun Zhong - BTIG Kristen Kluska - C ...

Bringing New Cures to Life CLN1 Disease Investor Day August 30, 2021 | 9:00 — 11:30 AM CT : 0 . 1 : 1 0 . ： ： ： | ： ● ○ Ⅰ ： ● … : | 0 · ： 0 · | ： ♥ 0 | Legal disclosure FORWARD LOOKING STATEMENTS This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this presentation, including statements regarding our strategy, future operations, future financial position, future revenues, projected cos ...

Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q2 2021 Earnings Conference Call August 16, 2021 8:00 AM ET Company Participants Kimberly Lee - Senior Vice President, Corporate Communications and Investor Relations RA Session II - President, Chief Executive Officer and Founder Suyash Prasad - Chief Medical Officer and Head, R&D Kamran Alam - Chief Financial Officer Conference Call Participants Elizabeth Webster - Goldman Sachs Joon Lee - Truist Securities Laura Chico - Wedbush Securities Gil Blum - Needham & Comp ...

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 June 30, 2021 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 84-31995 ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 For the quarterly period ended March 31, 2021 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) FORM 10-Q (Mark One) ☒ QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 Delaware 84-3199 ...

Taysha Gene Therapies, Inc. (NASDAQ:TSHA) Q1 2021 Earnings Conference Call May 11, 2021 8:00 AM ET Company Participants Kimberly Lee – Senior Vice President of Corporate Communications and Investor Relations RA Session II – President, Founder, and Chief Executive Officer Suyash Prasad – Chief Medical Officer and Head-R&D Kamran Alam – Chief Financial Officer Fred Porter – Chief Technical Officer Conference Call Participants Salveen Richter – Goldman Sachs Raju Prasad – William Blair Eun Yang – Jefferies Ope ...

GAN Program Acquisition Highlights - The GAN program transforms Taysha into a pivotal-stage gene therapy company[13, 103] - TSHA-120 has shown clear arrest of disease progression and long-term durability in patients treated for 3+ years[13, 68, 103] - TSHA-120 is well-tolerated with efficacy established at multiple doses in an ongoing clinical trial[13, 61, 103] - The estimated prevalence of GAN is 2,400 patients in the US & EU, representing a potentially greater than $2 billion near-term commercial opportunity[13, 21, 25, 31, 103] TSHA-120 Clinical Data - Clinical data demonstrated arrest of disease progression[16] - Bayesian analysis confirmed documented natural history data of an 8-point decline in the MFM32 total % score per year[70] - TSHA-120 dose of 1.8x10^14 total vg resulted in an arrest of disease progression that was statistically significant[70, 71] - 1.8x10^14 total vg dose confirmed nearly 100% probability of clinically meaningful slowing of disease compared to natural history decline of GAN patients[83, 84] - 1.2x10^14 total vg dose confirmed approximately 85% probability of clinically meaningful slowing of disease and 100% probability of any slowing of disease[83, 84] Vagus Nerve Redosing Platform - There is an opportunity to achieve human POC for vagus nerve redosing platform with previously treated low dose patients[13, 89, 103]

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2020 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 84-3199512 ( ...