TSHA / Taysha Gene Therapies, Inc. - Depositi SEC, Relazione annuale, dichiarazione di delega

Taysha Gene Therapies Reports Second Quarter 2025 Financial Results and Provides Corporate Update Commenced site activation for REVEAL pivotal trial in accordance with previously aligned upon key design elements, following receipt of No Objection Let

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Reports Second Quarter 2025 Financial Results and Provides Corporate Update Commenced site activation for REVEAL pivotal trial in accordance with previously aligned upon key design elements, following receipt of No Objection Letter (NOL) from Health Canada and feedback from the FDA; patient enrollment anticipated to begin in Q4 2025 High dose and low dose

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 2025 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.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 12, 2025 Taysha Gene Thera

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 12, 2025 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commis

Certificate of Amendment to Amended and Restated Certificate of Incorporation of the Company.

EX-3.1 Exhibit 3.1 CERTIFICATE OF AMENDMENT TO THE AMENDED AND RESTATED CERTIFICATE OF INCORPORATION OF TAYSHA GENE THERAPIES, INC. Taysha Gene Therapies, Inc. (the “Company”), a corporation organized and existing under and by virtue of the General Corporation Law of the State of Delaware (the “DGCL”), hereby certifies that: First: The name of the Company is Taysha Gene Therapies, Inc., and that t

Current Report

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 2, 2025 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissio

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 s

Exhibit 99.2 TSHA-102 Rett Syndrome Program Update May 2025 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 the potential of TSHA-102, the durability and reproducibility of the c

1

Exhibit 99.2 Company Overview We are a clinical-stage biotechnology company focused on advancing AAV-based gene therapies for the treatment of severe monogenic diseases of the central nervous system, or CNS. Our lead clinical program TSHA-102 is in development for the treatment of Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the geneti

46,868,687 Shares of Common Stock Pre-Funded Warrants to Purchase up to 25,858,586 Shares of Common Stock

Table of Contents Filed Pursuant to Rule 424(b)(5) Registration No. 333-283801 PROSPECTUS SUPPLEMENT (To Prospectus dated December 20, 2024) 46,868,687 Shares of Common Stock Pre-Funded Warrants to Purchase up to 25,858,586 Shares of Common Stock We are offering 46,868,687 shares of our common stock, par value $0.00001 per share, or the common stock and, in lieu of common stock to certain investor

Taysha Gene Therapies Announces Pivotal Part B Trial Design Details for TSHA-102 in Rett Syndrome Enabled by IRSF Natural History Data and Positive Clinical Data from Part A of the REVEAL Adult/Adolescent and Pediatric Trials Evaluating TSHA-102 Natu

Exhibit 99.1 Taysha Gene Therapies Announces Pivotal Part B Trial Design Details for TSHA-102 in Rett Syndrome Enabled by IRSF Natural History Data and Positive Clinical Data from Part A of the REVEAL Adult/Adolescent and Pediatric Trials Evaluating TSHA-102 Natural history data analysis established patients ≥ six years of age are in developmental plateau, with a ~0% likelihood of gaining/regainin

Underwriting Agreement by and between Taysha Gene Therapies, Inc. and Jefferies LLC, BofA Securities, Inc., Piper Sandler & Co. and Barclays Capital Inc., dated May 28, 2025.

Exhibit 1.1 Taysha Gene Therapies, Inc. Common Stock Underwriting Agreement May 28, 2025 Jefferies LLC BofA Securities, Inc. Piper Sandler & Co. Barclays Capital Inc. As representatives of the several Underwriters named in Schedule I hereto c/o Jefferies LLC 520 Madison Avenue New York, New York 10022 c/o BofA Securities, Inc. One Bryant Park New York, New York 10036 c/o Piper Sandler & Co. U.S. B

Current Report

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 28, 2025 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissio

Taysha Gene Therapies Announces Pricing of Public Offering of Common Stock and Pre-Funded Warrants

EX-99.3 Exhibit 99.3 Taysha Gene Therapies Announces Pricing of Public Offering of Common Stock and Pre-Funded Warrants Dallas – May 28, 2025—Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (Taysha or the Company), a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system (CNS), today announc

Taysha Gene Therapies Announces Proposed Public Offering of Common Stock and Pre-Funded Warrants

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Announces Proposed Public Offering of Common Stock and Pre-Funded Warrants Dallas – May 28, 2025—Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (Taysha or the Company), a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system (CNS), today announced

Regulation FD Disclosure

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K/A CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 28, 2025 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commiss

Form of Pre-Funded Warrant.

Exhibit 4.1 PRE-FUNDED WARRANT TO PURCHASE COMMON STOCK TAYSHA GENE THERAPIES, INC. Warrant Shares: [•] Issue Date: [•], 2025 THIS PRE-FUNDED WARRANT TO PURCHASE COMMON STOCK (the “Warrant”) certifies that, for value received, [•] or its assigns (the “Holder”) is entitled, upon the terms and subject to the limitations on exercise and the conditions hereinafter set forth, at any time on or after th

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 28, 2025 Taysha Gene Therapie

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 28, 2025 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissio

This presentation is intended to be viewed by investors in the U.S. only Legal disclosure FORWARD LOOKING STATEMENTS This presentation contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than st

EX-99.2 TSHA-102 Rett Syndrome Program Update May 2025 Exhibit 99.2 This presentation is intended to be viewed by investors in the U.S. only 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

Subject to Completion, dated May 28, 2025

424B5 Table of Contents Filed Pursuant to Rule 424(b)(5) Registration No. 333-283801 The information in this preliminary prospectus supplement is not complete and may be changed. This preliminary prospectus supplement and the accompanying prospectus are not an offer to sell the securities and are not soliciting an offer to buy the securities in any jurisdiction where the offer or sale is not permi

Taysha Gene Therapies Announces Pivotal Part B Trial Design Details for TSHA-102 in Rett Syndrome Enabled by IRSF Natural History Data and Positive Clinical Data from Part A of the REVEAL Adult/Adolescent and Pediatric Trials Evaluating TSHA-102 Natu

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Announces Pivotal Part B Trial Design Details for TSHA-102 in Rett Syndrome Enabled by IRSF Natural History Data and Positive Clinical Data from Part A of the REVEAL Adult/Adolescent and Pediatric Trials Evaluating TSHA-102 Natural history data analysis established patients ≥ six years of age are in developmental plateau, with a ~0% likelihood of gaining/

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 2025 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.

Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 15, 2025 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissio

Taysha Gene Therapies Reports First Quarter 2025 Financial Results and Provides Corporate Update Obtained written alignment from the FDA on key elements of TSHA-102 pivotal Part B trial design and next steps on enabling study initiation The FDA advis

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Reports First Quarter 2025 Financial Results and Provides Corporate Update Obtained written alignment from the FDA on key elements of TSHA-102 pivotal Part B trial design and next steps on enabling study initiation The FDA advised the Company to submit pivotal Part B trial protocol and associated statistical analysis plan as an amendment to the IND applic

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. 1)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. 1) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☐ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) ☒ Defi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☐ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

DEFA14A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☐ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2))

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☒ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a

Taysha Gene Therapies Reports Full-Year 2024 Financial Results and Provides Corporate Update High dose and low dose of TSHA-102 continue to be generally well tolerated with no treatment-related SAEs or DLTs in all pediatric, adolescent and adult pati

Exhibit 99.1 Taysha Gene Therapies Reports Full-Year 2024 Financial Results and Provides Corporate Update High dose and low dose of TSHA-102 continue to be generally well tolerated with no treatment-related SAEs or DLTs in all pediatric, adolescent and adult patients treated (high dose, n=6; low dose, n=4) across both REVEAL trials as of February 2025 data cutoff Completed dosing of the 10 patient

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): February 26, 2025 Taysha Gene The

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): February 26, 2025 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Comm

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-K

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, 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.

Insider Trading Policy

Exhibit 19.1 TAYSHA GENE THERAPIES, INC. INSIDER TRADING POLICY Amended and Restated on March 8, 2024 Introduction This policy determines acceptable transactions in the securities of Taysha Gene Therapies, Inc. (the “Company”) by our employees, directors and consultants. During the course of your employment, directorship or consultancy with the Company, you may receive important information that i

Filing Fee Table

EX-FILING FEES Exhibit 107 CALCULATION OF FILING FEE TABLES Form S-8 Taysha Gene Therapies, Inc.

Amendment to 2023 Inducement Plan (incorporated by reference to Exhibit 99.6 to the Company’s Registration Statement on Form S-8 (File No. 333-284167) filed with the Securities and Exchange Commission on January 7, 2025).

Exhibit 99.6 AMENDMENT TO TAYSHA GENE THERAPIES, INC. 2023 INDUCEMENT PLAN A. Taysha Gene Therapies, Inc., a corporation organized under the laws of the State of Delaware, (the “Company”) established the Company’s 2023 Inducement Plan (the “Plan”). B. The Plan currently provides for 4,000,000 shares of Common Stock to be reserved for issuance under the Plan; and C. The Company now wishes to amend

As filed with the Securities and Exchange Commission on January 7, 2025

As filed with the Securities and Exchange Commission on January 7, 2025 Registration No.

TAYSHA GENE THERAPIES, INC. 3000 Pegasus Park Drive Suite 1430 Dallas, Texas 75247

CORRESP TAYSHA GENE THERAPIES, INC. 3000 Pegasus Park Drive Suite 1430 Dallas, Texas 75247 December 20, 2024 Via EDGAR U.S. Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.E. Washington, D.C. 20549 Attn: Joshua Gorsky Re: Taysha Gene Therapies, Inc. Registration Statement on Form S-3 (File No. 333-283801) Request for Acceleration of Effective Date Mr. Gorsky: In

TAYSHA GENE THERAPIES, INC. 3000 Pegasus Park Drive Suite 1430 Dallas, Texas 75247

CORRESP TAYSHA GENE THERAPIES, INC. 3000 Pegasus Park Drive Suite 1430 Dallas, Texas 75247 December 19, 2024 Via EDGAR U.S. Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.E. Washington, D.C. 20549 Attn: Joshua Gorsky Re: Taysha Gene Therapies, Inc. Registration Statement on Form S-3 (File No. 333-283801) Request for Acceleration of Effective Date Mr. Gorsky: In

Form of Common Stock Warrant Agreement and Warrant Certificate.

EX-4.4 Exhibit 4.4 TAYSHA GENE THERAPIES, INC. AND , AS WARRANT AGENT FORM OF COMMON STOCK WARRANT AGREEMENT DATED AS OF TAYSHA GENE THERAPIES, INC. FORM OF COMMON STOCK WARRANT AGREEMENT THIS COMMON STOCK WARRANT AGREEMENT (this “Agreement”), dated as of [•], between TAYSHA GENE THERAPIES, INC. , a Delaware corporation (the “Company”), and [•], a [corporation] [national banking association] organ

As filed with the Securities and Exchange Commission on December 13, 2024

S-3 Table of Contents As filed with the Securities and Exchange Commission on December 13, 2024 Registration No.

Filing Fee Table

EX-FILING FEES Exhibit 107 Calculation of Filing Fee Tables Form S-3 (Form Type) Taysha Gene Therapies, Inc.

Form of Indenture, between the Registrant and one or more trustees to be named.

EX-4.2 Exhibit 4.2 TAYSHA GENE THERAPIES, INC. Issuer AND [TRUSTEE], Trustee INDENTURE Dated as of [•], 20  Debt Securities TABLE OF CONTENTS PAGE ARTICLE 1 DEFINITIONS 1 Section 1.01 Definitions of Terms 1 ARTICLE 2 ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE OF SECURITIES 5 Section 2.01 Designation and Terms of Securities 5 Section 2.02 Form of Securities and Trustee’s Certif

Form of Debt Securities Warrant Agreement and Warrant Certificate.

EX-4.6 Exhibit 4.6 TAYSHA GENE THERAPIES, INC. AND , AS WARRANT AGENT FORM OF DEBT SECURITIES WARRANT AGREEMENT DATED AS OF TAYSHA GENE THERAPIES, INC. FORM OF DEBT SECURITIES WARRANT AGREEMENT THIS DEBT SECURITIES WARRANT AGREEMENT (this “Agreement”), dated as of [•], between TAYSHA GENE THERAPIES, INC., a Delaware corporation (the “Company”), and [•], a [corporation] [national banking associatio

Form of Preferred Stock Warrant Agreement and Warrant Certificate.

EX-4.5 Exhibit 4.5 TAYSHA GENE THERAPIES, INC. AND , AS WARRANT AGENT FORM OF PREFERRED STOCK WARRANT AGREEMENT DATED AS OF TAYSHA GENE THERAPIES, INC. FORM OF PREFERRED STOCK WARRANT AGREEMENT THIS PREFERRED STOCK WARRANT AGREEMENT (this “Agreement”), dated as of [•], between TAYSHA GENE THERAPIES, INC., a Delaware corporation (the “Company”), and [•], a [corporation] [national banking associatio

TSHA / Taysha Gene Therapies, Inc. / Venrock Healthcare Capital Partners III, L.P. - SC 13G/A Passive Investment

SC 13G/A 1 tm2428137d16sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 2)* Taysha Gene Therapies, Inc. (Name of Issuer) Common stock, par value $0.00001 per share (Title of Class of Securities) 877619106 (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of this S

JOINT FILING AGREEMENT PURSUANT TO RULE 13d-1(k)

EXHIBIT 1 JOINT FILING AGREEMENT PURSUANT TO RULE 13d-1(k) The undersigned acknowledge and agree that the foregoing statement on Schedule 13G is filed on behalf of each of the undersigned and that all subsequent amendments to this statement on Schedule 13G shall be filed on behalf of each of the undersigned without the necessity of filing additional joint filing agreements.

TSHA / Taysha Gene Therapies, Inc. / Avoro Capital Advisors LLC - TAYSHA GENE THERAPIES, INC. Passive Investment

SC 13G 1 p24-3104sc13g.htm TAYSHA GENE THERAPIES, INC. SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Taysha Gene Therapies, Inc. (Name of Issuer) Common stock, par value $0.00001 per share (Title of Class of Securities) 877619106 (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of This Statem

TSHA / Taysha Gene Therapies, Inc. / RA CAPITAL MANAGEMENT, L.P. - SC 13G/A Passive Investment

SC 13G/A 1 tm2427451d22sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 2)* TAYSHA GENE THERAPIES, INC. (Name of Issuer) Common Stock, $0.00001 par value per share (Title of Class of Securities) 877619106 (CUSIP Number) September 30, 2024 (Date of Event Which Requires Filing of this S

Exhibit 1: Joint Filing Agreement

EX-99.1 2 tm2427451d22ex1.htm EXHIBIT 1 EXHIBIT 1 AGREEMENT This Joint Filing Agreement, dated as of November 14, 2024, is by and among RA Capital Management, L.P., Peter Kolchinsky, Rajeev Shah, and RA Capital Healthcare Fund, L.P. (the foregoing are collectively referred to herein as the “Filers”). Each of the Filers may be required to file with the United States Securities and Exchange Commissi

Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 13, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Comm

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 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.

Taysha Gene Therapies Reports Third Quarter 2024 Financial Results and Provides Corporate Update 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 a

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Reports Third Quarter 2024 Financial Results and Provides Corporate Update 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

Taysha Gene Therapies Reports Second Quarter 2024 Financial Results and Provides Corporate Update Presented cohort one (low dose) data from both trials of TSHA-102 at 2024 IRSF Rett Syndrome Scientific Meeting that demonstrated durable improvements a

Exhibit 99.1 Taysha Gene Therapies Reports Second Quarter 2024 Financial Results and Provides Corporate Update Presented cohort one (low dose) data from both trials of TSHA-102 at 2024 IRSF Rett Syndrome Scientific Meeting that demonstrated durable improvements across consistent clinical domains and an encouraging safety profile in adult (up to 52 weeks) and pediatric (up to 22 weeks) patients TSH

Exhibit 4.1

Exhibit 4.1 DESCRIPTION OF TAYSHA GENE THERAPIES, INC. COMMON STOCK The following description of the common stock of Taysha Gene Therapies, Inc., or the Company, and certain provisions of the Company’s amended and restated certificate of incorporation, or the certificate, the certificate of amendment to the certificate, or the amendment, and together with the certificate, the amended and restated

Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 12, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commis

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 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.

Taysha Gene Therapies Announces Pricing of Public Offering of Common Stock and Pre-Funded Warrants

Exhibit 99.1 Taysha Gene Therapies Announces Pricing of Public Offering of Common Stock and Pre-Funded Warrants Dallas – June 26, 2024 - Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system (CNS), today announced the pricing of an underwri

Taysha Gene Therapies Announces Proposed Public Offering of Common Stock and Pre-Funded Warrants

Exhibit 99.1 Taysha Gene Therapies Announces Proposed Public Offering of Common Stock and Pre-Funded Warrants Dallas – June 25, 2024—Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a clinical-stage 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 it has commenced an under

Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 25, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissi

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Exhibit 99.2 Company Overview We are a clinical-stage biotechnology company focused on advancing AAV-based gene therapies for the treatment of severe monogenic diseases of the central nervous system, or CNS. Our lead clinical program TSHA-102 is in development for the treatment of Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the geneti

Current Report

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 26, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissi

2024 Pre-Funded Warrant to Purchase Common Stock (incorporated by reference to Exhibit 4.1 to the Company’s Current Report on Form 8-K (File No. 001-39536), filed with the Securities and Exchange Commission on June 26, 2024).

Exhibit 4.1 PRE-FUNDED WARRANT TO PURCHASE COMMON STOCK TAYSHA GENE THERAPIES, INC. Warrant Shares: [●] Issue Date: [●], 2024 THIS PRE-FUNDED WARRANT TO PURCHASE COMMON STOCK (the “Warrant”) certifies that, for value received, [●] or its assigns (the “Holder”) is entitled, upon the terms and subject to the limitations on exercise and the conditions hereinafter set forth, at any time on or after th

14,361,113 shares of Common Stock Pre-Funded Warrants to Purchase up to 18,972,221 shares of Common Stock

Table of Contents Filed Pursuant to Rule 424(b)(5) Registration No. 333-260069 PROSPECTUS SUPPLEMENT (To Prospectus dated October 14, 2021) 14,361,113 shares of Common Stock Pre-Funded Warrants to Purchase up to 18,972,221 shares of Common Stock We are offering 14,361,113 shares of our common stock, par value $0.00001 per share, or the common stock and, in lieu of common stock to certain investors

Subject to Completion, dated June 26, 2024

424B5 Table of Contents Filed Pursuant to Rule 424(b)(5) Registration No. 333-260069 The information in this preliminary prospectus supplement is not complete and may be changed. This preliminary prospectus supplement and the accompanying prospectus are not an offer to sell the securities and are not soliciting an offer to buy the securities in any jurisdiction where the offer or sale is not permi

Underwriting Agreement by and between Taysha Gene Therapies, Inc. and Jefferies LLC and Goldman Sachs & Co. LLC, dated June 26, 2024.

Exhibit 1.1 Taysha Gene Therapies, Inc. Common Stock Underwriting Agreement June 26, 2024 Jefferies LLC Goldman Sachs & Co. LLC  As representatives of the several Underwriters   named in Schedule I hereto c/o Jefferies LLC 520 Madison Avenue New York, New York 10022 c/o Goldman Sachs & Co. LLC 200 West Street New York, New York 10282-2198 Ladies and Gentlemen: Taysha Gene Therapies, Inc., a Delawa

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 regardi

TSHA-102 in clinical evaluation for Rett syndrome: Cohort one data from the REVEAL Phase 1/2 Adolescent-Adult and Pediatric trials June 18, 2024 Exhibit 99.

Regulation FD Disclosure

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 18, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissi

Taysha Gene Therapies Announces Positive Clinical Data Across Adult and Pediatric Patients from Low Dose Cohort in Ongoing REVEAL Phase 1/2 Trials Evaluating TSHA-102 in Rett Syndrome Durable improvements across consistent clinical domains in both ad

Exhibit 99.1 Taysha Gene Therapies Announces Positive Clinical Data Across Adult and Pediatric Patients from Low Dose Cohort in Ongoing REVEAL Phase 1/2 Trials Evaluating TSHA-102 in Rett Syndrome Durable improvements across consistent clinical domains in both adult and pediatric patients, including motor skills, communication/socialization, autonomic function, seizures, and an encouraging safety

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 29, 2024 Taysha Gene Therapie

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 29, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissio

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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.

Taysha Gene Therapies Reports First Quarter 2024 Financial Results and Provides Corporate Update Completed dosing in cohort one (low dose, 5.7x1014 total vg) of REVEAL Phase 1/2 adolescent and adult trial with longer-term data supporting the safety p

Exhibit 99.1 Taysha Gene Therapies Reports First Quarter 2024 Financial Results and Provides Corporate Update Completed dosing in cohort one (low dose, 5.7x1014 total vg) of REVEAL Phase 1/2 adolescent and adult trial with longer-term data supporting the safety profile and durable response of TSHA-102; enrolled first patient in cohort two (high dose, 1x1015 total vg) with dosing scheduled for Q2 2

Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 14, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissio

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

DEF 14A Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☐ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2)) ☐ Defini

Taysha Gene Therapies, Inc. Incentive Compensation Recoupment Policy

Exhibit 97.1 TAYSHA GENE THERAPIES, INC. Incentive Compensation Recoupment Policy 1. Introduction The Board of Directors (the “Board”) of Taysha Gene Therapies, Inc., a Delaware corporation (the “Company”), has determined that it is in the best interests of the Company and its stockholders to adopt this Incentive Compensation Recoupment Policy (this “Policy”) providing for the Company’s recoupment

Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): March 19, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commiss

Filing Fee Table

Exhibit 107 CALCULATION OF FILING FEE TABLES Form S-8 Taysha Gene Therapies, Inc. Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount to be Registered (1) Proposed Maximum Offering Price Per Share Proposed Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Equity Common stock, $0.00001 par value per share, reserved for future issuan

As filed with the Securities and Exchange Commission on March 19, 2024

As filed with the Securities and Exchange Commission on March 19, 2024 Registration No.

Taysha Gene Therapies Reports Full Year 2023 Financial Results and Provides Corporate and Clinical Updates Data from first adult patient in REVEAL Phase 1/2 trial showed TSHA-102 (low dose, 5.7x1014 total vg) was well-tolerated with no treatment-emer

Exhibit 99.1 Taysha Gene Therapies Reports Full Year 2023 Financial Results and Provides Corporate and Clinical Updates Data from first adult patient in REVEAL Phase 1/2 trial showed TSHA-102 (low dose, 5.7x1014 total vg) was well-tolerated with no treatment-emergent SAEs as of 35-week assessment, with sustained improvement across key efficacy measures at decreased steroid levels and new improveme

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-K

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, 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.

Exhibit 1: Joint Filing Agreement

EX-99.1 2 tm246065d18ex-1.htm EXHIBIT 1 EXHIBIT 1 AGREEMENT This Joint Filing Agreement, dated as of February 14, 2024, is by and among RA Capital Management, L.P., Peter Kolchinsky, Rajeev Shah, and RA Capital Healthcare Fund, L.P. (the foregoing are collectively referred to herein as the “Filers”). Each of the Filers may be required to file with the United States Securities and Exchange Commissi

TSHA / Taysha Gene Therapies, Inc. / Venrock Healthcare Capital Partners III, L.P. - SC 13G/A Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 1)* Taysha Gene Therapies, Inc. (Name of Issuer) Common stock, par value $0.00001 per share (Title of Class of Securities) 877619106 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to desig

TSHA / Taysha Gene Therapies, Inc. / RTW INVESTMENTS, LP - TAYSHA GENE THERAPIES, INC. Passive Investment

SC 13G 1 p24-0716sc13g.htm TAYSHA GENE THERAPIES, INC. SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Taysha Gene Therapies, Inc. (Name of Issuer) Common Stock, par value $0.00001 per share (Title of Class of Securities) 877619106 (CUSIP Number) December 31, 2023 (Date of event which requires filing of this stateme

TSHA / Taysha Gene Therapies, Inc. / RA CAPITAL MANAGEMENT, L.P. - SC 13G/A Passive Investment

SC 13G/A 1 tm246065d18sc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G/A Under the Securities Exchange Act of 1934 (Amendment No. 1)* TAYSHA GENE THERAPIES, INC. (Name of Issuer) Common Stock, $0.00001 par value per share (Title of Class of Securities) 877619106 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of this Sta

TSHA / Taysha Gene Therapies, Inc. / TCG Crossover GP I, LLC - SC 13G/A Passive Investment

SC 13G/A 1 d860063dsc13ga.htm SC 13G/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. 1)* Taysha Gene Therapies, Inc. (Name of Issuer) Common Stock, $0.00001 par value per share (Title of Class of Securities) 877619106 (CUSIP Number) December 31, 2023 (Date of Event Which Requires Filing of This Statemen

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 10, 2024 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 10, 2024 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commi

Taysha Gene Therapies Announces First Pediatric Patient Dosed with TSHA-102 in REVEAL Phase 1/2 Pediatric Trial in Rett Syndrome Initiation of REVEAL pediatric trial in the U.S. broadens the clinical evaluation of TSHA-102 to female patients 5-8 year

Exhibit 99.1 Taysha Gene Therapies Announces First Pediatric Patient Dosed with TSHA-102 in REVEAL Phase 1/2 Pediatric Trial in Rett Syndrome Initiation of REVEAL pediatric trial in the U.S. broadens the clinical evaluation of TSHA-102 to female patients 5-8 years old with stage three Rett syndrome MHRA authorized the CTA for TSHA-102 in pediatric patients with Rett syndrome, enabling expansion of

Form of Option Grant Package under 2023 Inducement Plan.

EX-99.2 Exhibit 99.2 2023 INDUCEMENT PLAN FORM OF STOCK OPTION GRANT PACKAGE TAYSHA GENE THERAPIES, INC. STOCK OPTION GRANT NOTICE (2023 INDUCEMENT PLAN) Taysha Gene Therapies, Inc. (the “Company”), pursuant to the Company’s 2023 Inducement Plan (the “Plan”), has granted to you (“Optionholder”) an option to purchase the number of shares of the Common Stock set forth below (the “Option”). Your Opti

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): December 14, 2023 Taysha Gene The

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): December 14, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Comm

Form of RSU Award Grant Notice and RSU Award Agreement under the 2023 Inducement Plan (incorporated by reference to Exhibit 10.2 to the Company’s Current Report on Form 8-K (File No. 001-39536) filed with the Securities and Exchange Commission on December 20, 2023).

Exhibit 10.2 2023 INDUCEMENT PLAN FORM OF RSU GRANT PACKAGE TAYSHA GENE THERAPIES, INC. RSU AWARD GRANT NOTICE (2023 INDUCEMENT PLAN) Taysha Gene Therapies, Inc. (the “Company”) has awarded to you (“Participant”) the number of restricted stock units specified and on the terms set forth below (the “RSU Award”). Your RSU Award is subject to all of the terms and conditions as set forth herein, in the

As filed with the Securities and Exchange Commission on December 20, 2023

S-8 As filed with the Securities and Exchange Commission on December 20, 2023 Registration No.

Filing Fee Table

EX-FILING FEES Exhibit 107 Calculation of Filing Fee Tables Form S-8 TAYSHA GENE THERAPIES, INC.

Taysha Gene Therapies, Inc. 2023 Inducement Plan.

EX-99.1 Exhibit 99.1 TAYSHA GENE THERAPIES, INC. 2023 INDUCEMENT PLAN ADOPTED BY THE BOARD OF DIRECTORS: DECEMBER 15, 2023 1. GENERAL. (a) Eligible Award Recipients. The only persons eligible to receive grants of Awards under this Plan are individuals who satisfy the standards for inducement grants under Nasdaq Marketplace Rule 5635(c)(4) or 5635(c)(3), if applicable, and the related guidance unde

Form of Stock Option Grant Notice and Stock Option Agreement under the 2023 Inducement Plan (incorporated by reference to Exhibit 10.3 to the Company’s Current Report on Form 8-K (File No. 001-39536) filed with the Securities and Exchange Commission on December 20, 2023).

Exhibit 10.3 2023 INDUCEMENT PLAN FORM OF STOCK OPTION GRANT PACKAGE TAYSHA GENE THERAPIES, INC. STOCK OPTION GRANT NOTICE (2023 INDUCEMENT PLAN) Taysha Gene Therapies, Inc. (the “Company”), pursuant to the Company’s 2023 Inducement Plan (the “Plan”), has granted to you (“Optionholder”) an option to purchase the number of shares of the Common Stock set forth below (the “Option”). Your Option is su

Form of RSU Grant Package under 2023 Inducement Plan.

EX-99.3 Exhibit 99.3 2023 INDUCEMENT PLAN FORM OF RSU GRANT PACKAGE TAYSHA GENE THERAPIES, INC. RSU AWARD GRANT NOTICE (2023 INDUCEMENT PLAN) Taysha Gene Therapies, Inc. (the “Company”) has awarded to you (“Participant”) the number of restricted stock units specified and on the terms set forth below (the “RSU Award”). Your RSU Award is subject to all of the terms and conditions as set forth herein

Taysha Gene Therapies, Inc. 2023 Inducement Plan (incorporated by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K (File No. 001-39536) filed with the Securities and Exchange Commission on December 20, 2023).

Exhibit 10.1 TAYSHA GENE THERAPIES, INC. 2023 INDUCEMENT PLAN ADOPTED BY THE BOARD OF DIRECTORS: DECEMBER 15, 2023 1. GENERAL. (a) Eligible Award Recipients. The only persons eligible to receive grants of Awards under this Plan are individuals who satisfy the standards for inducement grants under Nasdaq Marketplace Rule 5635(c)(4) or 5635(c)(3), if applicable, and the related guidance under Nasdaq

Certificate of Amendment to the Amended and Restated Certificate of Incorporation of (incorporated by reference to Exhibit 3.1 to the Company’s Current Report on Form 8-K (File No. 001-39536), filed with the Securities and Exchange Commission on November 15, 2023).

EX-3.1 Exhibit 3.1 CERTIFICATE OF AMENDMENT TO THE AMENDED AND RESTATED CERTIFICATE OF INCORPORATION OF TAYSHA GENE THERAPIES, INC. Taysha Gene Therapies, Inc. (the “Company”), a corporation organized and existing under and by virtue of the General Corporation Law of the State of Delaware (the “DGCL”), hereby certifies that: First: The name of the Company is Taysha Gene Therapies, Inc., and that t

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 15, 2023 Taysha Gene The

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 15, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Comm

Taysha Gene Therapies Reports Third Quarter 2023 Financial Results and Provides Corporate and Clinical Updates Data from first adult patient in REVEAL Phase 1/2 trial showed TSHA-102 was well-tolerated with no treatment-emergent SAEs as of 20-week as

Exhibit 99.1 Taysha Gene Therapies Reports Third Quarter 2023 Financial Results and Provides Corporate and Clinical Updates Data from first adult patient in REVEAL Phase 1/2 trial showed TSHA-102 was well-tolerated with no treatment-emergent SAEs as of 20-week assessment with sustained improvement across key efficacy measures and new improvement in R-MBA, PGI-I and hand function, a hallmark charac

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 14, 2023 Taysha Gene The

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 14, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Comm

and the lenders from time to time party thereto as lenders, and Trinity Capital, Inc. as administrative agent and collateral

Exhibit 10.2 CERTAIN INFORMATION HAS BEEN EXCLUDED FROM THIS AGREEMENT (INDICATED BY “[***]”) BECAUSE TAYSHA GENE THERAPIES, INC. HAS DETERMINED SUCH INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. LOAN AND SECURITY AGREEMENT THIS LOAN AND SECURITY AGREEMENT is made as of November 13, 2023 (the “Closing Date”), by and among TAYSHA GENE THERAPIES, INC.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 30, 2023 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 30, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☐ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a

Regulation FD Disclosure

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): September 26, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Com

Taysha Gene Therapies Announces Second Patient Dosed with TSHA-102 in the REVEAL Phase 1/2 Adult Trial for the Treatment of Rett Syndrome Available clinical data from the two adult patients dosed with TSHA-102 in the first cohort (low dose) to be dis

Exhibit 99.1 Taysha Gene Therapies Announces Second Patient Dosed with TSHA-102 in the REVEAL Phase 1/2 Adult Trial for the Treatment of Rett Syndrome Available clinical data from the two adult patients dosed with TSHA-102 in the first cohort (low dose) to be discussed during upcoming quarterly earnings call following Independent Data Monitoring Committee (IDMC) review Dosing of third adult patien

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☒ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): September 19, 2023 Taysha Gene Th

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): September 19, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Com

Taysha Gene Therapies Provides Update on TSHA-120 Program in Giant Axonal Neuropathy (GAN) Following Type C meeting feedback from the U.S. FDA, Taysha is discontinuing development of TSHA-120 in GAN due to challenges with study design feasibility for

Exhibit 99.1 Taysha Gene Therapies Provides Update on TSHA-120 Program in Giant Axonal Neuropathy (GAN) Following Type C meeting feedback from the U.S. FDA, Taysha is discontinuing development of TSHA-120 in GAN due to challenges with study design feasibility for potential Biologics License Application (BLA) submission Taysha will pursue external strategic options for the TSHA-120 program to poten

166,663,354 Shares Common Stock Offered by the Selling Stockholders

424B3 Table of Contents Filed pursuant to Rule 424(b)(3) Registration No. 333-274264 PROSPECTUS 166,663,354 Shares Common Stock Offered by the Selling Stockholders This prospectus relates to the proposed resale from time to time of up to 166,663,354 shares, or the Shares, of our common stock, par value $0.00001 per share, or the common stock, by the selling stockholders named herein, together with

Taysha Gene Therapies, Inc. 3000 Pegasus Park Drive, Suite 1430 Dallas, Texas 75247

Taysha Gene Therapies, Inc. 3000 Pegasus Park Drive, Suite 1430 Dallas, Texas 75247 September 7, 2023 Via Edgar United States Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.E. Washington, D.C. 20549 Attn: Doris Stacey Gama RE: Taysha Gene Therapies, Inc. Registration Statement on Form S-3 File No. 333-274264 Acceleration Request Requested Date: September 8, 2023

Filing Fee Table

Exhibit 107 Calculation of Filing Fee Tables Form S-3 (Form Type) Taysha Gene Therapies, Inc.

As filed with the Securities and Exchange Commission on August 30, 2023

S-3 Table of Contents As filed with the Securities and Exchange Commission on August 30, 2023 Registration No.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 28, 2023 Taysha Gene Thera

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 28, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commis

TSHA / Taysha Gene Therapies Inc / Venrock Healthcare Capital Partners III, L.P. - SC 13G Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Taysha Gene Therapies, Inc. (Name of Issuer) Common stock, par value $0.00001 per share (Title of Class of Securities) 877619106 (CUSIP Number) August 16, 2023 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to designate

TSHA / Taysha Gene Therapies Inc / RA CAPITAL MANAGEMENT, L.P. - SC 13G Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* TAYSHA GENE THERAPIES, INC. (Name of Issuer) Common Stock, $0.00001 par value per share (Title of Class of Securities) 877619106 (CUSIP Number) August 16, 2023 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to designate

JOINT FILING AGREEMENT

EX-99.1 2 d454729dex991.htm EXHIBIT 1 Exhibit 1 JOINT FILING AGREEMENT The undersigned hereby agree that the foregoing statement on Schedule 13G is filed on behalf of each of the undersigned, and any amendments thereto executed by the undersigned shall be filed on behalf of each of the undersigned without the necessity of filing any additional joint filing agreement. The undersigned acknowledge th

TSHA / Taysha Gene Therapies Inc / TCG Crossover GP I, LLC - SC 13G Passive Investment

SC 13G 1 d454729dsc13g.htm SC 13G UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 (Amendment No. )* Taysha Gene Therapies, Inc. (Name of Issuer) Common Stock, $0.00001 par value per share (Title of Class of Securities) 877619106 (CUSIP Number) August 16, 2023 (Date of Event Which Requires Filing of This Statement) Check

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 24, 2023 Taysha Gene Thera

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 24, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commis

Taysha Gene Therapies Announces Fast Track Designation Granted by U.S. FDA for TSHA-102 in Rett Syndrome Fast Track Designation (FTD) is designed to accelerate the development and expedite the review of therapies with potential to address unmet medic

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Announces Fast Track Designation Granted by U.S. FDA for TSHA-102 in Rett Syndrome Fast Track Designation (FTD) is designed to accelerate the development and expedite the review of therapies with potential to address unmet medical needs for a serious or life-threatening condition TSHA-102 has also received Orphan Drug and Rare Pediatric Disease designatio

TSHA / Taysha Gene Therapies Inc / Manning Paul B - SC 13D/A Activist Investment

SC 13D/A 1 d510852dsc13da.htm SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No. 2)* Taysha Gene Therapies, Inc. (Name of Issuer) Common Stock, $0.00001 par value per share (Title of Class of Securities) 877619106 (CUSIP Number) Paul B. Manning c/o PBM Capital Group, LLC 200 Garrett Street, Suite S

JOINT FILING AGREEMENT

EX-99.A 2 d510852dex99a.htm EXHIBIT A EXHIBIT A JOINT FILING AGREEMENT Pursuant to Rule 13d-1(k)(1) promulgated pursuant to the Securities Exchange Act of 1934, as amended, the undersigned agree that the attached Schedule 13D is being filed on behalf of each of the undersigned. Dated: August 21, 2023 By: /s/ Paul B. Manning Name: Paul B. Manning THE PAUL B. MANNING REVOCABLE TRUST DATED MAY 10, 20

TSHA / Taysha Gene Therapies Inc / Astellas Pharma Inc. - SC 13D/A Activist Investment

SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D (Amendment No. 1) Under the Securities Exchange Act of 1934 TAYSHA GENE THERAPIES, INC. (Name of Issuer) Common Stock, par value $0.00001 (Title of Class of Securities) 877619106 (CUSIP Number) Astellas Gene Therapies, Inc. f/k/a Audentes Therapeutics, Inc. 225 Gateway Boulevard South San Francisco, CA 94

Taysha Gene Therapies Reports Initial Clinical Data from First Adult Rett Syndrome Patient Dosed in REVEAL Phase 1/2 Trial and Provides Corporate Update with Second Quarter 2023 Financial Results Data from first adult patient dosed in REVEAL Phase 1/

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Reports Initial Clinical Data from First Adult Rett Syndrome Patient Dosed in REVEAL Phase 1/2 Trial and Provides Corporate Update with Second Quarter 2023 Financial Results 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

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 14, 2023 Taysha Gene Thera

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 14, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commis

Form of Pre-Funded Warrant to Purchase Common Stock (incorporated by reference to Exhibit 4.1 to the Company’s Current Report on Form 8-K (File No. 001-39536), filed with the Securities and Exchange Commission on August 14, 2023).

EX-4.1 Exhibit 4.1 NEITHER THIS SECURITY NOR THE SECURITIES FOR WHICH THIS SECURITY IS EXERCISABLE HAVE BEEN REGISTERED UNDER THE SECURITIES ACT OF 1933, AS AMENDED, OR THE SECURITIES LAWS OF ANY STATE OF THE UNITED STATES. THE SECURITIES MAY NOT BE SOLD, OFFERED FOR SALE, PLEDGED, HYPOTHECATED, TRANSFERRED OR ASSIGNED IN THE ABSENCE OF AN EFFECTIVE REGISTRATION STATEMENT FOR THE SECURITIES UNDER

Amended and Restated Non-employee director compensation policy (incorporated by reference to Exhibit 10.1 to the Company's Quarterly Report on Form 10-Q (File No. 001-39536), filed with the Securities and Exchange Committee on August 14, 2023).

Exhibit 10.1 Taysha Gene Therapies, Inc. Non-Employee Director Compensation Policy Each member of the Board of Directors (the “Board”) who is not also serving as an employee of or consultant to Taysha Gene Therapies, Inc. (the “Company”) or any of its subsidiaries (each such member, an “Eligible Director”) will receive the compensation described in this Non-Employee Director Compensation Policy fo

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 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.

Form of Securities Purchase Agreement, by and among the Registrant and the Purchasers, dated August 14, 2023

EX-10.1 Exhibit 10.1 SECURITIES PURCHASE AGREEMENT This SECURITIES PURCHASE AGREEMENT (this “Agreement”), dated as of August 14, 2023, is made by and among TAYSHA GENE THERAPIES, INC., a Delaware corporation (the “Company”), and the Purchasers listed on Schedule 1 hereto, together with their permitted transferees (each, a “Purchaser” and collectively, the “Purchasers”). RECITALS: A. The Company an

Taysha Gene Therapies Announces $150 Million Private Placement Financing Financing led by RA Capital Management with participation from new and existing investors Expected net proceeds, along with existing cash and cash equivalents, are expected to e

EX-99.2 Exhibit 99.2 Taysha Gene Therapies Announces $150 Million Private Placement Financing Financing led by RA Capital Management with participation from new and existing investors Expected net proceeds, along with existing cash and cash equivalents, are expected to extend cash runway into the third quarter of 2025 DALLAS, August 14, 2023 (GLOBE NEWSWIRE) – Taysha Gene Therapies, Inc. (Nasdaq:

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 3, 2023 Taysha Gene Therap

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 3, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commiss

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): July 31, 2023 Taysha Gene Therapi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): July 31, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissi

Taysha Gene Therapies Announces Positive Recommendation from Independent Data Monitoring Committee of REVEAL Phase 1/2 Trial in Rett Syndrome Independent Data Monitoring Committee recommended REVEAL Phase 1/2 trial continuation and proceeding with do

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Announces Positive Recommendation from Independent Data Monitoring Committee of REVEAL Phase 1/2 Trial in Rett Syndrome Independent Data Monitoring Committee recommended REVEAL Phase 1/2 trial continuation and proceeding with dosing of second patient based on encouraging initial clinical data from the first adult with Rett syndrome dosed with investigatio

Regulation FD Disclosure, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 28, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissi

Taysha Gene Therapies Provides Clinical Updates for Investigational Programs TSHA-120 in Giant Axonal Neuropathy (GAN) and TSHA-102 in Rett Syndrome at R&D Day Company views that results of comprehensive data analysis of TSHA-120 and development of d

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Provides Clinical Updates for Investigational Programs TSHA-120 in Giant Axonal Neuropathy (GAN) and TSHA-102 in Rett Syndrome at R&D Day Company views that results of comprehensive data analysis of TSHA-120 and development of disease progression model (DPM) address U.S. Food and Drug Administration (FDA) feedback regarding the effort-dependent nature of

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 22, 2023 Taysha Gene Therapi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 22, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 20, 2023 Taysha Gene Therapi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 20, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissi

Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 31, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissio

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 5, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissio

Taysha Gene Therapies Announces First Patient Dosed with TSHA-102 in the REVEAL Phase 1/2 Trial Under Investigation for the Treatment of Rett Syndrome The Phase 1/2 REVEAL trial is a first-in-human, randomized, dose-escalation and dose-expansion stud

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Announces First Patient Dosed with TSHA-102 in the REVEAL Phase 1/2 Trial Under Investigation for the Treatment of Rett Syndrome The Phase 1/2 REVEAL trial is a first-in-human, randomized, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102 in adults with Rett syndrome TSHA-102 utilizes novel miRARE technolo

Taysha Gene Therapies Presents Preclinical Data on TSHA-102 for Rett Syndrome Demonstrating Cellular Regulation of MeCP2 Expression in Key Mouse Models at the American Society of Gene and Cell Therapy 26th Annual Meeting New preclinical data after ne

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Presents Preclinical Data on TSHA-102 for Rett Syndrome Demonstrating Cellular Regulation of MeCP2 Expression in Key Mouse Models at the American Society of Gene and Cell Therapy 26th Annual Meeting New preclinical data after neonatal administration in wild-type mice showed no detectable impact on survival, neurobehavioral functions and overall health, su

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 19, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commissio

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 11, 2023 Taysha Gene Therapie

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 11, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissio

Taysha Gene Therapies Reports First Quarter 2023 Financial Results and Provides Corporate Update Screening completed and dosing scheduled for first potential subject in the Phase 1/2 REVEAL trial in Rett syndrome; dosing of first adult patient with T

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Reports First Quarter 2023 Financial Results and Provides Corporate Update Screening completed and dosing scheduled for first potential subject in the Phase 1/2 REVEAL trial in Rett syndrome; dosing of first adult patient with TSHA-102 expected in Q2 2023; initial available Phase 1/2 clinical data, primarily on safety, expected in Q2 2023 Clinical Trial A

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 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.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

DEF 14A Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

DEFA14A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☐ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a-6(e)(2))

8,496,560 Shares Common Stock Offered by the Selling Stockholders

424B3 Table of Contents Filed pursuant to Rule 424(b)(3) Registration No. 333-271144 PROSPECTUS 8,496,560 Shares Common Stock Offered by the Selling Stockholders This prospectus relates to the proposed resale from time to time of up to 8,496,560 shares, or the Shares, of our common stock, par value $0.00001 per share, or the common stock, by the selling stockholders named herein, together with any

Form 10-K/A

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K/A Amendment No. 1 (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, 2022 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO Commission F

April 27, 2023

April 27, 2023 VIA EDGAR Joshua Gorsky U.S. Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.E. Washington, D.C. 20549 Re: Taysha Gene Therapies, Inc. Registration Statement on Form S-3 (File No. 333-271144) Request for Acceleration of Effective Date Acceleration Request Requested Date: Monday, May 1, 2023 Requested Time: 4:00 p.m. Eastern Time Dear Mr. Gorsky: In

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ☒ Filed by a Party other than the Registrant ☐ Check the appropriate box: ☒ Preliminary Proxy Statement ☐ Confidential, for Use of the Commission Only (as permitted by Rule 14a

Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers, Notice of Delisting or Failure to Satisfy a Continued Listing Rule or Standard; Transfer of Listing

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): April 24, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commiss

Securities Purchase Agreement, by and between the Registrant and the SSI Investors, dated April 5, 2023

EX-4.4 Exhibit 4.4 SECURITIES PURCHASE AGREEMENT THIS SECURITIES PURCHASE AGREEMENT (the “Agreement”), dated as of April 5, 2023, by and between Taysha Gene Therapies, Inc., a Delaware corporation (the “Company”), with its principal place of business at 3000 Pegasus Park Drive, Ste 1430, Dallas, Texas, 75247 and the purchasers named in Schedule 1 hereto (the “Purchaser”) with its principal place o

As filed with the Securities and Exchange Commission on April 5, 2023

S-3 Table of Contents As filed with the Securities and Exchange Commission on April 5, 2023 Registration No.

Form of Warrant to Purchase Common Stock dated April 5, 2023 (incorporated by reference to Exhibit 4.5 to the Company’s Registration Statement on Form S-3 (File No. 333-271144), filed with the Securities Exchange Commission on April 5, 2023).

EX-4.5 Exhibit 4.5 NEITHER THIS SECURITY NOR THE SECURITIES FOR WHICH THIS SECURITY IS EXERCISABLE HAVE BEEN REGISTERED WITH THE SECURITIES AND EXCHANGE COMMISSION OR THE SECURITIES COMMISSION OF ANY STATE IN RELIANCE UPON AN EXEMPTION FROM REGISTRATION UNDER THE SECURITIES ACT OF 1933, AS AMENDED (THE “SECURITIES ACT”), AND, ACCORDINGLY, MAY NOT BE OFFERED OR SOLD EXCEPT PURSUANT TO AN EFFECTIVE

Filing Fee Table

EX-FILING FEES Exhibit 107 Calculation of Filing Fee Tables Form S-3 (Form Type) Taysha Gene Therapies, Inc.

Common Stock

424B5 Filed Pursuant to Rule 424(b)(5) Registration No. 333-260069 PROSPECTUS SUPPLEMENT (To Prospectus dated October 14, 2021) $22,356,446 Common Stock This prospectus supplement (this “Supplement”) amends and supplements the information in our prospectus, dated October 14, 2021 (the “Base Prospectus”), the shelf registration statement on Form S-3 of which the Prospectus (as defined below) is a p

Power of Attorney (included on the signature page of this Form S-8).

S-8 As filed with the Securities and Exchange Commission on March 28, 2023 Registration No.

Executive Separation Agreement, effective as of March 7, 2022, by and between the Company and RA Session II (incorporated by reference to Exhibit 10.25 to the Company’s Annual Report on Form 10-K (File No. 001-39536), filed with the Securities and Exchange Commission on March 28, 2023).

Exhibit 10.25 Taysha Gene Therapies, Inc. March 7, 2023 RA Session II Dear RA: This letter sets forth the substance of the separation agreement (the “Agreement”) that Taysha Gene Therapies, Inc. (“Taysha” or the “Company”) is offering to you to aid in your employment transition. 1. Separation. You acknowledge and agree that your employment termination from the Company occurred on December 16, 2022

Filing Fee Table

Exhibit 107 CALCULATION OF FILING FEE TABLES Form S-8 Taysha Gene Therapies, Inc. Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount to be Registered (1) Proposed Maximum Offering Price Per Share Proposed Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Equity Common stock, $0.00001 par value per share, reserved for future issuan

Executive Employment Agreement, effective as of December 30, 2022, by and between the Company and Sean Nolan (incorporated by reference to Exhibit 10.23 to the Company’s Annual Report on Form 10-K (File No. 001-39536), filed with the Securities and Exchange Commission on March 28, 2023).

Exhibit 10.23 Taysha Gene Therapies, Inc. December 30, 2022 Sean Nolan Re: Offer of Employment Dear Sean: Taysha Gene Therapies, Inc. (the “Company”) is pleased to offer you employment in the position of Chief Executive Officer (“CEO”) on the terms and conditions set forth in this letter agreement (the “Agreement”). 1. Employment by the Company. Your employment with the Company began on December 1

Form 10-K

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, 2022 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.

Taysha Gene Therapies Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update Initiated screening of first potential subject in Phase 1/2 REVEAL trial in Rett syndrome; dosing of first adult patient with TSHA-102 exp

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Reports Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update Initiated screening of first potential subject in Phase 1/2 REVEAL trial in Rett syndrome; dosing of first adult patient with TSHA-102 expected in H1 2023; submitted protocol amendment to allow for younger patients; initial available Phase 1/2 clinical data, primaril

Executive Employment Agreement, effective as of December 30, 2022, by and between the Company and Sukumar Nagendran (incorporated by reference to Exhibit 10.24 to the Company's Annual Report on Form 10-K (File No. 001-39536), filed with the Securities and Exchange Commission on March 28, 2023.

Exhibit 10.24 Taysha Gene Therapies, Inc. December 30, 2022 Sukumar Nagendran, M.D. Re: Offer of Employment Dear Sukumar: Taysha Gene Therapies, Inc. (the “Company”) is pleased to offer you employment in the position of President and Head of Research and Development on the terms and conditions set forth in this letter agreement (the “Agreement”). 1. Employment by the Company. Your employment with

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): March 28, 2023 Taysha Gene Therap

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): March 28, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commiss

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K/A CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): December 16, 2022 Taysha Gene T

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K/A CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): December 16, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Co

Taysha Gene Therapies Provides Update on TSHA-120 Program in Giant Axonal Neuropathy and a 2023 Corporate Outlook Type B end-of-Phase 2 meeting with U.S. Food and Drug Administration (FDA) provided additional clarity for TSHA-120 for the treatment of

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Provides Update on TSHA-120 Program in Giant Axonal Neuropathy and a 2023 Corporate Outlook Type B end-of-Phase 2 meeting with U.S. Food and Drug Administration (FDA) provided additional clarity for TSHA-120 for the treatment of giant axonal neuropathy (GAN) ultra-rare disease program - FDA acknowledged MFM32 as an acceptable endpoint with a recommendatio

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 31, 2023 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 31, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 12, 2023 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 12, 2023 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commi

Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K/A (Amendment No. 1) CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): December 16, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of

Departure of Directors or Certain Officers; Election of Directors; Appointment of Certain Officers; Compensatory Arrangements of Certain Officers, Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): December 16, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Comm

Taysha Gene Therapies Announces Executive Leadership Changes Chair of the Board of Directors, Sean P. Nolan, appointed Chief Executive Officer Board Director, Sukumar Nagendran, M.D., appointed President and Head of R&D

Exhibit 99.1 Taysha Gene Therapies Announces Executive Leadership Changes Chair of the Board of Directors, Sean P. Nolan, appointed Chief Executive Officer Board Director, Sukumar Nagendran, M.D., appointed President and Head of R&D Dallas ? December 16, 2022 - Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric, pivotal-stage gene therapy company focused on developing and commercializin

Taysha Gene Therapies Reports Third Quarter 2022 Financial Results and Provides Corporate Update $50 million strategic investment from Astellas Pharma to support development of TSHA-120 in giant axonal neuropathy (GAN) and TSHA-102 in Rett syndrome P

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Reports Third Quarter 2022 Financial Results and Provides Corporate Update $50 million strategic investment from Astellas Pharma to support development of TSHA-120 in giant axonal neuropathy (GAN) and TSHA-102 in Rett syndrome Proceeds from follow-on offering along with Astellas strategic investment extends cash runway into first quarter of 2024 Type B en

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 8, 2022 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 8, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 2022 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.

TSHA / Taysha Gene Therapies Inc / Manning Paul B - SC 13D/A Activist Investment

SC 13D/A UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 (Amendment No. 1)* Taysha Gene Therapies, Inc. (Name of Issuer) Common Stock, $0.00001 par value per share (Title of Class of Securities) 877619106 (CUSIP Number) Paul B. Manning c/o PBM Capital Group, LLC 200 Garrett Street, Suite S Charlottesville, VA 22902 (434

JOINT FILING AGREEMENT

Exhibit A EXHIBIT A JOINT FILING AGREEMENT Pursuant to Rule 13d-1(k)(1) promulgated pursuant to the Securities Exchange Act of 1934, as amended, the undersigned agree that the attached Schedule 13D is being filed on behalf of each of the undersigned.

JOINT FILING AGREEMENT

EXHIBIT 4 EXHIBIT 4 JOINT FILING AGREEMENT The undersigned acknowledge and agree that the foregoing statement on Schedule 13D is filed on behalf of each of the undersigned and that all subsequent amendments to this statement on Schedule 13D shall be filed on behalf of each of the undersigned without the necessity of filing additional joint filing statements.

POWER OF ATTORNEY

EXHIBIT 1 EXHIBIT 1 POWER OF ATTORNEY Know all by these presents, that Astellas Pharma Inc.

Power of Attorney (Audentes Therapeutics, Inc.).

EXHIBIT 3 EXHIBIT 3 POWER OF ATTORNEY Know all by these presents, that Audentes Therapeutics, Inc.

POWER OF ATTORNEY

EXHIBIT 2 EXHIBIT 2 POWER OF ATTORNEY Know all by these presents, that Astellas US Holding, Inc.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 (Amendment No. 1) FORM 8-K/A CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 21, 2

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 (Amendment No. 1) FORM 8-K/A CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 21, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of I

TSHA / Taysha Gene Therapies Inc / Audentes Therapeutics, Inc. - SC 13D Activist Investment

SC 13D UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13D Under the Securities Exchange Act of 1934 TAYSHA GENE THERAPIES, INC. (Name of Issuer) Common Stock, par value $0.00001 (Title of Class of Securities) 877619106 (CUSIP Number) Audentes Therapeutics, Inc. 600 California Street 17th Floor San Francisco, CA 94108 Attention: President (415) 818-1005 With a copy

Securities Purchase Agreement, by and between the Company and Astellas, dated October 21, 2022 (incorporated by reference to Exhibit 10.2 to the Company’s Current Report on Form 8-K (File No. 001-39536), filed with the Securities and Exchange Commission on October 31,2022).

EX-10.2 Exhibit 10.2 SECURITIES PURCHASE AGREEMENT THIS SECURITIES PURCHASE AGREEMENT (the “Agreement”), dated as of October 21, 2022, by and between Taysha Gene Therapies, Inc., a Delaware corporation (the “Company”), with its principal place of business at 3000 Pegasus Park Drive, Ste 1430, Dallas, Texas, 75247 and Audentes Therapeutics, Inc. (d/b/a Astellas Gene Therapy) a Delaware corporation

Option Agreement, by and between the Company and Astellas, dated October 21, 2022 (incorporated by reference to Exhibit 10.1 to the Company’s Current Report on Form 8-K (File No. 001-39536), filed with the Securities and Exchange Commission on October 31, 2022).

Exhibit 10.1 CERTAIN INFORMATION HAS BEEN EXCLUDED FROM THIS AGREEMENT (INDICATED BY ?[***]?) BECAUSE TAYSHA GENE THERAPIES, INC. HAS DETERMINED SUCH INFORMATION (I) IS NOT MATERIAL AND (II) WOULD BE COMPETITIVELY HARMFUL IF PUBLICLY DISCLOSED. OPTION AGREEMENT This Option Agreement (this ?Agreement?) is dated as of October 21, 2022 (the ?Effective Date?) by and between Taysha Gene Therapies, Inc.

Registration Rights Agreement, by and between the Company and Astellas, dated October 21, 2022 (incorporated by reference to Exhibit 10.3 to the Company’s Current Report on Form 8-K (File No. 001-39536), filed with the Securities and Exchange Commission on October 31,2022).

EX-10.3 Exhibit 10.3 REGISTRATION RIGHTS AGREEMENT THIS REGISTRATION RIGHTS AGREEMENT (this “Agreement”) is made and entered into as of October 21, 2022, by and between Taysha Gene Therapies, Inc., a Delaware corporation (the “Company”), with its principal place of business at 3000 Pegasus Park Drive, Ste 1430, Dallas Texas, 75247 and Audentes Therapeutics, Inc. (d/b/a Astellas Gene Therapy) a Del

Taysha Announces Pricing of Public Offering of Common Stock

EX-99.1 Exhibit 99.1 Taysha Announces Pricing of Public Offering of Common Stock Dallas – October 26, 2022 (GLOBE NEWSWIRE) — Taysha Gene Therapies, Inc. (Nasdaq: TSHA) (“Taysha”), a patient-centric, pivotal-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS) in both rare and large

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 26, 2022 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 26, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commi

Underwriting Agreement by and between Taysha Gene Therapies, Inc. and Goldman Sachs & Co. LLC, dated October 26, 2022.

EX-1.1 2 d421669dex11.htm EX-1.1 Exhibit 1.1 Taysha Gene Therapies, Inc. Common Stock Underwriting Agreement October 26, 2022 Goldman Sachs & Co. LLC As representative of the several Underwriters named in Schedule I hereto c/o Goldman Sachs & Co. LLC 200 West Street New York, New York 10282-2198 Ladies and Gentlemen: Taysha Gene Therapies, Inc., a Delaware corporation (the “Company”), proposes, su

14,000,000 Shares Common Stock

424B5 Table of Contents Filed Pursuant to Rule 424(b)(5) Registration No. 333-260069 PROSPECTUS SUPPLEMENT (To Prospectus dated October 14, 2021) 14,000,000 Shares Common Stock We are offering 14,000,000 shares of our common stock, par value $0.00001 per share, or the common stock. Our common stock is listed on The Nasdaq Global Select Market under the symbol “TSHA.” The last reported sale price o

Subject to Completion, dated October 25, 2022

424B5 Table of Contents Filed Pursuant to Rule 424(b)(5) Registration No. 333-260069 The information in this preliminary prospectus supplement is not complete and may be changed. This preliminary prospectus supplement and the accompanying prospectus are not an offer to sell the securities and are not soliciting an offer to buy the securities in any jurisdiction where the offer or sale is not permi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 21, 2022 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 21, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commi

Astellas and Taysha Gene Therapies Announce Strategic Investment to Support Development of Taysha’s AAV-based Gene Therapy Programs - Taysha Gene Therapies is an emerging leader in the development of AAV gene therapies; new collaboration aimed at enh

EX-99.1 Exhibit 99.1 Press Release Astellas and Taysha Gene Therapies Announce Strategic Investment to Support Development of Taysha’s AAV-based Gene Therapy Programs - Taysha Gene Therapies is an emerging leader in the development of AAV gene therapies; new collaboration aimed at enhancing development of two of Taysha’s novel product candidates for rare monogenic central nervous system diseases w

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 25, 2022 Taysha Gene Ther

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 25, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or other jurisdiction of incorporation) (Commi

Taysha Gene Therapies Announces Proposed Public Offering of Common Stock

EX-99.1 Exhibit 99.1 Taysha Gene Therapies Announces Proposed Public Offering of Common Stock Dallas – October 25, 2022 - Taysha Gene Therapies, Inc. (Nasdaq: TSHA), a patient-centric, pivotal-stage gene therapy company focused on developing and commercializing AAV-based gene therapies for the treatment of monogenic diseases of the central nervous system (CNS) in both rare and large patient popula

Regulation FD Disclosure

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of The Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): September 9, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Comm

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 2022 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.

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 11, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commis

Taysha Gene Therapies Reports Second Quarter 2022 Financial Results and Provides Corporate Update TSHA-120 treated patients in GAN demonstrated durable improvement and recoverability of sensory nerve amplitude potential (SNAP), a definitive clinical

Exhibit 99.1 Taysha Gene Therapies Reports Second Quarter 2022 Financial Results and Provides Corporate Update TSHA-120 treated patients in GAN demonstrated durable improvement and recoverability of sensory nerve amplitude potential (SNAP), a definitive clinical endpoint, compared to natural history TSHA-120 commercial grade and clinical trial material considered comparable across all key quality

Submission of Matters to a Vote of Security Holders

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 17, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissi

Taysha Gene Therapies Reports First Quarter 2022 Financial Results and Provides Corporate Update Initiated clinical development of TSHA-102 for Rett Syndrome under recently approved Clinical Trial Application (CTA) with preliminary Phase 1/2 data exp

Exhibit 99.1 Taysha Gene Therapies Reports First Quarter 2022 Financial Results and Provides Corporate Update Initiated clinical development of TSHA-102 for Rett Syndrome under recently approved Clinical Trial Application (CTA) with preliminary Phase 1/2 data expected by year-end 2022 Received Orphan Drug Designation from the European Commission for TSHA-120 for giant axonal neuropathy (GAN) and r

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 16, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissio

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 2022 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.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.)

Table of Contents UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 14A Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.) Filed by the Registrant ? Filed by a Party other than the Registrant ? Check the appropriate box: ? Preliminary Proxy Statement ? Confidential, for Use of the Commission Only (as permitted by Rule 14a

SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No. )

SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): March 31, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commiss

Amendment No. 1 to Sales Agreement, dated March 30, 2022, by and among the Company, Goldman Sachs & Co. LLC, SVB Securities LLC and Wells Fargo Securities, LLC (incorporated by reference to Exhibit 10.19 to the Company's Annual Report on Form 10-K (File No. 001-39536), filed with the Securities and Exchange Commission on March 31, 2022).

Exhibit 10.19 TAYSHA GENE THERAPIES, INC. AMENDMENT NO. 1 TO SALES AGREEMENT March 30, 2022 GOLDMAN SACHS & CO. LLC 200 West Street New York, New York 10282 WELLS FARGO SECURITIES, LLC 30 Hudson Yards New York, New York 10001 SVB SECURITIES LLC 1301 Avenue of the Americas, 12th Floor New York, New York 10019 Ladies and Gentlemen: Reference is made to the Sales Agreement, dated October 5, 2021 (the

First Amendment to Lease Agreement, dated December 14, 2021, by and between Pegasus Park, LLC and the Company (incorporated by reference to Exhibit 10.18 to the Company's Annual Report on Form 10-K (File No. 001-39536), filed with the Securities and Exchange Commission on March 31, 2022).

Exhibit 10.18 FIRST AMENDMENT TO LEASE AGREEMENT This First Amendment to Lease Agreement (this "Amendment") is executed as of December 14, 2021, between PEGASUS PARK, LLC, a Delaware limited liability company ("Landlord"), f/k/a Pegasus Place, LLC, and TAYSHA GENE THERAPIES, INC., a Delaware corporation ("Tenant"), for the purpose of amending the Lease (defined below). Capitalized terms used but n

As filed with the Securities and Exchange Commission on March 31, 2022

As filed with the Securities and Exchange Commission on March 31, 2022 Registration No.

Filing Fee Table

Exhibit 107 CALCULATION OF FILING FEE TABLES Form S-8 Taysha Gene Therapies, Inc. Table 1: Newly Registered Securities Security Type Security Class Title Fee Calculation Rule Amount to be Registered (1) Proposed Maximum Offering Price Per Share Proposed Maximum Aggregate Offering Price Fee Rate Amount of Registration Fee Equity Common stock, $0.00001 par value per share, reserved for future issuan

Taysha Gene Therapies Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Corporate Update Strategic pipeline prioritization initiatives focused on giant axonal neuropathy (GAN), with feedback on registration pathway by mid-2022,

Exhibit 99.1 Taysha Gene Therapies Reports Fourth Quarter and Full Year 2021 Financial Results and Provides Corporate Update Strategic pipeline prioritization initiatives focused on giant axonal neuropathy (GAN), with feedback on registration pathway by mid-2022, and Rett syndrome, with preliminary clinical data expected by year-end 2022 under recently approved Clinical Trial Application (CTA) Ret

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-K

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.

Common Stock

Filed Pursuant to Rule 424(b)(5) Registration No. 333-260069 Supplement dated March 30, 2022 To Prospectus Supplement dated October 14, 2021 To Prospectus dated October 14, 2021 $150,000,000 Common Stock This supplement (this ?Supplement?) supplements the prospectus supplement, dated October 14, 2021 (the ?Prospectus Supplement?), relating to the offer and sale of shares of common stock, par value

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 31, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commi

Taysha Gene Therapies Reports Positive Clinical Efficacy and Safety Data for High Dose Cohort and Long-term Durability Data for TSHA-120 in Giant Axonal Neuropathy Efficacy data for high dose cohort demonstrated clinically meaningful and statisticall

Exhibit 99.1 Taysha Gene Therapies Reports Positive Clinical Efficacy and Safety Data for High Dose Cohort and Long-term Durability Data for TSHA-120 in Giant Axonal Neuropathy Efficacy data for high dose cohort demonstrated clinically meaningful and statistically significant improvement in MFM32 by Year 1 compared to natural history (n=3) Long-term durability data across all therapeutic dose coho

Taysha Gene Therapies Announces Positive Initial Biomarker Data For TSHA-101, the First Bicistronic Gene Therapy in Clinical Development, Demonstrating Normalization of ß-Hexosaminidase A Enzyme Activity in Patients with GM2 Gangliosidosis Patient 1

Exhibit 99.1 Taysha Gene Therapies Announces Positive Initial Biomarker Data For TSHA-101, the First Bicistronic Gene Therapy in Clinical Development, Demonstrating Normalization of ?-Hexosaminidase A Enzyme Activity in Patients with GM2 Gangliosidosis Patient 1 with Sandhoff disease realized normalization of Hex A enzyme activity by Month 1, achieving 58-fold above the presumed asymptomatic level

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): January 27, 2022 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commi

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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, 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.

Taysha Gene Therapies Reports Third Quarter 2021 Financial Results and Provides Corporate Update Anticipate clinical safety and MFM32 functional data for TSHA-120 from the highest dose cohort of 3.5x1014 total vg in GAN in December 2021 Expect prelim

Exhibit 99.1 Taysha Gene Therapies Reports Third Quarter 2021 Financial Results and Provides Corporate Update Anticipate clinical safety and MFM32 functional data for TSHA-120 from the highest dose cohort of 3.5x1014 total vg in GAN in December 2021 Expect preliminary clinical safety data and Hex A enzyme activity in the plasma and cerebral spinal fluid for TSHA-101 in GM2 gangliosidosis in Decemb

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): November 10, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Comm

TAYSHA GENE THERAPIES, INC. 3000 Pegasus Park Drive Suite 1430 Dallas, Texas 75247

CORRESP 1 filename1.htm TAYSHA GENE THERAPIES, INC. 3000 Pegasus Park Drive Suite 1430 Dallas, Texas 75247 October 12, 2021 Via EDGAR U.S. Securities and Exchange Commission Division of Corporation Finance 100 F Street, N.E. Washington, D.C. 20549 Attn: Jane Park Re: Taysha Gene Therapies, Inc. Registration Statement on Form S-3 (File No. 333-260069) Request for Acceleration of Effective Date Ms.

As filed with the Securities and Exchange Commission on October 5, 2021

Table of Contents As filed with the Securities and Exchange Commission on October 5, 2021 Registration No.

Taysha Announces Exclusive Option from UTSW to License Worldwide Rights to Clinical-Stage AAV9 Gene Therapy Program for CLN7 Disease, a Research Collaboration with UTSW to Develop Next-Generation Construct for CLN7 and a Grant Award to Batten Hope CL

Exhibit 99.1 Taysha Announces Exclusive Option from UTSW to License Worldwide Rights to Clinical-Stage AAV9 Gene Therapy Program for CLN7 Disease, a Research Collaboration with UTSW to Develop Next-Generation Construct for CLN7 and a Grant Award to Batten Hope CLN7 program currently in Phase 1 clinical proof-of-concept trial with preliminary data anticipated by year-end 2021 Intrathecal dosing of

Sales Agreement, dated as of October 5, 2021, by and among the Registrant, SVB Leerink LLC and Wells Fargo Securities, LLC (incorporated by reference to Exhibit 1.2 to the Company’s Registration Statement on Form S-3 (File No. 333-260069), filed with the Securities and Exchange Commission on October 5, 2021).

Exhibit 1.2 Taysha Gene Therapies, Inc. Shares of Common Stock ($0.00001 par value per share) SALES AGREEMENT October 5, 2021 SVB LEERINK LLC 1301 Avenue of the Americas, 12th Floor New York, New York 10019 WELLS FARGO SECURITIES, LLC 30 Hudson Yards New York, New York 10001 Ladies and Gentlemen: Taysha Gene Therapies, Inc., a Delaware corporation (the ?Company?), confirms its agreement (this ?Agr

Form of Indenture, between the Registrant and one or more trustees to be named.

Exhibit 4.2 TAYSHA GENE THERAPIES, INC., Issuer AND [TRUSTEE], Trustee INDENTURE Dated as of [?], 20 Debt Securities TABLE OF CONTENTS PAGE ARTICLE 1 DEFINITIONS 1 Section 1.01 Definitions of Terms 1 ARTICLE 2 ISSUE, DESCRIPTION, TERMS, EXECUTION, REGISTRATION AND EXCHANGE OF SECURITIES 5 Section 2.01 Designation and Terms of Securities 5 Section 2.02 Form of Securities and Trustee?s Certificate 8

Form of Preferred Stock Warrant Agreement and Warrant Certificate.

Exhibit 4.5 TAYSHA GENE THERAPIES, INC. AND , AS WARRANT AGENT FORM OF PREFERRED STOCK WARRANT AGREEMENT DATED AS OF TAYSHA GENE THERAPIES, INC. FORM OF PREFERRED STOCK WARRANT AGREEMENT THIS PREFERRED STOCK WARRANT AGREEMENT (this ?Agreement?), dated as of [?], between TAYSHA GENE THERAPIES, INC., a Delaware corporation (the ?Company?), and [?], a [corporation] [national banking association] orga

Form of Debt Securities Warrant Agreement and Warrant Certificate.

Exhibit 4.6 TAYSHA GENE THERAPIES, INC. AND , AS WARRANT AGENT FORM OF DEBT SECURITIES WARRANT AGREEMENT DATED AS OF TAYSHA GENE THERAPIES, INC. FORM OF DEBT SECURITIES WARRANT AGREEMENT THIS DEBT SECURITIES WARRANT AGREEMENT (this ?Agreement?), dated as of [?], between TAYSHA GENE THERAPIES, INC., a Delaware corporation (the ?Company?), and [?], a [corporation] [national banking association] orga

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): October 5, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commis

Form of Common Stock Warrant Agreement and Warrant Certificate.

Exhibit 4.4 TAYSHA GENE THERAPIES, INC. AND , AS WARRANT AGENT FORM OF COMMON STOCK WARRANT AGREEMENT DATED AS OF TAYSHA GENE THERAPIES, INC. FORM OF COMMON STOCK WARRANT AGREEMENT THIS COMMON STOCK WARRANT AGREEMENT (this ?Agreement?), dated as of [?], between TAYSHA GENE THERAPIES, INC., a Delaware corporation (the ?Company?), and [?], a [corporation] [national banking association] organized and

TSHA / Taysha Gene Therapies Inc / UNIVERSITY OF TEXAS/TEXAS AM INVESTMENT MANAGMENT CO Passive Investment

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 SCHEDULE 13G Under the Securities Exchange Act of 1934 Amendment No. 1 TAYSHA GENE THERAPIES, INC. (Name of Issuer) Common Stock, par value $0.00001 per share (Title of Class of Securities) 877619106 (CUSIP Number) September 22, 2021 (Date of Event Which Requires Filing of this Statement) Check the appropriate box to designate

Loan and Security Agreement, dated August 12, 2021, by and among the Company, the lenders party thereto from time to time and Silicon Valley Bank, as administrative agent and collateral agent.

Exhibit 10.2 LOAN AND SECURITY AGREEMENT This LOAN AND SECURITY AGREEMENT (this ?Agreement?) dated and effective as of August 12, 2021 (the ?Effective Date?) among (a) SILICON VALLEY BANK, a California corporation (?SVB?), in its capacity as administrative agent and collateral agent (?Agent?), (b) SVB, as a lender, (c) SVB INNOVATION CREDIT FUND VIII, L.P., a Delaware limited partnership (?SVB Cap

Regulation FD Disclosure, Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): August 16, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commis

Lease Agreement, dated January 11, 2021, by and between Pegasus Place, LLC and the Company.

Exhibit 10.1 LEASE AGREEMENT BETWEEN PEGASUS PARK, LLC, AS LANDLORD, AND TAYSHA GENE THERAPIES, INC., AS TENANT DATED January 8, 2021 3000 Pegasus park drive dallas, TEXAS BASIC LEASE INFORMATION Lease Date: January 8, 2021 Landlord: Pegasus Park, LLC, a Delaware limited liability company Tenant: Taysha Gene Therapies, Inc., a Delaware corporation Premises: Suite No. 1430, containing approximately

Taysha Gene Therapies Reports Second Quarter 2021 Financial Results and Provides Corporate Update Positive pre-IND/CTA feedback obtained from several key regulatory agencies for TSHA-102 in Rett syndrome, TSHA-101 in GM2 gangliosidosis and TSHA-118 i

Exhibit 99.1 Taysha Gene Therapies Reports Second Quarter 2021 Financial Results and Provides Corporate Update Positive pre-IND/CTA feedback obtained from several key regulatory agencies for TSHA-102 in Rett syndrome, TSHA-101 in GM2 gangliosidosis and TSHA-118 in CLN1 disease, paving the way for multiple anticipated IND/CTA filings in the second half of 2021 Entered into a non-dilutive term loan

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, DC 20549 FORM 10-Q

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.

Taysha Gene Therapies Secures up to $100 Million Non-Dilutive Term Loan Financing Financing strengthens balance sheet, furthers financial and operational flexibility and lowers overall cost of capital No financial covenants and no warrants issued in

Exhibit 99.2 Taysha Gene Therapies Secures up to $100 Million Non-Dilutive Term Loan Financing Financing strengthens balance sheet, furthers financial and operational flexibility and lowers overall cost of capital No financial covenants and no warrants issued in connection with non-dilutive financing Full drawdown expected to extend cash runway to support key value-creating milestones including av

Regulation FD Disclosure, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 29, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissi

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 s

RESEARCH & DEVELOPMENT DAY DAY 2 ? June 29, 2021 | 9:00 AM ? 12:00 PM CT ? Bringing New Cures to Life Exhibit 99.

Regulation FD Disclosure, Financial Statements and Exhibits

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 28, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissi

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 s

RESEARCH & DEVELOPMENT DAY DAY 1 ? June 28, 2021 | 9:00 AM ? 12:00 PM CT ? Bringing New Cures to Life Exhibit 99.

Submission of Matters to a Vote of Security Holders

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): June 17, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissi

Taysha Gene Therapies Reports First Quarter 2021 Financial Results and Provides a Corporate Update TSHA-120 program demonstrated clear arrest of disease progression and long-term durability at therapeutic dose levels in patients with giant axonal neu

Exhibit 99.1 Taysha Gene Therapies Reports First Quarter 2021 Financial Results and Provides a Corporate Update TSHA-120 program demonstrated clear arrest of disease progression and long-term durability at therapeutic dose levels in patients with giant axonal neuropathy (GAN); Expects clinical data from highest dose cohort in second half of 2021 and regulatory feedback from agencies by year-end 20

Quarterly Report - 10-Q

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, 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.

Financial Statements and Exhibits, Results of Operations and Financial Condition

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): May 11, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissio

- S-8

As filed with the U.S. Securities and Exchange Commission on May 11, 2021 Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-8 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Taysha Gene Therapies, Inc. (Exact name of Registrant as specified in its charter) Delaware 84-3199512 (State or other jurisdiction of incorporation or organization) (

Schedule 14A

Table of Contents SCHEDULE 14A INFORMATION Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934 (Amendment No.

Taysha Gene Therapies Announces New Data on Multiple Preclinical Programs and Upcoming R&D Day TSHA-113 significantly reduced tau mRNA and protein levels in mouse models of human tauopathies via cerebral spinal fluid (CSF) delivery supporting further

Exhibit 99.2 Taysha Gene Therapies Announces New Data on Multiple Preclinical Programs and Upcoming R&D Day TSHA-113 significantly reduced tau mRNA and protein levels in mouse models of human tauopathies via cerebral spinal fluid (CSF) delivery supporting further preclinical development TSHA-105 significantly reduced plasma citrate levels, normalized EEG brain activity, and reduced the number of s

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 s

Exhibit 99.1 Bringing New Cures to Life Corporate Presentation April 2021 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 positi

Regulation FD Disclosure, Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): April 14, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commiss

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): April 12, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commiss

Taysha Gene Therapies Acquires Exclusive Worldwide Rights to Clinical-Stage AAV9 Gene Therapy Program, Now Known as TSHA-120, for the Treatment of Giant Axonal Neuropathy, a Rare and Severe Neurodegenerative Disease Program invented in the lab of Dr.

Exhibit 99.1 Taysha Gene Therapies Acquires Exclusive Worldwide Rights to Clinical-Stage AAV9 Gene Therapy Program, Now Known as TSHA-120, for the Treatment of Giant Axonal Neuropathy, a Rare and Severe Neurodegenerative Disease Program invented in the lab of Dr. Steven Gray, Taysha?s Chief Scientific Advisor, immediately transforms Taysha into a sustainable pivotal-stage gene therapy company Clin

Financial Statements and Exhibits, Other Events

UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): March 9, 2021 Taysha Gene Therapies, Inc. (Exact name of registrant as specified in its Charter) Delaware 001-39536 84-3199512 (State or Other Jurisdiction of Incorporation) (Commissi

Taysha Gene Therapies Announces Collaboration to Advance Next-Generation Mini-Gene Payloads for an AAV Gene Therapy for the Treatment of Neurodevelopmental Disorders Taysha to have an exclusive option on new payloads, constructs, and intellectual pro

Exhibit 99.1 Taysha Gene Therapies Announces Collaboration to Advance Next-Generation Mini-Gene Payloads for an AAV Gene Therapy for the Treatment of Neurodevelopmental Disorders Taysha to have an exclusive option on new payloads, constructs, and intellectual property arising from research conducted under the agreement Agreement leverages Taysha?s existing partnership with UT Southwestern Gene The