As filed with the Securities and Exchange Commission on March 28, 2023

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)

3000 Pegasus Park Drive

Suite 1430

Dallas, Texas 75247

(Address of principal executive offices, including zip code)

Taysha Gene Therapies, Inc. 2020 Stock Incentive Plan

Taysha Gene Therapies, Inc. 2020 Employee Stock Purchase Plan

(Full titles of the plans)

Sean P. Nolan

Chief Executive Officer

3000 Pegasus Park Drive

Suite 1430

Dallas, Texas 75247

(214) 612-0000

(Name, address and telephone number, including area code, of agent for service)

Copies to:

Divakar Gupta

Madison A. Jones

Brian F. Leaf

Darren DeStefano

Cooley LLP

55 Hudson Yards

New York, NY 10001

Telephone: (212) 479-6000

Facsimile: (212) 479-6275

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act.  ☐

EXPLANATORY NOTE

REGISTRATION OF ADDITIONAL SHARES

Pursuant to General Instruction E of Form S-8, Taysha Gene Therapies, Inc. (the “Registrant”) is filing this Registration Statement on Form S-8 with the Securities and Exchange Commission (the “Commission”) for the purpose of registering (i) 3,160,375 additional shares of its common stock under the Registrant’s 2020 Stock Incentive Plan (the “2020 Plan”), pursuant to the provisions of the 2020 Plan providing for an automatic increase in the number of shares of common stock reserved and available for issuance under the 2020 Plan on January 1, 2023, and (ii) 632,075 additional shares of its common stock under the Registrant’s 2020 Employee Stock Purchase Plan (the “2020 ESPP,” and together with the 2020 Plan the “Plans”), pursuant to the provisions of the 2020 ESPP providing for an automatic increase in the number of shares of common stock reserved and available for issuance under the 2020 ESPP on January 1, 2023. In accordance with the instructional note to Part I of Form S-8 as promulgated by the Commission, the information specified by Part I of the Form S-8 has been omitted from this Registration Statement.

The Registrant previously registered shares of its common stock for issuance under the Plans on a Registration Statement on Form S-8 filed with the Commission on September 29, 2020 (File No.  333-249130), a Registration Statement on Form S-8 filed with the Commission on May 11, 2021 (File No. 333-256013) and a Registration Statement on Form S-8 filed with the Commission on March 31, 2022 (File No. 333-264025). Pursuant to General Instruction E to Form S-8, this Registration Statement hereby incorporates by reference the contents of the Registration Statements referenced above except as set forth below.

PART II

INFORMATION REQUIRED IN REGISTRATION STATEMENT

ITEM 3. INCORPORATION OF DOCUMENTS BY REFERENCE

The following documents filed by the Registrant with the Commission are incorporated by reference into this Registration Statement:

ITEM 8. EXHIBITS

SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, the Registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this Registration Statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Dallas, State of Texas, on this 28^th day of March, 2023.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Sean P. Nolan and Kamran Alam, and each one of them, as his or her true and lawful attorneys-in-fact and agents, with full power of substitution and resubstitution, for him or her and in their name, place or stead, in any and all capacities, to sign any and all amendments (including post-effective amendments) to this registration statement, and to file the same, with all exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents or any of them, or his or her substitute or substitutes, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act of 1933, this Registration Statement has been signed by the following persons in the capacities and on the dates indicated.

Exhibit 5.1

Madison A. Jones

T: +1 202 728 7087

madison.jones@cooley.com

March 28, 2023

Taysha Gene Therapies, Inc.

3000 Pegasus Park Drive, Suite 1430

Dallas, Texas, 75247

We have represented Taysha Gene Therapies, Inc., a Delaware corporation (the “Company”), in connection with the filing by the Company of a Registration Statement on Form S-8 (the “Registration Statement”) with the Securities and Exchange Commission (the “Commission”) covering the offering of up to 3,792,450 shares (the “Shares”) of the Company’s common stock, par value $0.00001 per share (“Common Stock”), consisting of (a) 3,160,375 shares of Common Stock issuable pursuant to the Company’s 2020 Stock Incentive Plan (the “SIP”) and (b) 632,075 shares of Common Stock pursuant to the Company’s 2020 Employee Stock Purchase Plan (together with the SIP, the “Plans”).

In connection with this opinion, we have examined and relied upon (a) the Registration Statement and the related prospectuses, (b) the Company’s certificate of incorporation and bylaws, each as currently in effect, (c) the Plans and (d) originals or copies certified to our satisfaction of such records, documents, certificates, memoranda and other instruments as in our judgment are necessary or appropriate to enable us to render the opinion expressed below. We have assumed the genuineness of all signatures, the authenticity of all documents submitted to us as originals, the conformity to originals of all documents submitted to us as copies, the accuracy, completeness and authenticity of certificates of public officials, and the due authorization, execution and delivery of all documents by all persons other than the Company where authorization, execution and delivery are prerequisites to the effectiveness thereof. As to certain factual matters, we have relied upon a certificate of an officer of the Company and have not independently verified such matters.

Our opinion is expressed only with respect to the General Corporation Law of the State of Delaware. We express no opinion to the extent that any other laws are applicable to the subject matter hereof and express no opinion and provide no assurance as to compliance with any federal or state securities law, rule or regulation.

On the basis of the foregoing, and in reliance thereon, we are of the opinion that the Shares, when sold and issued in accordance with the Plans, the Registration Statement and the related prospectuses, will be validly issued, fully paid and nonassessable (except as to Shares issued pursuant to deferred payment arrangements, which will be fully paid and nonassessable when such deferred payments are made in full).

Cooley LLP    1299 Pennsylvania Avenue NW    Suite 700    Washington, DC    20004-2400

t: +1 202 842 7800 f: +1 202 842 7899 cooley.com

We consent to the filing of this opinion as an exhibit to the Registration Statement. In giving such consent, we do not thereby admit that we are in the category of persons whose consent is required under Section 7 of the Securities Act of 1933, as amended, or the rules and regulations of the Commission thereunder.

Sincerely,

Cooley LLP    1299 Pennsylvania Avenue NW    Suite 700    Washington, DC    20004-2400

t: +1 202 842 7800 f: +1 202 842 7899 cooley.com

Exhibit 23.2

CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

We consent to the incorporation by reference in this Registration Statement on Form S-8 of our report dated March 28, 2023, relating to the financial statements of Taysha Gene Therapies, Inc. appearing in the Annual Report on Form 10-K of Taysha Gene Therapies, Inc. for the year ended December 31, 2022.

/s/ Deloitte & Touche LLP

Dallas, Texas

March 28, 2023

Exhibit 107

CALCULATION OF FILING FEE TABLES

Form S-8

Taysha Gene Therapies, Inc.

Table 1: Newly Registered Securities