# EDGAR Filing Document

**Accession Number:** 0001806310
**File Stem:** 0001193125-26-276738
**Filing Date:** 2026-6
**Character Count:** 55603
**Document Hash:** a1b7eded2fafe7ceaf3fe8bab543f51d
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001193125-26-276738.hdr.sgml**: 20260622

**ACCESSION NUMBER**: 0001193125-26-276738

**CONFORMED SUBMISSION TYPE**: 8-K

**PUBLIC DOCUMENT COUNT**: 41

**CONFORMED PERIOD OF REPORT**: 20260622

**ITEM INFORMATION**: Regulation FD Disclosure

**ITEM INFORMATION**: Other Events

**ITEM INFORMATION**: Financial Statements and Exhibits

**FILED AS OF DATE**: 20260622

**DATE AS OF CHANGE**: 20260622

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** Taysha Gene Therapies, Inc.
- **CENTRAL INDEX KEY:** 0001806310
- **STANDARD INDUSTRIAL CLASSIFICATION:** BIOLOGICAL PRODUCTS (NO DIAGNOSTIC SUBSTANCES) [2836]
- **ORGANIZATION NAME:** 03 Life Sciences
- **EIN:** 843199512
- **STATE OF INCORPORATION:** DE
- **FISCAL YEAR END:** 1231

**FILING VALUES:**
- **FORM TYPE:** 8-K
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 001-39536
- **FILM NUMBER:** 261105007

**BUSINESS ADDRESS:**
- **STREET 1:** 3000 PEGASUS PARK DRIVE
- **STREET 2:** SUITE 1430
- **CITY:** DALLAS
- **STATE:** TX
- **ZIP:** 75247
- **BUSINESS PHONE:** (214) 612-0000

**MAIL ADDRESS:**
- **STREET 1:** 3000 PEGASUS PARK DRIVE
- **STREET 2:** SUITE 1430
- **CITY:** DALLAS
- **STATE:** TX
- **ZIP:** 75247

?xml version='1.0' encoding='ASCII'? 8-K

### 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, 2026

## Taysha Gene Therapies, Inc.

#### (Exact name of registrant as specified in its charter)

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| | | |
|:---|:---|:---|
| **Delaware** | **001-39536** | **84-3199512** |
| **(State or other jurisdiction**<br> **of incorporation)** | **(Commission**<br> **File Number)** | **(IRS Employer**<br> **Identification No.)** |

---

---

| | |
|:---|:---|
| **3000 Pegasus Park Drive, Suite 1430**<br> **Dallas, Texas** | **75247** |
| **(Address of Principal Executive Offices)** | **(Zip Code)** |

---

(214) 612-0000

#### (Registrant's telephone number, including area code)

#### N/A

#### (Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

---

| | | |
|:---|:---|:---|
| **Title of each class** | **Trading<br>Symbol(s)** | **Name of each exchange**<br> **on which registered** |
| Common Stock, $0.00001 par value | TSHA | The Nasdaq Stock Market LLC |

---

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company ☐

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 13(a) of the Exchange Act. ☐

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| | |
|:---|:---|
| **Item 7.01** | **Regulation FD Disclosure.**  |

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On June 22, 2026, Taysha Gene Therapies, Inc. (the "**Company**") issued a press release entitled "Taysha Gene Therapies Announces Completion of Dosing in REVEAL Pivotal Trial and Reports Longer-Term Clinical Data from Part A of REVEAL Phase 1/2 Trials Evaluating TSHA-102 for Rett Syndrome". The press release provides certain clinical and regulatory updates on TSHA-102. The full text of the press release is attached as Exhibit 99.1 to this Current Report on Form 8-K and incorporated herein by reference.

The information in this Item 7.01 of this Current Report on Form 8-K (including Exhibit 99.1) is being furnished and shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the "**Exchange Act**"), or otherwise subject to the liabilities of that Section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.

---

| | |
|:---|:---|
| **Item 8.01** | **Other Events.**  |

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*Clinical and Regulatory Update Presentation* 

On June 22, 2026, the Company also made available a presentation to be used to discuss the clinical and regulatory updates on TSHA-102. A copy of the presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K.

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| | |
|:---|:---|
| **Item 9.01** | **Financial Statements and Exhibits.**  |

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(d) Exhibits

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| | |
|:---|:---|
| **Exhibit**<br> **Number** | **Exhibit Description** |
| 99.1 | [Press Release, dated June 22, 2026.](d20817dex991.htm) |
| 99.2 | [Corporate Presentation, dated June 22, 2026.](d20817dex992.htm) |
| 104 | Cover Page Interactive Data File (the cover page XBRL tags are embedded within the inline XBRL document). |

---

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#### SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

---

| | | |
|:---|:---|:---|
|  |  | **Taysha Gene Therapies, Inc.** |
|  | By: | /s/ Kamran Alam |
| Date: June 22, 2026 |  | Kamran Alam |
|  |  | Chief Financial Officer |

---

## Exhibit 99.1

**Exhibit 99.1** 

**Taysha Gene Therapies Announces Completion of Dosing in REVEAL Pivotal Trial and Reports Longer-** 

**Term Clinical Data from Part A of REVEAL Phase 1/2 Trials Evaluating TSHA-102 for Rett Syndrome** 

*Completed dosing of 17 patients in REVEAL pivotal trial; topline data from 6-month interim* 

*analysis and FDA feedback on next steps toward BLA submission pathway expected 1H 2027* 

*TSHA-102 was generally well-tolerated with no treatment-related SAEs or DLTs reported as of* 

*the June 2026 data cutoff across REVEAL Phase 1/2 and pivotal trials (N=29)* 

*100% of REVEAL Part A patients (N=12, 6-21 years) gained/regained* ≥*one developmental* 

*milestone by 12 months post-TSHA-102, with consistent responses across ages and disease severity* 

*Longer-term follow-up showed a durable and deepening treatment effect* ≥*12 months post-* 

*TSHA-102, with functional gains accumulating over time across core disease domains* 

*310 total functional gains demonstrated* ≥*12 months post-TSHA-102 (~26 per patient),* 

*comprising 31 developmental milestones and 279 additional skill gains/improvements* 

*Robust and clinically meaningful responses at both 6 and* ≥*12 months in REVEAL Part A further* 

*support potential for BLA submission based on REVEAL pivotal trial 6-month interim analysis* 

*Conference call and webcast today at 8:30 AM ET* 

DALLAS, June 22, 2026 — 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 the completion of dosing in the REVEAL pivotal trial and reported positive longer-term clinical data from Part A of the REVEAL Phase 1/2 trials evaluating TSHA-102 for the treatment of Rett syndrome.

"As we advance toward a potential BLA submission for TSHA-102, we remain committed to developing a comprehensive, scientifically rigorous data package informed by our ongoing discussions with the FDA. We are pleased to report the completion of dosing in our REVEAL pivotal trial and positive longer-term follow-up data from our REVEAL Phase 1/2 trials. The data demonstrated early, durable treatment effect across all 12 pediatric, adolescent and adult patients, with responses continuing to deepen over time. On average, patients achieved 26 functional gains across core disease domains that impact activities of daily living at ≥12 months post-treatment, with consistent benefits observed regardless of age or disease severity," said Sean P. Nolan, Chairman and Chief Executive Officer of Taysha.

Mr. Nolan continued, "We believe the robust, clinically meaningful responses observed at both 6 and ≥12 months post-treatment continue to demonstrate the potential for TSHA-102 to transform the treatment paradigm for this devastating disease and further support the potential for a BLA submission based on the six-month interim analysis from our pivotal trial. In early 2027, we plan to engage with the FDA to review the interim data and discuss next steps toward submitting the BLA, with topline results and regulatory feedback expected in the first half of 2027."

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**REVEAL Pivotal Trial and ASPIRE Trial Updates:** 

Completed dosing in the overenrolled REVEAL pivotal trial, with a total of 17 females in the developmental plateau population of Rett syndrome dosed with TSHA-102

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• The single-arm, open-label trial is evaluating a single intrathecal (IT)
administration of high dose TSHA-102 (1x10<sup>15</sup> total vector genomes (vg)) in females with Rett syndrome between the ages of 6 to <22 years. The primary
endpoint will assess response rate, defined as the percentage of patients who gain or regain ≥one of the 28 natural history-defined developmental milestones, with each patient serving as their own control. A response rate of 33% is the minimum
threshold for success sufficient to reject the natural history established null hypothesis of 6.7%

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• TSHA-102 continues to be generally well tolerated, with no
treatment-related serious adverse events (SAEs) or dose-limiting toxicities (DLTs) reported as of the June 2026 data cutoff

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• The interim analysis to support the planned Biologics License Application (BLA) submission is expected to occur
after all 17 patients complete six months of post-treatment follow-up. Subsequently, Taysha plans to discuss data from the 6-month interim analysis and next steps toward
the BLA submission pathway with the FDA in early 2027, with topline data and regulatory feedback anticipated in 1H 2027

ASPIRE trial ongoing with enrollment exceeding the initial target of (N=3); on track to complete dosing of the three patients in Q2 2026 and expect to dose one additional patient in July 2026, further strengthening potential BLA submission for TSHA-102

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• The ASPIRE safety-focused trial is designed to enable a broad label of TSHA-102 for patients aged ≥2 years with Rett syndrome

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Taysha has elected to overenroll the trial to include one additional screened and eligible patient and will now
dose a total of four females with Rett syndrome, aged 2 to <4 years, to evaluate the safety and preliminary efficacy of a single IT administration of high dose TSHA-102 (1x10<sup>15</sup> total vg), scaled to account for the lower brain volume in 2 to <4-year-olds

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• A minimum of three months of ASPIRE safety data will be included in the planned BLA submission, while efficacy in
the 2 to <6-year-old population will be extrapolated from data collected in the REVEAL pivotal trial

**Longer-Term Clinical Data from Part A of the REVEAL Phase 1/2 Adolescent/Adult and Pediatric Trials** 

REVEAL Part A efficacy data based on the May 2026 data cutoff included 12 females with Rett syndrome aged 6-21 years (high dose, n=8; low dose, n=4) treated with the high dose (1x10<sup>15</sup> total vg) or low dose (5.7x10<sup>14</sup> total vg) of TSHA-102, each with ≥12 months of follow-up

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• 100% of patients gained/regained ≥one developmental milestone across the core functional domains of fine
motor, gross motor and communication post-TSHA-102 (i.e., spoke in phrases with meaning, used utensils to eat without assistance, walked with support), as assessed by multiple independent raters through
video-evidenced evaluation

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Longer-term follow-up demonstrated a durable, deepening treatment effect across all patients, with additional
functional gains continuing to accumulate over time through ≥12 months

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Developmental milestone gains increased by 69% from 6 to 12 months and by 94% from 6 to ≥12 months post-TSHA-102

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Patients with longest follow-up at 30 months continued to demonstrate
functional gains

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&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Broad functional impact consistently demonstrated across core disease domains post-TSHA-102 regardless of age, disease severity or genotype

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• ≥12 months post-TSHA-102, a total of 310 functional gains were
observed (~26 per patient), comprising 31 developmental milestones and 279 additional skill gains/improvements

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Robust and clinically meaningful responses at 6 and ≥12 months exceed the FDA-aligned minimum threshold for efficacy and support potential for a BLA submission based on the REVEAL pivotal trial 6-month interim analysis

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Improvements observed across multiple clinician-assessed outcome measures, including Revised Motor Behavior
Assessment (R-MBA), Clinician Global Impression–Improvement (CGI-I) and Clinical Global Impression–Severity (CGI-S) corroborated the functional gains demonstrated

REVEAL Part A safety data based on the May 2026 data cutoff included 12 females with Rett syndrome aged 6-21 years treated with TSHA-102 (high dose, n=8; low dose, n=4), each with ≥12 months of follow-up

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• TSHA-102 has been generally well tolerated with no treatment-related SAEs
or DLTs

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• All treatment-emergent adverse events related to TSHA-102 were mild to
moderate in severity

"Longer-term data from the REVEAL Phase 1/2 trials demonstrate remarkable responses following treatment with TSHA-102, far exceeding what would be expected based on the natural history of patients aged six years and older in the developmental plateau population," said Elsa Rossignol, M.D., FRCP, FAAP, Professor in Neuroscience and Pediatrics at the Université de Montréal, Director of the Rett Multidisciplinary Clinic of the CHU Sainte-Justine and a Principal Investigator of the REVEAL trial. "TSHA-102 consistently drove early, durable functional gains across the core domains of the disease, including communicating with words or phrases, eating with utensils without assistance and walking with support, which continue to accumulate over time. These outcomes support greater independence, reduce caregiver burden and enhance social engagement. I believe this sustained trajectory, combined with a favorable tolerability profile and minimally invasive intrathecal delivery approach, reinforces the potential of TSHA-102 to deliver meaningful improvements for patients and families who continue to face profound unmet need."

**Anticipated Milestones** 

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Completion of dosing in the ASPIRE trial (N=4) is expected in July 2026

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Completion of BLA-enabling Process Performance Qualification (PPQ)
campaign for TSHA-102 is expected in the fourth quarter of 2026

&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;• Topline data from the REVEAL pivotal trial 6-month interim analysis and FDA feedback on the BLA submission
pathway for TSHA-102 is expected in the first half of 2027

**Conference Call and Webcast Information** 

Taysha management will host a live conference call and webcast today at 8:30 a.m. ET to discuss the longer-term data from the REVEAL Phase 1/2 trials. Participants may access the live webcast of the conference call by visiting Taysha's <u>website</u>.

**About TSHA-102** 

TSHA-102 is a self-complementary intrathecally delivered AAV9 investigational gene transfer therapy in clinical evaluation for Rett syndrome. Designed as a one-time treatment, TSHA-102 aims to address the genetic root cause of the disease by delivering a functional form of *MECP2* to cells in the CNS. TSHA-102 utilizes a novel miRNA-Responsive Auto-Regulatory Element (miRARE) technology designed to mediate

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levels of *MECP2* in the CNS on a cell-by-cell basis without risk of overexpression. TSHA-102 has received Breakthrough Therapy, Regenerative Medicine Advanced Therapy, Fast Track and Orphan Drug and Rare Pediatric Disease designations from the FDA, Orphan Drug designation from the European Commission and Innovative Licensing and Access Pathway designation from the Medicines and Healthcare products Regulatory Agency.

**About Rett Syndrome** 

Rett syndrome is a rare neurodevelopmental disorder caused by mutations in the X-linked *MECP2* gene encoding methyl CpG-binding protein 2 (MeCP2), which is essential for regulating neuronal and synaptic function in the brain. The disorder is characterized by loss of communication and hand function, slowing and/or regression of development, motor and respiratory impairment, seizures, intellectual disabilities and shortened life expectancy. Rett syndrome progression is divided into four key stages, beginning with early onset stagnation at 6 to 18 months of age followed by rapid regression, plateau and late motor deterioration. Rett syndrome primarily occurs in females and is one of the most common genetic causes of severe intellectual disability. Currently, there are no approved disease-modifying therapies that treat the genetic root cause of the disease. Rett syndrome caused by a pathogenic/likely pathogenic *MECP2* mutation is estimated to affect between 15,000 and 20,000 patients in the U.S., EU, and U.K.

**About Taysha Gene Therapies** 

Taysha Gene Therapies (Nasdaq: TSHA) is a clinical-stage biotechnology company focused on advancing adeno-associated virus (AAV)-based gene therapies for severe monogenic diseases of the central nervous system. Its lead clinical program TSHA-102 is in development for Rett syndrome, a rare neurodevelopmental disorder with no approved disease-modifying therapies that address the genetic root cause of the disease. With a singular focus on developing transformative medicines, Taysha aims to address severe unmet medical needs and dramatically improve the lives of patients and their caregivers. The Company's management team has proven experience in gene therapy development and commercialization. Taysha leverages this experience, its manufacturing process and a clinically and commercially proven AAV9 capsid in an effort to rapidly translate treatments from bench to bedside. For more information, please visit <u>www.tayshagtx.com</u>.

**Forward-Looking Statements** 

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Words such as "anticipates," "believes," "expects," "intends," "projects," "plans," and "future" or similar expressions are intended to identify forward-looking statements. Forward-looking statements include, but are not limited to, statements concerning the potential of TSHA-102 and Taysha's other product candidates to positively impact quality of life and alter the course of disease in the patients Taysha seeks to treat, Taysha's research, development and regulatory plans for its product candidates, communications with the FDA, including with respect to the BLA for TSHA-102, the potential for Taysha's product candidates to receive regulatory approval from the FDA or equivalent foreign regulatory agencies, and whether, if approved, these product candidates will be successfully distributed and marketed and the potential market opportunity for Taysha's product candidates, including anticipated clinician and caregiver demand. Forward-looking statements are based on management's current expectations and are subject to various risks and uncertainties that could cause actual results to differ materially and adversely from those expressed or implied by such forward-looking statements. Accordingly, these forward-looking statements do not constitute guarantees of future performance, and you are cautioned not to place undue reliance on these forward-looking statements. Risks regarding Taysha's business are described in detail in Taysha's Securities and Exchange

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Commission ("SEC") filings, including in our Annual Report on Form 10-K for the full-year ended December 31, 2025, which are available on the SEC's website at <u>www.sec.gov</u>. Additional information will be made available in other filings that Taysha makes from time to time with the SEC. These forward-looking statements speak only as of the date hereof, and Taysha disclaims any obligation to update these statements except as may be required by law.

**Company Contact:** 

Hayleigh Collins

Senior Director, Corporate Communications and Investor Relations

Taysha Gene Therapies, Inc.

<u>hcollins@tayshagtx.com</u>

**Media Contact:**

Carolyn Hawley

Inizio Evoke

<u>Carolyn.hawley@inizioevoke.com</u>

## Exhibit 99.2

![Slide 1](g20817ex99_2s1g1.jpg)

TSHA-102 Rett Syndrome program Update: Longer-term Results from REVEAL Phase 1/2 trials June 2026 Exhibit 99.2

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![Slide 2](g20817ex99_2s2g1.jpg)

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 regarding the potential of TSHA-102, the durability and reproducibility of the clinical data from the REVEAL trials, the anticipated Part B trial design, our research, development and regulatory plans, and our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "might," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are subject to a number of risks, uncertainties and assumptions. Risks regarding our business are described in detail in our Securities and Exchange Commission filings, including in our Annual Report on Form 10-K for the year ended December 31, 2025, our Quarterly Report on Form 10-Q for the quarter ended March 31, 2026, and our other filings with the SEC, which are available on the SEC's website at www.sec.gov. We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. The forward-looking statements contained in this presentation reflect our current views with respect to future events, and we assume no obligation to update any forward-looking statements except as required by applicable law. This presentation includes statistical and other industry and market data that we obtained from industry publications and research, surveys and studies conducted by third parties as well as our own estimates of potential market opportunities. All of the market data used in this presentation involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such data. Industry publications and third-party research, surveys and studies generally indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy or completeness of such information. Our estimates of the potential market opportunities for our product candidates include several key assumptions based on our industry knowledge, industry publications, third-party research and other surveys, which may be based on a small sample size and may fail to accurately reflect market opportunities. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation, or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

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![Slide 3](g20817ex99_2s3g1.jpg)

Agenda Rett Syndrome Overview & REVEAL Pivotal Trial Update TSHA-102 Clinical Data from Part A of REVEAL Phase 1/2 Trials Next Steps & Concluding Remarks

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![Slide 4](g20817ex99_2s4g1.jpg)

High caregiver burden with significant impact on quality of life and activities of daily living2 Current standard of care focused on symptom management1 There are no approved disease-modifying treatments that address the genetic root cause of Rett syndrome High Unmet Medical Need Significant Market Opportunity Estimated 15,000 to 20,000 patients in major global markets (U.S., EU+U.K.)3 1 of every 8,700 female births worldwide4,5 Commercial launch and uptake of DAYBUE highlights market demand6 1Fu, Cary et al. "Consensus guidelines on managing Rett syndrome across the lifespan." BMJ paediatrics open vol. 4,1 e000717. 13 Sep. 2020, doi:10.1136/bmjpo-2020-000717. 2Coenraads, Monica et al. "Voice of the Patient Report: Rett Syndrome Externally-Led Patient-Focused Drug Development Meeting." 9 Aug. 2022, https://rettpfdd.org/site/assets/files/1/2022-rett-syndrome-voice-of-the-patient-report.pdf. 3Amir, R E et al. "Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2." Nature genetics vol. 23,2 (1999): 185-8. doi:10.1038/13810. (estimated prevalence of 15,000-20,000 patients with typical Rett syndrome caused by a MECP2 mutation). 4Sarajlija, Adrijan, et al. "Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival." Neuroepidemiology, vol. 44, no. 1, 2015, pp. 1–5, https://doi.org/10.1159/000369494. 5Laurvick, Crystal L., et al. "Rett Syndrome in Australia: A Review of the Epidemiology." The Journal of Pediatrics, vol. 148, no. 3, 2006, pp. 347–52. 6Based on net product sales for the first quarter ended March 31, 2026 (source: Acadia Pharmaceuticals Reports First Quarter 2026 Financial Results and Operating Overview). Patients typically require 24/7 care and lifelong assistance2

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![Slide 5](g20817ex99_2s5g1.jpg)

~0% AGE: 0 1 2 3 4 5 10 15 20 25 >30 By age 6, there is a <6.7% likelihood that untreated individuals with Rett will gain new milestones or regain milestones that were lost after a defined number of years Probability of Gaining/Regaining Developmental Milestones Results support minimum inclusion age of 6 years in a well-controlled, single-arm interventional trial evaluating gain and regain of developmental milestones Developmental Plateau Population (age ≥6 years) Pre-Developmental Plateau Population (age <6 years) Rigorous analysis of the Rett Syndrome Natural History Study informed the inclusion criteria and endpoint design for the REVEAL pivotal trial1 Graph is for illustrative purposes only and is not derived from natural history data. 1Accessed from IRSF. ClinicalTrials.gov: NCT02738281: a prospective cohort of individuals with a pathologic mutation in the MECP2 gene, commonly associated with RTT. Cumulative incidence models of NHS data conducted by third-party statistical partners. Up to 97% likelihood of spontaneous milestone gain before age 6 may create challenges in distinguishing treatment effect from spontaneous improvement

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![Slide 6](g20817ex99_2s6g1.jpg)

Completed dosing in REVEAL pivotal trial for TSHA-102 to support BLA submission – on track to complete six-month interim analysis Response rate = 100% (N = 12) across all patients treated with TSHA-102 post-treatment3 1Based on June 2026 safety data cutoff (N=17). 2Based on Taysha's natural history data analysis, the null hypothesis is that one out of 15 patients aged ≥6 years may gain/regain one of the 28 natural history defined developmental milestone without treatment, corresponding to a response rate of 6.7%. vg=Vector genomes; SAE=Serious adverse event; DLT=Dose-limiting toxicity; SAP=Statistical analysis plan; BLA=Biologics license application; R-MBA=Revised Motor Behavior Assessment; CGI-I=Clinician Global Impression–Improvement Single-arm, open-label trial, using each patient as own control evaluating TSHA-102 in Rett syndrome TSHA-102 administered intrathecally at 1x1015 total vg (high dose) Dosed 17 females, ages 6 to <22 years (developmental plateau population) No treatment-related SAEs or DLTs1 Primary Endpoint: Response rate, defined as the % of patients who gain or regain ≥1 developmental milestone from a validated list of 28 Video-based determination of milestone gain/regain is performed by independent, blinded central raters SAP: 33% response rate is the minimum threshold for success sufficient to reject the null hypothesis of 6.7%2 12-month primary analysis FDA alignment on potential to submit BLA based on 6-month interim analysis Key Secondary Endpoints: Average number of developmental milestones gained/regained per patient R-MBA CGI-I

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![Slide 7](g20817ex99_2s7g1.jpg)

Longer-term REVEAL Part A data demonstrated broad, consistent functional gains that deepened over time regardless of patient age, disease severity or genotype1 Based on May 2026 data cutoff (N=12). 100% of patients (N=12, 6-21 years) in the developmental plateau population of Rett gained/regained ≥1 developmental milestone Longer-term follow-up demonstrated a durable and deepening treatment effect across all patients, with additional functional gains accumulating over time ≥12 months post-TSHA-102 Developmental milestone gains increased by 69% from 6 to 12 months and by 94% from 6 to ≥12 months Patients with longest follow-up at 30 months continued to demonstrate functional gains/improvements Broad functional impact consistently demonstrated across core disease domains regardless of age, disease severity or genotype At ≥12 months post-TSHA-102, a total of 310 functional gains were observed (~26 per patient), comprising 31 developmental milestones and 279 additional skill gains/improvements Durable, multi-domain gains enable independent engagement in daily activities, reduce caregiver burden and enhanced social engagement Robust, clinically meaningful responses at 6 and ≥12 months exceed FDA-aligned minimum threshold for efficacy, supporting the potential for a BLA submission based on REVEAL pivotal trial 6-month interim analysis FDA alignment on product comparability enables REVEAL Part A data to be included in the BLA, which further supports the potential for a BLA submission based on the pivotal trial interim analysis No treatment-related SAEs or DLTs observed in any patients, with all patients having ≥12 months of follow-up

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![Slide 8](g20817ex99_2s8g1.jpg)

Rigorous evaluation criteria applied to Part A data enabled reliable, objective assessment of TSHA-102 efficacy Evaluation of Functional Gains Developmental Milestones (DM) Primary evidence of efficacy The functional gain of ≥1 of the 28 DMs defined in the natural history study assessed via rigorous video-evidenced evaluation Evaluation Criteria: Baseline: Video data/medical history confirming milestone was either never gained or lost sufficiently long ago, such that the likelihood of spontaneous gain/regain is <6.7%1 Post-treatment: Video evidence of milestone demonstration Evaluation method: Determined by multiple independent central raters based on prespecified definitions of achievement for each milestone Additional Skills and Improvements Additional evidence of functional gain Functional gain or improvement in a core disease characteristic beyond the 28 natural history defined DMs assessed via rigorous video-evidenced evaluation and validated scales Evaluation Criteria: Adapted Mullen Scales of Early Learning (MSEL-A): Centrally rated video-recorded evaluation assessing expressive and receptive language skills Observer-Reported Communication Ability (ORCA): Caregiver-reported structured evaluation assessing communication skills Revised Motor Behavior Assessment (R-MBA): Clinician-reported video evaluation assessing frequency, severity or independence of Rett syndrome characteristics 1Accessed from IRSF. ClinicalTrials.gov: NCT02738281: a prospective cohort of individuals with a pathologic mutation in the MECP2 gene, commonly associated with RTT. Incidence models of NHS data conducted by third-party statistical partners. n=8 patients with ORCA data, n=7 with MSEL-A data, and n=12 with R-MBA data

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Based on May 2026 data cutoff (N=12). Developmental milestone gains and regains were assessed by multiple independent central raters through video evidence.1Incidence models derived from NHS data; accessed from IRSF. ClinicalTrials.gov: NCT02738281: a prospective cohort of individuals with a pathologic mutation in the MECP2 gene, commonly associated with RTT. Cumulative incidence models of NHS data conducted by third-party statistical partners. NHS=Natural history study; vg=Vector genomes; CGI-S=Clinical Global Impression-Severity (4=moderately ill, 5=markedly ill, 6=severely ill) Cohort 1: Low Dose 5.7x1014 total vg Cohort 2: High Dose 1x1015 total vg Age at Dosing: 20 yrs 21 yrs 6 yrs 7 yrs 15 yrs 21 yrs 8 yrs 15 yrs 16 yrs 6 yrs 7 yrs 6 yrs Baseline CGI-S Score: 6 4 5 4 5 5 5 5 5 4 6 5 Time Post-Dosing 30 mos. 30 mos. 24 mos. 24 mos. 18 mos. 18 mos. 18 mos. 12 mos. 12 mos. 12 mos. 12 mos. 12 mos. ≥1 Milestone Gained Post-TSHA-102 ≥1 Milestone Gained Post-TSHA-102 LD:P1 LD:P2 LD:P3 LD:P4 HD:P1 HD:P2 HD:P5 HD:P3 HD:P6 HD:P7 All 12 pediatric, adolescent and adult patients across a broad range of disease severity gained/regained ≥one developmental milestone post-TSHA-102 with a <6.7% likelihood of being achieved without treatment based on NHS data1 HD:P4 HD:P8 Cohort 2: High Dose 1x1015 total vg Cohort 1: Low Dose 5.7x1014 total vg

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Rapid and robust response rate in REVEAL Part A supports the pivotal trial is well-powered to establish efficacy 100% Response Rate (12/12) 83% Response Rate (10/12) 33% FDA-aligned Minimum Response Rate is sufficient to reject the null hypothesis of 6.7% REVEAL Phase 1/2 Part A Data 6 mos. 12 mos. REVEAL Part A data exceeded FDA-aligned response rate threshold for pivotal trial success Supports potential for 6-month REVEAL pivotal trial interim analysis to enable BLA submission 75% Response Rate (9/12) 3 mos. Based on May 2026 data cutoff (N=12). Developmental milestone gains and regains were assessed by multiple independent central raters through video evidence. Response Rate = the % of patients who gain or regain ≥1 developmental milestone from a list of 28

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31 total developmental milestones achieved across core disease domains post-TSHA-102 reflect meaningful improvements in daily living Based on May 2026 data cutoff (N=12). Developmental milestone gains and regains were assessed by multiple independent central raters through video evidence. Spoke in phrases with meaning Used word(s) with meaning Followed a command without a gesture Followed a command with a gesture Pointed for something they wanted Identified body parts Gross Motor Reflect self-care skills and purposeful hand use that enable independence Used utensils to eat without assistance Finger fed Holds bottle unpropped Reached for a toy Transferred an object from one hand to another Fine Motor Used a pincer grasp Used utensils to eat with assistance Enable expression of needs, preferences, emotions, and foster social connections Communication Enhance mobility and independence, and reduce the physical burden of caregiving Walked with support Climbed down stairs with support Stood while holding on Pulled to standing Sat without support

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TSHA-102 delivered consistent and clinically meaningful treatment benefit across pediatric and adolescent/adult patients with Rett syndrome 16 15 "Her hands are more relaxed, and she tries to grab everything. She can follow directions in a snap, like if we say, 'let's go,' she gets up, heads to the door. She's babbling now, which she didn't do before, and is definitely trying to tell us something." – Caregiver of pediatric participant Total Developmental Milestones Achieved Across 6 ADOLESCENT & ADULT Patients Total Developmental Milestones Achieved Across 6 PEDIATRIC Patients "She's a lot easier to care for. She can point a lot more deliberately to make choices and show us what she wants, and she will keep gesturing until we get it for her. And she pushes away what she doesn't want." – Caregiver of adolescent/adult participant Based on May 2026 data cutoff (N=12). Developmental milestone gains and regains were assessed by multiple independent central raters through video evidence. Results support the broad treatment potential of TSHA-102

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TSHA-102 drove early and sustained developmental milestone gains with additional gains over time across the three core disease domains # of Developmental Milestones Achieved Post-TSHA-102 Total = 13 Total = 16 Total = 27 Total = 31 N=12 N=12 N=12 N=12\* 1.1 average gains per patient 1.3 average gains per patient 2.3 average gains per patient 2.6 average gains per patient Based on May 2026 data cutoff (N=12). Developmental milestone gains and regains were assessed by multiple independent central raters through video evidence. \*N=7 patients with data >12 months post-TSHA-102 and N=5 patients with 12-month data. Milestones increased by 69% from 6 to 12 months and by 94% from 6 to ≥12 months post-TSHA-102 75% of patients in the high dose cohort achieved ≥2 milestones post-TSHA-102 Assessed by multiple independent central raters using video-evidenced review in accordance with the pivotal trial criteria

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Patients achieved durable, clinically meaningful skill gains and improvements that accumulated over time in addition to developmental milestones 1Developmental Milestones 2Skills and Improvements Based on May 2026 data cutoff (N=12). 1Gain/regain of ≥1 of the 28 natural history-defined developmental milestones from the REVEAL pivotal trial primary endpoint. 2Skill gains/improvements derived from MSEL-A, R-MBA and ORCA: N=8 patients with ORCA data, N=7 with MSEL-A data, and N=12 with R-MBA data. \*N=7 patients with data >12 months post-TSHA-102, N=5 patients with 12-month data. ~26 functional gains per patient across core disease domains reflect the broad functional impact demonstrated post-TSHA-102 # of Developmental Milestones and Additional Skills/Improvements Achieved Post-TSHA-102 N=12 N=12 N=12 N=12\* 18 average gains per patient 22 average gains per patient 23 average gains per patient 26 average gains per patient Total Functional Gains Achieved Post-TSHA-102

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310 total functional gains achieved post-TSHA-102 highlight its broad functional impacts Based on May 2026 data cutoff (N=12). 1According to gain/regain of ≥1 of the 28 natural history-defined developmental milestones from the REVEAL pivotal trial primary endpoint. 2According to the MSEL-A (53 skill gains), ORCA (128 skill gains) and R-MBA (98 improvements). 310 Functional Gains demonstrated across the 12 patients post-TSHA-102 31 developmental milestones, including:1 Walked with support Climbed down stairs with support Used utensils to eat without assistance Pulled to standing Finger fed Used word(s) with meaning Spoke in phrases with meaning Pointed for something they wanted 279 skill gains and improvements, including:2 Improved motor skills and hand use Understood and responded to questions Reduced/no seizure episodes Reduced/no hand stereotypies Reduced/no breath holding/hyperventilation Followed directions related to daily routine(s) Identified body parts (to indicate pain/discomfort) Engaged in play with others Functional gains listed are not inclusive of all that were observed in the study

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REVEAL caregiver testimonials post-TSHA-102 highlight the impact of functional gains on quality of life She can feed herself finger foods. She can bring the fork up to her face, she will get it to mouth – she's never done before!" Now, when I am brushing her teeth, she will reach for the toothbrush. So, I am working on teaching her to brush by herself." Huge quality of life gain – standing with support. It has been a godsend when it comes to toileting while out in the community because now, I can have her stand and hang on to my arm to toilet or wipe her." She has lots of interest in the world around her. She says what she wants, and we know what she doesn't! We can negotiate with her – if I ask her if she wants this or that, she'll respond, 'no way' and she will argue." " " " She's gained multiple words – 'no,' 'yeah,' 'mom,' 'dad' – and even says some phrases – 'ok, bye' and 'no more.'" " " She's walking well in gait trainer. I've never seen her initiate steps with such intent. At baseline she would just drag her feet. School staff was super impressed!" "

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Meet Jane, a 21-year-old woman living with Rett syndrome Non-verbal Low interest in social interactions Unable to express her wants and needs and rarely made choices Unable to follow commands No purposeful hand use and very rarely finger fed Walked independently with slow, unsteady movements, requiring close supervision Unable to use stairs Daily to weekly seizures Took more than 30 minutes to feed Based on May 2026 data cutoff. The name shown is a pseudonym used to protect the patient's identity.

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Jane, 21-years-old at dosing, achieved sustained, meaningful functional gains "All of our days are better. Her improvements are much beyond anything we had expected or hoped for." — JANE'S MOM "We would never go back to the way things were before. This has been a miracle!" — JANE'S MOM Speaks in phrases with meaning Consistently engaged and socially interactive Points to what she wants and consistently makes choices Follows commands without a gesture Consistently uses her fingers to self-feed and holds a juice box in her hands Improved gait and mobility with reduced bradykinesia Climbs the stairs with minimal support Monthly seizures No feeding difficulties "She has benefited strongly from this therapy. She has gained more autonomy, and her quality of life has improved. She is now able to interact purposefully with her environment and with her loved ones." — PRINCIPAL INVESTIGATOR Based on May 2026 data cutoff. The name shown is a pseudonym used to protect the patient's identity.

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Meet Sarah, a 6-year-old girl living with Rett syndrome Used one word with meaning Rarely responded to spoken words Takes a few steps with assistance Required assistance for positional transfers Frequent breath-holding and hyperventilation with cyanosis and cold, blue extremities Unable to use eating utensils Constant hand stereotypies with limited hand function Based on May 2026 data cutoff. The name shown is a pseudonym used to protect the patient's identity.

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Sarah, 6-years-old at dosing, achieved sustained, meaningful functional gains Reaches 100% of the time Pulls herself to a standing position and maintains a standing position with support Reduced frequency of breath-holding and hyperventilation Improved cyanosis with warm extremities, normal in color "…if we were given the choice to receive this therapy again, we would definitely do it again. This was all worth it!" — SARAH'S DAD "Her ability to communicate and to interact with her environment has improved notably since therapy. Her attention, eye gaze and engagement with others have significantly improved. Her hand function is also improved." — PRINCIPAL INVESTIGATOR Uses utensils to eat without assistance Reduced frequency of hand stereotypies Uses her hands to play with toys Based on May 2026 data cutoff. The name shown is a pseudonym used to protect the patient's identity. AAC=Augmentative and Alternative Communication Can use multiple words with meaning Uses an AAC device to communicate, express her needs, and make requests

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TSHA-102 delivered durable, multi-domain functional gains that enable activities of daily living Examples of functional gains observed across the 12 patients post-TSHA-102 Non-verbal Speaks in phrases / sentences with meaning Communication improvements Understood simple words Engages in conversations and play/activity with others Made choices <10% of time using eye gaze Consistently makes choices by pointing Rarely responds to spoken words Follows directions and responds to questions Post-TSHA-102 Pre-TSHA-102 Fine motor improvements Post-TSHA-102 Pre-TSHA-102 Stereotypies 76-100% of time Stereotypies 1-25% of time No purposeful hand use Plays with toys and self-feeds Required caregiver-assisted feeding Finger feeds and uses utensils to eat independently Holds a bottle unpropped Limited hand function Gross motor improvements Post-TSHA-102 Pre-TSHA-102 Most severe dystonia (fixed positional deformity) Non-ambulatory Walks with support Required caregiver support for positional transfers and to stand Pulls self to standing position and stands while holding on Unable to use stairs Climbs down stairs with support No dystonia Post-TSHA-102 Pre-TSHA-102 Hyperventilating/breath holding 26-50% of time Absent or reduced hyperventilating/breath holding Weekly to monthly seizure episodes Seizure-free ≥6 months Unable to eat by mouth and required a g-tube Eats/drinks by mouth Feeding took >30 minutes No feeding difficulties Based on May 2026 data cutoff (N=12). Autonomic/other improvements

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TSHA-102 (N=12): StDev=10.18 TSHA-102 (N=12): StDev=8.86 Natural History (N=75): StDev=5.97 Natural History (N=196): StDev=5.73 TSHA-102 demonstrated a statistically significant mean R-MBA score improvement indicating a reversal in the disease trajectory Lower R-MBA score is associated with developmental milestone acquisition and quality of life improvement Based on May 2026 data cutoff (N=12 at 6 and 12 months, N=7 at ≥18 months post-TSHA-102). Statistical analyses are based on May 2026 data cutoff (N=12). 1R-MBA assessed in Rett syndrome NHS at ~6 and ~12 months; MBA natural history data converted to R-MBA; mean scores reported were calculated from baseline to 6 and 12 months: Accessed from International Rett Syndrome Foundation (IRSF). ClinicalTrials.gov: NCT02738281: a prospective cohort of individuals with a pathologic mutation in the MECP2 gene, commonly associated with RTT. R-MBA=Revised Motor Behavior Assessment Average score ≥18 months post-TSHA-102: -15.7 in high dose cohort -7.8 in low dose cohort R-MBA Score Mean Change From Baseline in Patients ≥6 Years: REVEAL low and high-dose patients vs natural history1 -12 -10 -8 -6 -4 -2 0 6 months 12 months -11.0 -10.3 -0.81 -0.62 P = 0.0011 P = 0.0002

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TSHA-102 demonstrated early global improvement, with dose-dependent effects that deepened over time in CGI-I Based on May 2026 data cutoff (N=12). CGI-I average scores based on latest assessment for each patient. CGI-I=Clinical Global Impression-Improvement Low Dose: Average CGI-I Score 3.0 2.3 3.0 3.3 2.3 High Dose: Average CGI-I Score 2.7 2.5 2.5 2.6 1.7 N=7 N=8 N=8 N=4 N=4 N=2 N=4 N=4 100% of Patients Demonstrated an Improved CGI-I Score of <3 at Multiple Post-treatment Visits 3 months 6 months 9 months 12 months ≥18 months Time Post TSHA-102: N=8 N=3 CGI-I assesses clinician's impression of improvement from baseline (1 = Very much improved \| 7 = Very much worse)

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TSHA-102 was generally well-tolerated at low and high doses with no treatment-related SAEs or DLTs All TEAEs considered related to TSHA-102 were mild-moderate in severity, with the most common being: Elevated liver enzymes\* (n=4, 33%) CSF protein increased (n=3, 25%) (clinically insignificant) Pyrexia (n=3, 25%) Seizures have generally been well controlled following TSHA-102 1REVEAL Part A data cut May 2026 (N=12).2REVEAL Part A and pivotal trial safety data cut June 2026 (N=29) SAE=Serious adverse event; DLT=Dose-limiting toxicity; TEAE=Treatment-emergent AE; NfL=Neurofilament light chain; CSF=Cerebrospinal fluid; ULN=Upper limit normal Events Across the 12 Pediatric, Adolescent and Adult Patients Dosed in Part A of REVEAL Phase 1/2 Trials1 Low Dose 5.7x1014 vg (n=4) High Dose 1x1015 vg (n=8) Total (n=12) N E N E N E TEAE Related to TSHA-102: 4 17 5 20 9 37 Serious TEAE Unrelated to TSHA-102: 3 9 4 8 7 17 Serious TEAE Related to TSHA-102: 0 0 0 0 0 0 No treatment-related SAEs or DLTs across the REVEAL Phase 1/2 and Pivotal trials (N=29)2 N=Number of participants; E=Number of events \*Includes PTs: Gamma-glutamyltransferase increased, Hypertransaminasaemia, Liver function test increased, Transaminases increased

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FDA-aligned pathway supports potential 6-month interim registrational strategy PART A: REVEAL Phase 1/2 Trials DOSING COMPLETE PART B: REVEAL Pivotal Trial DOSING COMPLETE N=17 1x1015 total vg Adolescent and Adult (females ≥12 years) Low dose cohort 5.7x1014 total vg N=2 High dose cohort 1x1015 total vg N=4 Developmental Plateau Population (females 6 to <22 years) Pre-developmental Plateau Population (females 2 to <4 years) Pediatric (females 5-8 years) Potential Registrational Path Patients with Rett syndrome Age 2+ ASPIRE Trial DOSING ONGOING 1The 1x1015 total vg dose administered in ASPIRE will be scaled to account for the lower brain volume in 2 to <4-year-olds N=4 1x1015 total vg1 Written FDA alignment on: Potential to submit BLA based on REVEAL pivotal trial 6-month interim analysis Inclusion of ≥3 months of ASPIRE safety data in BLA submission to support a broad label in patients aged ≥2 years Evaluate safety and preliminary efficacy; efficacy data to be extrapolated from pivotal trial Evaluate efficacy and safety Low dose cohort 5.7x1014 total vg N=2 High dose cohort 1x1015 total vg N=4

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Robust and clinically meaningful responses at 6 and ≥12 months support potential for BLA submission based on the 6-month interim analysis from REVEAL pivotal trial Based on May 2026 data cutoff (N=12). 1R-MBA mean score change post-TSHA-102 is relative to baseline; lower score=improvement from baseline. 2CGI-S=Clinical Global Impression-Severity: a clinician-assessed scale ranging from 1 to 7, assessing severity of illness. Endpoint 6 Months Post-TSHA-102 n=12 12 Months Post-TSHA-102 n=12 ≥18 Months Post TSHA-102 n=7 Functional Gains % of Patients Gained/Regained ≥1 Developmental Milestone 83% 100% 100% Average Functional Gains Per Patient 22 gains per patient 23 gains per patient 26 gains per patient R-MBA1 Statistically Significant Mean Score Improvement vs Natural History -11.0 P = 0.0011 -10.3 P = 0.0002 -11.0 P = 0.0046 CGI-I % of Patients with CGI-I Score <3 at Multiple Post-treatment Assessments 100% 100% 100% CGI-S2 % of Patients with CGI-S Total Score Improvement 25% 25% 57% FDA alignment on product comparability enables REVEAL Part A data to be included in the BLA, which further supports the potential for a BLA submission based on the pivotal trial interim analysis

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TSHA-102 is a potential one-time treatment designed to address root cause of Rett syndrome, with a clear path to registration 1Amir, R E et al. "Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2." Nature genetics vol. 23,2 (1999): 185-8. doi:partners. 10.1038/13810. (estimated prevalence of 15,000-20,000 patients with typical Rett syndrome caused by a MECP2 mutation). 2Sarajlija, Adrijan, et al. "Epidemiology of Rett Syndrome in Serbia: Prevalence, Incidence and Survival." Neuroepidemiology, vol. 44, no. 1, 2015, pp. 1–5, https://doi.org/10.1159/000369494. 3Laurvick, Crystal L., et al. "Rett Syndrome in Australia: A Review of the Epidemiology." The Journal of Pediatrics, vol. 148, no. 3, 2006, pp. 347–52. 4Based on May 2026 data cutoff (N=12). CNS=Central nervous system; SAP=Statistical analysis plan; BLA=Biologics license application; SAE=Serious adverse event; DLT=Dose-limiting toxicity High Unmet Need and Significant Market Opportunity No approved therapies address genetic root cause of Rett syndrome 15,000-20,000 patients (U.S., EU+U.K.); 1 of 8,700 female births worldwide1-3 TSHA-102 delivered intrathecally, a minimally invasive procedure with outpatient potential, enabling broad, scalable access Transformative Potential Supported by Part A Data4 100% response rate in REVEAL Part A (N=12) for pivotal trial primary endpoint exceeds 33% minimum threshold for success Patients consistently demonstrated durable, multidomain functional gains that deepened over time No treatment-related SAEs or DLTs Clear Path Toward Registration for Broad ≥2 Years Label Completed dosing (N=17, 6 to <22 years) in FDA-aligned REVEAL pivotal trial; 6-month interim analysis may enable BLA submission FDA alignment on product comparability enables REVEAL Part A data to be included in the BLA; robust 6 and ≥12-month Part A results further support potential BLA submission based on pivotal trial interim analysis ASPIRE trial ongoing (N=4, 2 to <4 years); FDA alignment to include ≥3 months of safety data in BLA to support broad ≥2 years label Completion of dosing in ASPIRE trial (N=4) expected July 2026 Completion of BLA-enabling PPQ campaign expected Q4 2026 Topline data from REVEAL pivotal trial 6-month interim analysis and FDA feedback on BLA submission pathway expected 1H 2027 Next Steps

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Thank you