On this page of StockholderLetter.com we present the latest annual shareholder letter from Taysha Gene Therapies, Inc. — ticker symbol TSHA. Reading current and past TSHA letters to shareholders can bring important insights into the investment thesis.

 •  4/21/2025 Letter Continued (Full PDF)
 •  5/8/2023 TSHA Stockholder Letter
 •  4/18/2024 TSHA Stockholder Letter
 •  More "Biotechnology" Category Stockholder Letters
 •  TSHA Benford's Law Stock Score = 74

TSHA Shareholder/Stockholder Letter Transcript:

Bringing New
Treatments To Life
2024 ANNUAL REPORT


Letter From
The CEO
Sean Nolan
Chairman and Chief Executive Officer
Dear Stockholders,
2024 was an exciting year for Taysha, marked by progress in the advancement of our lead
gene therapy candidate, TSHA-102, in clinical evaluation for pediatric, adolescent and
adult patients with Rett syndrome. During the past year, we generated critical longerterm clinical data across a broad range of ages and stages of patients in our two ongoing
REVEAL Phase 1/2 trials to further elucidate the therapeutic potential of TSHA-102 and
inform the development plan for the pivotal phase of the trials.
We achieved several key milestones, including the completion of dosing of the 10
patients in the Part A dose escalation phase of the REVEAL Phase 1/2 adolescent/adult
trial and the REVEAL Phase 1/2 pediatric trial. Additionally, we advanced discussions
with the United States (U.S.) Food and Drug Administration (FDA) on the regulatory
pathway for TSHA-102 and received FDA permission to use our pivotal TSHA-102 product
in our REVEAL trials based on the successful demonstration of analytical comparability
between the clinical product and the product derived from the    nal commercial
manufacturing process. We also strengthened our balance sheet and extended our cash
runway into the fourth quarter of 2026, supporting the continued advancement of
TSHA-102. We believe the progress we have made has set the stage for a highly
impactful 2025 as we focus on advancing TSHA-102 toward the pivotal phase of the
REVEAL trials.
Our mission and work are driven by the high unmet medical need that exists in the
Rett syndrome community. Rett syndrome is a devastating, rare and progressive
neurodevelopmental disease that leads to complications in    ne and gross motor
function, socialization and communication, autonomic function and seizures. The
functional impairments and disease features often necessitate 24/7 care and lifelong
assistance, leading to a signi   cant caregiver burden and impact on quality of life.
There are no approved disease-modifying therapies that treat the genetic root cause of
Rett syndrome, which affects an estimated 15,000 to 20,000 patients in the U.S., Europe,

and the United Kingdom (U.K.). We believe our differentiated TSHA-102 gene therapy
candidate, designed as a one-time treatment that aims to address underlying cause of
the disease, has the potential to provide meaningful bene   t to a broad population of
patients with Rett syndrome.
Encouraging Clinical Data Across Broad Patient Population
TSHA-102 is being evaluated in our REVEAL Phase 1/2 adolescent and adult trial taking
place in the U.S. and Canada and our REVEAL Phase 1/2 pediatric trial taking place in
the U.S., Canada and the U.K. We completed dosing of the 10 patients in Part A, the dose
escalation portion, of both REVEAL trials. This includes six patients in cohort two, which
is evaluating the high dose of TSHA-102 of 1x1015 total vector genomes (vg), and four
patients in cohort one, which is evaluating the low dose of TSHA-102 of 5.7x1014 total vg.
Both the high and low dose of TSHA-102 have demonstrated an encouraging safety
pro   le. TSHA-102 has been generally well-tolerated with no treatment-related serious
adverse events or dose-limiting toxicities in the 10 pediatric, adolescent and adult
patients dosed as of the February 2025 data cutoff.
In June 2024, we presented preliminary clinical data from the adult and pediatric
patients with varying genotypes and disease severity treated in the low dose cohort
at the 2024 International Rett Syndrome Foundation (IRSF) Rett Syndrome Scienti   c
Meeting. The data demonstrated early clinical improvements and functional gains
across multiple domains post-treatment that persisted and strengthened over time. This
included improvements and functional gains across the domains of    ne motor, gross
motor, socialization and communication, autonomic function, and seizures.
The functional gains consistently achieved following treatment with TSHA-102 are not
expected to occur in the untreated population of patients in the post-regression stage
and directly represent improvements in activities of daily living that are meaningful to
caregivers. As such, these outcomes have shaped our interactions with the FDA regarding
the optimal regulatory pathway for TSHA-102.
Progress to Solidify Regulatory Pathway
From the outset, our strategy has been to utilize Part A of the trials to generate a dataset
that informs our development plan for the pivotal Part B phase of the trials. With dosing
of the 10 patients in Part A complete, we believe we have a strong, maturing dataset in
hand to further solidify the regulatory pathway for TSHA-102 with the FDA.
Based on our ongoing discussions with the FDA and the totality of clinical data generated
to date, our goal is to advance TSHA-102 toward a pivotal trial design that objectively
assesses functional gains across the key clinical domains impacted in Rett syndrome. In
November 2024, we announced that following interactions with the FDA, we intend to
focus on objective and clinically meaningful measures that capture improvements in the
core features of Rett syndrome in the pivotal Part B phase of our REVEAL trials.
Additionally, the FDA con   rmed that our existing nonclinical data package is adequate
to support a Biologics License Application submission and endorsed our intended
commercial manufacturing process, proposed analytical methods, and corresponding

quali   cation and validation plans, including key mechanism of action potency release
assays. Importantly, we also receieved approval from the FDA to use the pivotal
TSHA-102 product in our REVEAL trials based on the successful demonstration of
analytical comparability between the clinical product and the product derived from the
   nal commercial manufacturing process. Subsequently, we released the pivotal product,
which we intend to use in the pivotal Part B trial.
We remain encouraged by our productive, ongoing discussions with the FDA as we
work to further solidify the regulatory pathway for TSHA-102 based on the maturing
dataset, with a focus on bringing TSHA-102 to the Rett syndrome community as safely
and expeditiously as possible. Importantly, while a new presidential administration has
brought certain personnel changes to the FDA, to date we have not seen any impacts
related to our TSHA-102 program or our interactions with the agency thus far. While
we cannot predict future actions, to date, our discussions have remained consistent
with all key groups across the FDA, including the clinical, CMC and preclinical divisions.
Additionally, as a clinical-stage company with manufacturing operations based in the
U.S., at this time we, do not anticipate a direct impact from the tariff policy that was
recently announced by the U.S. administration.
Regulatory Designations Point to High Unmet Need and Potential of TSHA-102
In April 2024, we were granted Regenerative Medicine Advanced Therapy (RMAT)
designation for TSHA-102 following the FDA   s review of initial safety and efficacy data
from our two REVEAL trials. RMAT designation facilitates increased dialogue with the
FDA, including senior managers. Importantly, we believe this has enabled our ongoing
and productive discussions with the FDA to advance TSHA-102 toward the pivotal phase
of the REVEAL trials.
TSHA-102 has also received Fast Track, Orphan Drug and Rare Pediatric Disease
designations from the FDA and Orphan Drug designation from the European Commission
for the treatment of Rett syndrome. Additionally, TSHA-102 has received Innovative
Licensing and Access Pathway designation from the U.K. Medicines and Healthcare
Products Regulatory Agency. Collectively, these designations further reinforce the high
unmet medical need for patients with Rett syndrome and the therapeutic potential of
TSHA-102.
Key Catalysts Anticipated in 2025
We believe 2025 will be a transformational year for Taysha as we focus on advancing
TSHA-102 toward the pivotal phase of the REVEAL trials. With the dosing of Part A for
both of our REVEAL Phase 1/2 trials complete, and a strong, maturing dataset in hand,
we believe we are well positioned to further solidify the regulatory pathway for TSHA-102
with the FDA. We remain encouraged by our productive, ongoing discussions with the
FDA and look forward to providing an update on key milestones in the    rst half of 2025,
including the pivotal Part B trial design for TSHA-102 and clinical data from the high and
low dose cohorts across both of our REVEAL trials.
Our work with, and on behalf of, the Rett syndrome community continues to be a
cornerstone in the development of this potentially transformational treatment option.
I would like to extend my appreciation to the patients and advocacy communities, who



 4/21/2025 Letter Continued (Full PDF)