TSHAMEDIUM SIGNALOPERATIONAL10-K

TSHA completed enrollment in both REVEAL trials for Rett syndrome treatment and reported positive developmental milestone data, while financial losses deepened amid expanded R&D investment.

The completion of enrollment in both pediatric and adolescent REVEAL trials represents a significant operational milestone, with positive clinical data showing patients gaining developmental milestones across communication and motor functions. However, the company's burn rate has accelerated with substantially higher R&D spending, indicating increased investment in advancing their gene therapy pipeline toward potential regulatory approval.

Comparing 2026-03-19 vs 2025-02-26View on EDGAR →
FINANCIAL ANALYSIS

TSHA's financial picture reflects a company in active clinical development, with revenue growing modestly to $9.8M while R&D expenses increased meaningfully to $86.4M. Operating losses widened to $110.5M as the company invested heavily in advancing its clinical programs, and operating cash outflow increased to $93.1M. The financial trajectory suggests intensified development activity as trials progress toward potential pivotal studies.

FINANCIAL STATEMENT CHANGES
Capital Expenditure
Cash Flow
+97.3%
$374K$738K

Capital expenditure jumped 97.3% — major investment cycle underway; assess returns on deployment.

Interest Expense
P&L
+31.6%
$3.8M$5.0M

Interest expense surged 31.6% — significant debt increase or rising rates materially impacting earnings.

R&D Expense
P&L
+30.9%
$66.0M$86.4M

R&D investment increased 30.9% — signals commitment to future product development, though near-term margin impact.

Net Income
P&L
-22.1%
-$89.3M-$109.0M

Net income declined 22.1% — review whether driven by operations, interest costs, or non-recurring items.

Operating Income
P&L
-20.8%
-$91.5M-$110.5M

Operating profitability softening — costs rising faster than revenue, watch for margin recovery plan.

Revenue
P&L
+17.3%
$8.3M$9.8M

Revenue growing 17.3% — solid top-line momentum, watch margins for quality of growth.

Operating Cash Flow
Cash Flow
-14.6%
-$81.2M-$93.1M

Operating cash flow softened — monitor whether temporary working capital timing or structural deterioration.

LANGUAGE CHANGES
NEW — 2026-03-19
PRIOR — 2025-02-26
ADDED
As of March 19, 2026, the registrant had 287,269,885 shares of common stock, $0.00001 par value per share, outstanding.
We are evaluating TSHA-102 for the treatment of females with Rett syndrome in our REVEAL and ASPIRE clinical trials.
A total of six participants aged 15 to 21 years were treated with TSHA-102 in this study, and enrollment for this trial is complete.
Part A also includes the REVEAL Phase 1/2 Pediatric Trial, which is a first-in-human, open-label, randomized, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102 as a single lumbar intrathecal administration in pediatric females aged 5 to 8 years with Rett syndrome due to MECP2 loss-of-function mutation.
A total of six participants aged 6 to 8 years were treated with TSHA-102 in this study, and enrollment for this trial is also complete.
We reported positive clinical data in May 2025, demonstrating that the first 10 patients gained or regained one or more developmental milestone across communication, fine motor and gross motor function following TSHA-102 as of the May 19, 2025 data cutoff.
Patients also showed improvements across multiple standardized Rett syndrome assessments.
There have been no treatment-related serious adverse events or dose-limiting toxicities across the 12 participants treated with TSHA-102 as of the March 2026 data cutoff.
An update on longer-term safety and efficacy data from the Part A REVEAL Phase 1/2 trials is expected in the second quarter of 2026.
The TSHA-102 clinical development program is designed to support the potential future approval of TSHA-102 for a broad population of patients aged 2 years and older with Rett syndrome through an efficient and rigorously designed pathway.
REMOVED
As of February 26, 2025, the registrant had 205,001,632 shares of common stock, $0.00001 par value per share, outstanding.
We are also evaluating TSHA-102 in the REVEAL Phase 1/2 pediatric trial, which is an open-label, randomized, dose-escalation and dose-expansion study evaluating the safety and preliminary efficacy of TSHA-102 as a single lumbar intrathecal administration in pediatric females with Rett syndrome due to MECP2 loss-of-function mutation.
The trial is taking place in the United States, Canada and the United Kingdom.
As of the February 17, 2025 data cutoff, TSHA-102 was generally well tolerated, with no treatment-related serious adverse events, or SAEs, or dose-limiting toxicities, or DLTs, in the 10 patients dosed in Part A of the REVEAL trials.
We believe this maturing dataset continues to support advancement toward the Part B registrational trial.
We expect to report safety and efficacy data from cohort two of each of the REVEAL trials (high dose; n=3 for each trial) and an update on safety and efficacy data from cohort one of each of the REVEAL trials (low dose; n=2 for each trial), as well as an update on the anticipated pivotal trial design for TSHA-102, in the first half of 2025.
We have received orphan drug designation and rare pediatric disease designation from the United States Food and Drug Administration, or FDA, and orphan drug designation from the European Commission for TSHA-102 for the treatment of Rett syndrome.
We also received CTA clearance from the United Kingdom s Medicines and Healthcare Products Regulatory Agency, or U.K.
MHRA, in early 2024 for pediatric patients with Rett syndrome.
According to the Rett Syndrome Research Trust, Rett syndrome affects more than 350,000 patients worldwide.
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