uniQure Announces Updated Preliminary AMT-191 Phase I/IIa Data Showing Sustained Increases in α-Gal A Enzyme Activity in Patients with Fabry Disease

Rhea-AI Summary

uniQure (NASDAQ: QURE) reported updated preliminary Phase I/IIa AMT-191 data in 11 Fabry disease patients showing dose-dependent, sustained elevations in α-Gal A activity across three dose cohorts through a cutoff of Jan 8, 2026.

α-Gal A increases ranged from 0.34- to 312.52-fold versus mean normal by dose; six of 11 patients stopped enzyme replacement therapy, and plasma lyso-Gb3 remained stable. Safety showed manageable events, with protocol pause of additional mid/high dosing after two Grade 3 liver enzyme elevations at the mid dose.

Positive

• All 11 patients showed elevated α-Gal A activity post-dose
• Clear dose-dependent α-Gal A increases across three dose levels
• Durable enzyme activity with >1 year follow-up in longest treated patient
• Six of 11 patients discontinued enzyme replacement therapy after meeting criteria

Negative

• Two mid-dose patients had asymptomatic Grade 3 liver enzyme elevations confirmed as dose-limiting toxicity
• Company paused additional dosing in mid- and high-dose cohorts per protocol
• Previous high-dose patients experienced multiple SAEs including cardiac and neurologic events (stroke, chest pain, leptomeningeal enhancement)

Key Figures

Patients in trial: 11 patients High dose level: 6x10^13 gc/kg Mid dose level: 4x10^13 gc/kg +5 more

8 metrics

Patients in trial 11 patients Phase I/IIa AMT-191 Fabry disease study

High dose level 6x10^13 gc/kg High-dose cohort in AMT-191 trial

Mid dose level 4x10^13 gc/kg Mid-dose cohort in AMT-191 trial

Low dose level 2x10^13 gc/kg Low-dose cohort in AMT-191 trial

Max α-Gal A increase 223.7-fold above normal High-dose cohort α-Gal A activity

ERT discontinuation 6 of 11 patients Patients withdrawn from enzyme replacement therapy

Grade 3 liver AEs 2 patients Asymptomatic Grade 3 liver enzyme elevations at 4x10^13 gc/kg

SAEs at 6x10^13 5 serious adverse events Previously reported in two high-dose patients

Market Reality Check

Price: $25.65 Vol: Volume 1,627,632 is below...

normal vol

$25.65 Last Close

Volume Volume 1,627,632 is below 20-day average 2,159,005 (relative volume 0.75x). normal

Technical Price 24.52 is trading just above the 200-day MA at 24.47.

Peers on Argus

QURE is down 7.99% while close peers show a mixed pattern: EYPT +2.74%, OCS +4.3...

QURE is down 7.99% while close peers show a mixed pattern: EYPT +2.74%, OCS +4.33%, TSHA -2.00%, ABUS -5.41%, UPB -11.56%. With no peers in the momentum scanner and no same-day peer headlines, the move appears stock-specific rather than a coordinated biotech/gene-therapy shift.

Previous Clinical trial Reports

5 past events · Latest: Sep 24 (Positive)

Same Type Pattern 5 events

Date	Event	Sentiment	Move	Catalyst
Sep 24	Pivotal AMT-130 data	Positive	+247.7%	Pivotal Phase I/II AMT-130 trial met primary endpoint with strong efficacy signals.
Sep 05	Initial AMT-191 data	Positive	+1.2%	First AMT-191 cohort showed large α-Gal A increases and ERT discontinuation.
Feb 03	AMT-191 cohort complete	Positive	+0.1%	First AMT-191 cohort enrollment completed with IDMC recommending progression.
Jan 30	AMT-162 safety review	Positive	+3.6%	IDMC supported advancing AMT-162 EPISOD1 trial after no major safety issues.
Nov 21	AMT-260 first dosing	Positive	+2.5%	First MTLE patient dosed with AMT-260 AAV9 gene therapy in Phase I/IIa trial.

Pattern Detected

Clinical trial updates have historically produced positive price reactions for QURE, so today’s negative move contrasts with the usual pattern.

Recent Company History

This announcement adds to a series of gene-therapy clinical milestones for uniQure. Since Nov 2024, the company has reported first dosing in AMT-260 for refractory MTLE, favorable IDMC feedback for AMT-162 in SOD1-ALS, and cohort completion plus IDMC support for AMT-191 in Fabry disease. In Sep 2025, pivotal AMT-130 data in Huntington’s disease showed strong efficacy signals. Earlier AMT-191 data in Sep 2025 already demonstrated large α-Gal A increases and ERT discontinuations. Today’s Fabry update extends that story but now includes dose-limiting liver toxicity and a dosing pause at higher cohorts.

Historical Comparison

clinical trial

+51.0 %

Average Historical Move

Historical Analysis

Over the past year, QURE’s clinical trial updates have averaged a +51.04% 1-day move. Today’s -7.99% reaction to new AMT-191 data marks a notable break from that typically positive pattern.

Typical Pattern

Same-tag history shows a broad clinical build-out: first dosing in AMT-260 for MTLE, early safety clearance for AMT-162 in SOD1-ALS, stepwise cohort progress for AMT-191 in Fabry disease, and pivotal AMT-130 efficacy data in Huntington’s disease, together illustrating a multi-program gene-therapy pipeline advancing through Phase I/II and pivotal stages.

Market Pulse Summary

This announcement updates AMT-191 Phase I/IIa data in Fabry disease, highlighting sustained supraphy...

Analysis

This announcement updates AMT-191 Phase I/IIa data in Fabry disease, highlighting sustained supraphysiological α-Gal A elevations, stable lyso-Gb3, and 6 of 11 patients discontinuing ERT. At the same time, Grade 3 liver enzyme elevations led to a protocol-defined dosing pause at higher cohorts. Historically, uniQure’s clinical news has moved the stock sharply, so future updates on safety follow-up, dose selection, and program strategy will be key metrics to monitor alongside broader pipeline progress.

Key Terms

α-galactosidase A, lyso-Gb3, enzyme replacement therapy, AAV gene therapy, +4 more

8 terms

α-galactosidase A medical

"all 11 patients ... had elevated α-galactosidase A (α-Gal A) activity."

α-galactosidase A is an enzyme that acts like a cellular recycling worker, breaking down specific fat-like molecules inside cells so they don’t build up. Its absence or malfunction causes a hereditary condition where these materials accumulate and damage organs, so medicines that replace or fix this enzyme are major clinical programs. Investors watch developments around this enzyme because successful therapies, approvals or tests can drive company value and future revenue.

lyso-Gb3 medical

"Stable plasma lyso-Gb3 levels were maintained post-dose across all dose cohorts"

Lyso‑Gb3 (globotriaosylsphingosine) is a blood biomarker produced when a specific fatty molecule builds up due to an enzyme deficiency in Fabry disease; think of it as a measurable warning light that signals disease activity. Investors care because lyso‑Gb3 levels are used in diagnostics and to show whether treatments are working, so changes in its measurement can affect clinical trial outcomes, regulatory decisions, market uptake, and the commercial prospects of related therapies.

enzyme replacement therapy medical

"Six of 11 dosed patients were withdrawn from enzyme replacement therapy (ERT)"

Enzyme replacement therapy is a medical treatment that involves providing patients with artificial versions of natural enzymes their bodies are missing or not producing enough of. This approach can help manage certain health conditions by restoring essential functions, similar to replacing a faulty part in a machine to keep it running smoothly. For investors, advancements or approvals in this therapy can signal progress in biotech innovation and potential market growth.

AAV gene therapy medical

"Phase I/IIa trial of AMT-191, an investigational AAV gene therapy for the treatment"

AAV gene therapy uses a harmless adeno-associated virus as a delivery vehicle to carry a working copy of a gene into a patient’s cells, like a targeted mail carrier delivering a new instruction manual to fix a malfunctioning part. It matters to investors because these treatments can be one-time or long-lasting cures, driving high potential revenue and valuation but also carrying large development costs, regulatory hurdles and safety and manufacturing risks that affect returns.

Serious Adverse Events medical

"No Serious Adverse Events (SAEs) related to AMT-191 have been observed"

Serious adverse events are significant problems or negative outcomes that occur during a medical treatment or clinical trial, such as severe side effects, hospitalizations, or life-threatening conditions. They matter to investors because such events can impact a company's reputation, lead to regulatory scrutiny, or delay the development of new products, ultimately affecting the company’s financial performance.

dose-limiting toxicity medical

"Both were confirmed as dose-limiting toxicity following an Independent Data"

Dose-limiting toxicity is a serious, treatment-related side effect observed in clinical trials that prevents researchers from safely increasing a drug’s dose. It matters to investors because these toxic effects set the maximum tolerated dose, influence whether a drug can reach levels that are effective, and therefore affect development timelines, costs, and the chance of regulatory approval — like a safety speed limit on how far a drug program can go.

Independent Data Monitoring Committee medical

"following an Independent Data Monitoring Committee review, and per protocol"

A panel of independent medical, statistical and ethical experts who review ongoing clinical trial data to judge participant safety, study integrity and whether the trial should continue, change or stop. Like impartial referees or safety inspectors, their decisions can speed, delay or halt a drug’s development and therefore materially affect a company’s timelines, regulatory chances and investment risk.

corticosteroid therapy medical

"Both patients have responded to corticosteroid therapy and remain in follow up."

Corticosteroid therapy uses steroid medications that mimic naturally occurring hormones to reduce inflammation and suppress the immune system, much like turning down a building’s overactive sprinkler system to stop water damage. For investors, it matters because these drugs are widely used across many diseases, can drive steady sales, carry known safety and regulatory issues that affect labeling and market access, and influence demand for alternative treatments.

AI-generated analysis. Not financial advice.

~ Supraphysiological expression of α-Gal A activity maintained for over a year in longest treated patient as of data cutoff date ~

~ Stable Lyso-Gb3 levels maintained post-dosing, regardless of enzyme replacement therapy status across all cohorts ~

~ Six of 11 patients have discontinued enzyme replacement therapy as of data cutoff date ~

LEXINGTON, Mass. and AMSTERDAM, Feb. 06, 2026 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced updated preliminary safety and exploratory efficacy data from 11 patients in its Phase I/IIa trial of AMT-191, an investigational AAV gene therapy for the treatment of Fabry disease. The updated data was presented at the WORLDSymposium in San Diego, California.

As of the January 8, 2026 study data cutoff date, all 11 patients in the three dose cohorts (6x10¹³ genome copies/kilogram (gc/kg), 4x10¹³ gc/kg and 2x10¹³ gc/kg) had elevated α-galactosidase A (α-Gal A) activity.

Importantly, dose-dependent elevations were observed across the three dose levels with α-Gal A activity ranging from 0.34- to 82.2-fold above mean normal level¹ at the lowest dose, 1.6- to 312.52-fold at the mid dose, and 27.7- to 223.7-fold at the highest dose. These increases were durable for the measured time period ranging from the longest follow-up period of more than a year in a treated patient (high-dose cohort) to the shortest follow-up period of four months in a treated patient (mid-dose cohort).

Six of 11 dosed patients were withdrawn from enzyme replacement therapy (ERT) having met a pre-specified criteria including elevated α-Gal A activity. Stable plasma lyso-Gb3 levels were maintained post-dose across all dose cohorts, regardless of ERT status through the cutoff date.

“These updated preliminary data reinforce our confidence in the biological activity of AMT-191, including sustained and dose-dependent increases in α-Gal A activity across all dose cohorts of the treated patients,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “While the study remains ongoing, we believe the preliminary data collected are supportive of the potential for AMT-191 as a one-time administered gene therapy for people living with Fabry disease, and we look forward to providing additional updates on the program.”

AMT-191 continued to show a manageable safety profile. No Serious Adverse Events (SAEs) related to AMT-191 have been observed at the 4x10¹³ gc/kg and 2x10¹³ gc/kg doses. Two patients at the 4x10¹³ gc/kg dose experienced asymptomatic Grade 3 liver enzyme elevations.   Both were confirmed as dose-limiting toxicity following an Independent Data Monitoring Committee review, and per protocol, the company has paused additional dosing in the mid- and high-dose cohorts pending further evaluation. Both patients have responded to corticosteroid therapy and remain in follow up.

No additional SAEs have been observed at the 6x10¹³ gc/kg dose beyond the five previously reported in two patients: two SAEs unrelated to AMT-191 (stroke, diplopia), two related SAEs (chest pain, increased troponin), and one possibly related SAE (leptomeningeal enhancement). As previously reported, one patient at the 6x10¹³ gc/kg dose experienced an asymptomatic, Grade 3 liver enzyme elevation that fully resolved with a limited course of corticosteroid therapy.

These updated data were presented at the 22nd Annual WORLDSymposium during a poster presentation (Poster Ref: LB-07) on February 3, 2026. An oral presentation will take place on Friday, February 6, 2026 in the session from 10:30-11:30 a.m. Pacific Time.  The presentation will also be available on uniQure’s website on the Events & Presentations page after the oral presentation.

About the Phase I/IIa Clinical Program of AMT-191

The Phase I/IIa clinical trial of AMT-191 is a multi-center, open-label trial being conducted in the United States consisting of three dosing cohorts of three or more adult male patients each receiving an intravenous infusion of AMT-191. Patients were not excluded from the trial based on pre-existing neutralizing anti-bodies to AAV5. Patients continue to receive their regular enzyme replacement therapy until meeting withdrawal criteria and will be followed for a period of 24 months. The trial will explore the safety, tolerability, and early signs of efficacy by measuring the expression of lysosomal enzyme α-Gal A. Additional details are available on www.clinicaltrials.gov (NCT06270316).

AMT-191 has been granted both Orphan Drug and Fast Track designation by the U.S. Food and Drug Administration.

About Fabry Disease

Fabry disease is an X-linked genetic lysosomal storage disorder caused by a deficiency of the α-galactosidase A (α-Gal A) enzyme, leading to toxic accumulation of globotriaosylsphingosine (lyso-Gb3) that can damage the kidneys, heart, nervous system, eyes, gut and skin. It is estimated that type 1 classic Fabry disease affects at least one in 40,000 males and approximately one in 20,000 females, and type 2 Fabry disease may occur in some populations as frequently as 1 in 1,500 to 4,000 males. The current standard of care for Fabry disease is bi-weekly infusions of enzyme replacement therapy, a treatment with limited effectiveness in many patients due to poor cross-correction, with inefficient clearance of substrates in the target organs, in particular the kidney and the heart.

About uniQure

uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. The approvals of uniQure’s gene therapy for hemophilia B – an historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. uniQure is now advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases. www.uniQure.com

uniQure Forward-Looking Statements

This press release contains forward-looking statements. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," “establish,” "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," “seek,” "should," "will," "would" and similar expressions. Forward-looking statements are based on management's beliefs and assumptions and on information available to management only as of the date of this press release. Examples of these forward-looking statements include, but are not limited to, statements regarding: the potential of AMT-191 to be a one-time administered gene therapy for people living with Fabry disease; and plans to provide additional AMT-191 program updates. uniQure’s actual results could differ materially from those anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, without limitation: risks associated with the clinical results and the development and timing of uniQure’s programs; the risk that more patient data become available that results in different findings than that presented in preliminary or interim data; uniQure’s interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials and pathways and timing for regulatory approval; uniQure’s ability to continue to build and maintain the company infrastructure and personnel needed to achieve its goals; uniQure’s effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of gene therapies; uniQure’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; uniQure’s ability to obtain, maintain and protect intellectual property; and uniQure’s ability to fund its operations and to raise additional capital as needed. These risks and uncertainties are more fully described under the heading "Risk Factors" in uniQure’s periodic filings with the U.S. Securities & Exchange Commission (“SEC”), including its Annual Report on Form 10-K filed with the SEC on February 27, 2025, its Quarterly Reports on Form 10-Q filed with the SEC on May 9, 2025, July 29, 2025 and November 10, 2025, and in other filings that uniQure makes with the SEC from time to time. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements, and uniQure assumes no obligation to update these forward-looking statements, even if new information becomes available in the future.

uniQure Contacts:

FOR INVESTORS:	FOR MEDIA:
Chiara Russo	Tom Malone
Direct: 781-491-4371	Direct: 339-970-7558
Mobile: 617-306-9137	Mobile:339-223-8541
c.russo@uniQure.com	t.malone@uniQure.com

___________________________

¹ Normal range (1.38 – 8.66 nmol); mean normal of 3.57 nmol

FAQ

What α-Gal A activity increases did uniQure (QURE) report for AMT-191 in the Phase I/IIa trial?

According to uniQure, α-Gal A activity rose in all treated patients with dose-dependent ranges reported. The increases ranged from 0.34- to 82.2-fold at low dose, 1.6- to 312.52-fold at mid dose, and 27.7- to 223.7-fold at high dose.

How durable were the AMT-191 enzyme activity responses in uniQure's (QURE) study?

According to uniQure, enzyme activity increases were durable for the measured periods. Durability ranged up to more than one year in the longest treated patient and as short as four months for the shortest follow-up.

Why did uniQure (QURE) pause additional AMT-191 dosing in mid and high cohorts?

According to uniQure, dosing was paused after two mid-dose patients experienced asymptomatic Grade 3 liver enzyme elevations. Both events were confirmed dose-limiting toxicity and are under further evaluation while patients respond to corticosteroids.

Did AMT-191 enable patients to stop enzyme replacement therapy in uniQure's (QURE) trial?

According to uniQure, six of 11 dosed patients discontinued enzyme replacement therapy after meeting pre-specified criteria. Discontinuations were based on observed elevated α-Gal A activity post-dose through the cutoff date.

What safety signals did uniQure (QURE) report for AMT-191 at different dose levels?

According to uniQure, no SAEs related to AMT-191 were observed at the two lower doses, but mid-dose had two Grade 3 liver enzyme events; high-dose patients had previously reported SAEs including cardiac and neurologic events, some related or possibly related.