uniQure Announces Favorable Recommendation from Independent Data Monitoring Committee for its Phase I/II EPISOD1 Clinical Trial of AMT-162 for the Treatment of SOD1-ALS

Rhea-AI Summary

uniQure (NASDAQ: QURE) announced a favorable recommendation from the Independent Data Monitoring Committee (IDMC) for its Phase I/II EPISOD1 clinical trial of AMT-162, a gene therapy for SOD1-ALS. The IDMC reviewed 28-day safety data from the first study cohort and found no significant safety concerns, recommending progression to the second cohort.

AMT-162 is an AAVrh10-based gene therapy designed to reduce mutated SOD1 protein expression through miRNA. The therapy targets SOD1-ALS, where patients produce misfolded SOD1 protein that damages motor neurons, leading to muscle weakness and eventual death. The treatment is administered intrathecally as a one-time dose, aiming to slow or stop SOD1-ALS progression. The company plans to begin enrollment for the second dose cohort in Q1 2025.

Positive

• Successful safety review of first cohort with no significant concerns
• IDMC approval to proceed with dose escalation
• On track for second cohort enrollment in Q1 2025

Negative

• None.

Insights

Medical Research Analyst

The favorable IDMC review for uniQure's AMT-162 Phase I/II trial marks a important advancement in the SOD1-ALS treatment landscape. This milestone is particularly significant as it represents one of the few gene therapy approaches targeting this rare but severe form of ALS, which affects approximately 2-3% of all ALS patients.

The technology platform employs an AAVrh10 viral vector with a novel miRNA design to suppress mutant SOD1 protein expression. This approach differentiates from traditional small molecule treatments by potentially offering a one-time treatment that could fundamentally alter disease progression. The intrathecal administration method chosen for AMT-162 is important for targeting the central nervous system effectively while potentially minimizing systemic exposure.

From a market perspective, this development strengthens uniQure's position in the rare disease space. While the SOD1-ALS patient population is relatively small, the potential for premium pricing in gene therapy treatments could make this a valuable asset. The successful safety review also validates uniQure's platform technology, which could have broader applications across their neurology pipeline.

Looking ahead, key catalysts include:

• Second cohort enrollment expected in Q1 2025
• Potential interim data readouts from higher dose cohorts
• Long-term safety monitoring of treated patients

The progression to dose escalation suggests the development timeline remains on track, though investors should note that the path to market for gene therapies typically requires extensive safety follow-up.

~ Independent Data Monitoring Committee Recommends Proceeding with Dose Escalation After Planned Safety Assessment of First Dose Cohort ~

~ Company Expects to Initiate Enrollment of Second Dose Cohort in the First Quarter of 2025 ~

LEXINGTON, Mass. and AMSTERDAM, Jan. 30, 2025 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today announced that the Independent Data Monitoring Committee (IDMC) for EPISOD1, uniQure’s Phase I/II clinical trial of AMT-162, an investigational gene therapy for amyotrophic lateral sclerosis (ALS) caused by mutations in the superoxide dismutase 1 (SOD1) gene, has met and reviewed 28-day safety data from the first study cohort. The IDMC’s review identified no significant safety concerns and recommended proceeding with enrollment in the second cohort.

“We are pleased with the positive outcome of this initial IDMC meeting, which marks a meaningful step in the clinical development of AMT-162 for SOD1-ALS,” stated Walid Abi-Saab, M.D., chief medical officer of uniQure. “We will continue to advance the study and look forward to proceeding with dose-escalation in the second cohort of patients.”

AMT-162 is an investigational AAVrh10-based gene therapy that expresses a miRNA designed to knock down the expression of the mutated SOD1 protein. Patients with SOD1-ALS express a misfolded SOD1 protein. This misfolded protein is toxic to motor neurons causing degeneration that, over time, leads to muscle weakness, loss of function and eventually death. AMT-162 may offer a novel one-time, intrathecally administered approach to slowing or halting the progression of SOD1-ALS.

About the Phase I/II Clinical Program of AMT-162

EPISOD1 is a Phase I/II multi-center, open-label trial of AMT-162 for the treatment of SOD1-ALS being conducted in the United States consisting of three dose-escalating cohorts with up to four patients each receiving a short course of immunosuppression prior to and after an intrathecal infusion of AMT-162. The trial will explore the safety and tolerability of AMT-162 and will assess exploratory signs of efficacy by measuring neurofilament light chain, a biomarker of neuronal damage, and SOD1 protein. Additional details are available on www.clinicaltrials.gov (NCT06100276).

AMT-162 has been granted both Orphan Drug status and Fast Track designation by the U.S. Food and Drug Administration.

About Amyotrophic Lateral Sclerosis (ALS) caused by mutations in Superoxide Dismutase 1 (SOD1)

SOD1-ALS is a rare, progressive and fatal neurodegenerative disease that results in the loss of motor neurons in the brain and spinal cord. As ALS progresses, individuals experience muscle weakness and atrophy causing them to lose the ability to move their arms and legs, speak, swallow and eventually breathe, causing respiratory failure. Based on a 2021 study in Neuroepidemiology, there are an estimated ~170,000 individuals with ALS globally with SOD1 mutations representing 2% within that population. According to the National Institute of Neurological Disorders and Stroke, the average life expectancy for those diagnosed with ALS is three to five years from onset of symptoms.

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 plans to initiate enrollment in the second dose cohort of the AMT-162 study in the first quarter of 2025 and to proceed with dose escalation along with the potential efficacy profile of AMT-162 through one-time administration with the ability to slow or halt the progression of SOD1-ALS. The Company’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 the Company’s programs; the Company’s interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials and pathways to approval; the Company’s ability to continue to build and maintain the company infrastructure and personnel needed to achieve its goals; the Company’s effectiveness in managing current and future clinical trials and regulatory processes; the continued development and acceptance of gene therapies; the Company’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the Company’s ability to obtain, maintain and protect its intellectual property; and the Company’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 the Company’s periodic filings with the U.S. Securities & Exchange Commission (“SEC”), including its Annual Report on Form 10-K filed February 28, 2024 and its Quarterly Report on Form 10-Q filed November 5, 2024, and in other filings that the Company 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 the Company 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: 617-306-9137	Direct: 339-970-7558
Mobile: 617-306-9137	Mobile:339-223-8541
c.russo@uniQure.com	t.malone@uniQure.com

FAQ

What were the results of uniQure's EPISOD1 Phase I/II trial IDMC review for AMT-162?

The IDMC review of 28-day safety data from the first cohort showed no significant safety concerns and recommended proceeding with enrollment in the second cohort.

When will uniQure (QURE) begin enrollment for the second cohort of the AMT-162 trial?

uniQure plans to initiate enrollment of the second dose cohort in the first quarter of 2025.

How does uniQure's AMT-162 gene therapy work for SOD1-ALS treatment?

AMT-162 is an AAVrh10-based gene therapy that uses miRNA to reduce mutated SOD1 protein expression, which is toxic to motor neurons in SOD1-ALS patients.

What is the administration method for uniQure's AMT-162 gene therapy?

AMT-162 is designed as a one-time, intrathecally administered gene therapy treatment.