Last Patient Successfully Completes Treatment in OLE Study

Highlights:

• Last Open-Label Extension (OLE) study patient successfully completes 12-month treatment period
• Treatment with NUZ-001 continues to be well-tolerated and shows promising results in extending the life expectancy of patients with MND/ALS
• Key findings compared to untreated matched controls from the PRO-ACT Historical Database were:
  • NUZ-001 significantly increased survival (χ2=14.1, p=0.00017)
  • NUZ-001 significantly reduced the risk of death by 78.5% (HR=0.215, p=0.0015)
  • Patients are now in their 31^st month of continuous treatment with NUZ-001
• No serious adverse events related to NUZ-001 have been reported during treatment
• 7 of the original 12 patients from the Phase 1 MEND Study remain alive, with 6 patients continuing to receive treatment with NUZ-001 under a compassionate use program
• Release of top-line OLE results remains on track for Q3 CY2025

MELBOURNE, Australia, May 06, 2025 / Biotech Newswire / -- Neurizon® Therapeutics Limited (ASX: NUZ & NUZOA) (“Neurizon” or “the Company”), a clinical-stage biotech company dedicated to advancing innovative treatments for neurodegenerative diseases, is pleased to announce that the last patient enrolled on to the 12-month Open Label Extension (OLE) Study of NUZ-001 for amyotrophic lateral sclerosis (ALS) has successfully completed treatment. Treatment with NUZ-001 daily at 10 mg/kg was well-tolerated by all patients, consistent with the planned dose for the upcoming Phase 2/3 HEALEY ALS Platform Trial. The release of top-line results from the OLE study remains on track for Q3 CY2025.

Updated Survival Analysis

Neurizon’s statistical partners Berry Consultants have updated the survival probability analysis to quantify the survival benefit of treatment with NUZ-001 compared to untreated matched controls from the PRO-ACT historical control database (1). As of 02 May 2025, patients have been treated with NUZ-001 for varying durations, ranging from 11.3 to 30.9 months (median of 25.5 months) and at varying dose levels (2 to 10 mg/kg). Using disease onset location, pre-baseline ALSFRS-R slope, baseline ALSFRS-R score, and time since disease onset, Berry Consultants matched untreated PRO-ACT controls to each NUZ-001 treatment patient.

The Kaplan-Meier survival curves shown in Figure 1 highlight the consistent survival benefits across four different analysis datasets, ranging from the least conservative (which overestimates survival) to the most conservative (which underestimates survival). In all models, treatment with NUZ-001 significantly prolonged survival compared to historical controls from the PRO-ACT database. The improvement in life expectancy was highly statistically significant across all datasets (See Table 1). In the most conservative analysis dataset, the χ2 test statistic was 14.1, with a p-value of 0.00017. Using the companion analysis with the Cox proportional hazards model, the estimated hazard ratio (HR) was 0.215 (95% CI: 0.083–0.556, p = 0.0015), indicating that NUZ-001 treatment reduced the risk of death by 78.5%. The Kaplan-Meier survival curves suggest that treatment with NUZ-001 may provide substantial clinical benefits for this cohort of patients, potentially extending the median survival by approximately 11 months, with a possibility of a longer benefit. Importantly, this median survival estimate is conservative and currently anchored to the patient with the shortest treatment duration (24.9 months) who remains alive.  The possibility of a longer survival benefit cannot be excluded as follow-up continues. These results are particularly notable when compared to existing approved treatments, which typically extend life expectancy by 3 to 6 months. Collectively, the data underscore the potential of NUZ-001 to deliver a clinically meaningful improvement in patient outcomes.

Figure 1: Calculated Kaplan-Meier curves for each of the untreated matched-control PRO-ACT datasets described in Table 1 as well as the NUZ-001 treatment group. Here “Assumed” Dataset assumes that missing death status indicates living status, while “Confirmed” only uses data with non-missing death status. The imputation method “Drop” means that it excludes missing times of death for confirmed dead subjects, while “Last Visit” uses the last visit time as the time of death. Vertical dashed lines represent the exposure time for all patients.

Table 1: Estimated Survival Probability by Analysis Dataset

Managing Director and Chief Executive Officer, Dr Michael Thurn commented: “Reaching this milestone in the OLE study is a significant moment for Neurizon and the MND/ALS community. We are encouraged that some patients have now received NUZ-001 for 2.5 years and have chosen to continue treatment under a compassionate use program. The latest survival data reinforce our confidence in the clinical development strategy for NUZ-001 and further validate dose selection for the upcoming HEALEY ALS Platform Trial. As we look ahead, our focus remains on advancing NUZ-001 as a potential treatment that could make a meaningful difference for people living with MND/ALS.”

About the OLE Study

The OLE study investigated the long-term safety, tolerability, and efficacy of NUZ-001 in ALS patients who completed the Phase 1 MEND Study, which commenced in October 2022. Eligible patients received a daily dose of 10 mg/kg body weight of NUZ-001 for 12 months. The study has been conducted at two clinical sites in Australia: Calvary Health Care Bethlehem, led by Associate Professor Susan Mathers, and Macquarie University, led by Professor Dominic Rowe. The study is registered on ClinicalTrials.gov  (https://clinicaltrials.gov/study/NCT06177431).

Since the last 8-month interim update, 1 additional patient has died due to disease progression. As of this update, 6 of the 10 patients who enrolled on the OLE study are continuing treatment with NUZ-001 under a compassionate use program. For all 10 patients, the mean time since onset of disease is 41.2 months (median 41.5), and the total cumulative exposure to NUZ-001 is 21.9 years.

Associate Professor Susan Mathers commented: “We are deeply grateful to all of our participants and their families for collaborating with us on the OLE study to explore the long-term effects and potential benefits of NUZ-001 in MND/ALS. This study has demonstrated that NUZ-001 continues to be safe and well tolerated. Based on the promising results previously observed in preliminary efficacy markers, we look forward to the commencement of the next study phase”.

Next Steps

Once the FDA lifts the clinical hold on NUZ-001, anticipated in Q3 CY2025, Neurizon Therapeutics will proceed with the initiation of the HEALEY ALS Platform Trial, expected to commence in Q4 CY2025. These actions demonstrate our dedication to conducting this pivotal Phase 2/3 study and reinforce our confidence in delivering meaningful results for the MND/ALS community.

This announcement has been authorized for release by the Board of Neurizon Therapeutics Limited.

About Neurizon Therapeutics Limited
Neurizon Therapeutics Limited (ASX: NUZ) is a clinical-stage biotechnology company dedicated to advancing treatments for neurodegenerative diseases. Neurizon is developing its lead drug candidate, NUZ-001, for the treatment of ALS, which is the most common form of motor neurone disease.  Neurizon’s strategy is to accelerate access to effective ALS treatments for patients while exploring NUZ-001’s potential for broader neurodegenerative applications. Through international collaborations and rigorous clinical programs, Neurizon is dedicated to creating new horizons for patients and families impacted by complex neural disorders.

Neurizon® is a registered trademark of Neurizon Therapeutics Limited

Contacts

Neurizon Therapeutics Limited
Dr. Michael Thurn
Managing Director and Chief Executive Officer
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+61 (3) 9692 7222

Lidija Damjanovic
Head of Marketing and Corporate Affairs
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+61 (0) 425 700 504

Keywords: Amyotrophic Lateral Sclerosis; clinical development; drug development; Neurodegenerative Diseases; Motor Neuron Disease; Open-Label Extension study; Biotechnology; NUZ-001; OLE study; MND; ALS; survival benefit; Kaplan-Meier survival curves; Phase 1 MEND Study; compassionate use program; Neurizon Therapeutics; dose levels; survival analysis; safety; tolerability; efficacy; HEALEY ALS Platform Trial; neural disorders

1. Atassi N, Berry J, Shui A, Zach N, Sherman A, Sinani E, Walker J, Katsovskiy I, Schoenfeld D, Cudkowicz M, Leitner M. The PRO-ACT database: design, initial analyses, and predictive features. Neurology. 2014 Nov 4;83(19):1719-25. doi: 10.1212/WNL.0000000000000951.Epub 2014 Oct 8. PMID: 25298304; PMCID: PMC4239834.

Source: Biotech Newswire