monepantel (NUZ-001) / Neurizon Therapeutics - LARVOL DELTA

NIH funds Expanded Access Program for NUZ-001 in ALS (Listcorp) - "The NIH-funded EAP is expected to provide up to 200 people living with ALS who are otherwise ineligible to participate in clinical trials with access to NUZ-001 for up to 96 weeks. The program will run in parallel with Regimen I of the Phase 2/3 HEALEY ALS Platform Trial, where NUZ-001 is currently being evaluated in approximately 250 participants.The EAP will continue beyond the topline results, expected in late Q2 CY2027, contingent on a positive trial outcome...The Healey & AMG Center will lead the clinical and operational execution of the EAP, including site activation, participant recruitment and data collection. Neurizon will serve as regulatory sponsor with the EAP conducted under Neurizon’s IND, and will be responsible for supplying NUZ-001."

Clinical • P2/3 data • Amyotrophic Lateral Sclerosis

Neurizon to Outline ALS Trial Progress and NUZ-001 Strategy at Melbourne Investor Briefing (The Globe and Mail) - "The company will outline the completion of enrolment in Regimen I of the HEALEY ALS Platform Trial and detail the strategic significance of its supply agreement with Elanco in underpinning the long-term development pathway for its lead ALS candidate, NUZ-001....The presentation is also set to highlight forthcoming clinical, regulatory and operational milestones that will shape Neurizon’s next phase of growth and potentially influence its positioning in the ALS treatment landscape. By combining updates on trial progress, key partnerships and future milestones, the briefing aims to provide investors and stakeholders with greater visibility on the company’s trajectory in advancing NUZ-001 and its broader neurodegenerative portfolio."

Trial status • Amyotrophic Lateral Sclerosis

HEALEY ALS Platform Trial - Regimen I NUZ-001 (clinicaltrials.gov) - P2/3 | N=240 | Active, not recruiting | Sponsor: Merit E. Cudkowicz, MD | Enrolling by invitation ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

HEALEY ALS Platform Trial - Regimen I NUZ-001 (clinicaltrials.gov) - P2/3 | N=240 | Enrolling by invitation | Sponsor: Merit E. Cudkowicz, MD | N=160 ➔ 240

Enrollment change • Amyotrophic Lateral Sclerosis • CNS Disorders

Neurizon Therapeutics Limited…is pleased to advise that enrolment has been completed in Regimen I of the Phase 2/3 HEALEY ALS Platform Trial evaluating the Company's lead investigational therapy NUZ-001 for the treatment of amyotrophic lateral sclerosis (ALS). (PRNewswire) - "250 participants enrolled in less than five months from first participant dosing, representing the fastest site activation and enrolment in the HEALEY ALS Platform Trial so far; Anticipated topline efficacy and safety results for NUZ-001 now expected in late Q2 CY2027."

Enrollment closed • P2/3 data • Amyotrophic Lateral Sclerosis

β-alanine betaine and nAChRs in Ascaris. (PubMed, bioRxiv) - "However, injection of β - alanine betaine, produced characteristic pretzel coiling and injection of levamisole produced a rod-like spastic paralysis...Could it be that there are also more endogenous ligands other than acetylcholine allowing their simpler neuronal system to perform more complex control? We looked for additional analogues of acetylcholine in the body fluid of the large intestinal parasite of the pig Ascaris suum (a model for Ascaris lumbricoides ) and identified the anaerobic cholinergic compound β-alanine betaine. We found evidence that suggests that β-alanine betaine may serve as an endogenous ligand for an alternate subfamily of nicotinic receptors (DEG-3/DES-2) that could be developed as novel drug targets because their receptor analogues are not present in human or animal hosts."

Journal

Neurizon Therapeutics Limited...announced the execution of a strategic long-term supply agreement with Elanco Animal Health for Monepantel in developing its lead asset NUZ-001 for Amyotrophic Lateral Sclerosis (ALS). (RTTNews) - "The deal follows a global license agreement previously executed between the parties to develop NUZ-001 as a potential therapy for ALS and other neurodegenerative diseases...The agreement provides Neurizon long-term access to Elanco's GMP monepantel, which is the active ingredient in NUZ-001...The agreement is being executed with an initial five-year term and includes provisions relating to forecasting, production scheduling, and supply. Details of the first two supplies were provided, with Neurizon retaining the rights to defer further supply based on future regulatory approvals....A separate quality agreement allocates responsibility for GMP manufacturing, quality control, batch release, and related quality regulatory matters, while commercialisation remains subject to clinical development, regulatory approval, and future outcomes."

Licensing / partnership • Amyotrophic Lateral Sclerosis

Neurizon ALS platform trial passes 50pc dosing milestone ahead of schedule (The Australian) - "Neurizon reports 129 of 240 participants dosed in Regimen I of ALS platform trial evaluating NUZ-001..Neurizon Therapeutics...said as of June 9, 167 participants had been assigned to Regimen I, with 129 receiving treatment across 78 active clinical trial sites in the US...Neurizon said the expanded study is designed to generate a larger and more informative clinical dataset while maintaining the original statistical assumptions underpinning the primary efficacy analysis...Based on current recruitment momentum, Neurizon remains well positioned for last participant dosing in Q2 CY27 and release of topline results in early Q3 CY27."

P2/3 data • Trial status • Amyotrophic Lateral Sclerosis

Repurposing monepantel in oncology: A conceptual mini-review of proposed mechanisms. (PubMed, Biomed Pharmacother) - "This mini-review integrates preclinical and early clinical findings and highlights the anticancer mechanisms linked to MPL, including its ability to cause G1 arrest, activate endoplasmic reticulum stress pathways, and enhance the efficacy of conventional chemotherapies, all while maintaining an exceptional safety profile. The sections that follow examine the mechanistic basis and translational promise of MPL as a repurposed anticancer agent."

Journal • Review • Infectious Disease • Oncology

Evolution of Ivermectin Resistance in the Nematode Model Caenorhabditis elegans: Critical Influence of Population Size and Altered Emodepside Efficacy. (PubMed, Evol Appl) - "Evolution of ivermectin resistance led to reduced efficacy of the structurally related anthelmintic moxidectin, as anticipated, as well as reduced efficacy of the structurally unrelated anthelmintic emodepside, which has a distinct mode of action. In contrast, albendazole, levamisole, and monepantel efficacy were not influenced by the evolution of ivermectin resistance. We conclude that combining computational modeling with in vitro evolution experiments to test specific aspects of evolution directly represents a promising approach to guide the development of novel treatment strategies to anticipate and mitigate resistance evolution in parasitic nematodes."

Journal

Anthelmintic resistance in sheep nematodes in Australia: a compilation of recent test results. (PubMed, Aust Vet J) - "The FECRT figures suggest that there is little role for the benzimidazole, levamisole and macrocyclic lactone groups as single actives and that all anthelmintics will be used most effectively and sustainably as combinations of actives, but their efficacy on individual sheep properties should be confirmed with an FECRT."

Journal

New data builds Neurizon’s scientific case for lead drug candidate in ALS (The Australian) - "The preclinical findings were generated using established neuronal models designed to assess protein clearance pathways in physiologically relevant human cellular systems...Following treatment with NUZ-001, reductions in both markers were observed. The company said these changes were consistent with increased autophagic flux, and more efficient degradation of protein aggregates...At the same time, NUZ-001 was also shown to increase proteasomal activity, providing direct functional evidence that a second protein clearance pathway was activated....These findings further support the development of NUZ-001 as it progresses through Regimen I of the Phase 2/3 ALS Platfom Trial."

Preclinical • Trial status • Amyotrophic Lateral Sclerosis

HUMAN IPSC-BASED MODELS FOR TRANSLATIONAL EVALUATION OF ALS THERAPIES TARGETING TDP-43 DYSFUNCTION (ADPD 2026) - "Ncardia's iPSC-based ALS platform recapitulates key molecular and functional hallmarks, including TDP-43 pathology and STMN2 mis-splicing. The robust response to NUZ-001 highlights the platform's predictive translational value, providing a reliable human-relevant system for preclinical validation of ALS therapies and accelerating translation to patients."

Amyotrophic Lateral Sclerosis • CNS Disorders • STMN2 • TARDBP

Anthelmintic resistance on meat goat properties in Queensland and New South Wales, Australia, with a comparison of statistical methods. (PubMed, Vet Parasitol Reg Stud Reports) - "This study identified the first field cases of resistance, classifications to several anthelmintics: Moxidectin (MOX) on 70% of properties, Monepantel (MPL) + Abamectin (ABA) on 50%, Derquantel (DER) + ABA on 33%, ABA+Oxfendazole (OXF) + Levamisole (LEV) on 50% and ABA+Closantel (CLOS) + LEV+Albendazole (ABZ) on 50%. This has significant implications for the longevity of these treatments and poses a serious risk to successful control of GIN in goats using chemicals. The continued reliance on anthelmintics is not sustainable, the incorporation of non-chemical control management practices should be encouraged for all goat producers."

Clinical • Journal • Infectious Disease

First participant enrolled and dosed with NUZ-001 in Regimen I of the HEALEY ALS Platform Trial evaluating NUZ-001 for the treatment of ALS (Neurizon Press Release) - "Study is expected to complete enrolment in H2 CY2026."

Enrollment open • Amyotrophic Lateral Sclerosis

HEALEY ALS Platform Trial - Master Protocol (clinicaltrials.gov) - P2/3 | N=1500 | Recruiting | Sponsor: Merit E. Cudkowicz, MD | Active, not recruiting ➔ Recruiting | Trial primary completion date: Nov 2027 ➔ Jul 2027

Enrollment open • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

HEALEY ALS Platform Trial - Regimen I NUZ-001 (clinicaltrials.gov) - P2/3 | N=160 | Enrolling by invitation | Sponsor: Merit E. Cudkowicz, MD | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Amyotrophic Lateral Sclerosis • CNS Disorders

HEALEY ALS Platform Trial - Regimen I NUZ-001 (clinicaltrials.gov) - P2/3 | N=160 | Not yet recruiting | Sponsor: Merit E. Cudkowicz, MD

New P2/3 trial • Amyotrophic Lateral Sclerosis • CNS Disorders

Regulatory Update (Neurizon Press Release) - "The Company advises that it has received regulatory correspondence from the US Food and Drug Administration (FDA) stating that its request for Fast Track Designation has been denied at this time...Based on NUZ-001’s current stage of development, the FDA indicated that additional clinical information would be required to demonstrate its differentiation from other FDA approved therapies. Neurizon views this feedback as providing a clear regulatory pathway and will assess the additional data requirements as it continues to progress NUZ-001 and evaluates the timing of a subsequent new Fast Track Designation request."

Fast track • Amyotrophic Lateral Sclerosis

Development Update (Neurizon Press Release) - "The Company also reports that NUZ-001 has advanced to the next operational phases of the HEALEY ALS Platform Trial, with activities underway, including Institutional Review Board (IRB) submissions, clinical site activation, and associated study start-up activities. The Company expects the first patients to be enrolled very early this year, representing an important near-term clinical milestone....This progress follows Neurizon’s recent announcement that it has secured sufficient funding to complete the pivotal registration-adaptive Phase 2/3 clinical trial, providing clear visibility through to key clinical outcomes."

Financing • Trial status • Amyotrophic Lateral Sclerosis

HEALEY ALS Platform Trial - Master Protocol (clinicaltrials.gov) - P2/3 | N=1500 | Active, not recruiting | Sponsor: Merit E. Cudkowicz, MD | Trial completion date: Apr 2026 ➔ Aug 2028 | Trial primary completion date: Jul 2025 ➔ Nov 2027

Trial completion date • Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

Neurizon Therapeutics…said that the Sean M. Healey & AMG Center for ALS at Mass General Brigham in the US had received clearance from FDA following a 30-day review. (The Australian) - "This decision confirms NUZ-001 as Regimen I in the Healey ALS trial – a multicentre, double-blinded, placebo-controlled, adaptive trial for amyotrophic lateral sclerosis (ALS) created in partnership with the Network of Excellence for ALS (NEALS)...Milestone strengthens Neurizon’s path toward advancing a new treatment for ALS with patient enrolment expected to start early in 2026...Neurizon recently announced it had completed manufacturing three registration tablet batches of NUZ-001, supporting its readiness to enter the HEALEY ALS Platform Trial. Completion of the batches also enables the company to pursue a rolling review New Drug Application (NDA) with the FDA."

IND • New trial • Amyotrophic Lateral Sclerosis

Neurizon hits key manufacturing milestone for ALS drug candidate (The Australian) - "The registration batches were manufactured in partnership with Catalent, a leading global contract development and manufacturing organisation with extensive expertise in supporting commercial production of orphan drug products like NUZ-001....Manufacturing supports Neurizon’s readiness to advance NUZ-001 in the next phase of clinical development, including the prestigious HEALEY ALS Platform Trial, which is on track to start enrolment in Q1 CY26."

Commercial • Trial status • Amyotrophic Lateral Sclerosis

A Human iPSC-Based Platform for Functional and Molecular Evaluation of ALS Therapeutics Targeting TDP-43 Pathology (Neuroscience 2025) - "Collectively, these results underscore the predictive power of Ncardia's iPSC-based ALS platform for evaluating therapeutic compounds targeting TDP-43. The integration of molecular, cellular, and functional endpoints in a human-relevant system enhances translational value and provides a powerful tool for advancing ALS drug discovery."

Amyotrophic Lateral Sclerosis • CNS Disorders • STMN2 • TARDBP

Leveraging external controls from PRO-ACT for exploratory efficacy assessment in Early-Phase ALS trials (ALS-MND 2025) - "However, the use of ECs is methodologically complex due to potential heterogeneity between trial participants and external data sources... This study highlights the potential of using ECs derived from the PRO-ACT database to enhance exploratory efficacy assessment in single-arm early-phase ALS trials. While challenges remain, especially in mitigating unmeasured confounding, PS-based methods provide a viable framework for comparative analysis in the absence of randomization. These findings support the integration of EC methodologies in early-phase ALS trial designs to better inform clinical development strategies."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders