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

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

Using the new guideline for diagnosing anthelmintic resistance of gastrointestinal nematodes to different chemical components in sheep in the Rio Grande do Norte State, Brazil. (PubMed, Rev Bras Parasitol Vet) - "The faecal egg count reduction test (FECRT) was carried out to evaluate the pre- and post-treatment of anthelmintics, including albendazole, closantel, disophenol, ivermectin, levamisole, monepantel, moxidectin and trichlorfon, using the new classification criteria to analyze the results of an FECRT, which defined three possible classifications: susceptible, resistant and inconclusive...Two drugs (trichlorfon and monepantel) proved to be highly effective in treating gastrointestinal nematodes, presenting CI varying from 98 to 100% and 97 to 100%, respectively. Gastrointestinal nematodes from sheep raised in the in the Rio Grande do Norte State, Brazil are susceptible to the active principles trichlorfon and monepantel."

Journal

Neurizon Therapeutics Limited announced that the U.S. FDA has lifted the clinical hold on its investigational drug, NUZ-001… (TipRanks) - "This clearance allows Neurizon to proceed with the Phase 2/3 development of NUZ-001 as part of the HEALEY ALS Platform Trial, expected to start in Q4 2025."

FDA event • New P2/3 trial • Amyotrophic Lateral Sclerosis

PHASE 1 OPEN LABEL EXTENSION STUDY OF AN MTOR INHIBITOR IN PATIENTS WITH AMYOTROPHIC LATERAL SCLEROSIS (PACTALS 2025) - "Here, we investigate the long-term safety, tolerability, and efficacy of orally administered NUZ-001 in up to 12 evaluable subjects with ALS who previously completed the Phase 1 MON-2021- 001 Study The Phase 1 open-label extension study was a multicenter study of NUZ-001 administered orally for a duration of 12 months to up to 12 evaluable subjects with ALS. The following were assessed during the study: long-term safety and tolerability, efficacy (ALS Functional Rating Scale–Revised, ALSSQOL-R Quality of Life Questionnaire, Edinburgh Cognitive and Behavioural ALS Screen [ECAS], seated Slow Vital Capacity [SVC]), and biomarker measures (plasma and CSF neurofilament/light chain [NfL] and urinary p75ECD levels)."

Clinical • P1 data • Amyotrophic Lateral Sclerosis • CNS Disorders • NEFL • Plasma NfL • TARDBP

FDA Extends Review Timeline for Neurizon’s NUZ-001 Clinical Hold Response (finnewsnetwork) - "The FDA’s decision is now anticipated by October 3, 2025."

FDA event • Amyotrophic Lateral Sclerosis

Neurizon’s ALS drug shows safety and extended survival in open-label extension study (The Australian) - "Slow Vital Capacity (SVC) decline is a validated marker of disease progression and survival in ALS. In the OLE study, the mean vital capacity per cent predicted (VC PP) at baseline 72.4% and this declined gradually to 62.3% after 12 months....Biomarker data supported these findings, with plasma NfL (neurofilament light) levels staying mostly stable over 12 months and urinary p75ECD falling by about 17%."

Clinical data • Amyotrophic Lateral Sclerosis

Old world camels in Germany: parasitic nematode communities characterized by nemabiome analysis showed reduced anthelmintic efficacy according to the fecal egg count reduction test. (PubMed, Parasit Vectors) - "This study shows the insufficient efficacy of standard treatments chosen by farmers/veterinarians for OWCs in Germany. Since treatment eliminated some species but did not eliminate others, not underdosing but resistant nematode species presumably led to treatment failure. However, owing to the small sample size, assessment of animal weight only by visual estimation, and no drugs licensed for OWCs in Europe, the term resistance should be used with care. The species T. colubriformis and H. contortus that survived after anthelmintic treatment are also frequently resistant in ruminants in Germany."

Journal

Neurizon Therapeutics Advances ALS Drug with FDA Submission (TipRanks) - "Neurizon Therapeutics Limited has submitted a formal response to the FDA to address the clinical hold on its investigational drug, NUZ-001, intended for ALS treatment. This submission includes new pharmacokinetic data from animal studies, demonstrating significant safety margins and supporting dose selection for further clinical evaluation. The FDA’s review is expected to conclude within 30 days, and Neurizon aims to participate in the HEALEY ALS Platform Trial by Q4 2025, contingent upon regulatory clearance. This development marks a critical step in advancing NUZ-001 as a potential first-in-class therapy for ALS, reflecting Neurizon’s commitment to delivering meaningful treatment options ahead of schedule."

FDA event • Amyotrophic Lateral Sclerosis

Neurizon on track to lift FDA clinical hold on ALS drug, eyes Healey trial in Q4 CY25 (The Australian) - "Neurizon Therapeutics has announced it has received positive feedback from the US Food and Drug Administration (FDA) on its strategy to lift the clinical hold on its lead drug NUZ-001. The Company expects to enter the HEALEY amyotrophic lateral sclerosis (ALS) platform trial in Q4 CY25....Following recent formal interactions, the FDA has provided positive written feedback to Neurizon Therapeutics (ASX:NUZ) on its strategy of conducting two preclinical pharmacokinetic (PK) studies to lift the clinical hold on NUZ-001. Neurizon has already completed the two PK studies ahead of schedule, enabling continued momentum towards initiating the HEALEY ALS platform trial, a significant ongoing trial in the US aimed at accelerating ALS treatment development....Neurizon anticipates submitting the complete response containing data from these two PK studies to the FDA in the coming weeks as part of the formal hold resolution process."

FDA event • New trial • Amyotrophic Lateral Sclerosis

Neurizon inks global licensing deal with NYSE-listed Elanco (The Australian) - "Neurizon...said the license agreement represents a critical inflection point, further strengthening its strategic outlook for development, manufacturing and potential future commercialisation of NUZ-001...Under the deal Neurizon is granted exclusive global rights to Elanco’s data package and related intellectual property for monepantel to develop and commercialise NUZ-001 and its related compounds for the treatment, palliation, prevention, or cure of neurodegenerative diseases in humans...Elanco will receive total development milestone payments for the initial and subsequent licensed products, indications, or presentations of US$9.75 million and US$5.2m respectively....Elanco will also be eligible for milestone payments of up to US$65m based on sales milestones....Neurizon said the two companies remained focused on finalising a supply agreement, with a follow-up announcement anticipated in H2 CY25."

Licensing / partnership • Amyotrophic Lateral Sclerosis

Neurizon confirms positive results for prospective ALS treatment (Pharmafile) - "Neurizon Therapeutics has announced new preclinical data confirming that NUZ-001 and its active metabolite, NUZ-001 Sulfone, effectively cross the blood-brain barrier (BBB) and reach concentrations in the brain sufficient to reverse toxic TDP-43 protein aggregation – a key driver of neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS)...In a rodent pharmacokinetic study, both compounds achieved brain concentrations that closely matched the levels shown to significantly reduce TDP-43 aggregation in patient-derived neurons in vitro. The data provides critical translational validation for NUZ-001’s mechanism of action, reinforcing its therapeutic potential not only in ALS, but also in other TDP-43 proteinopathies such as frontotemporal dementia, Alzheimer’s disease, and limbic predominant age-related TDP-43 encephalopathy."

Preclinical • Amyotrophic Lateral Sclerosis

Positive preclinical data supports potential of Neurizon’s NUZ-001 in Huntington’s disease (The Australian) - "Neurizon Therapeutics...has rolled out new preclinical data demonstrating significant neuroprotective effects of NUZ-001 and its active metabolite NUZ-001 Sulfone, in a zebrafish model of Huntington’s disease....Neuronal cell death was significantly higher in the Htt knockdown group, while treatment with 1 μM and 10 μM NUZ-001, and 10 μM NUZ-001 Sulfone, significantly reduced apoptosis Haemoglobin levels were significantly decreased in the Htt knockdown group but partially restored by both concentrations of NUZ-001 and NUZ-001 Sulfone; and Expression of BDNF transcripts was significantly rescued with 10 μM NUZ-001 and 10 μM NUZ-001 Sulfone."

Preclinical • Huntington's Disease

An Open Label Extension Study of Monepantel in Individuals With Motor Neurone Disease (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Neurizon Therapeutics Limited | Active, not recruiting ➔ Completed

Trial completion • Amyotrophic Lateral Sclerosis