Announcement PDF Neurizon Therapeutics Limited ABN 35 094 006 023 www.neurizon.com Neurizon Presents Phase 1 MEND Study Data at Prestigious International ALS Annual Meeting Highlights:     Neurizon Therapeutics’ Chief Operating Officer, John Clark, presented the Phase 1 MEND study data at the 2024 Annual NEALS Meeting, October 21-24, 2024. Key data demonstrated that the drug is safe and well tolerated, and demonstrated a statistically significant survival benefit in ALS patients treated with monepantel (NUZ-001) compared to untreated matched controls from the PRO-ACT database. Neurizon continues to prepare for the Phase 2/3 HEALEY ALS Platform Trial, set to begin in Q1 2025. The abstract for the poster presentation has been published in the proceedings from the conference in the scientific Journal Muscle and Nerve October 25, 2024 – Melbourne, Australia: Neurizon Therapeutics (ASX: NUZ & NUZOA) (“Neurizon” or “the Company”) is excited to announce the presentation of its Phase 1 MEND study data at the prestigious 2024 Annual NEALS (Northeast Amyotrophic Lateral Sclerosis Consortium) Meeting. The event, which ran from October 21 to 24, is one of the world’s most significant gatherings in the field of Amyotrophic Lateral Sclerosis (ALS) research, bringing together physicians, key opinion leaders, and industry representatives to discuss advancements in ALS and motor neurone disease (MND) treatments. John Clark, Neurizon’s Chief Operating Officer, presented the data, showcasing the following key results from the Phase 1 MEND study completed earlier this year in patients with ALS (as announced on 27th February 2024):     Study met its primary endpoint showing long-term safety and tolerability of NUZ-001 - No deaths, no Serious Adverse Events related to treatment, and a very low incidence of Adverse Events A monthly 0.48-point improvement in ALSFRS-R scores for patients treated with NUZ-001 versus untreated PRO-ACT matched controls The effects of treatment with NUZ-001 on biomarkers demonstrated a large reduction in cerebrospinal fluid (CSF) Neurofilmant Light Chain (NfL) These findings demonstrate NUZ-001 shows promise as an innovative treatment for ALS. The abstract for the poster presentation has been published in the proceedings from the conference in the scientific Journal Muscle and Nerve1. Level 4, 96-100 Albert Road, South Melbourne, VIC 3205 Tel: +61 3 9692 7222 Neurizon Therapeutics Limited ABN 35 094 006 023 www.neurizon.com Looking Ahead: Phase 2/3 HEALEY ALS Platform Trial Neurizon Therapeutics is preparing to build on this success by advancing to the next stage of clinical trials. The Phase 2/3 HEALEY ALS Platform Trial, in collaboration with Massachusetts General Hospital, is scheduled to commence in Q1 2025. This prestigious trial is designed to further explore the potential of NUZ-001 in treating ALS and accelerate patient access to this promising therapy. Dr. Michael Thurn, CEO of Neurizon Therapeutics, commented: “We are honored to have presented our Phase 1 MEND study data at such a leading international event. Our mission at Neurizon is to bring innovative therapies to patients suffering from neurodegenerative diseases like ALS. Being part of the NEALS Annual Meeting reinforces our commitment to advancing science and patient care, as we work tirelessly to deliver life-changing treatments to those in need.” About the PRO-ACT Database The PRO-ACT database2 is the largest public repository of ALS clinical trial data, with information pooled from more than 10,000 patients. It provides valuable insights that have supported Neurizon's groundbreaking research and development. -ENDSThis announcement has been authorized for release by the Board of Neurizon Therapeutics Limited. For further information, please contact: Dr. Michael Thurn Managing Director and Chief Execufive Officer Neurizon Therapeufics Limited enquiries@neurizon.com +61 (3) 9692 7222 Jacky Pfenninger Sodali & Co jacky.pfenninger@sodali.com +61 (0)447 301 111 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. 1 S Mathers, D Rowe, P White, M Quintana, J Clark, M Thurn Phase 1. Study of a mTOR Inhibitor in Patients with Amyotrophic Lateral Sclerosis. Proceedings of the 23rd Annual NEALS Meeting. Muscle Nerve. 2024 Oct;70 Suppl 1:S1-S92. doi: 10.1002/mus.28259. PMID: 39417631. 2 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. Level 4, 96-100 Albert Road, South Melbourne, VIC 3205 Tel: +61 3 9692 7222 Neurizon Therapeutics Limited ABN 35 094 006 023 www.neurizon.com Appendix A: Poster Abstract Phase 1 Study of a mTOR Inhibitor in Patients with Amyotrophic Lateral Sclerosis Susan Mathers1, 2, Dominic Rowe3, Philip White4, Melanie Quintana4, John Clark5 and Michael Thurn5. 1 Calvary Health Care Bethlehem, Caulfield South VIC 3162 Australia School or Clinical Sciences, Monash University, Clayton, VIC 3800 Australia 3 Centre for Motor Neurone Disease Research Faculty of Medicine and Health Research, Macquarie University, Sydney NSW 2109 Australia 4 Berry Consultants, Austin, Texas 78746 USA 5 PharmAust Ltd, South Melbourne VIC 3205 Australia 2 Background: A key pathological feature of amyotrophic lateral sclerosis (ALS) is the formation of cytoplasmic protein aggregates. The induction of autophagy is viewed as a possible therapeutic approach to clear the toxic build-up of protein aggregates. Inhibition of mTOR (mammalian target of rapamycin) pathway has been shown to induce autophagy, clear protein aggregates and provide benefits in mouse models of ALS. Monepantel (MPL) is a potent oral small molecule inhibitor of mTOR being developed for a range of neurodegenerative conditions. Here, we investigate the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of orally administered MPL, in 12 subjects with ALS. Material/methods: The Phase 1 study was a multicenter, open label study comprised of a 24-hour escalating single-dose PK study and 4-week escalating multiple dose study of MPL administered orally to subjects with ALS. During the study, the following were assessed: safety and tolerability, PK (plasma and CSF) and pharmacodynamic parameters, preliminary efficacy (ALS Functional Rating Scale – Revised, ALSSQOL-R Quality of Life Questionnaire, Edinburgh Cognitive and Behavioural ALS Screen [ECAS], and seated Slow Vital Capacity [SVC]), and biomarker measures (plasma and CSF neurofilament/light chain [NfL] and urinary p75ECD levels). Discussion: Once daily oral administration of MPL at doses of up to 10 mg/kg body weight to 12 subjects with ALS over a 7- to 12-month period was well-tolerated and did not result in any dose-limiting toxicities. Preliminary assessments of MPL's therapeutic effect on survival and ALSFRS-R scores indicate promise when compared to historical control subjects from the PRO-ACT database with similar baseline characteristics. Functional and biomarker data will also be presented supporting progression of MPL into larger Phase 2 clinical study. Level 4, 96-100 Albert Road, South Melbourne, VIC 3205 Tel: +61 3 9692 7222