pegylated exenatide (NLY01-PD) / D&D Pharmatech - LARVOL DELTA

GLP-1 receptor agonists in Alzheimer's and Parkinson's disease: endocrine pathways, clinical evidence, and future directions. (PubMed, Front Endocrinol (Lausanne)) - "Early clinical trials in AD have produced mixed cognitive signals, though they have shown intriguing biological effects, such as preserved cerebral glucose metabolism with liraglutide on FDG-PET scans. In contrast, the evidence in PD has been more consistent, with agents like exenatide and lixisenatide demonstrating motor benefits, although one trial with a pegylated exendin (NLY01) did not meet its primary endpoint. The definitive test will come from large, ongoing phase 3 programs, such as the EVOKE and EVOKE+ trials for semaglutide. Should these trials are successful, GLP-1RAs could become a cornerstone of earlier, mechanism-based intervention strategies for neurodegenerative diseases."

Journal • Review • Alzheimer's Disease • CNS Disorders • Diabetes • Genetic Disorders • Inflammation • Metabolic Disorders • Movement Disorders • Obesity • Parkinson's Disease • Type 2 Diabetes Mellitus

Neuroprotection on the Horizon: Are GLP-1 Receptor Agonists the Next Breakthrough in Parkinson's Disease? (MDS Congress 2025) - " Five RCTs (N = 580 participants) met our inclusion criteria, evaluating Exenatide (n=2), Liraglutide, NLY01, and Lixisenatide, with follow-up durations ranging from 44 to 60 weeks. GLP-1 RAs demonstrate promising effects on motor symptoms in PD, supporting their potential therapeutic role. Ongoing trials may provide critical insights into the clinical utility of these drugs for PD patients. GLP-1RAs vs."

CNS Disorders • Movement Disorders • Parkinson's Disease

Glucagon Like Peptide-1 (GLP-1) Receptor Agonists for Parkinson's Disease: An Updated Systematic Review and Meta-Analysis (MDS Congress 2025) - " A comprehensive search was performed using PubMed, EMBASE, and Cochrane Library to find eligible RCTs comparing GLP-1 receptor agonists (exenatide, lixisenatide, liraglutide, and NLY01) to placebo. Motor symptoms have been improved by GLP-1 receptor agonist in PD according to this updated meta-analysis, especially when the patients are on medication, though the overall effectiveness remains variable. The constancy of high heterogeneity points to the need for standardized trial designs and larger, rigorously controlled studies. MDS-UPDRS part III (Off-medication state) MDS-UPDRS part III (On-medication state) MDS-UPDRS part II – On-medication state Change in PDQ 39 Change from baseline NMSS score"

Retrospective data • Review • CNS Disorders • Movement Disorders • Parkinson's Disease

A BAYESIAN REAPPRAISAL OF DISEASE-MODIFYING CANDIDATES FOR PARKINSON'S DISEASE (WCN 2025) - "The analysis performed using the Bayes Factor confirms the improvement in non motor symptoms related to Liraglutide, worsening of motor outcomes related to Deferiprone and shows non significant results regarding CoQ10, Cinpanemab, Exenatide, NLY01 and Lixisenatide trials."

CNS Disorders • Movement Disorders • Parkinson's Disease

From metabolism to mind: The expanding role of the GLP-1 receptor in neurotherapeutics. (PubMed, Neurotherapeutics) - "GLP-1 receptor agonists (GLP-1RAs), initially approved for diabetes and obesity, are now under investigation for neuroprotective effects in a range of neurological disorders...Newer agents, such as NLY01 and tirzepatide, are under development to enhance central nervous system penetration and efficacy. Although GLP-1RAs are generally safe in metabolic conditions, their use in neurological diseases requires careful monitoring and patient selection. Future directions include developing reliable biomarkers, implementing precision medicine strategies, and exploring the use of combination therapies to maximize therapeutic potential."

Journal • Review • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Diabetes • Genetic Disorders • Metabolic Disorders • Movement Disorders • Multiple Sclerosis • Obesity • Parkinson's Disease

DUAL GLP-1/GIP RECEPTOR AGONISTS THAT CAN CROSS THE BBB SHOW SUPERIOR NEUROPROTECTIVE EFFECTS (ADPD 2025) - "Methods Bydureon (exenatide) and Adlyxin (lixisenatide) showed disease-modifying protective effects in patients with PD in two phase 2 clinical trials...NLY01, a pegylated form of exenatide that can't cross the BBB did not show any effects in PD patients in a phase 2 trial...Results Currently, two phase 3 trials are ongoing, testing the diabetes drug Ozempic/Wegovy (semaglutide) in AD patients...In animal models of AD or PD, dual agonists were able to protect neurons better than GLP-1 class drugs such as liraglutide, semaglutide or tirzepatide that were designed to treat diabetes and that stay in the blood for longer periods. Conclusions The dual GLP-1/GIP receptor agonist KP405 (DA5-CH) is currently in a phase 1 clinical trial and Results will be shared at the conference."

Alzheimer's Disease • CNS Disorders • Diabetes • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Drug Development. (PubMed, Alzheimers Dement) - "The results demonstrate that enhanced BBB penetration of GLP-1 class drugs shows superior neuroprotective effects in a 3xtg mouse model of AD. This mirrors the observations from clinical trials in PD patients that show enhanced protection with drugs that can cross the BBB better."

Journal • CNS Disorders • Diabetes • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease

D&D Pharmatech receives FDA nod for phase 2 GLP-1R agonist trial for multiple sclerosis (Korea Biomedical Review) - "D&D Pharmatech...has received U.S. FDA approval to proceed with a phase 2 clinical trial of its experimental drug, NLY01, for multiple sclerosis (MS)...The main outcome measure will be the change in cerebral volume, a standard imaging metric in MS phase 2 trials...D&D Pharmatech's newly approved phase 2 clinical trial for MS will involve 240 patients and be conducted over 96 weeks."

IND • New P2 trial • CNS Disorders • Parkinson's Disease

A Clinical Study of NLY01 in Patient's With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=255 | Completed | Sponsor: Neuraly, Inc. | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Movement Disorders • Parkinson's Disease

D&D Pharmatech's US unit to work with NIH, Johns Hopkins for Parkinson's research (Korea Biomedical Review) - "Neuraly, a U.S. subsidiary of D&D Pharmatech, has announced a collaboration with the National Institute on Aging (NIA) under the National Institutes of Health (NIH) and Johns Hopkins University School of Medicine to advance biomarker research using serum samples from patients involved in the phase 2 clinical trial of NLY01, a treatment for Parkinson's disease...The collaboration aims to utilize EVs secreted by the brain, using serum samples from participants in the NLY01 phase 2 trial, to identify biomarkers associated with brain inflammation and Parkinson's disease. The goal is to identify biomarkers that can distinguish between patients who respond to NLY01 treatment and those who do not."

Licensing / partnership • CNS Disorders • Parkinson's Disease

The neuroprotective properties of GLP-1R agonists correlate with their ability to cross the blood-brain barrier (AAIC 2024) - "Exenatide and Lixisenatide both showed excellent protective effects in patients Parkinson's disease (PD) and both drugs can readily cross the BBB. Liraglutide showed limited effects and can only cross the BBB at a low rate. A pegylated form of exenatide NLY01 did not show any effects in a clinical trial and the drug does not cross the BBB... The results demonstrate that enhanced BBB penetration of GLP-1 class drugs shows superior neuroprotective effects in a 3xtg mouse model of AD. This mirrors the observations from clinical trials in PD patients that show enhanced protection with drugs that can cross the BBB better."

CNS Disorders • Diabetes • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease

Negative findings from trials with NLY01 or deferiprone for Parkinson's disease - Author's reply. (PubMed, Lancet Neurol) - No abstract available

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Negative findings from trials with NLY01 or deferiprone for Parkinson's disease. (PubMed, Lancet Neurol) - No abstract available

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial. (PubMed, Lancet Neurol) - P2 | "NLY01 at 2·5 and 5·0 mg was not associated with any improvement in Parkinson's disease motor or non-motor features compared with placebo. A subgroup analysis raised the possibility of motor benefit in younger participants. Further study is needed to determine whether these exploratory observations are replicable."

Journal • CNS Disorders • Depression • Gastroenterology • Gastrointestinal Disorder • Movement Disorders • Parkinson's Disease • Psychiatry

The Effects of NLY01, a Novel Glucagon-Like Peptide-1 Receptor Agonist, on Cuprizone-Induced Demyelination and Remyelination: Challenges and Future Perspectives. (PubMed, Neurotherapeutics) - "In summary, despite the promising anti-inflammatory and neuroprotective effects of GLP-1R agonists that have been previously described, our experiments provided no evidence to support a beneficial effect of NLY01 on limiting demyelination or enhancing remyelination. This information may be useful in selecting proper outcome measures in clinical trials of this promising class of drugs in MS."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Multiple Sclerosis • Parkinson's Disease • Solid Tumor • OLIG2 • PDGFRA

DND Pharmatech confirms statistical significance in 'NLY01' Parkinson's disease phase 2 'subgroup' [Google translation] (Yakup Shinmoon) - P2 | N=255 | NCT04154072 | Sponsor: Neuraly, Inc. | "DND Pharmatech announced on the 23rd that it obtained clinically significant results in the phase 2 clinical subgroup analysis of NLY01, a candidate for Parkinson's disease treatment....When the company compared the score changes of patients under the age of 60 after 36 weeks of administration, the placebo group deteriorated by about 9.2 points in the combined MDS-UPDRS Part II and III scores compared to the baseline, while the NLY01 low-dose group received 4.09 points and the high-dose group received 4.09 points. 4.20 points worsened, and compared to the placebo group, both groups showed a statistically significant improvement (low dose: -5.1 points, p-value = 0.006, high dose: -5.0 points, p-value = 0.007)."

P2 data • CNS Disorders • Parkinson's Disease

NLY01 decreases chronic neuroinflammation, infarct volume, and behavioral deficits in a mouse model of ischemic stroke (Neuroscience 2022) - "This suggests that NLY01 can reduce neuroinflammation and improve behavioral deficits when administered after stroke. NLY01 may also be effective in other neurological disorders and injuries where glial cells and nRAs exacerbate neuronal damage, such as Parkinson’s Disease."

Preclinical • CNS Disorders • Parkinson's Disease

Neuraly Announces Completion of Enrollment in Phase 2 Clinical Trial of NLY01 in Patients with Parkinson’s Disease (Businesswire) - "Neuraly...announced the completion of patient enrollment in its Phase 2 study of NLY01 for Parkinson’s disease (PD)....The Phase 2 study has enrolled 255 patients across 60 clinical sites in the United States and Canada....Enrolled patients have been randomized to receive either weekly injections of NLY01 (2.5 mg or 5.0 mg) or placebo for 36 weeks. Following 36 weeks of treatment, investigators will evaluate the impact of treatment with NLY01, as compared to placebo, using the Unified Parkinson's Disease Rating Scale assessment (MDS-UPDRS). Top-line study results are expected in the first half of 2023."

Enrollment closed • P2 data • CNS Disorders • Parkinson's Disease

A Clinical Study of NLY01 in Patient's With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=240 | Active, not recruiting | Sponsor: Neuraly, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Movement Disorders • Parkinson's Disease

A Clinical Study of NLY01 in Patient's With Early Parkinson's Disease (clinicaltrials.gov) - P2 | N=240 | Recruiting | Sponsor: Neuraly, Inc. | Trial primary completion date: Dec 2022 ➔ Mar 2023

Trial primary completion date • CNS Disorders • Movement Disorders • Parkinson's Disease

D&D Pharmatech Raises $51M in Series C Financing to Advance Potential Disease-Modifying Treatments for Neurodegenerative, Fibrotic, and Metabolic Diseases (Businesswire) - "D&D Pharmatech Inc...today announced that it has completed a $51 million Series C round of financing led by Praxis Capital Partners, a private equity firm that focuses on growth acquisitions and investments in Asia; other investors included DS Asset Management, Kudos Ventures and Korea Investment & Securities. The new round of financing builds upon the $137.1 million the company secured in Series B financing in August 2019. The company is planning an initial public offering in Korea in 2022....Proceeds will be used...continue support of Phase 2 studies of NLY01 in Parkinson’s and Alzheimer’s disease..."

Financing • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

Therapeutic Potential of a Novel Glucagon-like Peptide-1 Receptor Agonist, NLY01, in Experimental Autoimmune Encephalomyelitis. (PubMed, Neurotherapeutics) - "In the therapeutic paradigm, NLY01 significantly decreases the clinical score and second attack in a model of relapsing-remitting EAE. GLP-1R agonists may have dual efficacy in MS by suppressing peripheral and CNS inflammation, thereby limiting neuronal loss."

Journal • CNS Disorders • Immunology • Inflammation • Movement Disorders • Multiple Sclerosis • Parkinson's Disease

The GLP-1/GIP dual-receptor agonist DA5-CH inhibits the NF-κB inflammatory pathway in the MPTP mouse model of Parkinson's disease more effectively than the GLP-1 single-receptor agonist NLY01. (PubMed, Brain Behav) - "It was found that the pegylated NLY01 peptide did not cross the BBB in meaningful quantities while exendin-4 and the dual agonist DA5-CH did. The results show that DA5-CH shows promise as a therapeutic drug for PD."

IO biomarker • Journal • Preclinical • CNS Disorders • Immunology • Inflammation • Movement Disorders • Oncology • Parkinson's Disease • BDNF • GFAP • IL6 • TGFB1 • TLR4 • TNFA

Neuraly Announces Publication in Acta Neuropathologica Communications of Preclinical Data Detailing the Neuroprotective Effect of NLY01 in Models of Alzheimer’s Disease (Businesswire) - "Neuraly...today announced publication in the peer-reviewed journal Acta Neuropathologica Communications of preclinical data that contributed to the therapeutic rationale for clinical evaluation of NLY01 in Alzheimer’s and Parkinson’s diseases....The publication, entitled 'Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer’s disease'...'To date, we have shown that NLY01 can reduce β-amyloid plaque burden in mouse models of Alzheimer’s and abnormal alpha-synuclein build up in Parkinson’s models."

Preclinical • Alzheimer's Disease • CNS Disorders • Parkinson's Disease

D&D Pharmatech, a re-listed student, “Taking technology export and listing this year“ [Google translation] (eDaily) - "NEURALY is undergoing phase 2 clinical trials for Parkinson's treatment (NLY01-PD), a core pipeline, and plans to apply for a phase 2 clinical trial for Alzheimer's treatment (NLY01-AD) to the U.S. Food and Drug Administration (FDA)...'Phase 2 clinical trials for Parkinson's treatment will be completed in the second half of next year. It is too late to postpone the listing until that time.'"

New P2 trial • Trial completion date • Alzheimer's Disease • CNS Disorders • Parkinson's Disease