pegylated form of exenatide for Alzheimer's disease (NLY01-AD) / 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

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

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

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

D&D Pharmatech "Simultaneous clinical trials in the US" (Hankyung) - “Investors are paying attention to D&D Pharmatech because it has several new drug candidates that can work on the global stage. The best is 'NLY01', a brain disease treatment….D&D Pharmatech also challenged the Alzheimer's treatment market with the same substance. In the first half of next year, it plans to enter a phase 2 clinical trial targeting 540 patients. It also submitted a clinical trial plan to the FDA.”

New P2 trial • Alzheimer's Disease • CNS Disorders

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

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

Blocking microglial activation of reactive astrocytes is neuroprotective in models of Alzheimer's disease. (PubMed, Acta Neuropathol Commun) - "Our study indicates that the GLP-1 pathway plays a critical role in microglia-reactive astrocyte associated neuroinflammation in AD and the effects of NLY01 are primarily mediated through a direct action on Aβ-induced GLP-1R microglia, contributing to the inhibition of astrocyte reactivity. These results show that targeting upregulated GLP-1R in microglia is a viable therapy for AD and other neurodegenerative disorders."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • Immunology • Inflammation

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