Pipeline
NLY01
Drug Candidate
NLY01
Summary
First-in-Class GLP-1R agonist for Neurodegenerative Disease
Mechanism of Action
Long-acting, microglia-targeted GLP-1R agonist
Indication
Parkinson’s Disease (NLY01-PD)
Alzheimer’s Disease (NLY01-AD)
Development Stage
Phase II
Description
NLY01 is a pegylated exendin-4 analogue of Glucagon Like Peptide-1 Receptor (GLP-1R) agonist. NLY01 penetrates the blood–brain barrier (BBB) and its receptor (GLP-1R) is highly expressed on glial cells in Parkinson’s disease (PD) and Alzheimer’s disease (AD).
The neuroprotective potential of NLY01 was studied in four mouse models of PD and AD:
In PD, α –syn PFF (α –synuclein pre-formed fibrils) model of sporadic PD, and in a progressive, lethal constitutive α -synucleinopathy hA53T transgenic mouse model. In AD, two transgenic AD mouse models, 5xFAD and 3xTg-AD.
In both PD and AD models, NLY01 demonstrates unprecedented efficacy manifested by:
Inhibition of secretion of neuroinflammatory cytokines by microglial cells
Prevention of formation of neurotoxic A1 astrocytes
Limiting neuronal cell death both in vitro and in vivo
Limiting loss of motor function in PD
Dramatic increase in survival in PD
Improved spatial learning and memory in AD
NLY01 belongs to GLP-1R agonists, a class of drugs with well know safety profile approved for treatment of Type 2 diabetes. Combined with the overwhelming pre-clinical efficacy data in various models of neurodegenerative diseases and proven mechanism of action, NLY01 is expected to be potentially the first / best in class disease modifying agent with low development risks and fast path to the clinic.
Related Articles
Nature Medicine, volume 24, pages 931–938 (2018), “Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease”
Nature Medicine, volume 24, pages 900–902 (2018), “Fire prevention in the Parkinson’s disease brain”
NLY02
Drug Candidate
NLY02
Summary
Orally active, microglia/astrocyte-targeted small molecules for Neurodegenerative Disease
Mechanism of Action
Undisclosed
Indication
Parkinson’s & Alzheimer’s Disease
Development Stage
IND-Enabling
NLY02 is a proprietary BBB penetrating kinase inhibitor targeting glial activation. The lead candidate is currently being evaluated in various models of neurodegenerative diseases including PD and AD.
NLY03
Drug Candidate
NLY03
Summary
Orally active, neuroprotective agents for Neurodegenerative Disease
Mechanism of Action
Targets in the parthanatos cascade
Indication
Stroke / Parkinson’s Disease
Development Stage
Discovery ~ Preclinical
NLY03 is targeting neuronal survival pathways. It is currently in lead optimization stage.
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