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We are focusing on the development of global new medicine.

PIPELINE

Alzheimer’s disease (AD) is a late-onset, progressive, age-dependent neurodegenerative disorder. Amyloid beta deposits and neurofibrillary tangles are the major pathological features in an Alzheimer’s brain. Especially, hyperphosphorylated and aggregated tau is believed to be the main cause of neurodegeneration of AD and other tauopathies. In a transgenic mouse model overexpressing mutant tau, cognition deficits in addition to neuronal loss were observed. The load of neurofibrillary tangles correlates strongly with clinical progression of the disease. It has been observed that there is an inverse correlation between MMSE (mini-Mental State Examination) scores and intraneuronal NFT levels in post-mortem AD patients’ cerebral neocortex. Although tauopathy has been extensively studied as a key cause in AD, there are currently no clinical tau-targeted drugs that produce a noticeable improvement.

Intracellular tau binds to the microtubules of neurons, providing stabilization of neuronal structure. However, tau in a pathological state undergoes modifications such as hyperphosphorylation, which exerts a negative charge on the protein that causes its detachment from microtubules, and forms neurotoxic oligomers and aggregates.
DA-7503 is a novel, potent, and selective inhibitor of tau aggregation for the treatment of AD and tauopathies. It selectively binds to pathological and detached forms of tau monomers to inhibit tau oligomer formation and in turn, prevents the transition of tau from a disordered soluble protein to the insoluble aggregate. DA-7503 effectively decreases intracellular tau oligomer, protofibril, filament, and neurofibrillary tangles in vitro and in vivo. Ultimately, It protects against pathological tau-induced neuronal degeneration and brain atrophy. Following oral administration of DA-7503, alleviation of major symptoms of AD, such as memory and cognition loss, has been confirmed in AD animal models such as P301L Tau-BiFC and rTg4510 Transgenic mice. As a small molecule, DA-7503 acts mainly on intracellular and pathological tau, providing key competitiveness compared to tau-targeting antibodies or non-selective tau inhibitors.

Tau : a neuron-specific scaffolding protein that stabilizes microtubules
“Hyperphosphorylated and aggregated Tau is the primary cause of neurodegeneration in Alzheimer’s disease(AD).”

Potential First-in-class Tau Aggregation Inhibitor: A potent and selective inhibitor of Tau oligomerization and phosphorylation

High Specificity for Pathological Tau: Inhibition against pathological (aggregated, misfolded and phosphorylated)tau

Disease-Modifying Drug: Improvement of neurobehavior and brain pathology in AD models, Neuroprotection

Orally Available Small Molecule Drug: Action on intracellular pathological Tau, Improved access to the brain, More predictable efficacy and safety, Greater patient convenience