• Alzheimer's disease (AD) is worldwide 4th causing death
• Number of AD patient increase rapidly coming after elderly society
• Most of dementia is AD (over 60%)
• The causing agent for AD is believed beta-amyloid peptide
• In the brain, beta-amyloid over produced and make plaque outside neuron
• Beta-amyloid in plaque is very resistance to protease attack
• Solubilized beta-amyloid can be transfer to BBB through LRP receptor and eventually degraded
• DWP09031 showed aggregation inhibitor as well as toxicity blocking activity
• Proof of concept done by transgenic animal model
• Neurodegenerative disease caused by protein aggregation
• Alzheimer's disease
3. Market Feasibility
• Global AD market reach to 10B US$
• In US, every year over 100B US$ spend AD care cost
• Disease modification drug can be developed and it will expend market size
4. Technical Advantages
• Drug candidate for aggregation/toxicity blocker
• DWP09031 is to bind beta-amyloid peptide and block aggregation of beta-amyloid, therefore toxic form of oligomers of beta-amyloid could not be formed and soluble beta-amyloid might be transported outside the brain via LRP, scavenger receptor of brain.
• Using hippocampus, DWP09031 can be restore LTP(long term potentiation) after beta-amyloid challenge
• In animal model, the concentrations of beta-amyloid are lowered by 50% in the brain and recover the memory deficit induced by toxic beta-amyloid in the brain.
• Human clinical trial study results showed that maximum dose (single dose 2,000mg) did not showed any sign of toxicity.
5. Technical Highlighted Summary
• The concentration of beta-amyloid is lowered by 50% in the brain after treatment of DWP09031
• Recover the memory deficit induced by toxic beta-amyloid in the brain.
• Relatively high bio-availability in rodent and non rodent species
• Good BBB penetration profile of DWP09031. Over 20% more compound detected in brain than plasma
• Less drug drug interaction prediction. Seven isoforms of CYP enzyme cannot inhibited by DWP09031
• GLP-compliant safety studies on rodent and non rodent including 4 weeks repeated dose toxicity, genotoxicity and safety pharmacology were done.
• More importantly, in vitro hERG channel study showed low binding potential.
• No moderate and significant safety issues occurred during safety and toxicity studies.