|Optimization||Pre-clinical||ADMET/CMC||Ph Ⅰ||Ph Ⅱ|
Shaperon also develops an oral formulation of HY209 in the treatment of neuroinflammatory diseases. IND submission for phase 1 study for Alzheimer’s disease is in preparation with pre-clinical and CMC data all set for filing
While directly targeting amyloid-β or abnormal tau proteins to ameliorate the damages inflicted on neuronal cells is the mainstream of current drug development efforts in the field of Alzheimer’s disease, Shaperon’s neuroinflammatory approach aims at microglial cells in which phagocytosis activities are exhausted and inflammation reactions are uncontrolled.
In 5xFAD mouse model, HY209 treatment showed the increase of GPCR19 expression in microglial cells which had been down-regulated by the induction of Alzheimer's disease while reducing inflammatory P2X7 expression. HY209 significantly suppresses the inflammation signaling networks in the brain, leading to the inhibition of neuroinflammatory cytokines such as IL-1β, IL-18, TNF-α, etc.
As a result, the reduction of amyloid-β plaques and microgliosis was observed while the anti-inflammatory CD47 expression was increased and cognitive functions of 5xFAD mice was improved on 10-week treatment of HY209.
Nature, 2018, 559 (S2), Nature 2018, 559 (S16)
Park et al., The Open Neurology Journal, 2019, 13: 55-62
Ulcerative Colitis is another indication whose pathology fits for Shaperon’s novel inflammasome inhibitors. With pre-clinical data all set for filing, we are planning phase I study for UC.
Shaperon’s HY209 controls GPCR19-P2X7 expressions, downregulates component proteins of NLRP3 inflammasome, suppresses inflammatory cytokines and infiltrating immune cells, repairs damaged intestinal tissue and improves diarrhea caused by ulcerative colitis
In DSS-induced UC mouse model, HY209 treatment shows a strong potency in the suppression of IL-1β, IL-6, TNF-α, reduction of diarrhea frequency, and repair of intestinal tissue in comparison with current standard of care treatment such as 5-ASA and Jak inhibitor.
Zaki et al., Trends Immunol. 2011 Apr;32(4):171-9