Superiority of 1801 over Deucra in Psoriasis?1 Apr 2024 08:54
Worthy of posting again, below is an extract from report which indicates at this stage the superiority of efficacy of 1801 over Deucravacitinib. Late preclinical stage admiitedly.
Interested to hear from any poster that the information is either false, misleading or not true.
'Both Tyk2 mutant mice and mice treated with SAR-20347 showed significant reduction of IL-6 and IL-17 in imiquimod-induced skin lesions, but only SAR-20347-treated mice presented reduced levels of IL-23, decreased keratinocyte proliferation and improved clinical score [22]. In addition, SAR-20347-treated mice manifested lower IL-17 gene expression compared to Tyk2 mutant mice [22]. In this model, Works et al. demonstrated that SAR-20347 treated mice showed an almost complete loss of IL-22 gene expression in skin lesions, and they postulate that SAR-20347 would impair the ability of Th17 and γδ cells to induce IL-22 [22]. IL-22 is required for development of autoreactive Th17 cells [77,78]. However, not only IL-22 production was impaired, since IL-22 signaling was also affected in vitro in a human colonic cell line, and STAT3 phosphorylation dependent of IL-22 was completely blocked [22].'
In addition
'Blocking both Tyk2 and Jak1 in this study was more effective than inhibition of Tyk2 alone at reducing psoriasis-like disease severity, keratinocyte proliferation, as well as IL-23, IL-17, IL-6, IL-22, and antimicrobial peptide gene expression, and the authors postulate that targeting a combination of Jak1 and Tyk2 using an orally available inhibitor may be a viable approach for treating psoriasis, but currently there are no ongoing or completed clinical trials for SAR-20347 [22].'
The above report from early 2023.'
Deucravacitinib the allosteric inhibitor does not interact with either Jak1 or Jak2 in the human body.
20347 is not a purely Tyk2
Regards.
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