Abstract Psoriasis is a chronic autoimmune disease affecting the skin and characterized by aberrant keratinocyte proliferation and function. Immune cells infiltrate the skin and release proinflammatory cytokines that play important roles in psoriasis. The Th17 network, including IL-23 and IL-22, has recently emerged as a critical component in the pathogenesis of psoriasis. IL-22 and IL-23 signaling is dependent on the JAK family of protein tyrosine kinases, making JAK inhibition an appealing strategy for the treatment of psoriasis. In this study, we report the activity of SAR-20347, a small molecule inhibitor with specificity for JAK1 and tyrosine kinase 2 (TYK2) over other JAK family members. In cellular assays, SAR-20347 dose dependently (1 nM–10 μM) inhibited JAK1- and/or TYK2-dependent signaling from the IL-12/IL-23, IL-22, and IFN-α receptors. In vivo, TYK2 mutant mice or treatment of wild-type mice with SAR-20347 significantly reduced IL-12–induced IFN-γ production and IL-22–dependent serum amyloid A to similar extents, indicating that, in these models, SAR-20347 is probably acting through inhibition of TYK2. In an imiquimod-induced psoriasis model, the administration of SAR-20347 led to a striking decrease in disease pathology, including reduced activation of keratinocytes and proinflammatory cytokine levels compared with both TYK2 mutant mice and wild-type controls. Taken together, these data indicate that targeting both JAK1- and TYK2-mediated cytokine signaling is more effective than TYK2 inhibition alone in reducing psoriasis pathogenesis.
It would seem very astute to raise money for development by licensing TYK 2. In my opinion sareum are extremely vunerable if they do not raise significant funding. However, should funds be raised in whatever shape or form then this will add considerable worth to the company whilst development of other products in their pipeline progress. Good post Hoppy!
Scientists at Sareum, in collaboration with colleagues at the US research institute SRI International, have developed a novel molecule that significantly decreases psoriasis pathology in a disease model. This research has been reported in the latest edition of the Journal of Immunology*.
The potential psoriasis therapy targets members of the JAK family of kinase enzymes, which control the production of cytokines. Cytokines are signalling molecules produced by the immune system, usually in response to a danger such as invading pathogens. Cytokines responsible for psoriasis are thought to be controlled by JAK family kinases TYK2 and JAK1. Autoimmune diseases, such as psoriasis, can occur when the production of cytokines is not properly regulated and immune cells are overly activated.
In the psoriasis model system, the TYK2/JAK1 inhibitor molecule, known as SAR-20347, interrupted the psoriatic cascade of events and led to reduced activation of keratinocytes (skin cells that multiply excessively in psoriasis) and a reduction of pro-inflammatory cytokine levels.
Sareum and SRI International entered into a co-development agreement to develop TYK2 inhibitors for autoimmune and inflammatory diseases in April 2013.
Im sure I read on here a couple of years ago that Tims plan was to licence CHK1 to pay for the Aurora FLT3 phase 1/2 trials. But IMO things have changed. CHK1 is much more valuable than first thought (it can be used on more cancer types and is also showing signs that it can be used more on its own, rather than in combination with Radio and Chemotherapy).
So the plan changed and Tim plus the partners (CRUK and BACIT / ICR) want to retain as much of these two as possible. But this will cost. It makes perfect sense to try and licence TYK2 to cover the cost of both of these.It is much more advanced and valuable as a result of the SRI collaboration.
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