T-cell Acute Lymphoblastic Leukaemia (T-ALL) represents approximately 10 to 15% of newly diagnosed cases of Acute Lymphoblastic Leukaemia . Around 200 people are diagnosed with T-ALL in the UK every year, usually occurring in late childhood or early adolescence and predominantly in boys. Approximately 2000 cases per year occur in Europe, and another ~2000 cases per year arise in the US.
In contrast to B-ALL (B-cell Acute Lymphoblastic leukaemia), where targeted therapeutic options have emerged for different disease sub-types, targeted therapies have not yet been developed for T-ALL.
The scientific literature suggests that activation of the TYK2-STAT1-BCL2 pathway in T-ALL occurs either by gain of function TYK2 mutations, or by activation of Interleukin-10 (IL-10) receptor activation (signalling via TYK2) which represents an opportunity for a highly innovative personalised therapeutic approach.
Sareum has discovered a novel series of selective inhibitors of TYK2 from its TYK2 autoimmune disease programme, and have shown that they can prevent T-ALL cells from proliferating by causing programmed cell death.
A feasibility study, part-funded by the Innovate UK Biomedical Catalyst, was undertaken to further assess Sareum’s TYK2 inhibitors against T-ALL cell lines and to develop a broader understanding of the biology connecting T-ALL and TYK2. This investigation culminated in a T-ALL disease model study in which Sareum’s compounds, dosed orally, were well tolerated, presented good exposure to plasma and tumour tissue and showed a dose-dependent effect on a biomarker of TYK2 inhibition and tumour reduction of up to 80%.
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