Biotechnology - , Auvergne-Rhone-Alpes, France
Step Pharma is developing a novel class of oral nucleotide synthesis inhibitors specifically targeting cytidine triphosphate synthase 1 (CTPS1) to induce selective modulation of T and B cell populations. The discovery of CTPS1 as a potential target for immunomodulation was based on studies of humans with a CTPS1 deficiency (Martin et al., Nature. 2014 Jun 12;510(7504):288-92) providing genetic evidence that CTPS1 inhibition could be used to treat lymphoproliferative cancers and auto-immune diseases. Cytidine nucleotide triphosphate (CTP) is a precursor required for DNA synthesis, a crucial step in cell division. De novo synthesis of CTP depends on two enzymes, the CTP synthases 1 and 2 (CTPS1 and CTPS2).CTPS2 is expressed in most tissues whereas CTPS1 expression is low in all tissues including resting T and B cells, but rapidly and strongly up-regulated specifically in T and B cells following activation.Importantly, CTPS1-deficient patients only exhibit specific immunodeficiencies without other clinical problems and CTPS2 is not able to complement for the lack of CTPS1 in T and B cells. CTPS1 therefore represents a therapeutic target for a new class of highly selective immunomodulatory and oncology drugs.The anti-proliferative activity of CTPS1 inhibition has been demonstrated in multiple cancer cell lines and the pharmacokinetic/pharmacodynamic relationship has been established using several animal models of disease.Step Pharma lead compound, STP938, is now in IND/CTA enabling studies with the aim to enter clinical development in 1H2022 focused on relapsed/refractory T cell lymphoma patients.
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