Pipeline

S*BIO’s intense research efforts in this competitive area have resulted in two drug candidates: SB1518, a potent JAK2 inhibitor with an interesting selectivity profile and excellent pharmaceutical properties and SB1578, a follow up compound. These compounds have potential for the treatment of myeloproliferative disorders and hematologic malignancies as well as various autoimmune and inflammatory conditions. SB1518 is currently in Phase 2 clinical trials in US and Australia in patients with various hematologic malignancies.

Steps in the activation of the JAK-STAT pathway. Inhibition of this pathway may provide therapeutic benefit in pathological conditions driven by activation of this pathway

The Janus kinases constitute a family of 4 cytoplasmic tyrosine kinases (JAK1, JAK2, JAK3 and TYK2) that play pivotal roles in the signaling pathways of many cytokines, hormones and growth factors. These signaling pathways regulate important physiological processes such as immune response to pathogens, erythropoiesis, thrombopoiesis, etc. Aberrant signaling of the JAK kinases have been shown to lead to many diseases, including hematological malignancies, allergies, asthma, rheumatoid arthritis, severe combined immune deficiency, etc. In particular, constitutive signaling of JAK2 has been shown to be the key driver in several human malignant conditions including bcr-abl negative myeloproliferative disorders, lymphomas and other hematologic malignancies involving JAK2 translocations (e.g. TEL-JAK2 in certain leukemias).

The IL-23R signaling pathway (signaling through JAK2 and TYK2) has been implicated in many autoimmune inflammatory conditions, including Crohn’s Disease, rheumatoid arthritis and psoriasis. Elevated protein and mRNA levels of the cytokine IL-23 have been detected in diseased tissues from human patients and animal models. Polymorphisms in the IL-23R gene have been linked to susceptibility or protective effects in all of the above three disorders. Since IL-23 signals through both JAK2 and TYK2, the inhibition of these JAK kinases may provide a novel therapeutic modality for managing these debilitating conditions.

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