The company CasInvent Pharma was established in 2020 as a spin-off of Masaryk University (MU) in cooperation with the investment partner i&i Prague, s.r.o. (Ltd). The mission of the company is to develop new therapeutic options for the treatment of selected malignancies. The CasInvent technology is based on the use of proprietary highly selective inhibitors of enzymes belonging to the Casein Kinase 1 (CK1) family that are responsible for the migration of leukemia cells into lymphoid organs.
The CK1 inhibitors were discovered by the research groups of professors Vítězslav Bryja and Kamil Paruch at the Faculty of Science of MU, who have long-term expertise in the research areas of CK1 biology and chemistry of kinase inhibitors, respectively. CasInvent Pharma closely cooperates with these teams in advanced preclinical development of selected substances. The candidate compound is planned to enter clinical trials focused on the treatment of Chronic Lymphocytic Leukemia (CLL) and Acute Myeloid Leukemia (AML).
Target: Casein kinase 1 (CK1)
Goal: Development of highly potent and selective inhibitors of CK1
The small-molecule inhibitors developed by CasInvent Pharma are designed to target with high selectivity and activity individual isoforms of serine-threonine kinases from the Casein kinase 1 (CK1) family. In our research, we have focused on the isoforms CK1 δ, ε as therapeutic targets for the treatment of chronic lymphocytic leukemia (CLL), and CK1 α for acute myeloid leukemia (AML).
The development of the proprietary CK1 inhibitors is based on our studies of CLL biology. CLL is a lymphoproliferative malignancy with highly heterogeneous disease course and unclear pathogenesis. Our research of pathological cell signaling in CLL has been focused on regulators of cell migration and interaction of the leukemic cells with their protective microenvironment, which often enables survival of tumor cells, disease progression and therapy evasion. We discovered that targeting of CK1 δ and ε kinases alone in CLL cells is sufficient to block the leukemic cell migration and the microenvironmental interactions and delay the disease progression in mice. Importantly, when combined with standard CLL treatment (ibrutinib, potent inhibitor of B cell receptor signaling), CK1 inhibition provided the benefit of stronger, synergistic effects in vitro and stronger response to therapy in vivo in the used animal model of CLL.
Targeting of the kinase CK1 α has been also recently recognized as an attractive therapeutic strategy for the treatment of AML and myelodysplastic syndrome (MDS). However, most of the published studies have used small-molecule inhibitors with low potency and poor kinase selectivity. Our recently identified series of molecules contains potent and highly selective inhibitors of CK1 α, with minimal off-target effects at therapeutic doses.
The lead compound MU1630 was designed to efficiently target selected CK1 isoforms. Chosen out of a series of >300 compounds, MU1630 exhibits exceptional selectivity to CK1, combined with favorable PK and safety profiles. The kinome trees (on the left) show the improvement of the kinase selectivity from PF-670462 (left), which served as a model compound for the studies of the therapeutic effects of CK1 inhibition on hematological malignancies, to the novel patent-protected lead compound MU1630 (right).
To date, more than 250 compounds were prepared and tested:
CasInvent Pharma is developing selective small molecule inhibitors of casein kinase I (CK1). Our main development program is focused on drug candidate MU1630 for the treatment of Accute Myeloid Leukemia (AML). Concurrently, CasInvent is developing the molecule MU1630 as a potential treatment for CLL. Both programs are in the preclinical stage of development. Other indications in the field of oncology are being studied, using the lead candidate as well as other molecules in our portfolio. CasInvent intends to advance its lead candidate to the clinical phase Ib.
The IP is subject to the exclusive sublicenceable worldwide license from the Masaryk University.