Discovery of Next Generation Kinase Inhibitors to Treat Acquired Drug Resistance

Pipeline and Targets

Our pipeline of innovative drug discovery programs is being advanced through our profound expertise in kinase structure and function, kinase inhibitor design and synthesis, binding kinetics, cellular selectivity, pharmacokinetics and target occupancy.

Program

Indications

Preclinical

IND enabling

Phase
1

Phase
2

Phase
3

Upcoming milestones

Partnered
TTK/PLK1 (BAL0891)
 Oncology read more Phase 1 studies in patients Basilea
Progress TTK/PLK1 (BAL0891)
BTK Oncology read more Available
Progress BTK
LCK (NTRC 0652-0) Oncology, CRS read more Available
Progress LCK (NTRC 0652-0)
EPriL Platform Projects Oncology read more Available
Progress EPriL Platform Projects

BAL0891 is a first-in-class mitotic checkpoint inhibitor that pushes cells through mitosis without adequate time for correct chromosome segregation. This results in aberrant tumor cell division leading to tumor cell death.

The compound is a unique dual inhibitor of threonine tyrosine kinase (TTK) and polo-like kinase 1 (PLK1). The dual action of BAL0891 leads to rapid disruption of the mitotic spindle assembly checkpoint (SAC) driving the cells through mitosis before the chromosomes are properly aligned leading to premature cell division and tumor cell death.

BAL0891 has shown anti-proliferative activity across diverse tumor cell lines in vitro and single agent efficacy in in vivo models of solid human cancers.

NTRCtx is working on a best-in-class BTK inhibitor that targets wild- type as well as multiple BTK mutants.

BTK has a central role in several signaling pathways in B cells, particularly the B cell antigen receptor. Aberrant regulation of regulation of BTK BTKBT has been linked to numerous B cell malignancies including chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and diffuse large B cell lymphoma (DBCL). Although the efficacy of BTK inhibition as a single agent therapy is strong, many patients develop acquired drug resistance. In a large proportion of patients, this is due to mutations in the kinase domain of BTK.

Our unique EPriL class of BTK inhibitors show long target residence time on wt-BTK as well as its mutants, has excellent PK properties and show long target occupancy in vivo.

NTRC 0652-0 is a first-in-class kinase inhibitor that targets LCK, a kinase involved in the activation of Yes Associated Protein (YAP). YAP is a component of the Hippo pathway and alterations in this pathway have been implicated in cholangiocarcinoma (CCA) pathogenesis. Furthermore, LCK plays a central role in the activation of T-cells. Immuno-therapies like T-cell activating antibodies or CAR-T cells often lead to cytokine release syndrome (CRS). An LCK inhibitor normalizes these responses without effecting T-cell viability.

NTRC 0652-0 is a very potent and highly selective LCK inhibitor that has a long residence time on LCK. Furthermore, the compound has excellent PK properties and is very effective in in vivo models of CCA.

The EPriL platform allows us to rapidly identify inhibitors for kinases that show resistance to first generation inhibitors after mutation.

NTRCtx is working on several established targets for which there is a great medical need for next generation inhibitors.