This program is based on an inhibitor of TAK1 (Transforming growth factor-β-activated kinase 1). TAK1 is a central mediator, or a kind of switch, for various inflammatory signals and for activation of several inflammatory mediators (cytokines).

TAK1 is a ”master regulator” of both NF-κB and JNK signaling. It is a key kinase in innate immunity that integrates and controls signaling and production of key pathological cytokines. TAK1 integrates clinically and genetically validated pathways in human disease. Aqilion has discovered highly selective and potent TAK1 inhibitors with excellent drug-like properties within a unique chemical space.

Kinases are a very successful drug target class. Immune kinases including, JAK1, JAK2, JAK3, TYK2 and BTK have shown clinical effects in many autoimmune and inflammatory diseases. However, innate immunity kinase targets that are hypothesized to affect e.g. NF-kB or JNK signaling have failed to provide sufficient or sustained efficacy. These include p38⍺, SYK, TPL2 and IRAK4. Due to the central upstream node function of TAK1, inhibiting this kinase has the potential to provide a higher degree of efficacy by modulating the key cytokines IL-1β, IL-6 and TNF⍺.

The TAK1 program was started in the fall of 2019 and in 2023, Aqilion signed an exclusive license agreement and strategic research collaboration with Merck KGaA to discover, develop and commercialize small molecule inhibitors of TAK1. The collaboration ended 2024 due to new data affecting the risk-benefit profile in the intended disease indications. Aqilion’s internal drug development has led to unique small molecule inhibitors, and the collaboration with Merck KGaA has contributed with additional molecular assets. After reviewing and analyzing the entire data package, Aqilion decided to resume the development of the program as the company now owns the and controls the rights to the program.