Previous Phase 2 trials for this asset did not succeed, largely due to challenges in clinical positioning and trial execution rather than limitations of the mechanism itself. SYK is a pivotal kinase in immune cell signalling and a validated driver of disease in both ITP and CLL. In ITP, our inhibitor is designed to achieve best-in-class efficacy while avoiding the toxicity seen with the currently approved therapy. In CLL, it has the potential to overcome resistance to existing treatments, with the opportunity to benefit up to 30% of patients who no longer respond to standard of care.

The initial chemical series encountered genotoxicity during candidate selection, preventing advancement. PDE9 remains a compelling mechanism, capable of influencing multiple pathways relevant to complex diseases. Our approach is to overcome the earlier toxicity limitations through new chemistry and improved profiling. By doing so, we aim to unlock the potential of PDE9 inhibition for patients with overlapping cardio-metabolic morbidities, where safe and effective treatment options are still lacking.

This programme was acquired at Phase 2 following the emergence of neurotoxicity. CDK9 remains a highly promising target, with best-in-class credentials driven by excellent kinase selectivity and oral bioavailability. Our strategy is to reduce brain penetration and optimise pharmacokinetics, unlocking the full therapeutic potential of this target class.