DeuterOncology, a clinical-stage drug development company, has closed €5.65 million ($6.1 million) series A financing, to start the phase I clinical study for its lead product DO-2, an improved MET kinase inhibitor currently being developed as a potential best-in-class targeted therapy for lung cancer.
The financing included participation from historical investor Newton Biocapital and new investors Noshaq and Investsud Tech.
MET inhibitors have recently been approved for patients with non-small cell lung cancer (NSCLC) harboring the MET exon 14 skipping mutant. Unfortunately, they all suffer from the same issue: poor tolerability. This leads to frequent dose reductions and interruptions that result in suboptimal target inhibition and therapy resistance. All agents in this class report similar issues and, as a result, require maximum tolerated clinical doses to achieve efficacious exposures. However, these high daily doses cause the formation of increased levels of inactive metabolite(s) that continue to impart toxic effects.
DO-2 overcomes this at source, having a metabolically-liable hydrogen replaced with a stronger bond strength deuterium atom. This significantly reduces the impact of this metabolic liability during treatment. The strength of DO-2 has been proven in preclinical studies, where low doses resulted in an extended efficacious plasma exposure profile and potent in vivo efficacy.
Promising target
In addition, these studies have shown the formation of an active metabolite that maintains activity on the MET kinase as well as binding to an alternative kinase that is a constituent of the RAS pathway. This new target kinase is reported to play a role in the RAS signaling pathway that is involved in resistance to MET inhibitors, it therefore represents a promising target for overcoming or delaying the emergence of resistance.
The ability of DO-2 to sustainably inhibit MET opens potentially broader oncology applications as monotherapy and in combination therapy with other SOC (standard of care) and targeted agents.
Timothy Perera, founder and CEO of DeuterOncology, said: “The clinical study (EudraCT 2022-001681-35) is now open for recruitment of biomarker selected patients at two trial sites in Belgium (with Prof Jean-Pascal Machiels and Dr Rachel Galot, Cliniques universitaires Saint-Luc, UCLouvain Brussels and Prof Hans Prenen, UZA Antwerp) and one site in the Netherlands (with Dr Debbie Robbrecht, Erasmus MC Rotterdam). We expect to obtain phase I results by Q2, 2024.”