FERADICATE · Novel ferroptosis inducers for the treatment of non-small cell lung cancer

Despite significant advancements in the molecular characterization of certain types of cancer, many of these discoveries have yet to translate into substantial improvements in clinical outcomes. While targeted therapies are available, patients harbouring common oncogenic driver mutations often experience relapse. Prognosis is even poorer for those without identifiable oncogenic driver mutations. In cases with high PDL1 expression, single-agent immunotherapy typically leads to disease progression, whereas patients with low expression levels require additional toxic chemotherapy to achieve comparable outcomes. This underscores an urgent medical need for more effective therapeutic strategies for specific cancer subtypes. Ferroptosis, a form of necrotic cell death marked by the iron-dependent oxidative destruction of cell membranes, offers a pharmacologically tractable avenue for treatment. The strong reliance of certain tumour subtypes on cellular systems to suppress ferroptosis creates exciting opportunities for innovative therapies. We recently identified ferroptosis suppressor protein 1 (FSP1) as the second mainstay in ferroptosis suppression, functioning independently of the main regulator GPX4. Since the genetic or pharmacologic inhibition of FSP1 alone is sufficient to suppress certain tumour types in the in vivo context, FSP1 emerges as a compelling drug target. Here, we aim to further optimize the activity, selectivity, and pharmacokinetic profile of our newly identified FSP1 inhibitor family. We also seek strive to expand our patent portfolio to ensure broad IP coverage. Our primary objective is to identify a new lead compound—or potentially a preclinical candidate—for cancer treatment, thereby advancing FSP1 inhibitors toward preclinical and clinical development. This program has the potential to deliver a substantial value proposition and create opportunities for out-licensing or co-development partnerships.