1:00 PM CAREER PANEL with Amgen scientists at ISEB 1200

2:00 PM POSTER SESSION at ISEB plaza & lobby

3:00 PM LECTURE at ISEB Auditorium: "Design and Synthesis of the Macrocyclic pan-KRAS Inhibitor AMG 410" (Ryan Wurz)

KRAS is the most frequently mutated oncogene, with mutations found in over 20% of human cancers, including pancreatic, colorectal, and lung, endometrial, and gastric tumors. Building on key insights from the development of sotorasib, a covalent KRAS G12C inhibitor, we applied structure- and property-based design strategies to identify a new class of reversible, macrocyclic pan-KRAS inhibitors. This presentation describes the design rationale and synthetic approaches used to access these potent inhibitors and examines the structure-activity relationships that guided program evolution. These efforts culminated in the discovery of AMG 410, which is currently under clinical evaluation in patients harboring KRAS missense mutations or genetic amplifications who have progressed on standard-of-care therapies.

4:00 PM LECTURE at ISEB Auditorium: "Fluorochemicals: The Future We Want" (Veronique Gouverneur)

Fluorochemicals quietly power our modern lives serving as medicines, agrochemicals and strategic materials including refrigerants, batteries and electronics. All fluorochemicals are prepared from — the now critical — mineral Fluorspar (CaF2). The first step of any synthesis is the conversion of Fluorspar to hydrogen fluoride (HF) upon treatment with H2SO4 at 300 °C, a process reported by Scheele in 1771. Highly toxic HF has caused serious accidents, some with fatal casualties and severe damage to the environment. The fluorochemical industry is today exposed to supply shortages, safety constraints and environmental damage. Our goal is to reinvent fluorine chemistry from the ground up with innovative, safe and economically viable Fluorspar technologies that bypass HF, and with processes to recover the fluorine content of waste fluorochemicals such as PFAS for a circular fluorine economy. Such ground breaking development could support the fluorine sector, protect workers, simplify supply chains, and reduce the energetic and environmental burden of fluorochemical production. This lecture will discuss our results to date, and our approach to bridge the gap between academic discoveries and societal impact.