Flagship Pioneering has introduced Expedition Medicines™, a company focused on generative covalent chemistry to push the limits of medicine. After three years of internal development, Flagship has made an initial commitment of $50 million to enhance Expedition's platform, which aims to generate small molecule medicines for any target and advance its discovery programs in oncology, immunology, and other well-defined diseases. Furthermore, Expedition has kicked off a multi-target exploration agreement to discover novel therapeutic candidates for prostate cancer, thanks to its strategic partnership with Pfizer.

"Today, the majority of proteins known to be involved in disease have no medicines that can reach them. By harnessing AI and quantum covalent chemistry to rewrite what's possible in drug design, Expedition is transforming these undruggable proteins into tractable targets," stated Noubar Afeyan, Ph.D., Founder and CEO of Flagship Pioneering and Co-Founder and board director of Expedition Medicines. "Expedition is able to explore entirely new territory thanks to a unique insight from the quantum chemistry of protein-small molecule interactions, generative AI, and a team that bridges medicinal chemistry, artificial intelligence, and therapeutic development to redefine the drug discovery paradigm."

Traditionally, proteins with smooth surfaces have been deemed undruggable due to the absence of features for small molecules to bind. Instead of the conventional "binding-first" approach, Expedition employs a "reaction-first" covalent chemical insight, which utilizes quantum interactions between small molecules and reactive areas of protein surfaces for high potency binding, even in shallow pockets. This innovative approach has led to the development of a quantum chemistry AI platform, supported by a leading chemoproteomic screening and data generation engine. As a result, Expedition can access new protein targets, generate high-quality quantitative molecular interaction data at scale, and train generative chemistry models to produce de novo small molecules that interact effectively with elusive targets in the proteome, including transcription factors, adaptor proteins, regulators, and protein-protein interfaces that have been linked to various diseases.

"AI is transforming biology by learning the grammar of proteins and DNA. At Expedition, we are pioneering the same leap for small molecules grounded in the quantum chemistry of covalent interactions and fueled by unprecedented experimental data," remarked Molly Gibson, Ph.D., Co-Founder, CEO, and board director of Expedition and Origination Partner at Flagship Pioneering. "Our models are learning the rules of how molecules react and bind to any protein surface in order to make small molecule programmability a reality."

As part of Flagship's collaboration with Pfizer, Expedition has begun research to identify new potential therapeutic candidates for prostate cancer. This effort aims to develop a pipeline of innovative medicines targeting previously undruggable proteins associated with prostate cancer progression and treatment resistance.

Expedition is led by a team including Nathan Stebbins, Ph.D., Co-Founder and Chief Strategy Officer; Dean Stamos, Ph.D., Co-Founder and CSO – Chemistry & Proteomics; Todd Kinsella, Ph.D., CSO – Drug Discovery and Translation; Henry van den Bedem, Ph.D., Chief Technology Officer; and Marie Yurkovich, Ph.D., Co-Founder and Head of Strategy and Operations. Kinsella and Stamos previously led biology and chemistry innovation at Vividion Therapeutics, while van den Bedem directed Machine Learning at Atomwise. Geoffrey von Maltzahn, Ph.D., Co-Founder of Expedition and General Partner at Flagship Pioneering, will also serve on the company's board.

Expedition Medicines is at the forefront of expanding the boundaries of medicine through its AI-driven quantum chemistry platform, which systematically learns the rules of molecular reactivity to create small molecule drugs against disease-driving proteins long considered undruggable. The platform is set to deliver a pipeline of potential first-in-class therapies across oncology, immunology, and other well-defined diseases. Founded by Flagship Pioneering in 2022, Expedition is poised for significant advancements in drug discovery.