FogPharma’s overarching mission is to usher in a world with no Actionability Gap, where disease biology, and likely medical impact, determine which human protein targets become drugged.  FogPharma’s approach is deeply inspired by evolution, drawing upon biology’s own tried-and-true strategies for biomolecular recognition and membrane penetration. Our Helicon^TM peptides combine the cell penetration capabilities of small molecules with the broad targeting power of biologics, allowing us to take aim at some of the most common yet elusive targets in cancer.

Our Helicon^TM peptide technology is centered on constraining short chains of amino acids — polypeptides — in a specific folded shape known as an α-helical conformation, which confers upon them unique drug-like properties. The α-helical fold intrinsically cloaks the polarity of the peptide backbone, allowing sufficiently hydrophobic peptides to cross membranes and enter cells. Nature provides ample examples of the membrane compatibility of α-helices: they are the only structures ever observed in single-pass transmembrane proteins. In addition to aiding cell entry, this cloaking also allows Helicon^TM peptides to evade rapid renal clearance and achieve long plasma and tissue residence times, providing pharmacokinetic profiles that enable sustained target coverage. The α-helical fold also prevents recognition by both proteases and the MHC proteins that are required for immune recognition, resulting in both greater stability and suppressed immunogenicity. Lastly – and crucially – α-helices are able to display a diverse array of sidechains along an extended interface, which allows them to bind many “undruggable” target proteins that are out of reach for small-molecule drugs. This combination of cell penetration, drug-like properties, and broad targeting ability make Helicon^TM peptides uniquely suited to solving the druggability challenge in modern medicine.

FogPharma aims not only to achieve near-universal druggability, but also to dramatically accelerate the speed and scalability of drug discovery. Here again, we draw inspiration from evolution, and combine it with recent advances in chemistry, biology, data science, and automation to create the foundations of a truly next-generation multiplexed and machine learning-enabled drug discovery engine. This engine exploits the polymeric nature of peptides to enable the rapid creation and testing of Helicon^TM peptides in controlled mixtures, with no separation or purification, and deploys machine learning to rapidly derive new rules for design optimization. Using this multiplexing engine, small teams of FogPharma’s scientists are able to design, synthesize, and evaluate thousands of new peptides each week in both biochemical and cell-based assays, progressing early hits into leads in a matter of months.

In the 1970s, Steve Wozniak manually iterated through circuit board designs, hardware, and code to create his first computers by hand, eventually leading to the creation of the Apple I. Today, Apple’s engineers develop incomparably more powerful and sophisticated chips using highly automated software – no manual design required. Our aspiration is to follow the technology industry’s lead, push our multiplexing technology to its limits, and build the world’s fastest and most powerful drug discovery engine – one which can be deployed to address the needs of human medicine at an unprecedented scale.