Cytosolix

BlueYard Capital
2 min readAug 28, 2023

Due to abnormal metabolism, certain diseased tissues, most notably solid tumors, produce an acidic extracellular microenvironment that is still little understood. Nevertheless, today all drugs in oncology are developed by R&D teams using the same classic textbook definition of tumor acidity which leads to (among other issues) poor tumor targeting and specificity, resulting in a paradoxical situation: despite an increasing number of promising oncology treatments, most cancer therapeutics or chemotherapy agents still have significant toxicity issues and severe side effects, mainly due to off-target effects, ie. where drugs kill healthy cells.

The Cytosolix team has spearheaded a decade-long research program at the Engelman Lab at Yale that recently resulted in a paradigm shift in our understanding of tumor acidity by discovering that the tumor micro-environment is much more acidic than previously thought, opening up the possibility to create better acid-targeting cancer therapeutics. Based on this discovery, Cytosolix has developed a platform focused on small molecules, called TAP (tumor-activated permeability), and has developed a unique chemical library over the past decade as part of its goal to make order of magnitude better cancer therapeutics.

Our Thesis

In an era when a single blockbuster therapeutic for cancer can be worth billions of dollars in annual revenue, we believe Cytosolix’s TAP platform has the potential to be applied to nrealy all solid tumor targeting small molecules that are already approved and in development, meaning that Cytosolix could receive a part of the upside from a number of existing drugs if TAP is genuinely effective. Moreover, the company’s first oral lead small molecule has been shown to enhance in vivo biodistribution to tumor cells by several orders of magnitude, compared to the original drug, which could translate to a significant efficacy benefit and the company’s own best-in-class drug. Cytosolix will pursue several more candidates during the seed phase.

We look forward to joining Colin, John and the Cytosolix team on their journey.

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