Targeted protein degradation (TPD) aims to eliminate rather than inhibit disease-causing proteins. Unlike traditional small-molecule drugs that only inhibit targets, degradation-inducing molecules deplete their targets and do not require active binding sites to exert their effect. Thus, entities like molecular glues, heterobifunctional degraders known as proteolysis targeting chimeras (PROTACs), monovalent degraders, and deubiquitinase inhibitors can potentially target the large part of the human proteome that lacks active binding sites and is thus inaccessible to small-molecule inhibitors. This novel therapeutic mechanism makes protein degraders promising therapeutic agents for indications of high medical need unmet by conventional medicines.

Although protein degraders have the potential to become blockbuster drugs in many therapeutic areas including cancer and neurology, their discovery has been largely serendipitous. Thus, the target reach and selectivity of many TPD compounds is largely unknown. NEOsphere Biotechnologies fills that gap. NEOsphere Biotechnologies offers its strategic partners in-depth screening of compound libraries of any size against the full human proteome to initiate and advance drug discovery of degrader molecules.

NEOsphere Biotechnologies combines data-independent acquisition mass spectrometry (DIA-MS) with custom-built data interpretation to deliver high-throughput proteomic analysis with superior sensitivity, precision, and data completeness. The platform is fast and highly scalable to align with drug development cycles. It screens thousands of degrader compounds against more than 10,000 proteins. Once identified, candidates are validated as novel degrader targets using powerful technologies such as high-throughput interactomics or ubiquitination analysis to an unparalleled depth of 50,000 sites.

Prof. Henrik Daub, scientific founder and Chief Scientific Officer of NEOsphere Biotechnologies comments: “To exploit the full potential of TPD, proteome-wide analysis should ideally accompany any degrader molecule, from initial characterization at the screening stage to final drug candidate nomination. Our platform allows for deep proteomic screening compatible with both early target discovery and advanced compound optimization, granting unprecedented access to the previously undruggable target space. Working with our partners, we aim to connect their innovative degrader chemistries with the whole proteome. Thus, we create novel drug discovery opportunities at scale and enable our partners to build broad and robust pipelines of first-in-class therapeutics.”