On April 18, 2024 Outrun Therapeutics ("Outrun"), the E3 ligase inhibitor and protein stabilisation specialist, reported the company exits from stealth following a $10m seed financing round (Press release, Outrun Therapeutics, APR 18, 2024, View Source [SID1234642144]). Outrun’s platform has enabled it to rapidly build a pipeline of highly selective, small molecule, first-in-class E3 ligase inhibitors, as well as identify novel E3 ligase targets across multiple disease areas. Outrun’s lead programme is focused on hard-to-treat solid tumours.
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E3 ligase inhibition in protein stabilisation is of very high interest as a therapeutic approach to treating many diseases. Cells have evolved highly sophisticated ways of keeping disease at bay, and empowering the body to take care of itself is potentially the most effective way of suppressing disease. Inhibiting targeted E3 ligases enables protein stabilisation "at source", being directly part of the tagging mechanism involved in healthy cellular processing of destabilised, unwanted, or mis-formed proteins. This restores the body’s sophisticated natural disease suppression processes and could be applicable to a wide range of indications, including oncology and neurology.
Selective protein stabilisation by inhibiting specific E3 ligases will expand the disease indications that can be addressed with protein stabilisation and minimise side effects. There are ~700 E3 ligases representing the vast number of discrete cellular processes they control, providing potential targets for Outrun to develop effective precision medicines against.
Outrun has developed a proprietary, high throughput platform which allows robust, highly accurate, quantitative assessment of the specificity and selectivity of E3 ligase targets, thereby dramatically reducing the discovery time for E3 ligase inhibitors, improving specificity and target binding. Furthermore, the platform uses engineered protein sensors (EPS) to uncover the detailed biochemistry of E3 ligases, enabling discovery of drugs with potentially superior binding, specificity, and activity. Outrun’s approach is a scalable and modular strategy for developing next-generation small molecule drugs targeting E3 ligases, particularly inhibitors that stabilise proteins.
Dr Carolyn Porter, Chief Executive Officer of Outrun Therapeutics, said: "Protein stabilisation is the mirror image of protein degradation and seeks to maintain the levels of critical proteins that are otherwise unbalanced in certain diseases, disrupting the body’s highly sophisticated natural disease suppression processes. We are bringing our world class knowledge of E3 ligase biology and protein-to-protein interactions, combined with our proprietary discovery platform, to unlock the potential of this exciting new therapeutic area."
Dr Jeffrey Moore, President at MP Healthcare Venture Management, commented: "We believe protein stabilisation via E3 ligase inhibition is a potentially powerful new therapeutic modality. With world leading research under the guidance of a talented management team, we are confident that Outrun has the potential to transform a variety of disease areas, such as oncology and neurology."
Dr Bauke Anninga, Investment Director at M Ventures, added: "We are delighted to be one of the founding investors of Outrun. The Company’s novel platform enabling rapid assessment of the specificity and selectivity of E3 ligase inhibitors, provides a highly competitive edge to reduce discovery timelines and build a first in class pipeline."
Led by a seasoned management team and a strong Board, Outrun was spun out of founder Prof. Satpal Virdee’s world-renowned MRC Protein Phosphorylation and Ubiquitylation Unit at the University of Dundee. Outrun’s Scientific Advisory Board consists of highly relevant, world-leading experts in ubiquitylation and oncology. Outrun is backed by leading venture capital investors M Ventures and MP Healthcare Venture Management.