What Impact Could Protein Stabilisation Have for Cancer Patients?

The DD DW episode spotlights Outrun Therapeutics, a Dundee‑based biotech that has turned the elusive “E3‑ome” into a druggable landscape. By selectively inhibiting specific E3 ubiquitin ligases, Outrun’s proprietary Excel platform prevents the ubiquitin tag that normally earmarks proteins for destruction, effectively stabilizing them. This protein‑stabilisation strategy flips the paradigm of targeted protein degradation, offering a precision tool to rescue beneficial proteins that are otherwise lost in disease. With more than 650 human E3 ligases mapped, the company claims a new class of therapeutics that could rival the historic success of kinase inhibitors.

The lead program targets the E6AP ligase, a critical co‑factor hijacked by the HPV‑derived E6 protein to degrade the tumor‑suppressor p53 in HPV‑positive head‑and‑neck cancers. Pre‑clinical models showed that Outrun’s E6AP inhibitors restore p53 activity, trigger apoptosis, and shrink tumors without the systemic toxicity seen with broad‑spectrum proteasome blockers such as bortezomib. Unlike proteolysis‑targeting chimeras (PROTACs) that accelerate protein loss, Outrun’s approach preserves the native protein, delivering a safer, more selective therapeutic profile for a disease with a 5‑year survival rate below 10 %.

Beyond head‑and‑neck malignancies, the Excel platform is being annotated for dozens of previously undruggable E3 targets, opening avenues in cervical, lung and other HPV‑driven cancers. The company expects to nominate a development candidate for the E6AP inhibitor by year‑end and enter Phase 1 trials in 2027, positioning itself for partnerships with larger pharma players. Investors are drawn to the dual promise of a novel mechanism and a pipeline that could expand the market of protein‑stabilising drugs, potentially delivering high‑value, first‑in‑class therapies for unmet oncology needs.