Development of PS Targeting Synthetic Protein Drug Conjugates As A Genetic Alteration Agnostic Cancer Therapy

Pancreatic cancer (PDAC) patients face a lack of effective treatments, severe side effects from existing treatments and prolonged hospital stays, with limited impact on life expectancy. Globally, around 500,000 people are diagnosed annually (9,600 in UK), and this is expected to rise by 65% by 2040, one of the few cancers which is increasing in prevalence. New treatments which are more effective and safer are desperately needed. It is however an extremely challenging cancer to treat due to late diagnosis which usually rules out a surgical approach as the cancer has normally spread. Big advances in life expectancy for other cancers have relied on targeted approaches where therapy can be targeted to genetic alterations in the tumour such as Her2\. An example of this is the antibody drug conjugate Enhertu which has changed outcomes for patients with Her2 positive breast cancer. Unfortunately, very few pancreatic cancer tumours (7%) have genetic alterations that are targetable. Phosphatidylserine cancer membrane lipid is a genetic alteration agnostic marker of cancer which is found in the outer membrane of all cancer cells but is particularly prevalent in pancreatic cancer cell lines. New Path has made small proteins that bind selectively to phosphatidylserine and we have modified these to make PS targeted drug conjugates which have shown activity in animal models of pancreatic cancer. The aim of this project is to further develop these compounds to prepare for a clinical trial and to investigate which cancers they are effective for. We plan to develop the compounds further as a novel therapy for metastatic pancreatic cancer. In addition, our technology can be developed for use in other cancers with unmet medical need such as colon cancer, oesophageal cancer and ovarian cancer.