Clinical trials have begun for a drug candidate for hard-to-treat cancers, discovered at the University of Edinburgh and licensed by US biopharmaceutical company Nuvectis Pharma, Inc.
Nuvectis, which focuses on the development of innovative precision medicines for the treatment of serious conditions of unmet medical need in oncology, has launched a Phase 1a dose escalation clinical trial of NXP900 in the US.
The compound, NXP900, employs a novel mechanism of action to inhibit the activity of SRC family kinases (a particular group of enzymatic proteins), in particular YES1 and SRC. An association between the SRC family of kinases (SFKs) and cancer growth has been known for several decades but previous attempts at treating solid tumours using this mechanism have met with little success.
The study is designed to evaluate the safety, tolerability and pharmacokinetic properties of NXP900 in patients with advanced solid tumours.
SFKs are aberrantly activated in various cancer types and they are central mediators of various oncogenic processes such as proliferation, survival, cell adhesion, invasion, and angiogenesis. NXP900 is a potent and highly selective SFK inhibitor, including low nanomolar IC50 against YES1 and SRC (0.5nM and 2.4nM respectively) that demonstrated robust single agent anti-cancer activity against several solid tumor types in preclinical models.
The drug discovery programme was led by Professors Neil Carragher and Asier Unciti-Broceta at Edinburgh Cancer Research within the University of Edinburgh’s Institute of Genetics and Cancer, involving more than ten years of research.
Nuvectis licensed rights to NXP900 in September 2021 from the University of Edinburgh in a deal facilitated by Edinburgh Innovations, the University’s commercialisation service.
Professor Neil Carragher said:
This is the news we have been waiting for, as NXP900 makes the all-important transition from the lab into a clinical setting.
This is a great step towards a medicine that could treat some of the toughest cancers and extend the lives of many thousands of people. ”
Professor Unciti-Broceta (pictured above) said:
To know a drug discovered and developed preclinically in our lab is now to be given to patients is extremely rewarding – it is the realisation of years of work, collaboration and ambition. ”
Dr John Lonsdale, Head of Enterprise at Edinburgh Innovations, said:
I’m thrilled to see the progress of NXP900 into its first in-human clinical trial. We are delighted to have supported and enabled this world class research to transition from the lab out into the world, where it can begin to make a difference to people’s lives. ”
Ron Bentsur, Co-Founder, Chairman and Chief Executive Officer of Nuvectis, said:
Advancing NXP900 into its first in human clinical trial is an important milestone for Nuvectis. We believe that NXP900's unique mechanism of action which completely shuts down signaling via SFK, in conjunction with its high target specificity differentiates it from other multi-kinase inhibitors that also inhibit SFK and provides it with the potential to become the first SFK inhibitor for the treatment of solid tumours. ”
Read the paper, A Conformation Selective Mode of Inhibiting SRC Improves Drug Efficacy and Tolerability, in the journal Cancer Research