AZ and CRUK team up to go all-in on CRISPR

AstraZeneca and Cancer Research UK are collaborating to launch a centre of excellence in genetic screening, cancer modelling and big data processing that will develop CRISPR technology to better understand the biology of cancer.

The Functional Genomics Centre will help create biological models that may be more reflective of human disease, as well as advancing computational approaches to better analyse big datasets, with the aim of accelerating the discovery of new oncology medicines.

CRISPR is a gene editing technology that can be used to edit the desired parts of the genome, which makes it possible to identify a DNA sequence, remove it, replace it or add it more easily than ever before to result in the deletion or introduction of specific nucleotide changes into any gene.

Though it is still an emerging field, the first therapies utilising CRISPR are already being reviewed by the FDA, including Vertex’s CTX001.

“CRISPR in its broadest intent has become embedded in the majority of our therapeutic programmes in terms of our ability to build better disease models, help us identify better medicines and now increasingly in functional genomics to help us identify the targets that we’re working on in the first instance,” Steve Rees, AZ’s VP discovery biology, IMED Biotech Unit, told pharmaphorum at a media briefing. “The collaboration with CRUK in the Centre for Functional Genomics will allow us to run 150 of these screens each year from 2020 – half of those will be for AZ and half for CRUK – and this will apply to the majority of our oncology projects to help us identify targets in the first instance but also help us identify the resistance mechanisms to our drugs such that we can make improved medicines that address those resistances.

“In a couple of years’ time I expect that every drug candidate we select to go into the clinic somewhere along the way will have been touched by CRISPR, in terms of optimising the model system that it’s tested in.”

Functional genomics aims to understand the complex relationship between genetic changes happening within DNA and how these translate to cellular changes in disease. Knowing the functional genomic drivers of disease enables scientists to more accurately select the right drug targets and increases the probability of success in the clinic, and Mene Pangalos, AZ’s executive vice president, innovative medicines & early development, said that the collaboration is part of the company’s wider strategy to increase the success rate of its programmes.

“None of our programmes go in the clinic now without being able to demonstrate proof of mechanism – that you’re actually engaging the target, engaging the pathway and engaging the science, so you know that if it fails you’ve tested your hypothesis and you’ve learnt something as a consequence.”

Recently the company had two high-profile late-stage failures with its cancer immunotherapy Imfinzi (durvalumab), in phase 3 trials for head and neck cancer and lung cancer.

At the Centre, scientists will have access to the next generation of CRISPR libraries for silencing or activating every gene in the genome, accessed through an extension of the existing collaboration between AstraZeneca and the Wellcome Sanger Institute.

The centre will be housed in the Milner Therapeutics Institute at the University of Cambridge and operationalised through Cancer Research UK’s Therapeutic Discovery Laboratories – the charity’s in-house drug discovery unit focused on establishing drug discovery alliances with industry.