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25 July 2017

Milner Therapeutics Institute: a drug discovery ecosystem

“I started to wonder why this pharma academia collaboration does not happen more often”

Author: Louise Walsh, communications manager, features and research horizons, University of Cambridge

Prof Tony Kouzarides is passionate about ecosystems – well-balanced communities that flourish on mutual and dynamic interactions. But the ecosystems that excite him are not made up of plants, animals and environments. They are made up of experts.

The world needs new medicines. It is time-consuming and costly, and that is why we need an ecosystem that will nurture and speed up the success.

Kouzarides is the founding director of the Milner Therapeutics Institute, which is due to open in 2018 on the Cambridge Biomedical Campus. The ecosystem he sees thriving within its walls is one in which academic researchers – “experts in the biology of diseases” – work closely with pharmaceutical companies – “who know what is needed to get the drug to clinic” – to find new medicines. Put simply, he says, the institute will be “a pipeline for drug discovery within an academic setting”.

While the labs are being fitted out with robotics for customised drug screening, gene-editing facilities to rewrite DNA and bioinformatics support to help scientists deal with huge datasets, the partnerships between industry and academia are already under way.

In June 2015, a research agreement was signed between University of Cambridge, Wellcome Trust Sanger Institute and Babraham Institute with three pharmaceutical companies – AstraZeneca, Astex and GlaxoSmithKline (GSK). Since then, three more – Pfizer, Shionogi and Elysium Pharmaceuticals – have joined the Milner Therapeutics Consortium, the outreach program of the institute.

With this one agreement, doors opened. Kathryn Chapman, executive manager of the Milner Therapeutics Institute, explained: “Forming the consortium means there is now a free exchange of potential drug molecules between pharma and academia.

“This sounds straightforward but, before the agreement, this could take a year because of confidentiality and material transfer contracts. Now it takes two to three weeks. It lowers barriers of engagement, it speeds up research and it can involve hundreds of molecules in one go.”

One consequence is that drugs already approved for use against certain diseases are now being tested for use in fighting other conditions – a practice called repositioning or repurposing.

“An academic might have developed a brain disease model using an organoid – a mini-organ in a Petri dish,” said Kouzarides. “We can use this to test drugs that have been licensed for use in other diseases such as arthritis or cancer.”

It also means that novel therapeutic agents across the entire portfolio of drugs being developed by each of the companies can be screened at an early stage in biological assays, to see whether any are worth progressing along the drug development pipeline.

For example, one of the consortium’s first collaborative projects is a partnership between AstraZeneca and professor Carlos Caldas at the Cancer Research UK Cambridge Institute.

Breast cancer consists of several different genomic subtypes, which makes effective treatment challenging and prognosis variable. Some subtypes respond well to particular drugs or drug combinations whereas others are resistant.

Caldas has pioneered the development of a biobank of patient-derived breast cancer cells and tissues that have greater predictive power for clinical outcome than other preclinical models – such as cancer cell lines. Caldas and AstraZeneca are now working together to test how different subtypes of breast cancer respond to different AstraZeneca compounds and compound combinations, as well as looking at potential drug-resistance mechanisms.

From 2018, the consortium will form a major part of the Milner Therapeutics Institute, which has been made possible through a £5m ($6.5m) donation from Jonathan Milner, a former member of Kouzarides’ research group and entrepreneur. Milner and Kouzarides are two of the founders of Cambridge-based biotechnology company Abcam.

“One of the main aims of the institute will be to develop multiple disease models to understand how drugs could work on the real disease,” said Kouzarides. “We plan to focus on some of the most challenging diseases to start with – cancer, neurodegeneration and inflammation – but we are disease agnostic. If we have a method of testing for efficacy and a library of molecules to test, then we will test.”

Kouzarides’ enthusiasm for making sure the “Petri-dish-to-pill” pipeline works, comes from his own positive experience of a collaboration with GSK that has resulted in a leukaemia drug now being used to treat patients.

It came about through serendipity. “GSK was developing a molecule called I-Bet against an epigenetic protein. I was a consultant on the project and became aware that the molecule could be effective against mixed lineage leukaemia, the most common type of leukaemia in children under two years old. We had the cell assays and disease models in Cambridge, and we asked to test the drug. It worked and it is now in the clinic.

“I started to wonder why this pharma-academia collaboration does not happen more often. People have been talking about the translational gap between fundamental research and the clinic for years, and it is still there. While serendipity is good – and many amazing medical innovations have come out of chance encounters – we cannot trust only to chance.

“The world needs new medicines to be developed. It is time-consuming and costly, and that is why we need an ecosystem that will nurture and speed up the success.”

The Milner Institute will be within the Capella building at the Cambridge Biomedical Campus, alongside the relocated Wellcome Trust/MRC Cambridge Stem Cell Institute, the Cambridge Institute of Therapeutic Immunology and Infectious Disease, and the Cambridge Centre for Haematopoiesis and Haematological Malignancies.

This is an edited version of an article that first appeared on University of Cambridge’s website. It has been republished with permission from the author.

Copyright Mawsonia Limited 2010. Please don´t cut articles from www.globaluniversityventuring.com or the PDF and redistribute by email or post to the web without written permission.

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