̽��ֱ�� of Cambridge - Astex

Milner Therapeutics Institute: a drug discovery ecosystem

lw355 — Wed, 28 Jun 2017 14:30:05 +0000

Professor Tony Kouzarides is the founding Director of the Milner Therapeutics Institute, which is due to open in 2018 on the Cambridge Biomedical Campus. ̽��ֱ��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’s 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 the ̽��ֱ�� of Cambridge, the Wellcome Trust Sanger Institute and the Babraham Institute with three pharmaceutical companies – AstraZeneca (AZ), Astex and GSK. Since then, Pfizer, Shionogi and Elysium Pharmaceuticals have joined the Milner Therapeutics Consortium, the outreach programme of the Institute.

With this one agreement, doors opened. Dr Kathryn Chapman, Executive Manager of the Milner Therapeutics Institute, explains: “Forming the Consortium means there’s 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 drugs that have already been approved for use in certain diseases are now being tested for use in other diseases – 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,” explains 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 AZ 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).Carlos and AZ are now working together to test how different subtypes of breast cancer respond to different AZ 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 donation from Dr Jonathan Milner, a former member of Kouzarides’ research group and entrepreneur. Milner and Kouzarides are two of the founders of leading Cambridge 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,” explains 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’ll 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 in the clinic 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 (MLL), 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’s now in the clinic.

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

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

̽��ֱ��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 ̽��ֱ��Cambridge Centre for Haematopoiesis and Haematological Malignancies.

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’re made up of experts.

̽��ֱ��world needs new medicines to be developed. It’s time-consuming and costly, and that’s why we need an ecosystem that will nurture and speed up the success.

Tony Kouzarides

David Anderson

Neurons

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Cambridge researchers and pharma in innovative new consortium to develop and study early stage drugs

cjb250 — Tue, 28 Jul 2015 08:00:00 +0000

̽��ֱ��Therapeutics Consortium, announced today, will connect the intellectual know-how of several large academic institutions with the drug-developing potential of the pharmaceutical industry, to deliver better drugs to the clinic.

From early 2018, the Consortium will form a major constituent of the new Milner Therapeutics Institute, which has been made possible through a £5 million donation from Jonathan Milner and will be located in a new building at the Cambridge Biomedical Campus, the centrepiece of the largest biotech cluster outside the United States.

̽��ֱ��Consortium will connect academic and clinical researchers at the ̽��ֱ�� of Cambridge, the Babraham Institute and the Wellcome Trust Sanger Institute with pharmaceutical companies Astex Pharmaceuticals, AstraZeneca and GlaxoSmithKline (GSK). It will provide researchers with the potential to access novel therapeutic agents (including small molecules and antibodies) across the entire portfolio of drugs being developed by each of the companies, in order to investigate their mechanism, efficacy and potential. ̽��ֱ��terms of the Consortium allow for fast and easy access to these agents and information.

Each industry partner within the Therapeutics Consortium has committed funding to spend on collaborative projects and will collectively fund an executive manager to oversee the academic/industry interactions. Collaborative projects are expected to lead to joint publications, supporting a culture of more open innovation.

Professor Tony Kouzarides from the ̽��ֱ�� of Cambridge, who will head the Therapeutics Consortium and the Milner Institute, is currently deputy director at the Gurdon Institute. He says: “ ̽��ֱ��Milner Institute will act as a ‘match-making’ service through the Therapeutics Consortium, connecting the world-leading research potential of the ̽��ֱ�� of Cambridge and partner institutions with the drug development expertise and resources of the pharmaceutical industry. We hope many more pharmaceutical companies will join our consortium and believe this form of partnership is a model for how academic institutions and industry can work together to deliver better medicines.”

Dr Harren Jhoti, President and CEO of Cambridge-based company Astex Pharmaceuticals, now part of Japan’s Otsuka Group, said: “As a company that was founded right here in Cambridge we are delighted to support this new Consortium working together with leading Cambridge academic and clinical researchers to help us to research and develop ever better treatments for patients.”

Mene Pangalos, Executive Vice President, Innovative Medicines & Early Development at AstraZeneca said: “We are pleased to be part of this exciting new consortium that brings together world-leading science and technology into a dedicated multi-disciplinary institute focused on translational research. ̽��ֱ��proximity of the Institute to our new R&D centre and global headquarters in Cambridge will ensure our scientists can work closely with those at the Milner Institute.”

Professor Michael Wakelam, Director of the Babraham Institute, said: “ ̽��ֱ��Institute’s participation in the Therapeutics Consortium provides yet one more channel by which our excellence in basic biological research is built upon in partnership with industry-based collaborators. We know from experience that bringing together the best academics and the best pharmacological research is both efficient and enlightening and we look forward to making joint progress.”

Dr Rab Prinjha, Head of GSK’s Epigenetics Discovery Performance Unit, said: “Late-stage attrition is too high – very few investigational medicines entering human trials eventually become an approved treatment. As an industry, we must improve our success rate by understanding our molecules and targets better. This innovative institute which builds on GSK’s very successful collaboration with the Gurdon Institute and close links with many groups across Cambridge, aims to increase our knowledge of basic biological mechanisms to help us bring the right investigational medicines into human trials and ultimately to patients.”

̽��ֱ��Consortium will initially operate from the Wellcome Trust/Cancer Research UK Gurdon Institute, but will move into the Milner Institute in early 2018.

̽��ֱ��Milner Therapeutics Institute

One of the major aims of the Institute will be to help understand how drugs work and to push forward new ideas and technologies to improve the development of novel therapies. A major, but not exclusive, focus of the Institute will be cancer.

It is envisaged that the Milner Institute will be equipped with core facilities, such as high-throughput screening of small molecules against cell lines, organoids (‘mini organs’) and tumour biopsies, as well as bioinformatics support to help scientists deal with large datasets. Its facilities will be available to researchers working on collaborative projects within the Therapeutics Consortium and, capacity permitting, to other scientists and clinicians within the Cambridge community.

In addition, the Milner Institute will have space for senior and junior scientists to set up independent research groups. There will also be associated faculty positions, which will be taken up by scientists in different departments, whose research and expertise will benefit from a close association with the Milner Institute.

̽��ֱ��Milner Institute will be housed within the new Capella building, alongside the relocated Wellcome Trust/MRC Cambridge Stem Cell Institute, a new Centre for Blood & Leukaemia Research, and a new Centre for Immunology & Immunotherapeutics.

Jonathan Milner, whose donation has made the Milner Therapeutics Institute possible, is a former member of Tony Kouzarides’ research group and experienced entrepreneur. In 1998 they founded leading biotechnology company Abcam together with Professor David Cleevely, which has gone on to employ over 800 people and supply products to 64% of researchers globally.

An innovative new Consortium will act as a ‘match-making’ service between pharmaceutical companies and researchers in Cambridge with the aim of developing and studying precision medicines for some of the most globally devastating diseases.

We believe this form of partnership is a model for how academic institutions and industry can work together to deliver better medicines

Tony Kouzarides

Enzymlogic

Lab tubes (cropped)

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