̽��ֱ�� of Cambridge - treatments

Apollo Therapeutics launches with £100m investment

plc32 — Thu, 17 Jun 2021 09:19:00 +0000

A pioneering collaboration to speed development of breakthrough medical discoveries—devised by the ̽��ֱ�� of Cambridge, Imperial College London, ̽��ֱ�� College London and embraced by pharmaceutical giants AstraZeneca, GlaxoSmithKline, and Johnson & Johnson Innovation—launched on Thursday as a £100 million biopharmaceutical company.

Apollo Therapeutics, a portfolio-based biopharmaceutical company rapidly advancing potentially transformative treatments, has completed a £100 million financing led by Patient Square Capital and joined by Rock Springs Capital, Reimagined Ventures, and UCL Technology Fund.

̽��ֱ��investment will support advancement of Apollo’s robust pipeline into development; expansion of the company’s operations, including establishment of a presence in the Boston, Massachusetts area in the USA; and pursuit of new collaborations globally. Each of the joint venture founders will retain a minority stake in the company.

Conceived in 2011 by the technology transfer offices of three world-leading universities ( ̽��ֱ�� of Cambridge, Imperial College London, ̽��ֱ�� College London), Apollo was created to speed the development of therapeutics based on cutting-edge discoveries at the three universities. In 2014, the team pitched the pioneering model to AstraZeneca, GlaxoSmithKline, and Johnson & Johnson Innovation, which embraced the model.

Professor Andy Neely, Cambridge Pro-Vice-Chancellor for Enterprise and Business Relations said: “Apollo’s expanding pipeline of treatments across oncology, major inflammatory disorders and rare disease is an excellent demonstration of why funding, collaboration and the commercialisation of research at UK global research universities is so crucial for the future care of patients, the treatment of disease and the economy.”

Finalised in late 2015, the joint venture launched in early 2016. In the ensuing years Apollo has sought the best science with the potential to help patients. By bringing funding and industry expertise together with ̽��ֱ�� breakthroughs, Apollo has developed projects to industrial standards and exceeded traditional development benchmarks of capital- and time-efficiency. It has now invested in over 30 projects, some of which have already been successfully licensed. Apollo now launches its next phase as a multinational company.

Established to bridge the gap between deep academic science and eventual patient benefit, the Apollo model will function well as a company. By fostering relationships with top academic scientists and leveraging insights from partners with late-stage development and commercial expertise, Apollo works to develop therapeutics that have transformative potential. It evaluates breakthrough scientific discoveries across multiple criteria, including having a compelling and testable biological hypothesis or having a differentiated mechanism or technology compared to other therapeutics in development or on the market.

Iain Thomas, Head of Life Sciences at Cambridge Enterprise said: “Apollo’s unique, innovative and hugely capital efficient model has been validated by this very significant investment. Apollo has advanced a fantastic portfolio of programmes more cost effectively and quickly than could have been achieved by traditional grant and single asset investment routes. PSC’s partners have real knowledge and success in investing in portfolio opportunities, we are delighted they can bring their expertise to Apollo and are joining us as we take science from the bench to patients.”

To advance programmes efficiently, Apollo leverages a portfolio-based model with a centralized team of drug development ‘architects’ working alongside asset-level teams of subject matter experts. Together, these teams are able to evaluate therapeutic programmes rigorously, in an objective, data-driven fashion—prioritising critical experiments to de-risk programmes early. ̽��ֱ��model allows the company to evaluate programmes comprehensively, while committing minimal spend until biological validation is demonstrated. This capital efficiency allows Apollo to focus on scaling a robust and potentially transformative pipeline, with over 15 therapeutic programmes currently in development.

With proceeds from this financing, Apollo plans to advance its lead therapeutic programmes into clinical development as well as identify new programmes. In addition, the company plans to expand its UK operations in the Cambridge area, as well as in the United States with a new facility in Boston/Cambridge. Apollo’s growing team will also explore additional collaborative relationships with leading academic researchers around the world.

Pioneering collaboration initiated by the ̽��ֱ�� of Cambridge, Imperial College London and ̽��ֱ�� College London

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Synthetic organs, nanobots and DNA ‘scissors’: the future of medicine

lw355 — Thu, 12 Oct 2017 08:00:43 +0000

In a new film to coincide with the recent launch of the Cambridge Academy of Therapeutic Sciences, researchers discuss some of the most exciting developments in medical research and set out their vision for the next 50 years.

Professor Jeremy Baumberg from the NanoPhotonics Centre discusses a future in which diagnoses do not have to rely on asking a patient how they are feeling, but rather are carried out by nanomachines that patrol our bodies, looking for and repairing problems. Professor Michelle Oyen from the Department of Engineering talks about using artificial scaffolds to create ‘off-the-shelf’ replacement organs that could help solve the shortage of donated organs. Dr Sanjay Sinha from the Wellcome Trust-MRC Stem Cell Institute sees us using stem cell ‘patches’ to repair damaged hearts and return their function back to normal.

Dr Alasdair Russell from the Cancer Research UK Cambridge Institute describes how recent breakthroughs in the use of CRISPR-Cas9 – a DNA editing tool – will enable us to snip out and replace defective regions of the genome, curing diseases in individual patients; and lawyer Dr Kathy Liddell, from the Cambridge Centre for Law, Medicine and Life Sciences, highlights how research around law and ethics will help to make gene editing safe.

Professor Gillian Griffiths, Director of the Cambridge Institute for Medical Research, envisages us weaponising ‘killer T cells’ – important immune system warriors – to hunt down and destroy even the most evasive of cancer cells.

All of these developments will help transform the field of medicine, says Professor Chris Lowe, Director of the Cambridge Academy of Therapeutic Sciences, who sees this as an exciting time for medicine. New developments have the potential to transform healthcare “right the way from how you handle the patient to actually delivering the final therapeutic product - and that’s the exciting thing”.

Read more about research on future therapeutics in Research Horizons magazine.

Nanobots that patrol our bodies, killer immune cells hunting and destroying cancer cells, biological scissors that cut out defective genes: these are just some of technologies that Cambridge researchers are developing which are set to revolutionise medicine in the future.

̽��ֱ��Future of Medicine

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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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Apollo's mission to drive therapeutic innovation

lw355 — Tue, 20 Jun 2017 10:50:20 +0000

Over the past year, a four-strong team has had over a hundred meetings with scientists at three UK universities. By the end of this year, they will probably have had another hundred.

̽��ֱ��team is garnering the most comprehensive sense of what’s happening at the bench across three UK universities – Cambridge, Imperial College London and ̽��ֱ�� College London (UCL) – that anyone has ever amassed. Their job is to identify research that has the greatest potential of making it all the way through to becoming a new medicine, and then to help this happen. This is Apollo Therapeutics.

Dr Richard Butt, who heads up the team, explains the drive behind their meetings: “We live in an age of rapidly escalating biomedical innovation – an age where the development of new medicines should be at an all-time high. But the number of new drugs being developed is largely static.”

In drug discovery, the period between getting promising results in an academic lab and receiving real interest from an investor or pharmaceutical company has been called the ‘Valley of Death’ – and not without good reason. Discovering and developing potential new medicines requires not just money but also expertise and the rapid delivery of industrial-type science. Most drug candidates succumb along the way, long before it’s possible to know whether they might have fulfilled an unmet medical need.

In January 2016, the tech transfer offices (TTOs) of Cambridge, Imperial College and UCL joined forces with three global pharmaceutical companies – AstraZeneca (AZ), GSK and Johnson & Johnson – to create a £40m collaboration called Apollo Therapeutics. Their aim is to streamline the academia-to-industry pipeline by “finding the best translatable science, funding it fast and running the right development programme to make it attractive to industry,” says Butt.

In effect, Apollo aims to maximise the chance that a potential drug will be developed from emerging basic science by investing in a state-of-the-art drug discovery programme that a pharma company will find attractive to license.

“ ̽��ֱ��Apollo approach is wholly new and revolutionary,” says Dr Iain Thomas, Head of Life Sciences of Cambridge Enterprise (Cambridge’s TTO). “You could say that Apollo is building reassurance. ̽��ֱ��hardest part of our job at Cambridge Enterprise is selling really good technology to pharma. It relates to the psychology of buying – people don’t buy complicated stuff with lots of risk without a lot of analysis. Reassurance comes from being engaged with an opportunity for a long time.”

Engagement and partnership are at the heart of the Apollo model. First, Butt’s team speaks to the academics and TTOs of the universities to identify exciting prospects, before taking some of the ideas to the wider team of investors (each of the three companies and the TTOs). “As scientists, we will always be very happy to spend time engaging in discussions with any academic about their work. As drug discoverers, we’ve been very picky about what to take forward,” he says. “We filter very aggressively to maximise the chance of success.”

Once a project is selected for investment, Apollo and the academics work together to develop the discovery to a stage that will be attractive to a company to license and take further.

This work might take place in the academic’s laboratory, or in one of the pharma companies, or in a contract company. It might also take place at the Milner Therapeutics Institute – research laboratories that will open on the Cambridge Biomedical Campus in 2018 dedicated to fostering close collaborative interactions between academia and industry.

“ ̽��ֱ��key is bringing together the skill sets, philosophies and expertise of those who discover with those who know what to do with that discovery,” says Dr Ian Tomlinson, Chair of Apollo. “We are all motivated by the goal of finding new medicines for patients.”

Tomlinson adds: “ ̽��ֱ��conventional pipeline works like this: an academic does some great science, takes it as far as they are able to within the confines of the lab and then, if they want to take it further, either forms a spin-out or licenses to pharma. This still has its place, but it takes time and is costly. If Richard’s team brings the investment team an idea that looks good, Apollo can fund it and be working with the academic in a matter of weeks.”

Between them, Butt and his three colleagues have over 60 years of experience of the pharma industry. “We’ve been at the sharp end of drug discovery and failure,” he says. “We saw the boom of the late 80s/early 90s of drug approvals. And then genomics, high-throughput screening and a seeming wealth of targets led to the mindset of ‘we can scale this success’ – if we run three times more projects we’ll be three times more successful’. ̽��ֱ��basic biology almost ceased to matter. Projects were run that shouldn’t have been. R&D costs escalated but the output of new drugs flat-lined or even declined.

“Apollo is led by the science we see. ̽��ֱ��academic fully understands the biology and mechanisms of the disease target, and we understand the milestones that need to be overcome to become a medicine – drug discovery, formulation, toxicology, clinical trial design, regulators, business models.”

Already his team has identified eight projects across the three universities to receive Apollo funding. ̽��ֱ��first to be backed came out of a 20-year search by Dr Ravi Mahadeva at Cambridge’s Department of Medicine for a small molecule drug to treat Alpha-1 trypsin deficiency (AATD). AAT is a protein that normally protects the lungs. In AATD, a single genetic mutation causes it to aggregate in the liver and the resulting effects on the liver and lungs are disabling and ultimately fatal. There is currently no effective long-term treatment for the disease.

“Ravi came to us with an idea and some early compounds,” says Butt. “Quite simply, it wouldn’t have been picked up by a drug company based on the package that he had. We knew we could design a work package to generate more potent, more selective and more drug-like compounds, and create a package of data that pharma would find attractive.”

For Professor Randall Johnson, Apollo funds have meant that his research in Cambridge’s Department of Physiology, Development and Neuroscience has continued seamlessly through to a drug development programme without the stop-start of waiting for funding, licensing or forming a spin-out. “Randall was one of the first Cambridge academics I saw,” says Butt. “He was excited because he was about to publish a key publication on his genuinely novel work highly relevant to the emerging immune-oncology field. Before Randall’s Nature paper was published, we were already working on a project plan and made the commitment to collaborate on the project.

“Because we are embedded in the ̽��ֱ�� and work closely with Cambridge Enterprise, we have fully confidential access to talk to any academic at any of the three universities. When we worked in pharma, it could take months simply to sit around a table and talk about science and look at data with academics.”

Further down the line, potential therapeutics developed from any of the Apollo-funded programmes will first be offered for licensing to AZ, GSK and Johnson & Johnson, and then more widely; the capital gain of any licensing agreements will be divided between the three universities and the three pharma investors. And the interaction with the companies is not just transactional. Each of them is also committing time, resources and expertise to help the projects that are approved for collaboration.

“ ̽��ֱ��cost to license from us will be much lower than the sum cost to have done all that research internally,” says Tomlinson. “At a time when all the pharmas are cutting their costs and doing less R&D, this provides a different model that will be cost-effective to add potential drugs to their pipelines.

“There are very few totally new drugs every year. To get one of those, you’ve got to cast the net very wide and do everything you can to make the most of the opportunities.

“Apollo has the advantage of not being pigeonholed into working only on one disease or therapy area or limited by drug modality, as we would be if we were a pharma company. As a result, we don’t have to consider a ‘strategic fit’ – we’re simply following the best translatable science that should result in a higher success in getting new medicines to patients.”

Inset image: Read more about research on future therapeutics in Research Horizons magazine.

̽��ֱ��stirrings of a revolution are starting to ripple through hundreds of laboratories. It’s a revolution that aims to result in new medicines – faster and with fewer failures – and it’s being led by three UK universities and three global pharmaceutical companies.

̽��ֱ��key is bringing together the skill sets, philosophies and expertise of those who discover with those who know what to do with that discovery.

Ian Tomlinson, Apollo Therapeutics

Taema

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Take your medicine: how research into supply chains will help you take care of yourself

lw355 — Wed, 14 Jun 2017 15:20:27 +0000

“Like many people of my age, I have to take pills morning and night. I’m pretty good at taking them in the evenings, mainly because my wife makes me! But, left to my own devices in the mornings, I only remember to take them perhaps one day out of four,” says Dr Jag Srai.

“Wouldn’t it be fantastic if smartphones could remind patients, capture use and track activity, blood pressure, sugar level, and so on? And if, at the same time, their GP could see this data and call them in if there’s a problem?”

He explains that upwards of 30% of prescribed drugs are not taken by patients and, in the case of respiratory drugs, where application is more intricate, 70% are not taken as directed. ̽��ֱ��numbers vary depending on the type of condition being treated but they are disarmingly high across the board. This has consequences, and not only for the patient. ̽��ֱ��cost to the taxpayer of drugs that are not being used is considerable and reduces the pot of money available for patient care.

“In a world of scarce resources this in itself seems incredibly wasteful. But there are other reasons to be concerned,” adds Srai, who is Head of the Institute for Manufacturing (IfM)’s Centre for International Manufacturing. “Around 50% of patients taking antibiotics don’t complete the course. ̽��ֱ��consequences of this are potentially catastrophic as infections become increasingly resistant to drug treatment. And drugs contain active ingredients which, when disposed of inappropriately, end up as contaminants in our water supply.”

Tackling the thorny problem of patient compliance is just one aspect of the pharmaceutical industry that Srai and his team at the IfM are looking to revolutionise. They are working with other universities and major UK pharmaceutical companies AstraZeneca and GSK to make improvements across the whole supply chain, from how a pill is made to the moment it’s swallowed by the patient.

Advances in genetics and biochemistry are helping us move towards a much more tailored approach to medicine, focused on more targeted or niche patient populations, and ultimately the development of bespoke treatments to meet individual patient needs. ̽��ֱ��implications for how the pharmaceutical industry manufactures its medicines and gets them to the patient are clearly immense.

Most pharmaceutical manufacturing still takes place in huge factory complexes, where large volumes of chemicals are processed in a series of ‘batch-processing’ steps, and often a dozen or more are required to produce the final oral dose tablet. Developing new drugs is an expensive business and so big pharma companies hope for a ‘blockbuster’ drug – a medicine that could be used to treat a very common condition, such as asthma or high blood pressure, and which can be manufactured in large quantities.

But, says Srai, the manufacture of these blockbuster drugs is becoming a thing of the past. ̽��ֱ��batch process is costly, inefficient and makes less sense when producing medicines in small volumes.

New ‘continuous’ manufacturing processes mean that drugs can be made in a more flow-through model, requiring fewer steps in the manufacturing process, and in volumes better aligned with market demand. In the case of small volume manufacture, this technology breakthrough can support the move towards more personalised medicine.

“Combine this with the way in which digital technologies are transforming supply chains – through flexible production and automation, using sensors to track location, quality and authenticity, and big data analytics on consumption patterns – and it’s clear that the pharmaceutical industry is on the cusp of a huge change,” adds Srai.

Recognising this, and to make sure they harness the value these advances in science and technology can deliver, pharmaceutical companies are working together in a number of ‘pre-competitive forums’.

̽��ֱ��IfM team is playing a key part in two major related UK initiatives: the Continuous Manufacturing and Crystallisation (CMAC) Future Manufacturing Research Hub based at Strathclyde ̽��ֱ��, funded by £10m from the Engineering and Physical Sciences Research Council and a further £31m from industry; and REMEDIES, a £23m UK pharmaceutical supply-chain sector project, jointly funded by government and industry.

CMAC is focused on the move to continuous manufacturing and REMEDIES on developing new clinical and commercial supply chains. Srai’s team is leading the work on mapping the existing supply chains for different types of treatment, and modelling what the future might look like.

“We can envisage a future in which for some medicines, production is no longer a highly centralised large-scale batch operation but one where manufacturing is more about continuous processing, more distributed in nature, smaller scale and closer to the point of consumption.”

Asked how local this can become, Srai adds: “In some instances we are already able to ‘print’ tablet medicines on demand, and we are now exploring whether this might take place at more local production/distribution sites, or at the local pharmacy or even in our own homes. Of course, some critical hurdles still need to be overcome, not least in terms of assuring product quality at multiple sites and establishing appropriate regulatory regimes.

“New technologies are also opening up other possibilities in the way that patients receive healthcare. Wearable and smartphone apps could be feeding diagnostic and health information to our doctors – be they human or (with the advances in artificial intelligence) robot – who would assess our symptoms remotely. We may change our consultation habits completely and only go to the doctor for very specific types of treatment. Indeed, in the UK today, trials suggest some 30% of GP visits are unnecessary.”

As part of the REMEDIES project, the IfM team has been exploring the possibilities presented by technologies that are available now such as Quick Response (QR) codes that can be scanned by mobile apps on our smart phones – and how they can help ensure that patients are taking their medicine.

“A relatively easy thing to do with packaging is to use it as an information source for patients. For example, packs of pills come with a small leaflet that hardly anybody reads. If we want to help patients adhere to their treatment regimes, can we support them by giving them this plus more useful information in a more accessible electronic format?”

̽��ֱ��REMEDIES team is working on a mobile phone app that will allow patients to read the instructions on their phone (in a font size and language of their choice) or listen to some explanatory audio or watch a video. “This is simple, readily available technology that could have a significant impact on compliance,” says Srai.

̽��ֱ��potential for exploiting data to deliver bespoke healthcare in the future is enormous. With smart packaging, smartphones and wearable devices, information can become increasingly dynamic and interactive. Indicators such as time, location – even mood – can affect whether and how drugs are taken; and data such as blood pressure and pulse can show the effect they have on the patient.

“As in the world of e-commerce, we are at the early stages of understanding how this consumer and patient data can inform the supply chain,” says Srai. “But we can now contemplate scenarios in certain therapeutic areas, in which each dose a patient takes is fully optimised for the here and now, and manufactured continuously, or even printed on demand.”

And if the patient forgets to take it, they will, if they choose, be reminded to do so by a very insistent app.

Inset image: Read more about research on future therapeutics in Research Horizons magazine.

Researchers are working with pharmaceutical companies to make improvements across the whole supply chain, from how a pill is made to the moment it is swallowed by the patient.

We are already able to ‘print’ tablet medicines on demand, and we are now exploring whether this might take place at more local sites, or at the local pharmacy or even in our own homes.

Jag Srai

Kate Russell

Keep taking the tablets

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Future therapeutics: the hundred-year horizon scan

lw355 — Tue, 13 Jun 2017 08:04:43 +0000

It used to be all about fleabane for bites from venomous beasts, mugwort to induce and ease the pain of labour and boiled bedstraw to stimulate clotting. According to Nicholas Culpeper in his 1652 book ̽��ֱ��English Physitian, “a man may preserve his Body in Health; or cure himself, being sick, for three pence charge, with such things only as grow in England”.

Prescient words, in some respects – today it’s still all about giving the right patient the right drug, at the right dose at the right time, but it’s called precision medicine.

In fact, herbal remedies and small-molecule pharmaceuticals have dominated therapeutic medicines since Culpeper’s time, before being joined in the 1980s by ‘biologics’ when it became possible to build new forms of proteins, hormones, receptors and monoclonal antibodies after the DNA code was cracked in Cambridge in 1953.

Science moves fast and we now stand at the threshold of not one but several step changes. New understanding of the structures of cells and systems biology is pioneering the use of human and microbial cells as therapeutic agents. Meanwhile, novel bioelectronic medicines or ‘electroceuticals’ are shifting the therapeutic approach away from traditional medicines into optics, electronics, instrumentation and software. What will these and other developments in areas such as immunotherapy and nanotherapy mean to medicine over the next hundred years? And what’s taking place now in Cambridge to help this happen?

There seems little doubt that with increased genetic knowledge, precision medicine will define the 21st century. ̽��ֱ��development of massively parallel DNA sequencing by the Department of Chemistry moves us closer to the prospect of sequencing one billion kilobases per day per machine. Genomic information and computational approaches will refine diagnoses, stratify cancer into subtypes, guide personalised treatments and improve the efficiency of clinical trials.

Meanwhile, cell-based technologies provide exquisitely selective delivery agents that are naturally able to perform therapeutic tasks. In Cambridge, progress in regenerative medicine promises benefits for replacing human cells, tissues or organs; and the use of stem cells to manage and treat diabetes, degenerative nerve, bone and joint conditions, and heart failure.

̽��ֱ��convergence of information technologies like augmented reality, cloud-based applications, artificial intelligence and deep learning in digital healthcare will play an increasing role in medical decision support, robotic nursing and surgery, sensors and diagnostics, and so on.

So-called beyond-the-pill services, such as wearables, apps, medical tattoos and point-of-care sensors will offer consumers digital devices for monitoring health and compliance, although issues such as privacy, data integrity and cybersecurity remain concerns to be resolved satisfactorily in the ‘internet of people’.

Research into these key future technologies is being conducted in the Departments of Engineering, Materials Science and Physics, and the Centre for the Physics of Medicine. Meanwhile, the newly established Alan Turing Institute and the Leverhulme Centre for the Future of Intelligence bring world-leading expertise in big data, computer science, advanced mathematics and artificial intelligence.

How is the pharmaceutical industry responding to these shifting patterns in modern medical treatments? Global research-based companies have suffered from the downturn in the global economy, the demise of the blockbuster era and the rise in specialist markets. Industry is adapting by placing more emphasis on new therapeutic modalities and repurposing existing drugs, as well as strengthening academic–pharma collaborations at earlier stages of the drug discovery process.

̽��ֱ��Milner Therapeutics Institute, due to open in 2018, will foster close collaborative interactions between academia and industry to accelerate medical advancement via an ‘open borders’ paradigm. So too will Apollo Therapeutics, a £40m collaboration between the tech transfer offices of Cambridge, Imperial College London and ̽��ֱ�� College London and three global pharmaceutical industries (AstraZeneca, GSK and Johnson & Johnson) to streamline the academia-to-industry pipeline.

New technologies are likely to change the regulatory, legal and policy environments, and business models. For example, some forms of medicine – like gene editing – are both personalised and curative. How will the costs of research, development and marketing for ‘cures’ be met if the business model is more likely to be a service than a product?

Understanding complex issues such as these will be aided by the networks and convening power established by the Centre for Science and Policy, which coordinates the best scientific thinking to inform public policy, and the Centre for Law, Medicine and Life Sciences, which focuses on the legal and ethical challenges at the forefront of biomedicine. Meanwhile, the Institute for Manufacturing is analysing supply chains, and the Judge Business School is studying the management of innovation and entrepreneurship.

It’s likely that future healthcare will have a different geometry. A complex interplay of patients, industries and service operators will use sophisticated diagnostic tools, digital scrutiny and interpretation using artificial intelligence, and have access to an extensive toolbox of therapeutic approaches, all personalised to the individual patient, and available through a redesigned primary and hospital healthcare environment.

Cambridge is well placed to drive innovation in this highly multidisciplinary therapeutic scenario.

̽��ֱ�� ̽��ֱ�� has expertise relevant to all stages of the drug discovery, development and manufacturing process, from fundamental biology/chemistry, through drug development and clinical trials, to imaging, safety, delivery, supply-chain management and entrepreneurship.

There’s also large-scale investment in research and infrastructure for tackling disease. Take dementia, for instance: more than £17m awarded by the UK Research Partnership Investment Fund will help build a Chemistry of Health building for chemistry-based research in neurodegenerative diseases. Cambridge also hosts one of three UK Drug Discovery Institutes funded by Alzheimer’s Research UK (ARUK), and is one of five centres that will form the UK Dementia Research Institute, funded by the Medical Research Council, Alzheimer’s Society and ARUK.

Against this backdrop of activity, the Cambridge Academy of Therapeutic Sciences (CATS) has been established to increase the linking of academic research to big pharma, biotech and NHS structures on the Cambridge Biomedical Campus and in the region. ̽��ֱ��idea is to create a networking, training and enterprise structure that transcends traditional boundaries between clinicians, academics and industrialists, in which fundamental and applied research into diagnostics and therapeutics can flourish and be translated into patient treatments with maximum efficiency.

̽��ֱ��time is ripe for this to happen. AstraZeneca’s move to Cambridge, combined with close links with GSK and other big pharma companies, as well as the thriving local biotechnology industrial environment and sister institutes like the Wellcome Trust Sanger Institute, provide substantial impetus to co-develop and co-deliver these programmes.

In fact, one might thank Nicholas Culpeper for his vision for the future of medicine and at the same time upgrade his estimate of ‘three pence charge’ with 36 decades of financial inflation.

Inset image: Read more about research on future therapeutics in Research Horizons magazine.

How will precision medicine define 21st-century therapeutics? What will future healthcare look like? And what actually lies ‘beyond the pill’? Professor Chris Lowe, inaugural Director of the Cambridge Academy of Therapeutic Sciences, takes the long view on the future of therapeutics.

Future healthcare will have a different geometry... sophisticated diagnostic tools, cloud-based applications, artificial intelligence... an extensive toolbox of therapeutic approaches, all personalised to the individual.

Chris Lowe

̽��ֱ��District

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Opening the skull of patients after head injury reduces risk of death from brain swelling

sjr81 — Thu, 08 Sep 2016 07:44:32 +0000

Traumatic brain injury is a serious injury to the brain, often caused by road traffic accidents, assaults or falls. It can lead to dangerous swelling in the brain which, in turn, can lead to brain damage or even death.

A team led by researchers at the Department of Clinical Neurosciences, ̽��ֱ�� of Cambridge, and based at Addenbrooke's Hospital, recruited over 400 traumatic brain injury patients over a ten-year period from the UK and another 19 countries worldwide. They then randomly assigned the patients to one of two groups for treatment – craniectomy or medical management.

In research published this week in the New England Journal of Medicine, the researchers report that six months after the head injury, just over one in four patients (27%) who received a craniectomy had died compared to just under a half (49%) of patients who received medical management. However, the picture was complicated as patients who survived after a craniectomy were more likely to be dependent on others for care (30.4% compared to 16.5%).

Further follow-up showed that patients who survived following a craniectomy continued improving from six to 12 months after injury. As a result, at 12 months, nearly half of craniectomy patients were at least independent at home (45.4%), as compared with one-third of patients in the medical group (32.4%).

Peter Hutchinson, Professor of Neurosurgery at the Department of Clinical Neurosciences at Cambridge, says: “Traumatic brain injury is an incredibly serious and life-threatening condition. From our study, we estimate that craniectomies can almost halve the risk of death for patients with a severe traumatic brain injury and significant swelling. Importantly, this is the first high-quality clinical trial in severe head injury to show a major difference in outcome. However, we need to be really conscious of the quality of life of patients following this operation which ranged from vegetative state through varying states of disability to good recovery.”

Angelos Kolias, Clinical Lecturer at the Department, adds: “Doctors and families will need to be aware of the wide range of possible long-term outcomes when faced with the difficult decision as to whether to subject someone to what is a major operation. Our next step is to look in more detail at factors that predict outcome and at ways to reduce any potential adverse effects following surgery. We are planning to hold a consensus meeting in Cambridge next year to discuss these issues.”

̽��ֱ��research was funded by the Medical Research Council (MRC) and managed by the National Institute for Health Research (NIHR) on behalf of the MRC–NIHR partnership, with further support from the NIHR Cambridge Biomedical Research Centre, the Academy of Medical Sciences, the Health Foundation, the Royal College of Surgeons of England and the Evelyn Trust.

Reference

Hutchinson, PJ et al. Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension, NEJM; 2 Sept 2016

Craniectomy – a surgical procedure in which part of the skull is removed to relieve brain swelling – significantly reduces the risk of death following traumatic brain injury, an international study led by the ̽��ֱ�� of Cambridge has found.

Traumatic brain injury is an incredibly serious and life-threatening condition. From our study, we estimate that craniectomies can almost halve the risk of death for patients with a severe traumatic brain injury and significant swelling.

Peter Hutchinson

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Firefighters Training for Operation Fodient

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Oesophageal cancer treatments could be tailor-made for individual patients, study finds

sjr81 — Tue, 06 Sep 2016 09:42:35 +0000

̽��ֱ��findings, published in Nature Genetics on Monday, could help find drugs that target specific weaknesses in each subtype of the disease, potentially making treatment more effective and boosting survival.

Researchers looked at the complete genetic make-up of 129 oesophageal cancers and were able to subdivide the disease into three distinct types based on patterns detected in the DNA of the cancer cells called signatures.

̽��ֱ��first subtype they found had faults in their DNA repair pathways. Damage to this pathway is known to increase the risk of breast, ovarian and prostate cancers. Patients with this subtype may benefit from a new family of drugs called PARP inhibitors that kill cancer cells by exploiting this weakness in their ability to repair DNA.

̽��ֱ��second subtype had a higher number of DNA mistakes and more immune cells in the tumours, which suggests these patients could benefit from immunotherapy drugs already showing great promise in a number of cancer types such as skin cancer.

̽��ֱ��final subtype had a DNA signature that is mainly associated with the cell ageing process and means this group might benefit from drugs targeting proteins on the surface of the cancer cells which make cells divide.

Professor Rebecca Fitzgerald, lead researcher based at the MRC Cancer Unit at the ̽��ֱ�� of Cambridge, said: “Our study suggests we could make changes to the way we treat oesophageal cancer.

"Targeted treatments for the disease have so far not been successful, and this is mostly down to the lack of ways to determine which patients might benefit from different treatments. These new findings give us a greater understanding of the DNA signatures that underpin different subtypes of the disease and means we could better tailor treatment.

“ ̽��ֱ��next step is to test this approach in a clinical trial. ̽��ֱ��trial would use a DNA test to categorise patients into one of the three groups to determine the best treatments for each group and move away from a one-size-fits-all approach.”

Each year around 8,800 people are diagnosed with oesophageal cancer in the UK, with just 12 per cent surviving for at least ten years. Cancer Research UK, who along with the Medical Research Council funded the study, has prioritised research into oesophageal cancer to help more people survive the disease by bringing people together, building infrastructure and developing the next generation of research leaders.

Professor Peter Johnson, Cancer Research UK’s chief clinician, said: “Being able to distinguish distinct types of oesophageal cancer is a genuinely new discovery from this work. For the first time we may be able to identify and test targeted treatments designed to exploit the cancer’s specific weaknesses. Although survival rates from oesophageal cancer have been slowly rising in the last few years they are still far too low, and this research points the way to a completely new way of understanding and tackling the disease.”

̽��ֱ��study, funded by Cancer Research UK and the Medical Research Council, is part of the Cancer Research UK-funded International Cancer Genome Consortium.

Reference

Secrier, M. et al. Mutational signatures in esophageal adenocarcinoma reveal etiologically distinct subgroups with therapeutic relevance Nature Genetics, 2016.

Tailored, targeted treatment for patients with oesophageal cancer could be developed after scientists discovered that the disease can be classified into three different subtypes

Our study suggests we could make changes to the way we treat oesophageal cancer.

Rebecca Fitzgerald

Image of an oesophageal carcinoma

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