Creating the next generation of life-changing medicines has always been pharma's greatest challenge, but with pipelines drying up many companies need a helping hand. We speak to three organisations doing just that – building early stage projects into packages that pharma can take to market

If pharma's recent spending spree on small biotechs indicates anything, it's that the big players are no longer big players in the early stages of drug development.

"Pharma companies have a need for more quality projects in their pipelines, a situation driven by cutbacks and the reality that they are 'development' more than 'research and development' organisations now," says Dr Justin Bryans, director of drugs discovery at MRC Technology (MRCT), the technology transfer spin-out charity from the Medical Research Council.

He points to a number of companies that have closed R&D sites in the UK, most recently Pfizer's Neusentis site in Cambridge. "There are only a couple of major players in the country now when ten-15 years ago there were maybe a dozen," he says. "Companies need to fill up their pipelines again – they need to reach back into academia to find the next generation of drugs."

The industry is well aware of the benefits of collaboration, says Dr Keith Blundy, CEO of Cancer Research Technology (CRT), the commerical arm of world-leading charity Cancer Research UK. "There's been a cultural shift; the industry has decided that doing it all themselves is not the way to go and that having a 'mixed economy' within their R&D gives a better chance of success. They can't afford to do everything, so they need to form partnerships."

Risky business  

MRCT's goal is to bridge the gap between basic research and commercial application, advancing promising candidates into clinical development through what Bryans terms 'de-risking'.

"Being quite conservative, pharma is unwilling to put money or resources into projects at an early stage," he says. "We work in collaboration with academics to develop their science and move it towards an in vitro or potentially in vivo proof of concept. From there we create a strong data package and, ultimately, we partner with pharma companies."

MRCT's work has led to some notable successes, with four drugs currently on the market: Actemra (tocilizumab), marketed by Genentech for rheumatoid arthritis, Biogen's multiple sclerosis drug Tysabri (natalizumab), Entyvio (vedolizumab), marketed by Takeda for ulcerative colitis, and Merck's blockbuster cancer immunotherapy Keytruda (pembrolizumab), humanised by MRCT scientists.

Bryans cites a recent lung fibrosis project as an example of the journey treatments take: "We picked up an enzyme from one of the principal investigators in our network who felt it might have some impact on fibrosis in both lung and kidney. However, it needed a tool compound or antibody to drive proof of concept in animal models, so we developed an antibody together, humanised the antibody and turned it into what could be a potential drug."

With the science down, MRCT's business development team attended major conferences and contacted companies directly to tell them about the data. "We received a number of offers and then decided who to go with," he says, adding that its not-for-profit status allowed MRCT to worry less about money and more about finding the company with the best fit. "It's about which company is in the best position and has the greatest commitment to drive our product to patients. In the end, we partnered with a really good company that is very committed to lung fibrosis and to this project specifically."

The role that MRCT plays is vital, he adds. "If MRCT didn't exist, some of those early stage projects would simply not be translated to clinical benefit. We feel very passionately that that research deserves to get to the clinic if it holds up."

Spinning around  

London-based Magnus Life Science takes a novel approach to working with academia to advance early stage science – a 'spin-in' model.

Industry needs to work alongside academia over the long term, says CEO David Campbell. "In the past, pharma has sourced innovation from academia but we did not see its scientists working alongside academic scientists. That's what we're trying to change."

Unlike the traditional spin-out model – where innovation from inside a university is used to create a biotech company – Magnus' spin-in model creates a programme within the university, including University College London, where its founder and chief scientist, John Martin, is professor of cardiovascular medicine and Magnus itself is based.

This approach puts curiosity-driven academics into direct contact with commercially-driven scientists, says Campbell. "We're helping academics focus on the science by providing them with a structure to develop the science in a commercially motivated environment," he says. "The failure of the spin-out model is that academics are often challenged by running a business. We want to take that burden away from them, which gives them the freedom to be academics – to publish, to apply for grants – but within an environment where we can help them protect and secure IP."

Magnus has already established six programmes, each created as a separate company with founding scientists as shareholders. These include Magnus Metabolic, which targets cardiovascular effects of diabetes, Magnus Growth for obstetrics and pathologies of pregnancy, and Regenerate Life Science, recently formed following positive phase II results in stem cell therapy for cardiovascular disease.

Magnus provides overall strategic direction, management and project development capability to seek further investment or partnerships with biopharma companies for later-stage development.

While it is still early days, Campbell hopes they can change academics' mindset on drug development: "If we do nothing but show academics that you can innovate and make a difference while making those ideas commercially attractive, then we will be happy," he says. "There's simply no environment like that at the moment."

No project left behind  

Meanwhile, cancer charity Cancer Research UK (CRUK) is helping to create attractive packages for pharma companies through direct interaction with the industry itself. This is largely done via its Centre for Drug Development (CDD), a full-service drug development unit that advances molecules from pre-clinical to phase I, and Cancer Research Technology (CRT), its commercial arm that manages licensing of molecules to pharma companies.

Through Clinical Development Partnerships, the CDD makes projects from within the industry more attractive to their originator companies. "We take programmes from industry that for some reason have stalled," says Dr Nigel Blackburn, director of drug development at CRUK. "In the case of big pharma it's probably because, after a review of their portfolio, they've drawn a line and decided not to invest in the stuff below the line. With biotech, it's a case of putting all of their resources behind one or two assets as they do not have the resources to pursue others."

The charity takes these assets through to proof of mechanism and offers the originating company first right of refusal to any data. "If they decide to reinvest we get a licence fee, as well as milestones and royalties," says Blackburn, naming three from their many successful projects. "With GlaxoSmithKline, we ran a programme and showed modulation of target, safe dose and some early signs of efficacy. When GSK declined to reinvest as it didn't fit with its strategic direction, we did a deal with US biotech Nemucore that allows them to use our data for fundraising. If they're successful, we will share – with GSK – the milestones and royalties."

The second programme was for a glioblastoma drug that German biotech Immatics didn't have the resources to pursue at first but after its financial fortunes changed opted back into the programme and licensed the data. The third deal with Astex Pharmaceuticals saw the company exercise its option early (and receive preliminary data, including chemistry and CMC,) ahead of the trial closing, whereupon they will receive the full final report. "It costs the originator company nothing," adds Blackburn, "so they've got nothing to lose by talking to us."

Other projects include the Combinations Alliance, which, in collaboration with Experimental Cancer Medicine Centres, matchmakes companies with academics to test their cancer drugs in combination, as well as a £200,000 Pioneer Award fund given to high-risk, novel ideas with groundbreaking potential in tackling cancer.

Cancer Research UK's status as the world's largest charitable funder of cancer research gives its commercial arm CRT access to a huge network of scientists, pharma companies and other experts, says CRT's Blundy. "We bring people together under a biological theme and then partner with industry at an early stage," he says. "That's not easy for other companies to do and it's very attractive to pharma because they like the idea of getting in very early with novel, innovative breakthrough science. What particularly attracts major companies is the simplicity; if you need a multiparty collaboration, you don't have to work with a whole series of different institutions to put it together."

This approach works, says Michael Oredsson, president and CEO of BioInvent International, which is working with CRUK and CRT to fund and execute a first-in-man trial for its investigational drug BI-1206 in patients with chronic lymphocytic leukaemia (CLL) and non-Hodgkin lymphoma (NHL).

"CRUK and CRT have a very solid reputation," he says. "Through them it's easy to attract the best clinicians to work on a trial and access good opinion leaders in the UK. Access to patients can also be an issue in areas like this, as there are a lot of clinical trials happening, but CRUK gives a solid and robust opportunity to recruit patients. The fact that we didn't need to raise the significant levels of money that is often needed for clinical trials was obviously also an attraction."

The low risk of this approach is vital, adds Blackburn. "As it's not-for-profit, the CDD can work on projects that the industry views as risky, which opens up innovative stuff that may not have been done otherwise. There are obviously financial advantages as well, particularly with the Clinical Development Partnership scheme where we're doing early phase work at our expense."

A tension will always exist between the need for scientific experimentation and the need for marketable drugs but it is clear that pharma has an important role to play, wherever the innovation comes from. That role may well become more and more skewed towards the late stages of a drug's development cycle, but few will complain if scientific sparks are leading to exciting new treatments for patients.