MedImmune: building a biologics future

pharmafile | April 19, 2010 | Feature | Research and Development |  MedImmune, biologics 

I paid my visit to MedImmune’s UK headquarters in Cambridge only days after its parent company AstraZeneca announced the closure of its Charnwood R&D site just 90 miles away in Leicestershire.

The company announced that it was closing R&D sites in the UK, Sweden and the US, with nearly 3,500 R&D jobs affected, and 1,800 job losses confirmed as it re-calibrates its structure and exits research in 10 therapeutic areas.

The fact that MedImmune was untouched by the latest round of R&D cuts seems a very clear signal about the future direction of R&D in AstraZeneca and the wider industry. The group has disinvested in certain therapeutic areas in small molecule research, and is investing in more risk-sharing external deals and, of course, biologics.

MedImmune’s UK site is just a few miles away from where Cambridge Antibody Technology (CAT) was first set up in 1989, becoming one of the UK’s more successful first generation of biotech companies. It was purchased by AstraZeneca in 2006 for £702 million, and then merged with the larger US vaccines and biologics acquisition MedImmune in 2007.

Its heritage means MedImmune UK is one of very few European centres which can boast having discovered a biologics blockbuster, Humira. Today the rheumatoid arthritis treatment Humira (adalimumab) is one of the biggest selling drugs in the world, racking up sales of $5.48 billion in 2009.

Adalimumab was the first fully human monoclonal antibody drug, and was discovered by CAT as D2E7, then further developed by Abbott Labs.

CAT sold on the marketing rights to Abbott, so today only earns royalties from its sales, but its success is something the MedImmune team in Cambridge remain proud of, and hope to repeat.

If the UK site can produce another molecule of similar potential, AstraZeneca and MedImmune will be able to hold on to the rights and market the drug themselves, and the team is working hard towards such a breakthrough. MedImmune hopes to be in a position to submit one Biologics License Application a year by 2016.

Jane Osbourn

Dr Jane Osbourn is one of the scientists who have been at the company since the earliest Cambridge Antibody Technology days. Jane joined CAT shortly after completing her PhD, and over the course of her 17-year career at the company, she has seen the science of monoclonal antibodies develop from an early optimism to commercial realisation of biologics becoming some of the world’s most important drugs.

The sleek and modern twin buildings on the site are named Milstein and Aaron Klug – in honour of the two Nobel prize winning Cambridge-based scientists who contributed to the development of monoclonal antibody therapy. Inside, the buildings have works of art created by cancer patients which line the walls – a helpful reminder of who, ultimately, the scientists are serving.

Jane says: “The patient is the reason why each of us gets out of bed and comes to work in the morning.”

I asked Jane first about how MedImmune in Cambridge had managed to stay focused during the upheaval mergers and reorganisation. “I think the first thing was to establish a uniform culture and tradition within the company and to maintain that throughout any mergers and acquisitions. AstraZeneca has been fantastic at wanting to preserve the biotech culture that we have from both MedImmune and CAT. It’s really important to know what you value in your organisation – for us – it is the science and the process of thinking through how you create and maintain innovation in medicine.

“If these values are clear, then working philosophies resulting from mergers and acquisitions can only build upon our pre-existing core values. We work with AstraZeneca and MedImmune to create team projects and ‘share the science’. For me personally it was a huge opportunity when we [CAT] merged into MedImmune and I found it was full of like-minded people who were creative and innovative, but had been innovative in different ways to us.”

The merger united CAT’s phage display and Ribosome display technology for the design and development of human monoclonal antibodies, with the heritage of work with MAbs in infectious disease at MedImmune’s US labs, its headquarters located in Maryland.

“Before the merger we were of course ‘competing’ with MedImmune and therefore had to come up with new and innovative ways of doing things. So when you put these two things together as a whole, you end up with a really strong technology platform.”

A history of MAb therapy

Monoclonal antibodies (MAbs) have come a long way since the late 1970s, when their potential in medicine was first realised. Jane says: “It was the 1970s where the big breakthrough for MAb therapy occurred – the breakthrough was the demonstration by Georges Köhler and Cesar Milstein’s seminal papers that showed you can make MAbs for potential use as a successful medicinal treatment. That was the turning point in making MAbs accessible for therapies.”

The 1980s saw much work done to refine the technology, and the first murine antibody was successfully approved for use in transplant rejection in 1984.

“When I came into the field in the early 1990s, there was a lot of excitement about the potential of MAbs. The big opportunity that we saw was to make MAbs completely human rather than murine – then you can bring them into wider disease settings such as oncology and infectious diseases – of course we achieved this with adalimumab some years later and it continues to be a huge sense of pride for us here.”

“In retrospect, I think there was a little bit of naivety about how difficult it was to make large amounts of antibodies. A lot of time was focused on building the technology needed to enable the size and complexity of MAbs, but really understanding the biology well enough in its disease settings and where to deploy them was lacking. We have made significant progress on this in the past decade and today, there are 30 MAbs on the market including the major market leaders Humira, Avastin and Herceptin.”

MedImmune’s pipeline

The most advanced molecule in MedImmune’s pipeline is motavizumab. The drug is a follow-up to MedImmune’s successful Synagis, a preventative treatment in infants with the Respiratory Syncytial Virus [RSV].

The virus causes inflammation and blockage in the airways of the lungs (acute bronchiolitis) and is the most common reason for a child under 12 months’ old to be admitted to hospital with a lung infection in Europe.

But the drug has been hit by delays. In December of last year, MedImmune replied to a ‘complete response letter’ from the FDA regarding motavizumab. Nevertheless Jane is optimistic that it will gain approval and be launched in 2010. Analysts say motavizumab, if approved, has the potential to make $1.3 billion a year by 2014.

Looking at the company’s earlier stage pipeline, Jane is excited about the MEDI-545 anti-interferon alpha compound, currently in development for the rare but difficult-to-treat autoimmune disease lupus. She says: “There are very few treatments for this disease, and the symptoms can severely disable patients living with it. That means treating this disease requires an innovative approach as it remains as an unmet medical need. We are currently in phase II trials waiting to see how its development evolves.”

She adds that the oncology programmes have started to move into early clinical trials: “We are seeing some interesting early developments,” and continues: “We have a series of interesting oncology compounds ranging from the straightforward antibody blocking pathways, to newer mechanisms such as antibodies fused to toxin proteins. We are currently developing CAT8015 anti-CD22 endotoxin fusion that’s being used to investigate certain blood cancers, which is also producing some interesting results.”

There is much potential for MAbs in other areas besides oncology. “We have an existing in-depth portfolio in oncology and in respiratory, inflammation and autoimmune diseases (RIA),” she says. “The focus on oncology in the pipeline comes from the various mergers from CAT, MedImmune and AstraZeneca. When we were bought by AstraZeneca we took on a large portfolio in oncology – there will be some attrition in this pipeline and having a lot in the early stages gives us more flexibility in our choice of what we’re going to take forward.

“We’re also very determined to build up our portfolio in neuroscience for instance, so in two or three years’ time, we should have a more balanced one in terms of disease. We currently have around 100 product candidates in various stages of research and development. One of the challenges of bringing this organisation together was to make sure we focused on the highest priority and most beneficial of opportunities.”

The future of innovation

Concerns about the quality of graduates and university funding of science has been present for a number of years in the UK, creating worries that the country won’t be able to provide the expertise needed to sustain cutting edge research. Jane, however, is confident about being able to attract talent in the future: “Given where we are geographically, we certainly don’t have difficulty recruiting talented people and very innovative scientists, so I think those people still exist.

“We are in the hi-tech ‘Silicon Fen’ area around Cambridge, which is an excellent location for recruitment, so I don’t think there’s a worry about our next generation of researchers and leaders. But as an industry, we do everything we can to find, support and develop that talent, because that’s your greatest asset.”

Jane and MedImmune have taken an active interest in this development: in November of last year the site hosted its first ‘European Cancer Research Abstract Competition’. The Competition was open to students and post doctoral fellows from across Europe and was won by Nicole Simonavicius, a PhD student at the Institute of Cancer Research, London. The winning abstract involved Nicole’s research into the role of tumour pericyte receptor endosialin in angiogenesis.

Jane is already planning for a second competition for this November to further encourage young researchers to flex their innovative muscles and nurture future researchers for the industry.

Leadership in science

In February this year Jane was the winner of the East England Business Woman of the Year Award 2009. “It was great to step back and reflect on my contribution, and that of the business to the region; as CAT, as MedImmune and ultimately now as part of AstraZeneca,” says Jane. “I could also step back and see what I had contributed individually throughout my 17 years here. I think this is good for the organisation, and for me, as the evolution of my career has very much mirrored how the organisations have moved through its different stages of change.

“The Award also brought a lot of pride to the site and allowed us to see how we have made a difference to millions of patients across the world and affirmed the business and our leadership within it.

“The Award also helped us to draw attention to our transformation into a major worldwide biotech operation. As the Award was for business and not for science, we used the competition to help us benefit from other business models in the local area.”

In light of her win, I asked Jane whether business and science can, or should remain separate in pharma. “No, they can’t be separate – you’ve got to make sure everything you are doing from a science perspective makes corporate sense and brings value. We are very strong on defining value as creating benefits to patients, but you do of course need to bring value in terms of a return on investment for further drug development.”

As the Roche-Genentech model has shown, pharma-biotech collaborations have the potential to enrich not just the companies but market as well.

With its history of innovation and strong early-stage pipeline, AstraZeneca’s acquisition of CAT and MedImmune seems set to propel them into a more stable future, and one reliant on the new technologies of biologics.

JANE OSBOURN, PH.D.UK & VICE PRESIDENT, RESEARCH

Dr Jane Osbourn, site leader at MedImmune’s Cambridge, UK-based site, has significant experience in the antibody engineering and drug discovery field, gained during her 17-year career at Cambridge Antibody Technology, now MedImmune.  She initially worked in antibody-generation before moving on to lead technology development teams, making a significant contribution to MedImmune’s research and generating many key publications and patents.

Dr Osbourn holds a first-class degree in natural sciences (biochemistry) from the University of Cambridge. She completed a doctorate at the John Innes Centre for Plant Science Research in Norwich, followed by a British Heart Foundation Post doctoral fellowship at Addenbrooke’s Hospital in Cambridge. 

MEDIMMUNE – INSIDE AND OUT

MedImmune is AstraZeneca’s global biologics business and now constitutes approximately 25 % of AZ’s product pipeline.

MedImmune has its headquarters in Maryland in the US but also has a strong European presence. In October 2007, MedImmune merged with Cambridge Antibody Technology (CAT) based in Cambridge, UK, inheriting the strong biologics experience that CAT had established.

Since the merger, the largely R&D-focused Cambridge facility has expanded significantly. It is dedicated to leading research in the UK though work done at the Aaron Klug building, a £10m research centre in Cambridge that includes a specialist laboratory (antibody generation, protein sciences, peptide and DNA chemistry).

There are currently around 400 people working at the Cambridge site and MedImmune expects this to have increased to 450 by the end of 2010.

In Europe, MedImmune also has manufacturing bases in Liverpool, UK and Nijmegen in the Netherlands, with a total of 11 sites worldwide.

There are more than 100 product candidates in the pre-clinical stage or further advanced stages of MedImmune’s pipeline. Between January and August 2009, MedImmune filed five investigational new drug applications.

MedImmune is built on a focus on developing novel compounds to treat infectious disease, with a focus on paediatric conditions, respiratory and other inflammatory disease, and oncology.

MedImmune is a recognised industry leader in successfully bringing biologics-related products to market. It has been an innovator within the biotech sector through a number of firsts, such as:

• Developing and commercialising Synagis, the first monocolonal antibody for infectious disease

• Developing Virus Like Particile (VLP) technology for human papilloma virus vaccines

• Discovering the technology that led to the drug Humira, a treatment for rheumatoid arthritis that is now one of the best selling drugs worldwide

• Developing and commercialising the first advance in flu technology in 60+ years via FluMist