Whatever happened to yesterday’s ‘magic bullets’?
pharmafile | November 3, 2009 | Feature | Research and Development |Â Â Les Rose, biotechÂ
How many of you remember when monoclonal antibodies were called `magic bullets’? Enough time has passed since the term first emerged that many of you will be too young to have lived through its full development.Going back to the start, there was a time when both public and private money seemed to pour into biotechnology companies; not quite like the dot-com boom of ten years ago, but not too far off it. Then it all went quiet, as the scientific challenges proved tougher than anyone had thought. It was a long time before treatments derived from recombinant DNA technology started to make a clinical impact, and if anyone predicted that by now most treatments would be of that type, time has proved them wrong. The field received a boost in the late 1980s, when recombinant thrombolytic drugs appeared, which seemed to revolutionise the treatment of acute myocardial infarction. Large clinical trials confirmed their efficacy, especially when given within the first few minutes of an infarct, leading to major changes in emergency care such as `cardiac ambulances’ crewed by paramedics trained to inject thrombolytics. But then angioplasty and stents arrived, slightly taking the shine off thrombolytics by offering better long term protection against reocclusion. Advertisement
Lessons and developments One of the lessons from this was that the biotechnology industry needed to be diverse and adaptable. The last decade or so has seen the technology percolating into various therapeutic areas, particularly auto-immune diseases – which are steadily growing in prevalence. Several recombinant treatments for rheumatoid arthritis have been available for several years. These are a major therapeutic advance, as unlike non-steroidal anti-inflammatories they can actually modify the progression of the disease. Biotechnology medicines are also making inroads into oncology, now the top therapeutic area globally in terms of sales. These encouraging developments have not gone unnoticed by the British government. Back in 2003 the Biosciences 2015 initiative was launched by the Bioscience Innovation and Growth team (BIGT), under the auspices of the then Department of Trade and Industry, in collaboration with the BioIndustry Association (BIA). BIGT’s vision is that by 2015, the UK will have secured its position as a global leader in bioscience. There were three main components of this: to establish a core of world class companies that would be second in size only to the US; to make the UK the most efficient and effective setting in the world for clinical trials; and to create a health, business and regulatory environment that encourages innovation. We are now half way through the period laid down by the BIGT, and are we half way through meeting the objective? It seems not, but some of the obstacles are not too difficult to identify. Among them are the UK is not seen as a particularly favourable environment for marketing innovative medicines; NICE’s inevitable delaying effect on the availability of these medicines; and the chilling effect on R&D from the unexpected renegotiation of the PPRS. But the battery went flat On top of these obstacles is the current financial difficulties biotechnology companies face. Recent survey results show that 75% are having difficulty with funding, and that 44% are only looking for less than $1 million – a figure too small for most venture capital companies. The result is that many biotechs only have funding for the next six months. Various factors have contributed to this scenario. Venture capitalists (VCs) are looking for short lead times to an exit strategy, usually less than 12 years – most VC funds only last 10 years anyway! So the bioscience sector lacks financial credibility, as can be seen by the lack of stock market launches since 2007. As the VCs walk away on their cold feet, the sector is being kept alive largely by groups of `business angels’ – wealthy individuals who like to gamble. What can biotechs do to look more credible?With cash burn their biggest worry, biotechs must stay lean. Their most expensive resource is people, so they must contain headcount and use consultants for key roles. Many biotechs are headed by top grade scientists, but commonly lack seasoned individuals who can steer products through development and towards commercialisation. Grant funding is available, and the sector probably under-uses it. However applying for a grant takes time and skill – another role for experienced consultants perhaps? Of course, it is going to help enormously if some revenue can be generated. Not only does this mitigate the cash burn, but it builds confidence both internally, and with those providing the funding. At the same time, biotech boards need to be creative in developing different financial models. Writing different business plans for different funders (and I speak from experience) can feel like a full time job, but it has to be done – and generally you only need one or two of them to strike home. It should also be remembered that there is stiff competition for VC funding from other sectors. Examples are delivery systems, sensors, and medical devices (stents continue to be attractive), as well as a proliferating range of products in regenerative medicine. Outside health care, biotechnology finds applications in new environmental products such as biofuels – yet more ideas competing for cash. OK chaps, I’ve got a great idea!
So what happened to BIGT and its big ambitions? There were some related initiatives designed to address the UK’s problems in innovative drug development. I have touched on these elsewhere, such as the UK Clinical Research Collaboration and the Office for Strategic Coordination of Health Research, but the decline in UK clinical trials activity continues unrelentingly. So last year BIGT, with an impending crisis on its hands, attempted a relaunch, in the form of the Review and Refresh of Bioscience 2015. BIGT correctly identified the main problem, that of funding. It might be said that this was not exactly rocket science, and that in the middle of a recession what else could anyone expect? However to my certain knowledge there are companies out there continuing to secure investment, even if they are not biotechs. The reality is that the UK investment market is notoriously risk-averse, something that biotech entrepreneurs have to address. VCs will not go anywhere near a product that has no guarantee of successful development (and nothing does), if its market is very small. The return on investment is simply not there. Yet there are biotechs who are trying to do just that. They commonly fail to analyse the competition (which may include very cheap generic products) because they are carried away with their technology. This has been recognised by the Review and Refresh, which emphasises that the focus must be on outcomes not processes. BIGT accepts that the original Biosciences 2015 initiative was over-optimistic, although nobody could have predicted the extent of the hostile financial environment we now face. The Review also draws attention to the failure of the UK to stem the decline in clinical trial activity. I make no apology for repeating this, because it is widely reported from many sources. Much of the blame has been placed on the EU Directives on Clinical Trials and Good Clinical Practice, and it is true that Europe is suffering as a whole. A key issue is that the Directives have not achieved the harmonisation at which they were aiming, as member states have interpreted the legislation with considerable flexibility. In passing, it is worth reflecting that much the same has happened with the supposed harmonisation of GCP between Europe, North America and Japan. As it is widely reported that the UK implementation is among the most rigorous in the world, it is natural to link over-regulation with poor performance of UK clinical trials. The true picture is more complex however. But whatever the reasons, the UK is now at the bottom of the EU league table for clinical trial performance – and is near the top for cost. Bridging the credibility gap Biotechnology is increasingly seen as the pipeline feeding into big pharma, so the will is still there to put all this right. Indeed the UK has for some years led Europe for putting new drugs into the pipeline, only to see an increasing proportion developed elsewhere. A number of new actions are being taken, with the establishment of centres of innovation. Scotland appears to be doing well here, with for example the Edinburgh Bioquarter. Cambridge has its Biocampus, and Birmingham its Science Park, and London, Oxford and Cambridge are described as a `golden triangle’ for bioscience. To an extent some of this looks like window dressing, but that’s to be expected. To attract funding the sector has to look credible, and indeed these companies, although they are offering products to big pharma, should be looking like pharmaceutical companies themselves. It seems to me that, if they are operating to the same standards, technology transfer will be easier, and that’s a key consideration for investors. Footnote: Due acknowledgement is made to Dr Catherine Beech for material presented at a seminar organised by The Harten Group on 29 September 2009, referenced here with kind permission. Les Rose is a freelance clinical science consultant and medical writer. www.pharmavision-consulting.co.uk |
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