Europe’s largest medical charity, the Wellcome Trust has launched a GBP 91 million programme to bridge the funding gap in drug discovery. The aim is to give researchers the means to take small molecules forward to the point where they are ready for clinical trials, and thus of commercial interest.
The first three awards under the scheme have gone to Steve Bloom, professor at Imperial College London and chief scientific officer of Thiakis Ltd, who is getting GBP 2.3 million to develop a long-acting version of a natural hormone involved in appetite control as a treatment for obesity; Prolysis Ltd, a spin out from Oxford University, which will get GBP 3.48 million to develop a treatment for life-threatening, drug-resistant, staphylococcal infections; and ProXara, a spin out from the University of Bristol, which will receive GBP 2.8 million to develop a small molecule inhibitor of Protein kinase B, an enzyme involved in the proliferation of tumour cells.
The three start-up companies have received venture capital funding for their wider portfolios, with Prolysis raising a total of GBP 10 million in two rounds in November 2002 and May 2005, and Thiakis attracting GBP10 million in its first formal round on August 2006, while ProXara has received seed funding including a contribution from Wellcome’s venture capital arm, Catalyst Biomedica.
Ted Bianco, Director of Technology Transfer at the Wellcome Trust said the awards from the Wellcome Trust are hypothecated for specified projects. “We are not putting money into companies to further the development of the company, but to speed the individual projects,” he told ScienceBusiness.
"Even though obesity, cancer and MRSA are three of the most urgent challenges faced by our society today, there are many more innovative approaches to how they might be tackled than there are drugs being progressed in clinical development."
It is expected to take five years to award all GBP91 million, which Bianco says will support 30 projects in total. All projects must be based in the UK, but the award winners may have international collaborators.
Bianco said the researchers that received the first awards have made exciting discoveries at the basic research level, which the Trust hopes can be translated into tangible health benefits. “Our funding is designed to take the research forward to a point that makes these projects more attractive to venture capital firms, industry and public-private partnerships.”
He added, “We hope these projects will encourage closer collaboration between academic researchers, the biotech sector and its investors, and the pharmaceutical industry.”
The compounds being developed by Prolysis under the award from the Wellcome Trust block the ability of the MRSA bacteria to divide and multiply. They do this by inhibiting a bacterial protein FtsZ, which is essential for cell division. As FtsZ is not found in humans this reduces the potential for inhibitor to causeside-effects in patients.
And because of the novel mode of action bacteria should take some time to develop resistance.
"The antibiotic that we are developing is far more selective than those currently in use, targeting only staphylococcal infections," said Lloyd Czaplewski, Director of Research at Prolysis. "Other, broad-spectrum antibiotics tend to kill the patient's natural bacteria, leaving them open to secondary infection by other pathogenic bacteria."
Czaplewski said the GBP 3.48 million award could result in a new medicine being fast-tracked into clinical trials by 2009.
Meanwhile, Bloom and his team at the Hammersmith Hospital in London have discovered a hormone called pancreatic peptide, which is secreted during a meal to signal to the brain when a person has eaten enough. "Developing a treatment based on natural appetite suppression, mimicking our body's response to being full, has the potential to be safe and effective," said Bloom.
The problem is, that as a natural hormone, pancreatic peptide has a short half life. The challenge under the Wellcome award is to develop a longer acting version. If successful, Bloom believes the project could lead to a treatment within five to eight years.
All cells contain protein kinase B, the naturally occurring enzyme which is targeted in ProXara’s project. Certain types of genetic damage, common to many cancer cells, lead to protein kinase B migrating from the interior of the cell to the cell membrane. From here the enzyme sends out a signal that prevents apoptosis, or programmed cell death, in cancer cells.
Other groups have focused on protein kinase B as a target, developing drugs that block the signal it sends. However, drugs based on doing this are non-specific and can have many side effects. ProXara’s approach is to interrupt the action of protein kinase B at an earlier stage, by preventing it from binding to the cell membrane in the first place.
Despite increasing interest from pharmaceutical companies and venture capitalists in earlier stage projects, the Wellcome Trust says it is no longer sufficient to have a putative drug target or novel chemistry to attract funding.
What is required is a higher level of evidence that a target or biochemical pathway is 'druggable', or that a proprietary chemistry has biological relevance that can be measured in the context of disease. Typically, to attract commercial interest there must be intellectual property around a novel disease mechanism and an optimised lead compound, (or better).
The awards, “Might or might not result in wealth creation, but the primary aim is to get new treatments in areas of unmet medical need,” said Bianco.
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