Semi-virtual drug development…
Profile MGB Biopharma
Core business: Anti-bacterial drugs
Date incorporated: 2010
Number of employees: 4
Funding: £2.2 million
Semi-virtual drug development
It may be walking in the footsteps of Alexander Fleming, who discovered penicillin in 1928, but Glasgow-based MGB Biopharma is not only developing a new class of anti-bacterial drugs but also a new way of doing pre-clinical research – and a new way of building a drug development business.
The new class of anti-bacterial drugs, which will soon be ready for clinical testing, was discovered by Professor Colin Suckling of the University of Strathclyde, and MGB Biopharma (MGB) was the company formed to take the new technology onto the next stage, aiming to develop and commercialise a drug which is expected to prove more effective against hospital-acquired diseases than currently available therapies.
DNA minor groove binders (MGB) are the small molecules that inspired the new company name and they were discovered by a team of medicinal chemists, molecular modellers and microbiologists at the University of Strathclyde, led by Suckling. The initial development was funded by the University of Strathclyde and Scottish Enterprise’s Proof of Concept Programme, with help from royalties from Leucovorin®, an anti-cancer drug which emerged from research at Strathclyde in the 1980s, also led by Suckling.
The new drug, now known as MGB-BP-3, has demonstrated “very significant in vitro and in vivo activity against Gram positive bacteria, including MRSA, VRE and Clostridium difficile.” And MGB Biopharma CEO Miroslav Ravic says the market for such drugs could be worth at least $6 billion a year.
Ravic, who was born and educated in the former Yugoslavia, and worked as a Consultant in Belgrade University Hospital before coming to the UK 25 years ago to complete his PhD at St Bartholomew’s Hospital in London, has a very clear vision for the new class of drugs – and how to advance it through pre-clinical and clinical research.
His experience on “both sides of the fence” as a practising physician and in clinical research (he has been involved in more than 100 clinical studies) has shaped Ravic's attitude to drug development and enabled him to take a very different approach to the business. He also spent almost ten years as the European Director of Clinical Research at Eisai – an experience which ultimately convinced him that there must be a “better, quicker and cheaper” way to develop new drugs. “Old habits die hard,” Ravic says. “But I wanted to develop drugs my way.”
After leaving Eisai, Ravic then spent three years at Antisoma, where he learned what life was like at a small drug development company. Whilst there, he helped to restructure the company’s clinical drug development group and also played a key role in the development of a new anti-cancer drug which was later licensed to Novartis in a deal worth $900 million.
This industry experience has taught Ravic several lessons and inspired his current approach to research. The big pharmaceutical companies dominate late-stage research and tend to use standardised methods – the same protocols again and again – rather than take any shortcuts. When they’re aiming to show that the new drug is “active,” having already proved it is safe, researchers may engage in several studies one after another, each costing millions of dollars. That is why it can take 8–15 years to develop new products, and meanwhile many people may be dying for lack of the more active drugs.
“Time is money,” says Ravic, who says that the conventional drug development cycle contains too much “dead space” – not just waiting for final approval but also in the earlier stages. And the answer, he says, is what is called “adaptive design,” combining various aspects of the drug development process, treating it as one continuum and designing bespoke studies tailored to candidate drugs. “Current drug development is very fragmented and, as a result, instead of integrating the development process from beginning to end, there is often little communication amongst those involved in pre-clinical research and even less between them and the clinical development teams,” says Ravic.
As well as having firm views about how to develop new drugs, Ravic had a clear idea of what kind of drugs he would like to develop, when he set up his own drug development business.
Whilst working as an industry consultant, he started searching for a new class of molecules which “ticked all the boxes” in terms of design and targeted acute diseases rather than chronic diseases, thus promising faster financial returns. He was also keen to focus on a drug that works on well-defined targets. “Another key factor,” says Ravic “is that the new drug is designed to target severe diseases that are difficult to treat – an area of high unmet need.” And the quest soon led Ravic to Glasgow, where Professor Suckling and his team had already tested new anti-bacterial compounds in vitro and were looking for a partner to help them move on to pre-clinical testing and turn the candidate molecule into a commercial product. Ravic felt convinced that some of these compounds had the potential to meet all of his criteria.
By this time, Ravic had also teamed up with his colleague Gavin Clark who, with 25 years’ experience in commercial roles at Johnson & Johnson, Bayer, NoVartis and GSK, had coincidentally been one of Suckling’s chemistry students in the late ’70s, and the two of them negotiated with the University of Strathclyde to license the technology. After due diligence, Ravic brought in Raymond Spencer, a highly experienced Chief Financial Officer from Antisoma and, together with Clark, founded MGB Biopharma and approached the new business with the same kind of radical outlook that Ravic applied to research. Rather than hiring a team of researchers and setting up a dedicated new facility, Ravic has created what he calls a “semi-virtual” company.
The reason the majority of new drug development companies fail is simply because they run out of money,” says Ravic. “Research projects tend to take longer than anyone ever expects and new firms also find it hard to attract top researchers, who demand higher salaries and can regard start-ups as too small and risky to join. In addition, one project isn't enough to support a large research team or require our full attention all the time.”
The solution devised by MGB was to build a “virtual” team of top researchers and experienced advisors who already knew each other from previous projects, including Suckling plus Professor Iain Hunter and Professor Curtis Gemmell of Strathclyde, and former GSK senior scientist, Professor David Scales. Today, the company employs three executive managers on a part-time basis, and one full-time project manager, Dr Dawn Firmin. Although they are active as external consultants in non-competitive projects, Ravic says that “part-time is full-time” for all of the team. Thanks to this semi-virtual structure, the company has essentially been able to channel an unprecendented 70 per cent of its funds into direct research – way beyond the industry norm – and also managed to finish pre-clinical testing much faster, completing the process in only two years.
In the early days of MGB, Ravic, Clark and Spencer were successful in attracting potential investors and raised £2.2 million in start-up funding from an angel syndicate led by Archangel Informal Investments, in association with TRI Cap, Barwell and the Scottish Co-investment Fund.
Manufacturing is a key factor for the success of the new drug and this is handled by two separate partner companies: Almac Group in Northern Ireland and Scottish firm Encap Drug Delivery in Livingston.
The basic development process involves proving safety (i.e. the drug is not toxic) and then demonstrating activity (the new drug has an effect on its target) and efficacy (how well it performs), followed by clinical testing to confirm these results and demonstrate compliance with all the required regulations. Last year, MGB-BP-3 was formally selected as a candidate for clinical testing after demonstrating “potent and rapid activity” against a range of Gram positive bacteria including MRSA, VRE, Streptococcus and C. difficile. This was what triggered the investors to inject the second tranche of fresh funds to move on to the next stage of development.
MGB presented its findings last year at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago, USA, and in April this year it announced that it had published the results of activity of MGB-BP-3 against Gram positive bacteria, including MRSA and vancomycin-resistant enterococci, presenting those data at the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) in London.
For MGB and its backers, this creates exciting possibilities. Clinical testing can be highly expensive, so either they fund this themselves, license the technology or sell it to a partner, providing a relatively early exit for the existing investors. Future sales could be significant, with similar new products being purchased for considerable sums of cash over the remainder of the development and the commercialisation, but the new drug will require much more additional investment before it is ready for hospital use.
“I deeply appreciate all those individuals who have put all the money together,” says Ravic. “If they exit now, that will be well deserved, and if we go on to the next stage, the returns could be even greater.“ In addition, Ravic believes that the compound will make it “with or without our investment,” simply because it has so much potential in such a “needy” market.
“The results so far are promising,” adds Ravic. “While the problem of MRSA is not increasing as fast as previously, the cost of treating Clostridium difficile continues to rise, and MGB-BP-3 promises not only to treat the disease but also to prevent its recurrence – thus saving even more lives and money.”
The company’s business model may change in future, says Ravic, but being semi-virtual has delivered very real results so far for him and the rest of his team – and could lead to a made-in-Scotland anti-bacterial drug that will not only save many lives but ultimately generate billions of dollars in sales.