Cross-Atlantic Collaboration

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British science is taking leading-edge academic research and using it to build a portfolio of commercial products and technologies that top pharmaceutical companies worldwide are applying to the field of human medicine. ProMetic BioSciences Ltd.’s (Cambridge, U.K.) innovative approach to the development of affinity reagents for use in the separation and purification of proteins is being used in the search for cancer treatments, and — more prosaic, but no less important — to guarantee the purity of donated blood and blood products.

British science is making connections that, at first glance, defy logic, but when developed can go on to lead significant medical advances around the world. “It’s about the cross fertilization of ideas, finding new applications for existing technologies, then improving the process,” claims Steve Burton, PhD, executive vice-president, ProMetic BioSciences. He should know.

ProMetic BioSciences, discreetly positioned on a science park on the outskirts of Cambridge, U.K., grew out of an earlier firm called Affinity Chromatography Ltd. (ACL) (Cambridge, U.K.) — itself a spin-off from Cambridge University’s Institute of Biotechnology where Burton studied for his doctorate.
ACL had noted some interesting characteristics of synthetic dyestuffs as used in the textile industry: first, that they had a peculiar molecular structure that facilitates their attachment to cellulose and other materials and makes the dye permanent; second, that it was accepted that some dyestuffs had medical properties. For example, methylene blue is an antiseptic, and trypan blue is an active anti-malarial agent.

Innovative Thinking
The innovative connection was to investigate these properties to see if the dyes could interact with proteins, with the chromophoric part removed. If they could, they had the basis for a new category of synthetic ligands capable of providing new drugs for specific areas of need within human medicine, the purification of biopharmaceuticals, or the ability to “capture” specific harmful proteins, toxins or pathogens so they can be removed from the bloodstream.

“We started as a company looking at separation and purification technologies,” claims Burton, “and focused in on looking at new ways to separate and purify proteins using simple chemical entities. The goal is similar to that achieved by using monoclonal antibodies, but this is quite complex as monoclonals are themselves produced by genetic engineering and the inclusion of protein ligands in a protein purification process can give rise to unwanted immunogenic side-effects. Our Mimetic Ligands™ are non-toxic, non-immunogenic (and) very stable.”

Meanwhile ACL’s developing promise — to take a platform technology arising from basic research and extrapolate it into commercially successful products and technologies applicable to a wide spectrum of applications in the biotech, biomedical and pharmaceutical fields — had caught the attention of another company, more than 5,000 kilometres away in Canada.
ProMetic Life Sciences Inc., based in Montreal, was keen to expand from its pharmaceutical base into biotech — an industry that provides greater opportunities to raise the added-value side of the business and is easier from which to build competitive differentiation because it is less generic. ACL was already in this arena, had the strong research base ProMetic lacked, and had a growing revenue line. At the same time, ACL was looking for ways to gain access to capital to help it enter the vital North American markets.

Market Synergies
The first move was to form a joint venture, and in July 1998, ProMetic Life Sciences went public on the Toronto Stock Exchange — a move that provided much needed capital. A full merger with ACL went ahead shortly afterwards and the Cambridge company changed its name to ProMetic BioSciences Ltd. This allowed for a move to larger premises and an opportunity to invest in new and refurbished laboratory facilities at the Cambridge Science Park. The next phase of the company was under way.
The Cambridge facility retains the key R&D functions for the larger company, and the ligands discovery and separations role. It’s led to a number of commercial applications, and enabling technologies, which help pharmaceutical and biotech companies to develop their own proprietary products.

Partnering Projects
The company is proud of its international collaborative projects, where its know-how is helping well-known companies, and includes work on the industrial purification of recombinant proteins derived from microbes (with Aventis Pasteur Ltd., Toronto); mammalian cell culture (with Novo Nordisk Canada Ltd., Mississauga, ON, and Italy-based Menarini Biotech); and animal transgenics (with GTC Biotherapeutics, Framingham, MA).

ProMetic has also established high added-value joint venture companies with selected appropriate partner companies. In a joint venture with California-based Arriva Pharmaceuticals Inc., a recombinant Alpha 1-antitrypsin is being developed for use in dermatological indications.
In response to the urgent need for a means of detecting and removing infectious agents from blood and blood products, ProMetic and the American Red Cross (Washington, DC) have formed a joint venture company, Pathogen Removal and Detection Technologies Inc., which is engaged in the development of a medical device for capture and removal of prions from blood and blood cell concentrates. A driver for this is the urgent and growing need for confidence in donated blood, with current concerns surrounding blood harbouring the human variant of mad cow disease proteins. A spin-off application has been the development of a diagnostic test to seek these proteins.

Another collaboration with the American Red Cross has been entered into to provide an improved protein purification process to the Red Cross and, under licence, to other third parties. ProMetic and the Red Cross Plasma Services will generate royalties on the sales of the therapeutics produced from this new process. ProMetic will also supply the separation media to the manufacturing facilities using the process.

ProMetic has made a step change in the application of its technology and is already looking to the future. The market is confident, with the company maintaining its value on both sides of the Atlantic.
“We see fantastic long-term opportunities,” says Burton. “At present we have our separation products on the market, and there’s a continuing and increasing demand for these. We also have lab kits for the R&D market and are seeking licensing opportunities for our technology for bioprocess applications. The future however is in biopharmaceuticals and straight pharmaceutical applications, and we already have early research and clinical trials for a cancer therapy treatment that will be smaller, simpler and less likely to cause side-effects than the alternatives.

“Ultimately I’d like to see ProMetic with its own proprietary branded products in the market place. Having moved the science along, this will confirm our lead in this area. That’s where the real rewards lie.”

Steve Minett, PhD is owner and senior partner with Minett Media.