Carbohydrate chemistry expertise
What began with research into the properties of seaweed more than 30 years ago has evolved into a world leading discovery and development programme using synthetic compounds to create the next generation of drug treatments for a range of diseases and conditions.
The Carbohydrate Chemistry group at GlycoSyn’s parent company, Industrial Research Limited (IRL), was founded in 1985. Under leader Dr Richard Furneaux, the team moved from looking for anti-cancer treatments in natural raw materials to focusing on small, synthetically available molecules with potent biological properties that could be produced from carbohydrates.
Their approach, which has placed the team at the forefront of drug development for some of the world’s most serious diseases, uses carbohydrate compounds as building blocks from which active drugs are synthesised for more effective delivery within the body.
A meeting of minds
A partnership forged between the Carbohydrate Chemistry team and Professor Vern Schramm at Albert Einstein College of Medicine in New York in 1994 was a crucial milestone. Professor Schramm had spent a decade working on a new idea of ‘transition state enzyme inhibitor design’, but had been unable to find chemists in the United States prepared to undertake the challenging work of taking his idea from theory to practice.
Professor Schramm wrote the structure he wanted on a paper napkin when Dr Furneaux and Dr Peter Tyler met him in a yacht club bar in New York. It took three years of intensive research to work out how to make the compound but the result justified the investment. The compound proved to be nearly a thousand times more potent than any other inhibitor of the same enzyme target available at the time.
Called forodesine HCl, the anti-cancer drug was licensed to US biotechnology company BioCryst Pharmaceuticals Inc., which subsequently executed a sub-licence with MundiPharma Pharmaceuticals for development outside North America. It has now completed a pivotal Phase IIb human clinical trial for CTCL (cutaneous T-cell lymphoma)
Another pharmaceutical drug candidate (BCX-4208) developed through the IRL/ Einstein partnership and licensed to BioCryst targets T-cell mediated auto-immune diseases. It is now undergoing a Phase 2b human clinical trial in patients with gout in combination with allopurinal.
A recent focus for the partnership has been development of an anti-malarial drug which builds on the immucilins already developed for treating cancer and auto-immune diseases. The drug is designed to kill the malaria-causing parasite spread by particular species of tropical mosquito and provide the world’s first effective prevention and treatment for the disease.
In total, the collaboration has generated a highly valuable intellectual property portfolio with more than 20 patent family applications, many of which have been licensed. It has also put the Carbohydrate Chemistry team in a leading position worldwide with its approach to targeted drugs.
Seamless service
In 2003, the establishment of GlycoSyn was another milestone in IRL’s carbohydrate chemistry capability. GlycoSyn takes discovery of high value therapeutics from the laboratory bench to small scale manufacturing for use in human clinical trials.
The research horsepower at IRL combined with state-of-the-art facilities at GlycoSyn also provide biotechnology and pharmaceutical companies with capability to solve complex problems and tackle difficult projects involving synthesis and scale-up.
The Carbohydrate Chemistry Team’s expertise in manufacturing glycotherapeutics has also been harnessed by New Zealand Pharmaceuticals (NZP) to develop large scale, commercial production opportunities. This allows New Zealand to offer a seamless service, with GlycoSyn manufacturing small quantities of drugs for human trials and NZP able to provide the quantities needed for full commercial manufacture.
Compound interest
A promising new area of research and development for the Carbohydrate Chemistry Team is developing compounds that can increase the effectiveness of vaccines. Dr Furneaux says the team is discovering new compounds that have the potential to be effective adjuvants for vaccines, boosting a vaccine’s ability to ensure a good immune response (read story).
One such adjuvant is based on natural glycolipids, found in the cell wall of mycobacteria, which are commonly found in the environment. A synthetic version developed at IRL has produced cell-mediated immunity. “This is where the T-cells bind to the surface of other cells that display the antigen and trigger a response rather than encouraging the production of antibodies, which is the case with most adjuvants currently being used,” says Dr Furneaux.
The other candidate is based on plant-derived natural products with the team having developed a synthetic version in conjunction with the University of Otago.
From a staff of 11 in the early 1990s, the IRL Carbohydrate Chemistry Team has grown to number 32 with a further 22 staff employed in GlycoSyn. IRL is now recognised as having the largest combined concentration of carbohydrate chemistry and GMP manufacturing expertise in the world.