Starpharma scoops up two ARC grants

Starpharma (ASX:SPL) has received two competitive linkage grants, worth a total of AUD$440,000 over the next three years, from the Australian Research Council to further develop pharmaceutical applications of its proprietary dendrimer macromolecules.

The grants cover Starpharma's research collaborations with Monash University's Victoria College of Pharmacy (VCP), and the University of South Australia's Ian Wark Research Institute (IWRI).

VCP researchers Dr David Chalmers and Dr Martin Scanlon will use a supercomputer to model dendrimers, and predict the structures of the complexes they form when interacting with their pharmacological targets. IWRI's Assoc Prof Clive Prestidge and Prof Hans Griesser will investigate how dendrimers interact with viruses, bacteria and cancerous cells.

Starpharma's Vivagel, a dendrimer-based topical microbicide gel developed to prevent sexual transmission of the human immunodeficiency virus, is currently in Phase I clinical trials. The US Food and Drug Administration has accorded Vivagel investigational new drug (IND) status, in recognition of the lack of effective drugs to reduce HIV transmission.

Starpharma hopes the new projects will reduce the time required to develop new pharmaceutical applications of its unique dendrimer molecules, by clarifying how they interact with drug targets, pathogens and other biological structures.

Dendrimers are among the largest synthetic molecules, approaching the size of small proteins. They are built up around a synthetic core, in a series of elaborately branched layers, with projecting functional groups that can be designed to interact with range of molecular targets.

Where most synthetic drugs bind to single targets, such as cell-surface receptors, dendrimers can bind simultaneously to multiple targets, including the surface receptors that viruses and bacteria exploit as portals to infect host cells.

While Vivagel is being trialled for its ability to prevent HIV infection, it also shows promising protective activity against other sexually transmitted pathogens like Chlamydia, genital herpes, human papilloma virus (the agent of genital warts and cervical cancer), and the gonorrhoea bacterium Neisseria.

A single dendrimer molecule can 'grasp' multiple receptors in the same region of cell membrane, causing the membrane to 'pucker' and rendering the receptors inaccessible to a variety of pathogens. Dendrimers can also immobilise and neutralise pathogenic bacteria and viruses by binding to proteins on their surface.

Alex Szabo, Starpharma's vice-president of business development, said that rather then trying to understand the efficacy of dendrimers, the new research projects aimed to identify mechanisms that might limit the effectiveness of dendrimers, or cause toxicity problems.

"The goal is develop predictability [of activity and toxicity] at an early stage of drug development," he said. "All drug-development companies are trying to do it, either through experimentation or computation.

"Toxicity is a general concern for any potential new drug. There's always a risk of off-target activity, so we're trying to design dendrimers that will be less susceptible to the problem than most small molecules and polymer therapeutics."

Szabo said the Adelaide trial was proceeding well, with no serious adverse events. Results will be available some time in September.

He said there was a "very high degree of commercial interest" in the trial. "We're fortunate to be in a world-leading position for a very new category of products," he said. "Not much progress has been made towards vaccines to prevent or treat AIDS during the past years, and Vivagel is a novel concept with an enormous market opportunity, as well as being of fundamental benefit to humankind."

Szabo said Vivagel was potentially a revolutionary concept for preventing HIV infection -- as a drug, it was analogous to installing belts and air bags in cars to prevent injury, rather than putting in more hospital beds to treat accident victims.

Szabo said Starpharma was also exploring oncology and respiratory disease applications for dendrimer drugs. "We have a foundational position in dendrimer chemistry, and an extremely strong IP position. We're applying dendrimer technology to a wide variety of therapeutic areas, typically through partnerships with entities that have strong positions in biology that complement our chemistry," he said.

In the oncology field, Starpharma was working on dendrimers that would block angiogenesis -- the growth of new blood vessels that feed and oxygenate tumours.

The recent success of Genentech's angiogenesis inhibitor Avastin, and the promising performance of Progen Industries' PI-88 in clinical trials, had lifted the gloom that accompanied early failures with experimental angiogenesis inhibitors several years ago.

"We think we're not only a huge prospect, but that there will be many opportunities for angiogenesis inhibitors with different targets -- nobody is going to corner the market," Szabo said.