Send in the gas: NicOx S.A

Abstract

The NO-NSAIDs’ main competition is the Cox2 inhibitors, which hit the inflammation-induced Cox2 enzyme, but spare its constitutive relative, Cox1. The selectivity is important because Cox1 helps to protect the stomach lining.The Cox2 compounds nearly killed the NO-NSAID project before it started. Armed with an idea and a compound, Wallace says he and his colleagues “shopped it around to big pharma, [but] at the time these companies were developing Cox2 inhibitors so we didn’t get much interest. We realized we would be better off developing it ourselves.”That was easier said than done. “For three years we lived on our own financial resources,” says NicOx CEO Michele Garufi. “In Italy in 1994 it was impossible to find venture capital,” and British venture capital “didn’t invest beyond the Channel.” Finally the money arrived but with one condition: that the company move to France.Not that the team was forgotten in Italy. “We are very famous in Italy only because we are the first two crazy guys to do something that is quite normal in the US,” says Garufi. “We were non-conventional Italians — we wanted to take risks.”The funding was still modest, so to make it last longer the company contracted most of its work out to university researchers. “We were a little forced to do that because we didn’t have the funds to do otherwise,” says Garufi. “But sometimes you are forced into a model and then you realize it’s the right model.” NicOx has stayed with contract research and even now has only 20 full-time employees.Working in a field as vast as NO biology, Garufi says that “it would have been too pretentious and too limited to group within our company only a few good scientists. It’s much more productive to have all the top professors working for us in their own laboratories or institutes.”“That gives you flexibility in closing your projects by finishing the research contract rather than having to fire five people,” he says. “And it gives a lot of credibility to our research. The data are coming from top level professors who have credibility and a reputation.”The main focus in-house is the chemical laboratories, which help the company keep the most important preclinical information proprietary. But if the company ever wants some biological work done “we always find more people than we need,” says Garufi, “because NO is a hot field.”The number of collaborations has allowed the company to branch out. By adding NO-generating moieties to a variety of common drugs, the company is moving into areas such as urinary incontinence (both NO and NSAIDs have an effect), osteoporosis (NO inhibits bone-eating osteoclasts), asthma (NO and a steroid relax bronchial smooth muscles), thrombosis (NO augments the anti-clotting effects of aspirin), high blood pressure (NO may improve standard drugs such as beta blockers) and even Alzheimer’s disease (with NO acting as an anti-inflammatory).Even in pain and inflammation, Del Soldato feels NicOx has the upper hand. “In terms of safety we have an advantage because Cox2-specific inhibitors are good [only] when the tissue is not [already] compromised,” he says. And, he says, “Cox1 is critical. It has a relevant role in inflammation and thrombosis.” A recent study, for example, indicates that the heart-protecting effect of naproxen is lost when Merck’s Cox2 inhibitor Vioxx is used instead.“I saw the flaws in the Cox2 approach early on,” says Wallace. “The marketing was getting way ahead of the science. We are being vindicated now.” Garufi’s assessment of the situation is more understated, perhaps more European. When NicOx began, he says, “there were many risks. But so far so good.”