LONDON - Alizyme plc has agreed to a deal with SmithKline Beecham plc under which it will develop SmithKline's renzapride compound for treatment of irritable bowel syndrome (IBS).
The London-based pharmaceutical company already has carried out Phase I studies of renzapride, a 5-HT4 agonist/5-HT3 antagonist, in the treatment of gastric reflux disorders.
IBS is a motility disorder of the small intestine and large bowel. Alizyme said renzapride will combat the disorder by stimulating intestinal motility.
Richard Palmer, CEO of Alizyme, told BioWorld International, “This is a very significant deal for us because it gives us a compound that we can move rapidly into Phase II. SmithKline already has a lot of experience with it, the market opportunity is significant and the scientific rationale is pretty strong for its use in constipation-predominant IBS.“
Palmer pointed out that Novartis AG, of Basel, Switzerland, has just progressed a similar compound into Phase III in this indication.
Alizyme, a Cambridge, U.K., discovery and development company specializing in obesity and gastrointestinal disorders, plans to begin Phase II trials of renzapride early in 1999.
Under terms of the agreement, SmithKline has the first right of acceptance to license back the compound and any associated rights generated by Alizyme once the Phase II proof of efficacy trial is completed.
In agreeing to these terms Alizyme must have had its thoughts on the plight of Vanguard Medica Ltd., the Guildford, U.K., development company that saw its share price fall by more than 25 percent to £4.35 in May when SmithKline dropped plans to market Vanguard's lead product, frovatriptan. This migraine treatment, which completed Phase IIIa, was licensed from SmithKline by Vanguard in 1994. Since then Vanguard's stock price has halved, closing at £2.05 Friday.
SmithKline's excuse for not taking up frovatriptan was that it would have required a huge marketing effort at a time when the company was preparing to launch other products.
“We are very aware of the real world of pharmaceutical and biotechnology companies,“ Palmer said. “Two or three years down the line, you can't make predictions of what any company will be doing. However, our position is different from Vanguard Medica's because the decision will be taken earlier. In the event that SmithKline decides not to license back renzapride, we will have plenty of opportunity to find other partners.“
SmithKline already has a compound with a different mode of action that it is developing for the treatment of IBS.
Alizyme also said it extended a licensing agreement with BTG plc (British Technology Group), of London, on its patented colon-specific drug delivery technology. The exclusive worldwide license is for all application areas, and Alizyme has the right to sublicense the technology on a drug-by-drug basis.
Alizyme previously had options on the technology for use in specified gastrointestinal disorders. It now intends to evaluate the potential of the drug coating technology in the development of renzapride.
“Our primary objective is to push colonic drug delivery forward on Alizyme's own projects, but we also intend to take in new opportunities or codevelop with other people. Successful colonic delivery has not been achieved so far,“ Palmer said.
The drug coating cannot be broken down in the stomach and is digested only by microbial amylase enzymes that are present in the colon.
Obesity Drug Trials To Begin In '99
Palmer also reported Alizyme is now optimizing a lead compound in its program to develop a lipase inhibitor for treatment of obesity, and he expects clinical trials to begin next year. The compound will have the same mode of action as Basel-based Hoffmann-La Roche Ltd.'s Xenical, which has been approved and launched in New Zealand and has received an approvable letter from the FDA.
“Even though the U.S. launch of Xenical has slipped, the terms and conditions of the FDA letter are not out of the ordinary, and are certainly not insurmountable,“ commented Palmer.
Alizyme, which is quoted on London's Alternative Investment Market, completed a £5.5 million financing at the end of April, with £4.25 million coming from a placing and the rest from existing shareholders.
“This was extremely good, given the market circumstances,“ Palmer said. “It is important to stress that this [fund raising] took into account the expectation that we would do these deals [with SB and BTG], and there is enough money to pay for their development.“ *