Inflazyme Pharmaceuticals Ltd. expanded its ongoing respiratory disease therapy collaboration with Aventis Pharmaceuticals Inc., an amendment that could be worth as much as US$90 million to Inflazyme while at the same time allowing it to focus its research efforts beyond respiratory indications.
"Small biotech is good at making decisions quickly, but when it comes to putting resources in place, big pharma is better at getting it done quickly," President and CEO Ian McBeath told BioWorld Today. "Respiratory is a high-priority area for Aventis, and this deal allows them to accelerate development of these oral compounds. And new oral compounds in asthma is something there is clearly a high market need for."
Aventis will fully fund further clinical development of Inflazyme's IPL512,602 candidate for asthma, and at the same time begin preclinical studies on the same compound for an added indication - allergic rhinitis. The new program will be conducted in parallel with the existing asthma program, both of which will be supervised jointly. But Inflazyme maintains responsibility for investigational new drug application filings.
"There's a 70 percent crossover with allergic rhinitis patients also having asthma," McBeath said. "And Aventis is a market leader in allergic rhinitis with Allegra [fexofenadine HCl], which sold $1.7 billion last year. Clearly this helps them maintain their market position."
A $10 million development milestone payable to Inflazyme would be due for the first of the two programs to successfully complete a defined Phase II study, at which point Aventis would take over the oral, second-generation compound. Under the original agreement, entered into more than three years ago, Aventis would have paid $10 million and taken over the leukocyte-suppressing anti-inflammatory drug (LSAID) following a successful Phase IIa asthma study. (See BioWorld Today, Feb. 10, 1999.)
Earlier this month, Inflazyme reported the compound was safe and well tolerated at all doses studied in a Phase I trial.
The studies involved 114 male patients, 86 of whom received either single or multiple doses of IPL512,602 for up to 10 days. McBeath said Inflazyme would file by the end of next month an investigational new drug application for the compound, after which Aventis plans to advance it into two separate clinical programs, one in asthma and the other in allergic rhinitis.
Bridgewater, N.J.-based Aventis, the U.S. pharmaceutical company of Aventis AG, already has provided Inflazyme $16 million in up-front payments and equity investments, plus supplied manufacturing and other resources. Further milestones, totaling $35 million, plus double-digit royalties on sales are payable to Richmond, British Columbia-based Inflazyme if the product is commercialized.
"This is completely positive - the Phase I results confirm that the drug is safe, and earlier studies with the first-generation LSAID prove that these drugs will work orally in the lung," McBeath said. "We improve our chances of getting to that milestone, but they only pay per drug - so '602 for two indications gives us one milestone, but obviously when the drug gets to market we get a percentage on all the sales."
He said Aventis would advance the drug for both indications, regardless of whether development lags for one, but eventually provide data in both indications upon FDA review.
In addition, the collaboration now includes Inflazyme's IPL12 series, a new series of LSAIDs. Aventis potentially will pay up to $45 million in milestones and double-digit royalties if an IPL12-series molecule is brought to market - an arrangement structured identically to the other. The payments would be in addition to those paid for IPL512,602 if both products are developed concurrently and commercialized.
Molecules in the IPL12 series are chemically distinct from IPL512,602, but with demonstrated activity in preclinical models of respiratory inflammation. Inflazyme will be responsible for identification of a lead molecule, and when it is accepted into development, Aventis will take over further development costs.
"That's targeted for the first half of next year," McBeath said. "Aventis will then develop it. They will do it all - manufacturing, toxicology, everything - to take that drug forward, into the clinic and then to market."
McBeath said the expanded Aventis arrangement improves Inflazyme's burn rate by about a third, though he said his company's cash position is sufficient for at least two years of operation. Specifically, he said the deal increases Inflazyme's window to explore further options.
"Our intention now is to concentrate on developing our new LSAIDs on non-respiratory conditions," McBeath said. "Respiratory is taken care of, so we're now going to develop these very powerful anti-inflammatory drugs for other anti-inflammatory conditions. Over and above Aventis, the LSAIDs are a very novel and unique group of molecules for inflammation, and we believe we should be able to do other similarly strong deals with other pharmaceutical partners."
Other LSAIDs, all of which are different drugs in different series, might address conditions such as rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, psoriasis and lupus. Those in development include IPL550,260, which is undergoing Phase Ib trials and has been shown to be safe and well tolerated at doses administered. Inflazyme continues to investigate the molecule in a number of preclinical models of inflammatory disease.
The first-generation LSAID, IPL576,092, originally was explored in the Aventis collaboration and showed proof of principle, but now continues in separate development. Inflazyme said it is being reviewed by potential partners in preclinical models of inflammatory diseases of the eye, and further studies are planned for inflammatory diseases of the skin.
A new series, IPL99, is being developed specifically for non-respiratory conditions.
Beyond its LSAID programs, Inflazyme regards as promising a phosphodiesterase-4 compound. In collaborative development with Farmingdale, N.Y.-based Helicon Therapeutics Inc., the candidate has shown positive results in models of learning and memory.
Inflazyme's stock (TSE:IZP) climbed C23 cents Thursday, or 51.1 percent, to close at C68 cents.