Redirecting its resources toward core anti-inflammatory programs, Inflazyme Pharmaceuticals Inc. dropped development of an antithrombotic agent when it showed an increase in liver enzymes in a Phase Ib trial.
GH9001, the most advanced product from Inflazyme's acquisition of GlycoDesign Inc., will no longer be studied with partner Leo Pharma.
Elevated liver enzymes are seen in other heparin products, said Ian McBeath, president and CEO of Vancouver, British Columbia-based Inflazyme, and the company "could continue to work with this compound to potentially resolve the safety concern." But he said the reason for not pursuing it further was monetary.
McBeath noted that the changes in liver enzymes were fully reversible and asymptomatic in all cases. The elevations were not observed in preclinical toxicology studies or the Phase Ia single-dose study.
However, the combination of GlycoDesign's medium-molecular-weight heparin and Leo's highly sulfated, low-molecular-weight dermatan sulfate was expected to show an advantage over several other anticoagulation products on the market. In order to continue development, Inflazyme needed to conduct additional Phase I studies looking at medium-molecular-weight heparin and low-molecular-weight dermatan sulfate separately, and then together at different ratios, to determine the cause of the increasing liver enzymes.
"We were looking at numerous increases in studies, therefore in costs, therefore that took away a lot of the commercial interest in the product," McBeath told BioWorld Today. "If this product had been in our core area of our business, then we might consider doing this."
Inflazyme focuses mainly on anti-inflammatory drugs. Its internally developed programs center on orally active, small-molecule compounds, called LSAIDs (Leukocyte-Selective Anti-Inflammatory Drugs). Partnered with Lyon, France-based Aventis Pharma, its lead LSAID - IPL512,602 - is completing a Phase IIa asthma trial in the U.S. McBeath said the trial completed enrollment of all patients and results are expected this summer.
Inflazyme intends to transfer all resources from the GH9001 program to APT070 and other candidates acquired through the company's acquisition of Adprotech Ltd., of Cambridge, UK. By not doing a Phase II trial of GH9001, the company will save about C$5 million, McBeath said. Short term, it will save another C$600,000 by dropping the product. The company has about C$35 million (US$25 million) in cash that should last it through the end of 2005.
Results from Phase I/II trials being conducted in the UK of APT070 in rheumatoid arthritis are expected by the end of the year. The product is a truncated recombinant form of human complement receptor-1, further modified with Adprotech's Prodaptin targeting technology to deliver it to the cell surface. It is injected into the knee joints of patients experiencing a disease flare.
Inflazyme acquired Adprotech last month for about C$20 million in shares. (See BioWorld Today, April 13, 2004.)
Inflazyme acquired GlycoDesign last June, issuing 22 million shares, in a deal worth C$12.8 million. The company gained about C$17.5 million in working capital through the acquisition. (See BioWorld Today, April 10, 2003.)
"We didn't buy the company for this technology," McBeath said. "We got cash in that acquisition. The products were not core products to us."
Toronto-based GlycoDesign fell on hard times in 2002 when its lead product, GD0039, failed in a Phase II renal cancer trial. The company terminated development due to discovered toxicities. Its other product, GH9001, partnered with Ballerup, Denmark-based Leo, showed promise at the time of the acquisition, when it was completing its Phase Ia trials. (See BioWorld Today, April 10, 2003.)
McBeath said GH9001 still might have some value to a potential partner, but Inflazyme will not spend any more money to conduct trials of the product. For now, it is shelved.
"We believe that anybody wanting to partner it would prefer to have that data available before partnering," he said.
Aside from GH9001, GlycoDesign brought two other potential products to Inflazyme. Researchers are looking for lead compounds in the CORE2 inflammation program, which is focused on small-molecule inhibitors of core-2 glycosyl transferase. And Inflazyme also is moving forward with the other program focused on an antithrombin heparin complex, called ATH.
"We're looking at getting it manufactured to do some toxicological evaluations and late-stage preclinical evaluations with a view of taking that forward into the clinic," said Kevin Mullane, the company's senior vice president of research and development, in a conference call.
Inflazyme's stock (TSE:IZP) rose C2 cents on Friday to close at C$1.18.