Repligen Corp. has initiated its third Phase I trial of the year,with chronic lung inflammation patients at the University ofMichigan starting a safety study of a potential anti-inflammatory compound under development with Eli Lilly andCo.
This is the first time people will be administered an agenttargeted against a component on neutrophils that lets theseinfection-fighting white blood cells move out of thebloodstream and into tissue. This function normally allowsneutrophils to travel to the site on [of?] an infection.
However, the protein component, integrin, plays a key role inacute tissue injury that can occur when neutrophilsinappropriately respond to a perceived "injury," such as loss ofblood flow caused by a heart attack or wound.
The compound, dubbed m60.1, is a fragment of an antibody tothe CD11b integrin. In preclinical studies, m60.1 blockedneutrophil binding sites and inhibited release of tissue-damaging substances.
Inflammation of major organs can be life threatening, and inanimal studies, m60.1 exhibited protective effects in suchorgans as the lung, heart and liver.
The Phase I trial of 15 to 20 patients will be an open-label,single-arm study.
"In addition to safety data, we expect the results to providepreliminary indications of biologic activity which ideally willtranslate into clinical efficacy," said chief investigator JosephLynch III, an associate professor of internal medicine at theUniversity of Michigan Medical School.
Other conditions that might be remedied by this potentialproduct, he said, are systemic inflammatory responsesyndrome (SIRS), heart attack, and multiple-trauma shock.
Repligen (NASDAQ:RGEN) of Cambridge, Mass., licensed m60.1from the University of Michigan in 1991, and entered a $14million, three-year collaboration with Lilly of Indianapolis in1992 to focus on antibody-based therapeutics forinflammation.
Lilly will get exclusive worldwide marketing rights to productsfor trauma shock, adult respiratory distress syndrome, and twoundisclosed indications.
Repligen will have marketing and sales rights to otherproducts. In December, the company said such potential uses asmultiple trauma, heart attack and sepsis have a combined U.S.incidence of about 900,000 patients a year.
In other clinical trials, Repligen began enrolling cardiaccatheterization patients in a Phase I study of recombinantplatelet factor 4 in March, and earlier this month, started aPhase I trial with the potential therapeutic vaccine RP400c in"relatively healthy" HIV-positive patients.
-- Nancy Garcia Associate Editor
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