For the Treatment of Preterm Labor
MN-221 is a novel, highly selective β2-adrenergic receptor agonist under development for the treatment of preterm labor. In pre-clinical pharmacology studies in pregnant rats and sheep conducted by Kissei Pharmaceutical, MN-221 reduced the number of spontaneous or drug-induced uterine contractions. In rat and sheep studies in which MN-221 was compared to ritodrine and/or terbutaline, the potency of MN-221 was greater than those β2-adrenergic receptor agonists. In addition, MN-221 delayed both normal and preterm labor in rats and caused a marked increase in the bodyweight of rat pups as a result of prevention of premature birth. Moreover, the β1-adrenergic receptor stimulating activity of MN-221 was less than that of other β2-adrenergic receptor agonists in isolated rat atrium and in cardiac function tests in rats, dogs and sheep. Due to its greater β2-adrenergic receptor selectivity, MN-221 may be effective in reducing premature births and/or providing for longer gestation, while reducing the stimulating action on the heart compared to older, less selective β2-adrenergic receptor agonists.
MN-221 pharmacokinetic and safety data has been generated in Phase I clinical studies in healthy male and non-pregnant female volunteers conducted by Kissei Pharmaceutical in Japan and the U.K. MN-221 was generally well tolerated, and the adverse events were mild and typical of beta 2 adrenergic receptor agonist. A pilot double-blind, placebo-controlled Phase II clinical trial of MN-221 was completed in 2004 by Kissei Pharmaceutical in the U.K. A trend towards a reduction in the number of uterine contractions was observed in MN-221-treated patients.
We completed a Phase Ib clinical trial in ten healthy pregnant women who were not in labor in 2007. These women received a single-dose intravenous infusion regimen of MN-221, consisting of two consecutive rounds of a 15-minute priming and a 105-minute maintenance infusion to deliver 294 micrograms of MN-221 over four hours. The primary objectives of this clinical trial were to determine the pharmacokinetics, safety and tolerability of this infusion regimen of MN-221 in pregnant women. No significant safety concerns with MN-221 were identified in this clinical trial.
We will limit our development efforts on MN-221 for the treatment of preterm labor to those activities necessary to maximize MN-221’s value for such indication while pursuing a variety of initiatives to monetize this product candidate.