Santhera Presents New Data on MC-4R Antagonist Program for Treatment of Cancer Cachexia
News Dec 08, 2009
The Company's latest generation of orally active compounds increased food intake by a factor of 3 to 5 and inhib¬ited the development of cachexia in a disease-relevant animal tumor model. In addition, the preclinical candidate exhibited a significant antidepressant-like effect which is considered relevant since depression is frequent in patients suffering from cancer cachexia. Santhera is in partnering discussions for clinical development and marketing of the MC-4R antagonist program.
The preclinical activity spectrum of Santhera's latest generation of compounds indicate potential effects in all key aspects of cachexia such as lack of appetite, enhanced basic energy expenditure and increased catabolism. The compound presented at the Cachexia conference was shown to have dose-dependent acute positive effects on food intake, i.e. during the first four hours after ad¬ministration the compound increased food intake 3-5 fold. Moreover, post treatment energy expen¬diture was significantly decreased in normal mice but not in mice deficient of MC-4R. In a well char¬acterized murine model of cancer cachexia (C26 adenocarcinoma model) daily oral treatment sig¬nificantly inhibited the development of cachexia and normalized the expression of biochemical markers of muscle wasting. Moreover, the lead compound was shown to exhibit antidepressant-like activity in the rat chronic mild stress model, the most sophisticated rodent model of depression. This effect repre¬sents a valuable additional benefit since depression is frequently present in patients suffering from cancer cachexia. Santhera's compounds were found to be orally active and to easily penetrate the blood brain barrier. They were well tolerated in exploratory seven-day tolerability studies in mice and rats and were devoid of undesirable ancillary activities. In addition, the compounds exhibited a clean genotoxicity profile and little liability for drug-drug interactions.
Thomas Meier, Chief Scientific Officer of Santhera, said: "The data strongly support MC-4R antago¬nists as a promising new therapy option for cancer cachexia, a severe and often deadly metabolic syndrome. The latest generation of our orally bioavailable compounds shows an acute MC-4R me¬diated increase in food intake and decrease in energy expenditure. Both effects add significantly to the prevention of body weight loss in disease-relevant models and, as a result, qualify MC-4R an¬tagonists as an attractive potential treatment for cancer cachexia and related metabolic syndromes."