Santhera Presents New Data on MC-4R Antagonist Program for Treatment of Cancer Cachexia
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 administration the compound increased food intake 3-5 fold. Moreover, post treatment energy expenditure was significantly decreased in normal mice but not in mice deficient of MC-4R. In a well characterized murine model of cancer cachexia (C26 adenocarcinoma model) daily oral treatment significantly 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 represents 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.
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