Santhera Presents Preclinical Data on Oral MC4 Receptor Antagonists for Treatment of Cancer Cachexia at AICR Research Conference

 

LIESTAL, Sweden, Nov. 7, 2008--Santhera Pharmaceuticals (SIX: SANN), a Swiss specialty pharmaceutical company focused on neuromuscular diseases, today announced preclinical data on a novel generation of melanocortin-4 (MC4) receptor antagonists for potential treatment of cancer cachexia (severe muscle wasting). The most advanced candidates significantly increase food intake in healthy animals and prevent cancer-induced body weight loss in disease-relevant models. In-vivo data will be presented today at the 2008 Research Conference on Food, Nutrition, Physical Activity & Cancer of the American Institute for Cancer Research (AICR) in Washington DC [1].

Santhera's two novel, yet chemically unrelated MC4 receptor antagonists were both found to significantly increase appetite in healthy mice. In studies of mice carrying a C26 adenocarcinoma repeated oral administration significantly inhibited the development of cachexia, i.e. reduced tumor-induced weight loss, and showed beneficial effects on body weight, lean mass and fat mass. Both compounds are orally available, were shown to be highly selective and have crossed the blood/brain barrier.

Thomas Meier, Chief Scientific Officer of Santhera, said: "Cancer cachexia represents a life-threatening metabolic condition contributing to the morbidity and mortality of cancer patients. Current treatment options for cachexia are very limited and, consequently, this syndrome is an area of high unmet medical need. Our data confirm that MC4 receptor antagonists offer a new and promising treatment strategy for this severe muscle wasting. Santhera's advanced candidates significantly increase food intake and prevent body weight loss in disease-relevant models."

Klaus Schollmeier, Chief Executive Officer of Santhera, said: "Santhera's research team has discovered and developed two series of novel MC4 receptor antagonists with promising preclinical results in cancer cachexia. Preclinical work is expected to be completed by the end of 2009 with an anticipated entry into the clinic in 2010. We are now seeking to build a strategic partnership for further development and commercialization of the program. The preferred partner would bring a complimentary expertise in oncology or cancer support."

Cancer cachexia affects about one million patients in the North America and Europe. Up to 80% of cancer patients suffer from the syndrome which accounts for approximately 20% of cancer deaths. Despite this high unmet medical need, no effective treatments are available. Currently used pharmacological interventions have limited utility or produce severe side-effects. The potential market size of the cancer cachexia market is estimated to be above USD 1 billion.

About cachexia syndrome and MC4 receptor antagonists Cachexia (Greek for "poor condition") syndrome is one of the most debilitating and life-threatening aspects of cancer and other severe chronic illnesses. The syndrome is associated with anorexia (lack of appetite), fat and muscle tissue wasting, psychological distress and a progressively decreasing quality of life. Cachexia is characterized by major metabolic abnormalities and maladaptations such as reduced food and energy intake, increased resting energy expenditure and accelerated catabolism. Typically, the involuntary weight loss in excess of 5% in 12 months cannot be compensated for by increased food intake, which results in wasting of both adipose and skeletal muscle tissue and poor physical performance.

The exact nature of the underlying processes remains largely unknown, however, appetite regulating peptides, pro-inflammatory cytokines and other regulatory peptides are considered to be major factors. One pathway by which cytokines can induce anorexia is via an increase of proopiomelanocortin (POMC) expression in hypothalamic feeding circuits, leading to an enhanced production of alpha-melanocyte stimulating hormone (alpha-MSH), a strong inhibitor of appetite. The MC4 receptor in the hypothalamus is a crucial target in the pathway through which alpha-MSH exerts its appetite inhibiting effects. AgRP (agouti related protein) or small molecule MC4 receptor antagonists enhance food intake, reduce energy expenditure and catabolic activity. Accordingly, an interruption of this signaling pathway by means of MC4 receptor antagonists is seen as a promising treatment option for cachexia.

Reference [1] Philipp Weyermann, Corinne Anklin, Isabelle Courdier-Fruh, Robert Dallmann, Judith Dubach-Powell, Martina Hufschmid, Josef P. Magyar, Bernd Löffler, Bettina Cardel, Florian Schärer, Gesa Santos, Reto Bolliger, Marco Henneböhle, Holger Herzner, Stéphane Kervennic, Audrey LeGall, Sonja Nordhoff, Hervé Siendt, Michael Soeberdt, Miroslav Terinek, Achim Feurer, Cesare Mondadori & Thomas Meier: New types of selective, orally active melanocortin-4 receptor antagonists stimulate food intake and reduce cancer-induced cachexia in mice. Poster presented at the AICR 2008 Research Conference on Food, Nutrition, Physical Activity & Cancer in Washington DC from November 6 to 7, 2008.

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About Santhera Santhera Pharmaceuticals (SIX: SANN) is a Swiss specialty pharmaceutical company focused on the discovery, development and commercialization of small-molecule pharmaceutical products for the treatment of severe neuromuscular diseases, an area of high unmet medical need which includes many orphan indications with no current therapy. Santhera currently investigates three compounds in five clinical-stage development programs. The Company's first product, SNT-MC17 (INN: idebenone), has received a marketing approval with conditions from Health Canada to treat Friedreich's Ataxia and is marketed under its brand name CATENA®. The product is also under review by health authorities in the EU and in Switzerland, while in the United States, a pivotal Phase III trial is recruiting patients. The compound has also shown efficacy in a clinical trial as a potential treatment for Duchenne Muscular Dystrophy and is currently in further clinical development. For additional information, please visit the Company's website www.santhera.com.

CATENA® is a trademark of Santhera Pharmaceuticals, registered in Canada and the United States.

For further information, contact Klaus Schollmeier, Chief Executive Officer Phone: +41 (0)61 906 89 52 klaus.schollmeier@santhera.com

Barbara Heller, Chief Financial Officer Phone: +41 (0)61 906 89 54 barbara.heller@santhera.com

Thomas Meier, Chief Scientific Officer Phone: +41 (0)61 906 89 87 thomas.meier@santhera.com

Thomas Staffelbach, Head Public & Investor Relations Phone: +41 (0)61 906 89 47 thomas.staffelbach@santhera.com

Disclaimer/Forward-looking statements This communication does not constitute an offer or invitation to subscribe for or purchase any securities of Santhera Pharmaceuticals Holding AG. This publication may contain certain forward-looking statements concerning the Company and its business. Such statements involve certain risks, uncertainties and other factors which could cause the actual results, financial condition, performance or achievements of the Company to be materially different from those expressed or implied by such statements. Readers should therefore not place undue reliance on these statements, particularly not in connection with any contract or investment decision. The Company disclaims any obligation to update these forward-looking statements.


 
 

Posted: November 2008

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