Dr Johannes Bange, Lead Discovery Center GmbH
Lead Discovery Center GmbH
Cachexia, the ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and which leads to progressive functional impairment, is one of the most critical factors for the clinical outcome of patients in many acute or chronic disorders. In fact, mortality rates of patients with cachexia range from up to 30% per year in chronic diseases to 80% in cancer. Accordingly, 20-30% of all cancer deaths are estimated to result from the effects of cachexia rather than tumor burden.
Growth differentiation factor 15 (GDF15) or Macrophage Inhibitory Cytokine 1 (MIC-1) is a stress related cytokine which is rarely found in healthy tissues but whose elevated circulating levels have been correlated with the onset and progression of body weight loss and bad prognosis in cancer patients and other diseases. Accordingly numerous reports provide evidence of GDF15 as a causative cachectic factor not only in cancer but also for example in COPD, Chronic Kidney Disease, Heart Failure etc..
The LDC GDF15 antibody has demonstrated excellent GDF15 blocking activity in vitro and in vivo. Furthermore in in vivo prevention and intervention models of cancer related cachexia, loss of body weight was completely restored at clinical relevant doses. Thus anti-GDF15 therapy can play an important role to efficiently improving cancer therapy and patient quality of live. The chimeric lead antibody LDC-B1D4 now needs to be humanized and further developed for clinical application. Status of LDC-B1D4 is 9 months from entry into preclinical development and ~2,5 years from clinical trials.
Chimeric Lead Antibody
Know-how is with LDC, a patent application will be filed once partner is identified
Argilés, J. M., Fontes-Oliveira, C. C., Toledo, M., López-Soriano, F. J., & Busquets, S. (2014). Cachexia: a problem of energetic inefficiency. Journal of cachexia, sarcopenia and muscle, 5(4), 279-286.
Brown, D. A., Lindmark, F., Stattin, P., Bälter, K., Adami, H. O., Zheng, S. L., ... & Wiklund, F. E. (2009). Macrophage inhibitory cytokine 1: a new prognostic marker in prostate cancer. Clinical cancer research, 15(21), 6658-6664.