Dr. Sylviane Muller – Presentation Abstract from 2014 European Lupus Conference
6th May 2014 - 10:50 amImmuPharma PLC (LSE: IMM), (“ImmuPharma” or the “Company”), the specialist drug discovery and development company, provides a summary of the presentation given by Dr. Slyviane Muller at the European Lupus Conference which recently took place in Athens, Greece.
The “European Lupus Meeting” is a major forum for all people interested in the disease: with approximately 800 physicians of various disciplines (internal medicine, rheumatology, nephrology, dermatology, obstetrics and gynecology, neurology), health professionals, regulatory agencies, pharmaceutical industry and patient representatives.
Dr. Sylviane Muller is the Research Director at CNRS, Strasbourg, France and the key inventor of Lupuzor, (also known scientifically as P140). The title of the session was called “A novel way of immunomodulation in lupus”.
Her presentation focused partly on the on the highly competitive and efficacious mode of mechanism of LupuzorTM, ImmuPharma’s potential blockbuster drug for Lupus, a chronic autoimmune disease. LupuzorTM has received Special Protocol Assessment and Fast Track Designation from the FDA for a Phase III trial.
Dr. Sylviane Muller’s Abstract : Summary
“In the pipeline of molecules with a potential for treating lupus patients, the P140 peptide holds a lot of promise. P140 is a 21-mer linear peptide (sequence 131-151) derived from the spliceosomal small nuclear ribonucleoprotein U1-70K. It contains a phosphoserine residue at position 140. In a multicenter, randomized, placebo-controlled phase IIb study, P140/Lupuzor was safe and met its primary efficacy end points in lupus patients (Zimmer et al., ARD 2013). These results confirm data generated in MRL/lpr lupus-prone mice in which the preclinical studies were conducted (Monneaux et al., EJI 2003; Schall et al., J Autoimmunity 2012). In this setting, as in human, P140 was shown to behave as an immunomodulator and not as an immunosuppressant. In a step further, our studies demonstrated that the P140 peptide mechanism of action does involve autophagy processes. In a lupus context in which macroautophagy is affected (Gros et al., Autophagy 2012), P140 readily binds HSPA8/HSC70 chaperone proteins (Page et al., PLoS ONE 2009) and reduces autophagic flux in MRL/lpr B cells (Page et al., ARD 2011). We recently showed that a selective form of autophagy, chaperone-mediated autophagy (CMA), is a key target of P140. By interfering with this particular pathway, P140 peptide may affect the endogenous (auto)antigen processing and the peptide loading to MHCII molecules, and as a consequence, induces a lower activation of autoreactive T and B cells, and a reduction of autoantibodies secreted by plasma cells (Muller and Wallace, Lupus 2014). Our recent results shed light on mechanisms by which P140 can modulate lupus disease and by which it may operate in humans affected by this disorder that affect more than 5 million individuals in the world.”