13th December 2017 / Sciad Newswire / Amyndas Pharmaceuticals, which is committed to developing innovative therapeutics for complement-mediated conditions, today announced positive preliminary results from a Phase 1 clinical trial of its C3-targeted complement inhibitor, AMY-101. The phase I which has just been completed, was a prospective, single-center, open-label, First-In-Human (FIH) clinical study, designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) after a Single Ascending Dose (SAD) and Multiple Doses (MD) of AMY-101 administered systemically (via the subcutaneous or intravenous route) in healthy male volunteers.
Preliminary analysis of the study results shows that AMY-101 was safe, well tolerated, and that AMY-101’s PK / PD profile can support a therapeutic schedule of efficient complement C3 inhibition, via subcutaneous administration every 48 hours.
Commenting on the results of the Phase I trial, Prof. John D Lambris, founder of Amyndas and inventor of compstatins, including AMY-101, said: “This is a major milestone in the clinical development of AMY-101 and the results are very encouraging. The study shows that AMY-101 has a very good safety profile, and demonstrates once again that inhibiting complement at the C3 level can be safely achieved in the clinical setting. In view of its potent, broad complement inhibitory activity and promising clinical profile AMY-101 can provide a new therapy for patients with complement-mediated diseases.”
AMY-101 is the most advanced compstatin analogue to progress to clinical development and Amyndas is now preparing to initiate Phase Ib/II clinical trials in patients with the rare diseases C3G (C3 glomerulopathy) and PNH (Paroxysmal Nocturnal Hemoglobinuria) for which AMY-101 has received orphan designation from the FDA and the EMA. Moreover, clinical studies are being planned for evaluating AMY-101 as a new treatment in periodontal disease and other complement-mediated inflammatory disorders.
“The positive results from this phase I clinical study are very promising” said Prof. Antonio Risitano, leading PNH expert at the Department of Hematology at the Federico II University of Naples. “Irrespective of the excellent results seen with current anti-C5 therapy in the past 10 years, significant unmet clinical needs remain for PNH patients, and these should be addressed by alternative strategies of therapeutic complement inhibition. Inhibiting complement centrally, at the level of C3 is a novel mechanism of action, which blocks all pathways of complement activation and through this new mechanism, we expect that AMY-101 could improve the current treatment of PNH. Indeed, due to its possible effect on C3-mediated extravascular hemolysis, AMY-101 may benefit PNH patients who are not optimally responding to anti-C5 therapy, but possibly also improve the clinical benefit of patients with adequate response to the current standard therapy. Well-designed clinical trials will tell us how we can best use this novel strategy of complement inhibition to achieve broader therapeutic coverage and effectively address the full spectrum of clinical complications in this debilitating disorder. Already, initial results from an ongoing PNH trial of another C3 inhibitor in development, have provided a good indication of this potential.”
Prof. Richard Smith, a leading researcher in C3G and Director of the Institute of Human Genetics and the Molecular Otolaryngology and Renal Research Laboratories (MORL) at the University of Iowa, commented: “I am excited about the results of the phase I AMY-101 study. The strong involvement of C3 activation in the pathogenesis of C3G suggests that, if we can inhibit C3, we may have a good chance to develop an effective treatment. In vitro, AMY-101 has been tested in sera from patients with C3G and it completely inhibited complement dysregulation (Zhang et al. Immunobiology 2015; 220:993-8). We are looking forward to clinical studies that will test AMY-101 in patients with C3G”.
Prof. George Hajishengallis, at the School of Dental Medicine’s Department of Microbiology of the University of Pennsylvania said: “AMY-101 offers a promising possibility for treating periodontitis. We already have impressive data showing that AMY-101 blocks pre-existing, naturally occurring periodontitis in aged non-human primates and we are now eager to test this novel immunomodulatory therapy in humans. The good safety profile established in the phase I trial of AMY-101 gives us the green light for the first application of AMY-101 in patients with periodontal disease”.
For further information, please contact:
Despina Yancopoulou, PhD, MBA
Amyndas Pharmaceuticals SA
N. Zerva 28, Glyfada 16675, Greece.
T: +30 (694) 722-1847
e-mail: [email protected]
Notes for Editors
AMY-101 is a novel therapeutic based on the third-generation compstatin analogue Cp40. Compstatins are synthetic cyclic peptides with strong affinity and selectivity for human and primate C3, discovered at the University of Pennsylvania by Dr. John Lambris, a leading researcher in the field of complement drug discovery and the founder of Amyndas Pharmaceuticals. Amyndas has an exclusive, worldwide licensing agreement with the University of Pennsylvania that provides broad rights to develop and commercialize the new generation compstatin AMY-101.
AMY-101 inhibits complement at the level of C3 and interrupts all downstream pathways of the complement activation cascade. Based on its mode of action – inhibiting complement centrally, at the level of C3 – AMY-101 may prove more effective in treating a wide range of complement-mediated diseases. AMY-101 has consistently shown efficacy in various preclinical models ranging from PNH, C3G and haemodialysis to periodontal disease, hemorrhagic shock and malaria-induced inflammation. With a target affinity in the sub-nanomolar range, almost 6,000‑fold greater than that of the first-generation compstatin, and an extended plasma half-life of more than 60 hours, AMY-101 is well suited for prolonged therapeutic administration. The unique pharmacokinetic profile of AMY-101 eliminates the need for further peptide modifications to enhance its plasma residence.
About Amyndas Pharmaceuticals
Amyndas Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel therapeutics to treat a broad range of inflammatory diseases and disorders with unmet medical need, based on its patented technologies for modulating the complement system. For additional information about Amyndas please visit www.amyndas.com