28th August 2019 / Sciad Newswire / Amyndas Pharmaceuticals, a clinical-stage biopharmaceutical company focused on the development of novel complement therapeutics, announced today the launch of its Phase 2a clinical study, evaluating AMY-101 in adults with periodontal inflammation and gingivitis. AMY-101 is a novel synthetic cyclic peptide designed to inhibit the complement cascade centrally at the level of C3 (Complement component 3).
Periodontitis is a clinical condition involving inflammation of the ligaments and bones that support the teeth. Periodontitis occurs when gingivitis goes untreated and persists. It is a significant cause of tooth loss in adults, and one of the most prevalent diseases worldwide, affecting around 20-50% of the population across the globe. Approximately 743 million people (about 11.2% of the global population) have a severe form of periodontitis that can raise the risk of cardiovascular disease, diabetes, arthritis, and pregnancy complications.
Dr. John Lambris, leading complement researcher and Dr. Ralph and Sallie Weaver Professor of Research Medicine at the University of Pennsylvania, and Dr. George Hajishengallis, Thomas W. Evans Centennial Professor at the Department of Basic & Translational Sciences at the University of Pennsylvania, previously demonstrated the involvement of the complement system in periodontal disease and inflammatory bone loss, in non-human primates. Moreover, they showed that C3 activation has a pivotal role in the disease process by fueling gum inflammation that exacerbates periodontal disease leading to tooth destruction. They further demonstrated that therapeutic targeting of C3 with the C3 inhibitor AMY-101 reversed pre-existing, naturally occurring periodontal inflammation in aged monkeys, a study which set the stage for further development of AMY-101 as a potential treatment for human periodontal disease (https://www.ncbi.nlm.nih.gov/pubmed/26728318).
In an earlier Phase I study of AMY-101 in 50 healthy volunteers, AMY-101 was administered systemically and was found to be well tolerated with no serious adverse events. This new phase 2a trial of AMY-101 (ClinicalTrials.gov Identifier: NCT03694444) is a 3-month randomized, double-blind, split-mouth study in adults with existing chronic periodontal inflammation, determined by the level of the gingival index and bleeding on probing. In the trial, different halves of the mouth will be randomized (split-mouth design), and AMY-101 or placebo will be injected into the affected gingival tissues, once a week for three consecutive weeks. The primary endpoint of change in the gingival index will be evaluated at 21, 28, and 90 days after initial treatment.
Dr. Lambris, founder of Amyndas Pharmaceuticals, commented: “When we discovered the involvement of C3 activation in periodontitis, we contemplated that if we can inhibit C3, we may have a good chance to develop an effective treatment. The monkey studies were very promising in that regard, and this clinical trial is designed to test whether AMY-101 can attenuate periodontal inflammation in patients and improve the current standard of care. We believe that C3 inhibition locally has the potential to not only block inflammation but also to shift the balance of gum bacteria, producing an overall beneficial effect”.
To conduct this phase 2a study, Amyndas has teamed up with the Forsyth Institute, a world leader in oral healthresearch, in Cambridge, MA. The Institute’s multidisciplinary scientific team uses system-wide approaches to biomedical innovation, and its research has helped to transform the way the world understands oral health. Scientists at Forsyth have previously demonstrated distinct connections between oral diseases and health challenges like heart disease, diabetes, and even certain cancers.
Dr. Hatice Hasturk, DDS, PhD, Director of Forsyth’s Center for Clinical and Translational Research, will be overseeing the AMY-101 trial. “We are excited to have the opportunity to test this novel complement-targeted therapy in patients with periodontal inflammation and gingivitis, and this is the first clinical study, testing a complement inhibitor as a potential therapy for periodontal disease. The information to be gained in this study could be a paradigm shift in how periodontal diseases are treated and may potentially launch a new host-modulatory approach to their treatment”, commented Dr Hasturk.
“Amyndas is actively pursuing the clinical application of AMY-101 in a wide range of therapeutic areas, and the initiation of the first of our planned Phase 2 trials of AMY-101 is a significant milestone” said Dr. Despina Yancopoulou, PhD, MBA, Amyndas’ Managing Director. "There's a significant unmet need in patients with periodontal diseases and if the preclinical findings for AMY-101 can translate into effective human studies, we hope to be able to provide a better treatment option for the large number of people who suffer from periodontal inflammation.”
The study is expected to be completed by Q1 2020. In parallel, Amyndas plans to advance AMY-101 into clinical trials in other complement-mediated conditions, while also developing a robust pipeline of new candidates for further human clinical testing.
Editor’s Note: Dr. Lambris and Dr. Hajishengallis are both inventors of intellectual property licensed to Amyndas by the University of Pennsylvania and may be entitled to license consideration. Dr. Lambris is also a founder of Amyndas Pharmaceuticals, and both he and the University of Pennsylvania are equity holders of the company.
About Amyndas Pharmaceuticals
Amyndas Pharmaceuticals is a clinical-stage biopharmaceutical company committed to developing the most advanced complement therapies to treat inflammatory disorders, in areas of unmet medical need for which patients need better and safer therapies. Amyndas has a robust R&D complement program with the strongest and most diversified pipeline of C3 complement inhibitors in the field. For additional information about AMY-101 and Amyndas Pharmaceuticals, please visit www.amyndas.com.
About the Forsyth Institute
Founded in 1910, the Forsyth Institute is the only independent research organization in the United States dedicated to understanding the important connections between oral health and overall wellness. Forsyth scientists are shaping the direction of personalized medicine through pioneering biomedical research and its direct application to new diagnostics, devices, and therapies. Forsyth combines its expertise in oral and associated systemic diseases with a relentless drive to ask — and answer — critical questions about how to best alleviate daily health challenges for billions. Forsyth is a not-for-profit organization that is also committed to treating underserved populations in local communities and on a national and global scale. To learn more about Forsyth, visit www.forsyth.org.
AMY-101 is a novel complement C3-targeted therapeutic based on the 3rd-generation compstatin analog Cp40. Compstatins are synthetic cyclic peptides with strong affinity and selectivity for human and primate C3, discovered at the University of Pennsylvania by Professor John Lambris and his team. Compstatins inhibit complement centrally, at the level of C3, and interrupt all downstream pathways of the complement activation cascade.
By inhibiting complement centrally, at the level of C3, AMY-101 and 4th generation compstatins may prove more effective in treating a wide range of complement-mediated diseases than is possible with partial inhibitors of complement (such as anti-C5 inhibitors) or other C3 inhibitors. Moreover, the novel characteristics of AMY-101 and 4th-generation compstatins (increased target affinity, improved PK profile and enhanced solubility) can broaden the spectrum of administration routes and allow for a reduced dosing frequency in chronic regimens in comparison with other C3 inhibitors.
AMY-101 has shown preliminary efficacy in various preclinical models ranging from periodontal disease, PNH, and C3G, to hemodialysis-induced inflammation, hemorrhagic shock and malaria-induced inflammation. With a target affinity in the sub-nanomolar range and an extended plasma half-life of more than 60 hours, AMY-101 is well suited for acute, transient, or prolonged therapeutic administration. Phase 1b/II studies of AMY-101 are planned in ABO-incompatible kidney transplantation and haemodialysis-induced inflammation, while new AMY-101 formulations for bi-weekly or weekly administration, will be tested in future studies in PNH and C3G patients.
AMY-106 is a 4th generation compstatin in preclinical development by Amyndas, with enhanced PK and solubility, which has shown an extended residence time in the vitreous of non-human primates of over 3 months and has the potential to significantly aid in the treatment of human complement-mediated retinal diseases. AMY-106 is designed for intravitreal administration and application in the treatment of age-related macular degeneration (AMD) and other ophthalmic conditions.
Despina Yancopoulou, PhD, MBA
Managing Director, Amyndas Pharmaceuticals