May 30th, 2020 – Amyndas Pharmaceuticals, a clinical-stage biopharmaceutical company focused on the development of the most advanced C3 complement therapeutics, announced today that it received FDA approval to start its Phase 2 clinical study, evaluating the efficacy of AMY-101 in COVID-19 patients with acute respiratory distress syndrome (ARDS). ARDS, a common complication in severe COVID-19 patients, is a life-threatening type of lung failure. It is fueled by a maladaptive immune response, involving over-activation of complement, a part of the body’s innate immune system. Derailed complement activation has also been suggested to fuel an overactive blood clotting reaction that spreads through the body, damaging vessels and affecting various organs in COVID-19 patients.
Dr. John Lambris, the founder of Amyndas, Professor of Research Medicine at the University of Pennsylvania, and leading complement researcher commented: “While a “cytokine storm” (involving IL-6 and other cytokines) has been documented in these COVID-19 patients, complement C3 activation is involved as an initial, pivotal mechanism that triggers a broad inflammatory response leading to lung damage. If we inhibit C3, we should be able to control this harmful inflammatory response and its, often, lethal consequences. AMY-101 is the most advanced C3 inhibitor currently available for this type of acute intervention”.
AMY-101 is a new-generation potent complement inhibitor, designed to inhibit the complement system centrally at the level of C3. The idea that AMY-101 can halt the broad thromboinflammatory response associated with COVID-19 is backed by impressive data from Amyndas’ ongoing Compassionate Program of AMY-101 in COVID-19 patients, at San Raffaele Hospital in Italy, which started at the beginning of April. Prof. Antonio Risitano, the scientist who pioneered the beneficial effects of C3 inhibition in hematological diseases and teamed up with Amyndas to design the COVID-19 study, commented: “Patients treated with AMY-101 in this Compassionate Program have shown a quick drop of inflammatory biomarkers to normal levels (within 48 hours), as well as a significant improvement of lung function leading to successful resolution of ARDS, and the weaning of patients from oxygen support a few days later”. Prof. Fabio Ciceri, Principal Investigator of the AMY-101 Compassionate Program and Deputy Scientific Director at San Raffaele Hospital, added: “The patients’ response to AMY-101 is impressive and it is the fastest response we’ve seen when comparing it to other COVID-19 experimental treatments under evaluation” (see also: The first case of COVID-19 treated with the complement C3 inhibitor AMY-101).
Based on these exciting initial results, with the support of a team of international experts, Amyndas designed a controlled phase 2 trial, to evaluate the potentially significant benefit of AMY-101 in severe COVID-19 patients, who do not have other treatment options. Following expedited review, the FDA approved the study, which is set to launch in July 2020. The randomized, controlled Phase 2 study is expected to enroll 144 hospitalized patients with COVID-19 and respiratory failure, diagnosed with Acute Respiratory Distress Syndrome.
Prof. Antonio Risitano (Director of the Bone Marrow Transplantation Program at the Federico II University of Naples, Italy), Prof. Markus Huber-Lang (Director of the Institute of Clinical and Experimental Trauma-Immunology, Ulm University Hospital, Germany), Dr. Dimitris Mastellos (National Center for Scientific Research ‘Demokritos’, Greece), Prof. Simona Iacobelli (University of Rome Tor Vergata), and Prof. Sander Connolly (Bennett M. Stein Professor of Neurological Surgery, Columbia University) teamed up with Amyndas to design this study, and are excited with the approval of the clinical trial.
Prof. Risitano commented: “AMY-101 is a potent complement C3 inhibitor, which is much more that a drug for rare diseases, because complement-mediated inflammation is a broad mechanism of tissue damage contributing to a number of human diseases; we definitely have to test AMY-101 in COVID-19 patients with pneumonia and ARDS. We are in the middle of a public health emergency, we don’t yet have effective therapies and C3-targeted complement inhibition is especially promising. With complement inhibitors such as AMY-101 we may have a good chance to save patients.”
Professor Huber-Lang added: “The FDA approval for testing complement inhibition at the central level of C3 with AMY-101, is an important milestone and great hope for both patients and clinicians. This approach can be a game changer as it can have broader application in other clinical indications involving systemic inflammation and organ dysfunction”. Dr Mastellos said: “We are excited with the approval of this study. The fact that C3 inhibition can broadly suppress not only the maladaptive inflammatory response but also the vascular or thrombotic defects that affect multiple vital organs, makes AMY-101 a unique candidate drug for COVID-19”.
To conduct this phase 2 study Amyndas is partnering with leading clinical centers in the US. Professor Sander Connolly commented: “This study approval is great news for our patients. And if AMY-101 is successful, we are keen to try it in other clinical indications with complement involvement”.
Amyndas is now progressing quickly to launch the trial. “This study will help us understand the role of complement in COVID-19 and it is an important step in the clinical development of AMY-101; we are grateful to the team of scientists that helped us design the study and we hope to be able to contribute to the management of this global health crisis” said Despina Yancopoulou, Managing Director of Amyndas.
For more information about the Phase 2 AMY-101_SAVE study, visit www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT04395456).
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 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.
AMY-101 is a novel complement C3 inhibitor, 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). In addition, the novel characteristics of new-generation AMY-101 and 4th-generation compstatins (increased target affinity, improved PK profile and enhanced solubility) 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 2 studies of AMY-101 are also planned in hematological, renal, neurological and other indications. New AMY-101 formulations for bi-weekly or weekly administration, will be tested in future studies in the rare indications PNH and C3G.
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 which has the potential to revolutionize the treatment of 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