Research Focus

THE COMPLEMENT SYSTEM

Complement is a network of more than 50 proteins in the blood and on cell surfaces, part of the innate immune system, that quietly cruise the body, keeping a low profile until triggered into action. But this defense system can also be inappropriately activated and attack cells, contributing to a broad spectrum of immune, inflammatory, and age-related diseases. Inhibition or modulation of complement activity is therefore recognized as a promising therapeutic strategy. The Complement System is a very attractive target for development of anti-inflammatory drugs because of its central role in inflammatory processes. So far, the only complement drugs approved in the clinic are the C1 inhibitor and the anti-C5 therapy, which are effective in a number of complement-mediated conditions. However, there are still significant unmet medical needs in complement-mediated complications, not targeted by the available drugs. Amyndas is developing novel therapeutics with enhanced properties to fight complement-mediated diseases that remain untreated and improve existing treatment modalities.

AMYNDAS’ PRIORITY CLINICAL PROGRAMS

Kidney Transplantation: ABO-incompatible (ABOi) kidney transplantation is a method of allocation in kidney transplantation that permits more efficient use of available organs regardless of ABO blood type, which would otherwise be unavailable due to hyperacute rejection. Recent studies reveal that complement is instrumental in preventing ABOi organ rejection during transplantation. Amyndas is developing the novel C3 complement inhibitor AMY-101, for prevention of organ rejection during ABOi kidney transplantation and the treatment of patients with end-stage renal disease (ESRD). For the development of AMY-101, Amyndas has been awarded a European Union 7th Framework Program grant. AMANDEN shows a very attractive safety profile and excellent PK/PD in pre-clinical studies.

Paroxysmal Nocturnal Hemoglobinuria (PNH): PNH is a rare but life-threatening hemolytic anemia. Currently the only available therapy for PNH is eculizumab, an antibody, which acts by inhibiting the C5 component of the complement system. Anti-C5 treatment generally leads to significant improvement in the patient’s quality of life; however about a third of all patients do not respond to the drug, thus continuing to require blood transfusions to manage ongoing anemia. Amyndas is developing a new strategy to treat PNH by targeting the C3 component, a more central part of the complement system; using the small inhibitor AMY-101 to inhibit C3, Amyndas intends to prevent both intravascular and extravascular hemolysis, thus aiming to also benefit the currently untreated PNH patients. Moreover, as a small peptide AMY-101 is also more cost-effective when compared to the existing antibody-based treatment. Amyndas is planning to move AMY-101 into the clinic for first-in-human trials in Q4 of 2015. Indeed, a number of high impact scientific publications endorse the development of AMY-101 for the treatment of PNH.