Apellis Dosed First Patient in Phase 3 Study

Apellis Pharmaceuticals Inc.recently announced the dosing of the first patient in the Phase 3 clinical study PRINCE (APL2-308), evaluating the efficacy and safety of APL-2 for treatment-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH). PRINCE is the second Phase 3 study that Apellis has initiated to investigate the potential of APL-2 to treat PNH.

“PNH is a rare, chronic blood disorder that can progress to cause life-threatening complicationsi. We are conducting the PRINCE study to better understand how targeting the complement cascade at C3 can help us improve treatment for all patients with this disease,” said Federico Grossi, MD, PhD, Chief Medical Officer of Apellis. “At Apellis, we believe there is a significant opportunity for APL-2 to be a transformative therapy that could benefit people living with PNH.”

The PRINCE study is a Phase 3, randomized, multicenter, open-label, controlled study that aims to enroll 54 treatment-naïve adult patients with PNH. The primary objective of this study is to evaluate the efficacy of APL-2 in patients with PNH who are currently not being treated with complement inhibitors, as assessed by hemoglobin stabilization from baseline in the absence of transfusion through Week 26 and reduction in lactate dehydrogenase (LDH) level from baseline to Week 26.

PNH is a rare, acquired, potentially life-threatening disease characterized by complement-mediated hemolysis with or without hemoglobinuria, an increased susceptibility to thrombotic episodes and/or some degree of bone marrow dysfunction. Some of the prominent symptoms of PNH include severe anemia, abdominal pain, headaches, back pain, excessive weakness, fatigue and recurrent infectionsii. If not treated, PNH results in the death of approximately 35 percent of affected individuals within five years of diagnosis and 50 percent of affected individuals within 10 years of diagnosisiii.

APL-2, an investigational drug, is designed to inhibit the complement cascade centrally at C3 and may have the potential to treat a wide range of complement-mediated diseases more effectively than is possible with partial inhibitors of complement. APL-2 is a synthetic cyclic peptide conjugated to a polyethylene glycol (PEG) polymer that binds specifically to C3 and C3b, effectively blocking all three pathways of complement activation (classical, lectin, and alternative). Apellis is currently evaluating APL-2 in clinical studies in patients with PNH who are being treated with eculizumab or who are naïve to complement inhibitor treatment, in patients with geographic atrophy (GA), in patients with cold agglutinin disease (CAD) and warm autoimmune hemolytic anemia (wAIHA), and in patients with C3 glomerulopathy (C3G) and other glomerular diseases. For additional information regarding our clinical trials, visit www.apellis.com/clinical-trials.html.

Apellis is currently evaluating subcutaneous administration of APL-2 in PEGASUS, a Phase 3 trial for patients with PNH currently on treatment with eculizumab, as well as in two Phase 1b trials (PHAROAH and PADDOCK) in patients with PNH. Previously reported interim data from these Phase 1b trials showed improvements in lactate dehydrogenase and hemoglobin levels in patients who are suboptimal responders to eculizumab and untreated patients, respectively. Apellis is also testing APL-2 in a Phase 2 open-label trial assessing the safety, tolerability, efficacy, and PK of multiple doses of APL-2 administered daily in patients with warm autoimmune hemolytic anemia (wAIHA) or cold agglutinin disease (CAD). Previously reported interim data from this trial showed the potential to improve hemoglobin, reticulocytes, bilirubin and lactate dehydrogenase levels. APL-2 was well tolerated in these studies.

Apellis Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company focused on the development of novel therapeutic compounds for the treatment of a broad range of life-threatening or debilitating autoimmune diseases based upon complement immunotherapy through the inhibition of the complement system at the level of C3. Apellis is the first company to advance chronic therapy with a C3 inhibitor into clinical trials. For additional information about Apellis and APL-2, visit http://www.apellis.com.

i McKinley C. Extravascular Hemolysis Due to C3-Loading in Patients with PNH Treated with Eculizumab: Defining the Clinical Syndrome. Blood. 2017;130:3471.

ii Hill. Paroxysmal nocturnal haemoglobinuria. Nature. 2017; 3. Available at: https://www.nature.com/articles/nrdp201728. Accessed August 26, 2019.

iii Hillmen. Natural History of Paroxysmal Nocturnal Hemoglobinuria. New England Journal of Medicine. 1995; 333:1253-1258.