CAMBRIDGE, Mass.--(BUSINESS WIRE)--Ra Pharmaceuticals, a clinical stage biopharmaceutical company focusing on the development of next-generation therapeutics for diseases of complement dysregulation, today announced the presentation of scientific data at the 21st Congress of the European Hematology Association (EHA), June 9-12, 2016 in Copenhagen, Denmark.
“The data presented at EHA show that RA101495, our proprietary lead product candidate for the treatment of paroxysmal nocturnal hemoglobinuria, is a potent inhibitor of C5-mediated hemolysis in this first-in-human study,” said Jeffrey M. Johnston, MD, FACP, Senior Vice President and Chief Medical Officer of Ra Pharma. “These data demonstrate a favorable safety and tolerability profile, and the pharmacokinetic and pharmacodynamic properties support our strategy for developing RA101495 as a self-administered, subcutaneous option for patients suffering from PNH.”
RA101495 is a synthetic macrocyclic peptide inhibitor of complement C5-mediated hemolysis. The molecule is currently in development for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), an acquired hematopoietic stem cell disease resulting in pathologic red blood cell lysis caused by unregulated activity of the membrane attack complex (MAC). RA101495 binds a unique site on the C5 protein to inhibit cleavage into C5a and C5b, thereby preventing red blood cell lysis by inhibiting the production and assembly of the MAC.
“We are highly encouraged by these Phase 1 data, which demonstrate a rapid and sustained effect on hemolysis, a favorable safety profile, predictable drug pharmacokinetics and low inter-subject variability,” said Doug Treco, PhD, Co-Founder, President and CEO of Ra Pharma. “We remain committed to the development of this novel therapeutic as an alternative to the intravenously-administered monoclonal antibody therapy for PNH. The convenience and consistent pharmacokinetics among subjects should result in better control of disease compared to existing antibody therapies. We look forward to providing future updates as we move RA101495 into Phase 2 studies.”
Summaries of the data presented by Ra Pharma at the conference are as follows:
Poster Title: A Phase 1 Single-ascending-dose Clinical Study of RA101495, A Subcutaneously Administered Synthetic Macrocyclic Peptide Inhibitor of Complement C5 for Treatment of Paroxysmal Nocturnal Hemoglobinuria
Date and Time: Saturday, June 11, 2016, 17:30-19:00 Central European Time
Location: Poster area (Hall H)
Abstract Number: P632
Session: Bone marrow failure syndromes incl. PNH – Clinical
Summary: RA101495 is being developed for the treatment of PNH as a daily, self-administered subcutaneous (SC) treatment. In this double-blind, placebo-controlled study, four cohorts of healthy volunteers (N=22; 8 placebo and 14 RA101495-treated) were evaluated with ascending doses of RA101495 (0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg) via SC injection to assess its safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile, and to identify doses that achieve ≥90% inhibition of hemolysis for greater than 24 hours. Subjects were monitored for 48 hours post-dosing in an in-clinic setting and for four weeks overall. After a single dose, RA101495 exhibited rapid and sustained dose-dependent inhibition of hemolysis, with a maximum PD effect approximately three hours after dosing and up to >90% suppression of hemolysis maintained for at least 4 days. These results, combined with in silico modeling studies, suggest that daily dosing with RA101495 at 0.2 mg/kg should result in full suppression of complement activity and complete inhibition of hemolysis. RA101495 was well-tolerated, with no clinically significant changes observed in vital signs, clinical laboratory parameters, physical exams or EKGs. Mild and reversible injection site erythema (ISE) was only observed at the highest dose level (0.4mg/kg). These findings support continued development of RA101495 in PNH.
E-Poster Title: A Phase 1 Multiple-dose Clinical Study of RA101495, A Subcutaneously Administered Synthetic Macrocyclic Peptide Inhibitor of Complement C5 for Treatment of Paroxysmal Nocturnal Hemoglobinuria
Date and Time: Friday, June 10, 2016, 9:30 Central European Time – Sunday, June 12, 2016, 11:00 Central European Time
Abstract Number: LB2249
Summary: This Phase 1, randomized, double-blind, placebo-controlled, multiple-dose study in healthy volunteers was designed to evaluate the safety, PK and PD of multiple 0.2 mg/kg doses of RA101495 and to confirm the prediction that daily dosing can suppress ≥90% hemolysis as measured by an ex vivo RBC lysis assay. Four subjects received 0.2mg/kg of RA101495 by SC injection once daily for seven days and two subjects received placebo on the same schedule. Subjects were then monitored for eight days in-clinic and five weeks overall. Repeat dosing of RA101495 was found to be safe and well-tolerated. Inhibition of hemolysis was rapid and sustained at ≥95% across the dosing period in all subjects, and returned to pre-dose levels within two weeks following the final dose. The findings from this Phase 1 study confirm that daily dosing with RA101495 (0.2mg/kg) results in full suppression of complement activity and nearly complete inhibition of hemolysis, and warrant further development of RA101495 in a Phase 2 study.
Ra Pharma is developing RA101495 for paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), and other debilitating conditions. The product is designed for convenient, subcutaneous self-administration. RA101495 is a synthetic, macrocyclic peptide discovered by Ra’s Proprietary Extreme Diversity™ platform. The peptide binds complement C5 with subnanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative or lectin pathways. In vitro studies demonstrate that RA101495 also directly binds to C5b, disrupting the interaction between C5b and C6 and preventing assembly of the membrane attack complex (MAC). This activity defines a novel mechanism for the inhibition of C5 function. Repeat dosing in vivo demonstrated sustained and predictable inhibition of complement activity with an excellent safety profile.
About Ra Pharmaceuticals
Ra Pharmaceuticals is a clinical stage biopharmaceutical company focusing on the development of next-generation therapeutics for diseases of complement dysregulation and for a variety of orphan indications. The Company utilizes small molecules and peptide approaches to address pathological targets in the complement cascade. Derived from its proprietary Extreme Diversity™ peptide chemistry platform, RA101495 is a macrocyclic peptide inhibitor of complement C5, and is currently in Phase 1 development for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). For more information, please visit: www.rapharma.com.