Ra Pharmaceuticals Presents Data on Oral, Small Molecule Complement Inhibitors and Phase 2 RA101495 SC Program in PNH at the 23rd Congress of the European Hematology Association

“The characterization of our first-in-class, orally bioavailable, small molecules highlights their feasibility as effective C5 inhibitors, illustrated by their drug-like properties and favorable pharmacokinetic (PK) behavior,” said Alonso Ricardo, PhD, Senior Vice President and Head of Research at Ra Pharma. “Along with the established PK/pharmacodynamic (PD) relationship, these data provide a valuable foundation supporting the further investigation of these molecules with potential applicability in a broad range of complement-mediated diseases.”

“At EHA, we also highlight the results from our global, Phase 2 program evaluating RA101495 SC in paroxysmal nocturnal hemoglobinuria (PNH), in which RA101495 SC was shown to be safe and well-tolerated, and achieved and maintained robust control of lactate dehydrogenase (LDH) levels in treatment-naïve and transfusion-independent eculizumab-switch PNH patients,” said Ramin Farzaneh-Far, MD, Chief Medical Officer of Ra Pharma. “These data suggest that RA101495 SC, a once-daily, low-volume, subcutaneous, self-administered therapy, has the potential to serve as a more convenient and accessible therapeutic option for patients with PNH and provide support for initiation of our Phase 3 program.”

Inhibition of C5 is a clinically-validated approach for the therapeutic treatment of multiple complement-mediated disorders. Ra Pharma’s portfolio includes RA101495, a macrocyclic peptide inhibitor of C5 being developed for convenient, once-daily, subcutaneous self-administration for the treatment of several debilitating disorders, including PNH, generalized myasthenia gravis (gMG), and atypical hemolytic uremic syndrome (aHUS). In parallel, the Company is pursuing the identification of orally-available inhibitors of C5 with the goal of providing additional options for patients diagnosed with these and other complement-mediated disorders.

“These data highlight the breadth of our work in the complement inhibition space,” said Doug Treco, PhD, President and Chief Executive Officer of Ra Pharma. “Leveraging the validation of C5 inhibition as an effective treatment for complement-mediated diseases, we remain committed to addressing the limitations of currently available therapies, which require burdensome, high-volume intravenous infusions. These data mark significant achievements in our mission to provide transformative complement treatments that benefit the largest population of patients possible.”

A summary of the data presented is as follows:

Title: Characterization of Orally Bioavailable Small Molecule Inhibitors of Complement C5
Session Title: Bone marrow failure syndromes incl. PNH – Biology & Translational Research
Presenter: Alonso Ricardo, Ph.D., Senior Vice President and Head of Research, Ra Pharma
Date/Time: Sunday, June 17, 8:15-8:30 CEST
Location: Room A8
Abstract Code: 3854
Summary: This presentation describes studies designed to evaluate the pharmacology in human whole blood-based assay models, pharmacokinetics in several pre-clinical species, and the ex vivo PK/PD relationship of orally bioavailable, small molecule inhibitors of complement C5 after oral administration. In pre-clinical models, the PK data demonstrate that compounds within this series display dose-dependent oral exposure and low clearance values. The ex vivo and in vitro assays demonstrate selective engagement of complement C5. The PK/PD relationship informs the level of exposure required to achieve therapeutic efficacy in humans. Collectively, these data confirm the feasibility of an oral, small molecule inhibitor of complement C5.

Title: RA101495, A Subcutaneously-administered Peptide Inhibitor of Complement Component C5, For the Treatment of Paroxysmal Nocturnal Hemoglobinuria: Phase 2 Results
Session Title: Bone marrow failure syndromes incl. PNH – Clinical
Date/Time: Friday, June 15, 17:30-19:00 CEST
Location: Poster area
Abstract Code: 1430
Summary: This poster describes the results of the Phase 2, global, multi-center, open-label, dose-finding program. RA101495, self-administered by low volume, daily, subcutaneous injection, appears safe and well-tolerated in patients with PNH. RA101495 SC rapidly and robustly reduces LDH to the levels seen in patients receiving eculizumab and which are associated with improved long-term outcomes in PNH. These Phase 2 findings indicate that RA101495 SC may provide a more convenient and cost-effective treatment for PNH patients.

About RA101495 SC

Ra Pharma is developing RA101495 SC for paroxysmal nocturnal hemoglobinuria (PNH), generalized myasthenia gravis (gMG), atypical hemolytic uremic syndrome (aHUS), and lupus nephritis (LN). The product is designed for convenient, once-daily subcutaneous self-administration. RA101495 SC is a synthetic, macrocyclic peptide discovered using Ra Pharma’s powerful proprietary drug discovery technology. The peptide binds complement component 5 (C5) with sub-nanomolar affinity and allosterically inhibits its cleavage into C5a and C5b upon activation of the classical, alternative, or lectin pathways. By binding to a region of C5 corresponding to C5b, RA101495 SC is designed to disrupt the interaction between C5b and C6 and prevent assembly of the membrane attack complex (MAC). This activity may define an additional, novel mechanism for the inhibition of C5 function.

About RA101495 SC Phase 2 PNH Clinical Program

The global, dose-finding Phase 2 program was designed to evaluate the safety, tolerability, preliminary efficacy, PK, and PD of RA101495 SC in patients with PNH. The study evaluated RA101495 SC in three cohorts. The first cohort included eculizumab-naïve patients, the second cohort included patients switching from eculizumab to RA101495 SC, and the third cohort included patients who were currently treated with eculizumab but had evidence of an inadequate response. Patients in all three cohorts were eligible for entry into a long-term extension study following the completion of the initial 12-week studies. The primary efficacy endpoint was the change in LDH from baseline to the mean level from week 6 to week 12.

About Ra Pharmaceuticals

Ra Pharmaceuticals is a clinical stage biopharmaceutical company focusing on the development of next-generation therapeutics for complement-mediated diseases. The Company discovers and develops peptides and small molecules to target key components of the complement cascade. For more information, please visit: www.rapharma.com.

Forward-Looking Statement

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the safety, efficacy and regulatory and clinical progress, convenience and cost-effectiveness of our product candidates, including RA101495 SC, statements regarding the feasibility, efficacy and potential use of our small molecules in pre-clinical development, and statements regarding trial design, timeline and enrollment of our ongoing and planned clinical programs. All such forward-looking statements are based on management’s current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include the risks that Ra Pharma’s product candidates, including RA101495 SC, will not successfully be developed or commercialized; the risk that topline results as of February 7, 2018 from the Company’s global Phase 2 clinical program evaluating RA101495 SC for the treatment of PNH may not be indicative of final study results; as well as the other important factors discussed in the “Risk Factors” section in Ra Pharma’s most recently filed Annual Report on Form 10-K, as well as other risks detailed in Ra Pharma’s subsequent filings with the Securities and Exchange Commission . There can be no assurance that the actual results or developments anticipated by Ra Pharma will be realized or, even if substantially realized, that they will have the expected consequences to, or effects on, Ra Pharma. All information in this press release is as of the date of the release, and Ra Pharma undertakes no duty to update this information unless required by law.

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