Successful completion of Phase 2 trial of zilucoplan in generalized myasthenia gravis (gMG) with rapid, clinically meaningful, and statistically significant reductions in QMG and MG-ADL

Zilucoplan extended release (XR) achieves greater than one week of target drug concentrations in non-human primates following a single subcutaneous injection, supporting once weekly or less frequent dosing

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Mar. 7, 2019-- Ra Pharmaceuticals, Inc. (Nasdaq:RARX) today announced financial results for the fourth quarter and year ended December 31, 2018, and provided an update on recent corporate and clinical developments.

“The fourth quarter of 2018 was transformational for Ra, with the successful completion of our Phase 2 clinical trial of zilucoplan for the treatment of gMG, the strengthening of our balance sheet with a $150 million financing, and further advancing our mission of expanding patient access to important therapies,” said Doug Treco, Ph.D., President and Chief Executive Officer of Ra Pharma. “We look forward to engaging in End-of-Phase 2 discussions with regulatory agencies in the first half of 2019 and initiating a registrational Phase 3 program in gMG later this year.”

Dr. Treco continued: “The strong Phase 2 results in gMG and zilucoplan’s competitive profile as an accessible and convenient self-administered therapy support the potential to serve a broad population of patients with gMG. We plan to leverage the unique properties of our small peptide C5 inhibitor and expand development into other tissue-based, complement-mediated disorders with high unmet medical need.”

“Lastly, we are excited to announce significant progress in our zilucoplan extended release program, in which a single subcutaneous injection of zilucoplan rapidly achieved target drug concentrations in a non-human primate model, with near complete inhibition of an ex vivo hemolysis assay for greater than one week, supporting once weekly or less frequent dosing. Importantly, the peptide properties of zilucoplan enable extended interval subcutaneous dosing without the need for prior intravenous loading required by monoclonal antibody C5 inhibitor therapies. In addition to advancing the development of this and other XR formulations in 2019, we plan to progress our other pipeline programs, including our oral C5 small molecule inhibitor program, and anticipate entering human clinical studies in both programs in the first half of 2020.”

Fourth Quarter 2018 Highlights and Recent Developments

• In December 2018, Ra Pharma announced the successful completion of the Phase 2 clinical trial evaluating zilucoplan for the treatment of gMG, achieving rapid, clinically meaningful, and statistically significant reductions in pre-specified primary and key secondary endpoints for both zilucoplan dose groups tested versus placebo at 12 weeks.
  • Zilucoplan dosed at 0.3 mg/kg SC daily achieved a mean reduction from baseline of 6.0 points in the Quantitative Myasthenia Gravis (QMG) score (placebo-corrected change = -2.8; p=0.05) and a mean reduction from baseline of 3.4 points in the MG Activities of Daily Living (MG-ADL) score (placebo-corrected change = -2.3; p=0.04), with no patients treated with the 0.3 mg/kg dose of zilucoplan requiring rescue therapy.
  • Based on these data, Ra Pharma plans to engage with regulatory agencies, including the U.S. Food and Drug Administration (FDA), in the first half of 2019 regarding the design of a Phase 3 registrational trial evaluating zilucoplan versus placebo in patients with gMG. Ra Pharma anticipates initiating the Phase 3 gMG program in the second half of 2019.
• Ra Pharma today announced significant progress on its first XR formulation of zilucoplan, with a single subcutaneous dose resulting in rapid attainment of target drug concentrations for greater than one week in non-human primates, supporting once weekly or less frequent dosing. Of note, near complete inhibition of terminal complement activity for greater than one week was achieved without the need for prior intravenous loading doses, as measured by an ex vivo hemolysis assay. Data from the XR development program will be presented at the 6^th Annual Peptides Congress, April 24-25, 2019, in London, UK. Ra Pharma continues to evaluate the pharmacokinetic profiles of this and other formulations to optimize the XR dosing regimen. Ra Pharma anticipates the XR program entering human clinical studies in the first half of 2020.
• In December 2018, the Company strengthened its balance sheet with a follow-on offering, raising approximately $150 million in gross proceeds.
• In December 2018, the Company announced the receipt of a $2.5 million development milestone payment under its collaboration agreement with Merck & Co. (known as MSD outside the U.S. and Canada). The milestone payment is associated with the companies’ collaboration for a non-complement cardiovascular target with a large market opportunity.
• In December 2018, Ra Pharma completed dosing in a Phase 1 ethno-bridging study in healthy subjects of Japanese and non-Japanese descent, enrolling 16 subjects in a multi-dose cohort and 20 subjects in a single-dose cohort. The Phase 1 study is designed to support development of zilucoplan in Japan.
• In September 2018, based on FDA feedback, as well as advice provided by the Medicines and Healthcare products Regulatory Agency in the UK (MHRA) and Health Canada, Ra Pharma announced the design of a single-arm Phase 3 study in treatment-naïve paroxysmal nocturnal hemoglobinuria (PNH) patients. In January 2019, Ra Pharma concluded Scientific Advice and protocol design discussions with the European Medicines Agency (EMA). The EMA was not receptive to a single-arm study design to support approval of zilucoplan in PNH. Ra Pharma does not plan to alter the design of the Phase 3 PNH program, but is reassessing the likelihood of obtaining marketing authorization for PNH in the European Union.
• In November 2018, Ra Pharma elected Bo Cumbo to its Board of Directors. Mr. Cumbo serves as Senior Vice President and Chief Commercial Officer of Sarepta Therapeutics, Inc. (Nasdaq:SRPT).

Fourth Quarter 2018 and Full Year Financial Results

For the fourth quarter of 2018, the Company reported a net loss of $16.2 million, or a net loss of $0.47 per share (basic and diluted), compared to a net loss of $15.1 million, or a net loss of $0.67 per share, for the same period in 2017. For the full year 2018, Ra Pharma reported a net loss of $64.9 million, or a net loss of $2.06 per share (basic and diluted), compared to a net loss of $54.4 million, or a net loss of $2.41 per share, for the full year 2017.

Research and development (R&D) expenses for the fourth quarter of 2018 were $15.4 million, compared to $12.6 million for the same period in 2017. Research and development expenses for the full year 2018 were $54.5 million, compared to $45.3 million for the full year 2017. The increase in R&D expenses for both the fourth quarter and full year were primarily due to clinical development costs associated with Ra Pharma’s lead program, zilucoplan.

General and administrative (G&A) expenses for the fourth quarter of 2018 were $3.8 million, compared to $2.7 million for the same period in 2017. G&A expenses for the full year 2018 were $14.4 million, compared to $9.8 million for the full year 2017. The increase in G&A expenses for both the fourth quarter and full year were primarily due to employee-related costs due to the increase in headcount to support the growth of the Company and costs associated with pre-commercialization planning.

Total revenue earned in the fourth quarter and year ended December 31, 2018 was $2.5 million, compared to no revenue in the comparative prior periods. The increase was due to a $2.5 million payment for the achievement of a pre-clinical milestone under the Company’s collaboration agreement with Merck.

As of December 31, 2018, Ra Pharma reported total cash and cash equivalents of $209.8 million. The Company expects that its cash and cash equivalents will be sufficient to fund operating expenses and capital expenditures through at least the first quarter of 2021.

About Zilucoplan (formerly RA101495 SC)

Ra Pharma is developing zilucoplan for generalized myasthenia gravis (gMG), paroxysmal nocturnal hemoglobinuria (PNH), and other complement-mediated disorders. The product candidate is designed for convenient, once-daily subcutaneous self-administration. Zilucoplan 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, zilucoplan is additionally designed to disrupt the interaction between C5b and C6 and prevent assembly of the membrane attack complex. This activity may define an additional, novel mechanism for the inhibition of C5 function.

About Ra Pharmaceuticals

Ra Pharmaceuticals is a clinical-stage biopharmaceutical company focused on leading the field of complement biology to bring innovative and accessible therapies to patients with rare 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 Statements

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 Ra Pharma's ability to expand patient access to important therapies, the potential, safety, efficacy and regulatory and clinical progress of Ra Pharma's product candidates, including without limitation zilucoplan, beliefs regarding clinical trial data, statements regarding trial design, timeline and enrollment of Ra Pharma's ongoing and planned clinical programs, including without limitation the Phase 3 trial of zilucoplan for the treatment of PNH, the Phase 3 trial of zilucoplan for the treatment of gMG and the XR and oral C5 small molecule inhibitor programs, pending End-of-Phase 2 discussions with regulatory agencies in the first half of 2019, plans to reassess the likelihood of obtaining marketing authorization for PNH in the European Union, and the expectation that Ra Pharma's cash and cash equivalents will be sufficient to fund operating expenses and capital expenditures through at least the first quarter of 2021. 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 zilucoplan, will not successfully be developed or commercialized, in the timeframe we expect or at all; the risk that USAN does not approve the name zilucoplan; as well as the other 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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Source: Ra Pharmaceuticals, Inc.

Investors:
Ra Pharmaceuticals, Inc.
Natalie Wildenradt, 617-674-9874
nwildenradt@rapharma.com

Media:
Argot Partners
David Rosen, 212-600-1902
david.rosen@argotpartners.com