Ra Pharmaceuticals Announces Positive gMG Phase 2 and Open-Label, Long-Term Extension Data at the 2019 AAN Annual Meeting

Open-label, long-term extension data show durability of zilucoplan
treatment effect, with sustained improvements observed in primary and
secondary endpoints at 24 weeks

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Ra
Pharmaceuticals, Inc. (Nasdaq:RARX) today announced the presentation
of data from the Company’s Phase 2 clinical trial evaluating zilucoplan
for the treatment of generalized myasthenia gravis (gMG), including data
from the open-label, long-term extension study, at the 2019 American
Academy of Neurology (AAN) Annual Meeting, in Philadelphia, PA, from May
4-10, 2019.

“Zilucoplan achieved rapid, clinically meaningful, and statistically
significant reductions in primary and secondary endpoints in this Phase
2 study, with a durable and sustained treatment effect observed at 24
weeks for patients in the long-term extension,” said James F. Howard,
M.D., Distinguished Professor of Neuromuscular Disease and Chief of the
Neuromuscular Disorders Section, Department of Neurology, University of
North Carolina School of Medicine. “These data provide continued support
for the role of this convenient, subcutaneously (SC) self-administered
C5 inhibitor as a potential treatment option for a broad range of
patients with gMG.”

Base Study Results

• The 0.3 mg/kg dose of zilucoplan consistently achieved rapid,
  sustained, and near-complete complement inhibition. The 0.1 mg/kg dose
  of zilucoplan achieved rapid, sustained, but sub-maximal complement
  inhibition. Based on the pharmacokinetic, pharmacodynamic, and
  efficacy results, the 0.3 mg/kg dose of zilucoplan was selected for
  evaluation in the upcoming pivotal Phase 3 trial.
• As previously reported, the pre-specified primary efficacy endpoint of
  change from baseline to week 12 in Quantitative Myasthenia Gravis
  (QMG) score was met with zilucoplan dosed at 0.3 mg/kg SC daily,
  resulting in a clinically meaningful and statistically significant
  improvement over placebo (QMG reduction from baseline at week 12 =
  -6.0; placebo-corrected change in QMG at week 12 = -2.8; p=0.05). The
  key secondary efficacy endpoint of change from baseline to week 12 in
  the MG Activities of Daily Living (MG-ADL) score was met with
  zilucoplan dosed at 0.3 mg/kg SC daily, resulting in a clinically
  meaningful and statistically significant improvement over placebo
  (MG-ADL reduction from baseline at week 12 = -3.4; placebo-corrected
  change in MG-ADL at week 12 = -2.3; p=0.04).
• The 0.3 mg/kg dose of zilucoplan led to rapid, statistically
  significant, and clinically meaningful reductions in additional
  pre-specified secondary endpoints, the MG Composite (MG-COMP) and the
  15-item MG Quality of Life revised scale (MG-QoL15r), versus placebo
  at week 12 (MG-COMP reduction from baseline at week 12 = -7.4;
  placebo-corrected change at week 12 = -4.1; p=0.04); MG-QoL15r
  reduction from baseline at week 12 = -5.9; placebo-corrected change at
  week 12 = -3.7; p=0.06).
• Rescue therapy with intravenous immunoglobulin or plasma exchange was
  required by 3/15 (20%) patients in the placebo arm, 1/15 (7%) patients
  in the 0.1 mg/kg zilucoplan arm, and in zero (0%) patients in the 0.3
  mg/kg zilucoplan arm.
• Treatment with zilucoplan had a favorable safety and tolerability
  profile in the study, consistent with previously-completed Phase 1 and
  Phase 2 studies. The majority of adverse events (AEs) reported were
  mild and were not considered by the investigators to be related to
  study drug. There were no serious AEs observed related to treatment
  with zilucoplan.

Open-Label, Long-Term Extension Results

• Sustained responses were observed for all four efficacy endpoints
  after 24 weeks at the 0.3 mg/kg dose of zilucoplan, with changes from
  baseline to week 24 as follows:
  • QMG = -8.7, p<0.0001
  • MG-ADL = -4.5, p<0.0001
  • MG-COMP = -10.2, p<0.0001
  • MG-QoL15r = -7.5, p=0.0006
• Placebo subjects crossing over to the 0.3 mg/kg dose of zilucoplan
  after 12 weeks experienced rapid, clinically meaningful, and
  statistically significant improvements for all four efficacy endpoints
  from weeks 12 to 24, with changes from week 12 to week 24 as follows:
  • QMG = -3.1, p=0.01
  • MG-ADL = -3.6, p=0.0004
  • MG-COMP = -5.5, p=0.004
  • MG-QoL15r = -4.0, p=0.04

Based on feedback provided by the U.S. Food and Drug Administration
(FDA), Ra Pharma plans to initiate a single, 12-week, pivotal, Phase 3,
randomized, double-blind, placebo-controlled trial evaluating the
efficacy of a once-daily, SC self-administered dose of 0.3 mg/kg of
zilucoplan versus placebo. The trial is expected to enroll approximately
130 patients with gMG who are acetylcholine receptor
(AChR)-antibody-positive, regardless of their prior therapies. The
primary endpoint will be the change in the MG-ADL score from baseline to
week 12. Following completion of the Phase 3 clinical trial, patients
will have the option to enroll into an open-label, long-term extension
study.

“These Phase 2 data support the competitive profile of zilucoplan in
gMG, and as a convenient, SC self-administered therapy, we believe
zilucoplan has the potential to bring complement inhibition to the
forefront of treatment in this disease,” said Doug Treco, Ph.D.,
President and Chief Executive Officer of Ra Pharma. “We look forward to
initiating our pivotal Phase 3 trial in gMG in the second half of this
year, as part of our mission of expanding patient access to convenient
and accessible therapies.”

Details of the presentation are as follows:

Abstract Title: Zilucoplan, a Subcutaneously Self-Administered
Peptide Inhibitor of Complement Component 5 (C5), for the Treatment of
Generalized Myasthenia Gravis: Results of a Phase 2 Randomized,
Double-Blind, Placebo-Controlled Trial and Open-Label Long-Term Extension
Session
Title: Emerging Science
Date/Time: Tuesday, May 7,
Poster Presentation: 11:45 a.m.-12:45 p.m. E.T., Data Blitz Oral
Presentation: 12:06 p.m. E.T.

The presentation and poster from the 2019 AAN Annual Meeting can be
accessed by visiting the “Presentations and Publications” section of the
Ra Pharma website: www.rapharma.com.

About Zilucoplan Phase 2 gMG Clinical Trial

The Phase 2, multi-center, randomized, double-blind, placebo-controlled
trial was designed to evaluate the safety, tolerability, and preliminary
efficacy of zilucoplan in patients with generalized myasthenia gravis
(gMG), regardless of prior therapies, who had an MGFA Disease Class of
II-IVa at screening and a Quantitative Myasthenia Gravis (QMG) score, a
physician-administered assessment of MG-related muscle weakness, of ≥ 12
at screening and randomization. The trial enrolled 44 patients in the
U.S. and Canada. At the outset of the 12-week treatment period, patients
were randomized in a 1:1:1 ratio to receive daily, subcutaneous (SC)
doses of 0.1 mg/kg of zilucoplan, 0.3 mg/kg of zilucoplan, or matching
placebo. The pre-specified primary efficacy endpoint was the change in
QMG score from baseline to week 12. The key secondary efficacy endpoint
was the change in MG Activities of Daily Living (MG-ADL) score, a
patient-reported outcome measure, from baseline to week 12. Significance
testing was pre-specified at a 1-sided alpha of 0.1. All 44 patients
completed the 12-week study and, of these, 42 (95%) entered a long-term
extension to receive active study drug.

About gMG

Myasthenia gravis (MG) is a chronic, autoimmune, neuromuscular disease
characterized by weakness and fatigue of skeletal muscles. Patients with
MG present with muscle weakness that becomes increasingly severe with
repeated use and recovers with rest. Weakness can be localized to
specific muscles, such as those responsible for eye movements, but often
progresses to affect a broader range, including head, limb, and
respiratory muscles. This progression is often described as the
generalized, or severe, form of the disease. gMG is estimated to affect
approximately 60,000 people in the U.S. alone.

About Zilucoplan

Ra Pharma is developing zilucoplan for generalized myasthenia gravis
(gMG) and other tissue-based, complement-mediated disorders with high
unmet medical need. The product candidate is designed for convenient,
once-daily, subcutaneous (SC) self-administration. Zilucoplan is an
investigational, synthetic, macrocyclic peptide discovered using Ra
Pharma’s powerful proprietary drug discovery technology. The peptide is
designed to bind to complement component 5 (C5) with sub-nanomolar
affinity and allosterically inhibit its cleavage into C5a and C5b upon
activation of the classical, alternative, or lectin pathways.

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 our expectations
surrounding the initiation, enrollment, and design of our planned Phase
3 clinical trial of zilucoplan and timing thereof, our efforts to
develop and expand patient access to treatment options for a wide range
of C5-mediated diseases, and bringing innovative and accessible
therapies to patients with rare diseases. 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; 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.

Contacts

Investors:
Ra Pharmaceuticals, Inc.
Natalie Wildenradt,
617-674-9874
[email protected]

Media:
Argot
Partners
David Rosen, 212-600-1902
[email protected]