Trevena Announces Successful End-of-Phase 2 Meeting with FDA and Outlines Phase 3 Program for Oliceridine

KING OF PRUSSIA, Pa.–(BUSINESS WIRE)–Trevena, Inc. (NASDAQ: TRVN), a clinical stage biopharmaceutical company
focused on the discovery and development of biased ligands targeting G
protein coupled receptors, today announced the successful completion of
the End-of-Phase 2 Meeting process with the United States Food and Drug
Administration (FDA). The company has reached general agreement with the
FDA on key elements of the Phase 3 program to support a New Drug
Application (NDA) for oliceridine (TRV130), to which the FDA has granted
Breakthrough Therapy designation.
“We are very pleased with the outcome of our End-of-Phase 2 discussion
with the FDA,” said Maxine Gowen, Ph.D., chief executive officer. “We
appreciate the valuable guidance the FDA has provided, and look forward
to continuing a constructive relationship as we advance our Phase 3
registration program. We remain focused on bringing oliceridine to
market as a new and potentially differentiated analgesic for patients
and caregivers seeking alternatives to conventional opioids.”
End-of-Phase 2 meeting
The FDA agreed that pivotal efficacy trials in bunionectomy and
abdominoplasty patients include appropriate patient populations to
support an indication for moderate to severe acute pain. The agency also
confirmed the need for at least 1,100 patients exposed to oliceridine
across the development program for the purposes of evaluating safety and
tolerability. This database should include a sufficient number of
patients with higher exposures and longer durations of oliceridine
therapy. In addition, general agreement was reached on the company’s
planned clinical, nonclinical, clinical pharmacology, and chemistry,
manufacturing and control (CMC) activities to support the planned NDA.
Overview of the Oliceridine Phase 3 program

• The oliceridine Phase 3 program includes two pivotal efficacy trials
  evaluating moderate-to-severe acute pain: the APOLLO-1 study will
  evaluate pain for 48 hours following bunionectomy, and the APOLLO-2
  study will evaluate pain for 24 hours following abdominoplasty. In
  each trial, patients will be randomized to receive placebo, morphine,
  or one of three regimens of oliceridine by patient-controlled
  analgesia (PCA) for the management of their post-operative pain. Each
  study will enroll approximately 375 patients, allocated equally across
  study arms.
• The primary endpoint for both APOLLO studies will be a responder
  analysis proposed by the company comparing active treatment arms to
  placebo. A responder is defined as a patient experiencing a sum of
  pain intensity difference (SPID) at the end of the treatment period
  that corresponds to at least a 30% improvement from baseline without
  early discontinuation and without rescue pain medication.
• Secondary endpoints in both APOLLO studies will include comparisons of
  oliceridine efficacy, safety, and tolerability to morphine. A
  respiratory safety endpoint will measure prevalence and duration of
  hypoventilation, which will be a clinical assessment as in the
  company’s Phase 2b abdominoplasty study.
• The APOLLO study designs were informed in part by the company’s Phase
  2b abdominoplasty study, which also used PCA dosing. Powering
  assumptions included similar performance of PCA-administered
  oliceridine in both APOLLO studies as was observed in the Phase 2b
  study. In a post-hoc evaluation using the Phase 3 responder analysis,
  both doses in the company’s Phase 2b study in abdominoplasty yielded
  analgesic efficacy similar to morphine, and significantly higher than
  placebo (p ≤ 0.0005 for both oliceridine treatment arms). In addition,
  using the Phase 3 respiratory safety endpoint, both doses in the
  company’s Phase 2b study showed significantly less respiratory safety
  burden for oliceridine than morphine (p ≤ 0.0003 for both oliceridine
  treatment arms).
• The development program will include at least 1,100 patients exposed
  to oliceridine. The on-going open-label ATHENA-1 safety study is
  enrolling patients experiencing pain as a result of either a medical
  diagnosis or surgery. In this study, patients may receive oliceridine
  as-needed either as an intermittent bolus or via PCA device, with
  doses and durations appropriate to manage their pain.

Both APOLLO-1 and APOLLO-2 are expected to start in the second quarter
of this year, and the company expects to report top-line data in the
first quarter of 2017. The company continues to expect to file an NDA
for oliceridine in the second half of 2017. The company also continues
to expect that its available cash and investments will be sufficient to
fund operations into 2018.
Conference Call and Webcast
The company will host a conference call and webcast to discuss its Phase
3 plans. The webcast will be available for replay for 30 days.

About oliceridine
Oliceridine (TRV130) is a new chemical entity (NCE) designed to optimize
mu opioid receptor pharmacology to deliver an improved analgesic
profile, and has been granted Breakthrough Therapy designation by the
U.S. Food & Drug Administration. Oliceridine is the first mu receptor G
protein pathway selective modulator (muGPS) – a biased mu opioid
receptor ligand that in preclinical studies activated pathways
associated with analgesia while avoiding pathways that can promote
respiratory depression and gastrointestinal dysfunction and limit
analgesia. In Phase 2, intravenous oliceridine demonstrated rapid and
powerful analgesic efficacy with reduced frequency of opioid-related
adverse events including nausea, vomiting, and hypoventilation compared
to intravenous morphine. Trevena believes that oliceridine may offer an
improved safety and tolerability profile compared to conventional opioid
analgesics while providing powerful pain relief to patients. Trevena
anticipates that the initial market opportunity for oliceridine will be
in the acute care settings, with a focus on moderate to severe acute
pain in the hospital.
About Trevena
Trevena, Inc. is a clinical stage biopharmaceutical company that
discovers, develops and intends to commercialize therapeutics that use a
novel approach to target G protein coupled receptors, or GPCRs. Using
its proprietary product platform, Trevena has identified four biased
ligand product candidates – oliceridine (TRV130) to treat moderate to
severe acute pain intravenously (Phase 3), TRV027 to treat acute heart
failure (Phase 2b), TRV734 to treat moderate to severe acute and chronic
pain orally (Phase 1), and TRV250 for acute episodic migraine and other
CNS disorders (preclinical).
Cautionary Note on Forward Looking Statements
Any statements in this press release about future expectations, plans
and prospects for the Company, including statements about the Company’s
strategy, future operations, clinical development of its therapeutic
candidates, plans for potential future product candidates and other
statements containing the words “anticipate,” “believe,” “estimate,”
“expect,” “intend,” “may,” “plan,” “predict,” “project,” “suggest,”
“target,” “potential,” “will,” “would,” “could,” “should,” “continue,”
and similar expressions, constitute forward-looking statements within
the meaning of The Private Securities Litigation Reform Act of 1995.
Actual results may differ materially from those indicated by such
forward-looking statements as a result of various important factors,
including: uncertainties related to the Company’s intellectual property;
the status, timing, costs, results and interpretation of the Company’s
clinical trials, including whether oliceridine will prove to be a
differentiated analgesic for patients and caregivers seeking
alternatives to conventional opioids; the uncertainties inherent in
conducting clinical trials, including the timing around the initiation
of the pivotal efficacy studies in the Phase 3 program and the potential
filing of an NDA; whether interim results from a clinical trial will be
predictive of the final results of the trial or results of early
clinical trials, including the Phase 2 oliceridine studies and any
post-hoc analysis of such trial results, will be indicative of the
results of future trials; expectations for regulatory approvals,
including the Company’s assessment of the results of the End-of-Phase 2
meeting with FDA and whether the Company ultimately will achieve
regulatory approval for oliceridine; availability of funding sufficient
for the Company’s foreseeable and unforeseeable operating expenses and
capital expenditure requirements; other matters that could affect the
availability or commercial potential of the Company’s therapeutic
candidates; and other factors discussed in the Risk Factors set forth in
the Company’s Annual Report on Form 10-K and Quarterly Reports on Form
10-Q filed with the Securities and Exchange Commission (SEC) and in
other filings the Company makes with the SEC from time to time. In
addition, the forward-looking statements included in this press release
represent the Company’s views only as of the date hereof. The Company
anticipates that subsequent events and developments may cause the
Company’s views to change. However, while the Company may elect to
update these forward-looking statements at some point in the future, it
specifically disclaims any obligation to do so, except as may be
required by law.