About Trevena

Trevena, Inc. operates as a biopharmaceutical company. The company focuses on developing and commercializing novel medicines for patients affected by central nervous system, or CNS, disorders. The company’s product, OLINVYK (oliceridine) injection, or OLINVYK, was approved by the United States Food and Drug Administration, or FDA, in 2020. The company initiated commercial launch of OLINVYK in the first quarter of 2021. OLINVYK is an opioid agonist for use in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. OLINVYK is the first new chemical entity, or NCE, in this intravenous, or IV-, drug class in decades and it offers a differentiated profile that addresses significant unmet needs in the acute pain management landscape. OLINVYK delivers IV opioid efficacy with a rapid 1-3 minute median onset of action. In addition, OLINVYK requires no dosage adjustments in patients with renal impairment, a large patient population with significant medical complications. The U.S. Drug Enforcement Administration, or DEA, has classified oliceridine as a Schedule II controlled substance. OLINVYK is being studied in a post-approval clinical trial, focused on respiratory safety, cognitive function and gastrointestinal tolerability. Using its proprietary product platform, the company also has identified and are developing the following product candidates: TRV045: TRV045 is the company’s novel sphingosine-1-phosphate, or S1P, receptor modulator that may offer a new, non-opioid approach to managing chronic pain, as well as for treating epilepsy and seizure disorders. TRV045 has also demonstrated an anti-inflammatory effect in nonclinical studies that may have broad potential application in CNS disorders, autoimmune disease and inflammatory disease. TRV045 targets the S1P subtype 1 receptor and nonclinical data suggests that TRV045 effectively reverses neuropathic pain and reduces seizure risk without the immune-suppressing activity, or lymphopenia, observed with approved therapeutics targeting S1P receptors. The company announced Phase 1 data in November 2022, with TRV045 demonstrating a favorable tolerability profile, no reported serious adverse events and no lymphopenia. In this study, the company studied a targeted set of laboratory measures, including total lymphocyte counts, ECGs, and ophthalmologic examinations, as these adverse events have been associated with existing S1P-targeted compounds. No lymphopenia, cardiac, pulmonary or ophthalmologic adverse events were reported in the Phase 1 study for TRV045. In December 2022, the company initiated a new Phase 1 proof-of-concept study for TRV045, designed to test the mechanism of action and measure evidence of target engagement for TRV045 in approximatley 24 subjects. In March 2023, the company initiated a second Phase 1 proof-of concept study for TRV045, using transcranial magnetic stimulation, or TMS, to evaluate TRV045 for epilepsy and seizure disorders in approximately 24 subjects. Both studies are being conducted at a site outside of the United States and not under the Investigational New Drug Application, or IND, for TRV045, and it expects each study will complete enrollment by mid-2023. TRV250: The company is developing TRV250, a G-protein biased delta-opioid receptor, or DOR, agonist as a compound with a potential first-in-class novel mechanism for the treatment of acute migraine. TRV250 also may have utility in a range of other CNS indications. The company focuses on IND-enabling activities to develop an oral dosage formulation to support future clinical development. TRV734: The company also has identified and have completed the initial Phase 1 studies for TRV734, an NCE targeting the same novel mechanism of action at the mu opioid receptor, or MOR, as OLINVYK. TRV734 was designed to be orally available, and its mechanism of action suggests it may offer valuable benefits for two distinct areas of important unmet medical need: acute and chronic pain, and maintenance-assisted therapy for patients with opioid use disorder, or OUD. The company is collaborating with the National Institute on Drug Abuse, or NIDA, to further evaluate TRV734 for the management of OUD, and NIDA initiated a proof-of-concept study for this indication in December 2019. In June 2021, the company announced that the study, which had been paused due to the global COVID-19 pandemic, had resumed recruiting patients. The company intends to continue to focus its efforts for TRV734 on securing a development and commercialization partner for this asset. Product and Pipeline OLINVYK (oliceridine) Injection OLINVYK is a G-protein biased MOR ligand that the company is commercializing in hospitals or other controlled clinical settings for acute pain in adults that is severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. It is an NCE with a novel mechanism of action. OLINVYK was approved by the FDA in August 2020 for both bolus and patient-controlled analgesia, or PCA, delivery and the company initiated commercial launch of OLINVYK in the first quarter of 2021. The DEA has classified oliceridine as a Schedule II controlled substance. Like other opioids, the label for OLINVYK contains a boxed warning and important safety information. Please consult www.olinvyk.com to view the prescribing information together with important safety information and boxed warning. The company conducted two pivotal efficacy trials evaluating OLINVYK in patients with moderate-to-severe acute pain: the APOLLO 1 study, which evaluated pain for 48 hours following bunionectomy, and the APOLLO 2 study, which evaluated pain for 24 hours following abdominoplasty. In both studies, all dose regimens achieved the primary endpoint of statistically greater analgesic efficacy than placebo, as measured by responder rate. The company conducted a Phase 3, open label, multicenter study evaluating the safety and tolerability of OLINVYK in patients with moderate-to-severe pain caused by surgery or medical conditions. In May 2021, the company announced an open-label, multi-site clinical trial to further characterize the impact of OLINVYK on respiratory, gastrointestinal, or GI, and cognitive function outcomes in the postoperative setting. The study, intended to enroll approximately 200 adults undergoing major surgery, led by clinical outcomes research experts from Cleveland Clinic and Wake Forest Baptist Health. Respiratory safety was assessed by continuous monitoring. Additional outcomes included GI tolerability as measured by GI complete response, and cognitive function as measured by standardized somnolence, sedation, and delirium assessment scales. The company completed enrollment in this study in December 2022, and it expects to begin reporting topline data from this study during the first half of 2023. In July 2022, the company reported positive topline data from its study evaluating the impact of OLINVYK on cognitive function and pain thresholds compared to IV morphine in 23 healthy subjects. The study was a randomized, double-blind, placebo-controlled, dose-ranging crossover study. In the primary endpoint, OLINVYK showed a statistically significant reduction in sedation versus IV morphine, measured by saccadic eye movement peak velocity, a sensitive laboratory measure of sedating action of medications. In March 2022, the company announced positive topline data from a study evaluating the physiologic impact of OLINVYK on respiratory function in high-risk subjects including elderly and obese subjects (mean age of 71.2 years). The company is committed to the ethical promotion of OLINVYK. For OLINVYK, the company has established commercial supply agreements for the manufacture of the API and finished (compounded, filled and packaged) drug product. Sterling Pharma Solutions, or Sterling, is contracted to supply all of its commercial API from its Germantown, WI manufacturing facility. The company has existing commercial supply agreements with two separate companies for the supply of drug product. Alcami Corporation, or Alcami, is contracted to supply commercial drug product from its facilities in Charleston, SC and Wilmington, NC and was included as part of its approved new drug application, or NDA, submission. Pfizer CentreOne is also contracted to supply commercial drug product in the future, but was not included in its NDA submission. In October 2020, the company announced that the DEA has classified OLINVYK as a Schedule II controlled substance. All third-party facilities throughout the supply chain have the appropriate licenses from the DEA for handling Schedule II controlled substances according to each of their respective contractual roles (manufacturing, testing, distribution, etc.). Intellectual Property The company’s wholly own the OLINVYK patent portfolio, including five issued U.S. patents (U.S. Patent Nos. 8,835,488; 9,309,234; 9,642,842; 9,849,119 and 11,077,098), which claim, among other things, OLINVYK, compositions comprising OLINVYK, and methods of using OLINVYK. The issued patents are expected to expire no earlier than 2032, subject to any disclaimers or extensions, and any U.S. patent to issue in the future is also expected to expire no earlier than 2032, subject to any disclaimers or extensions. The company also has issued patents in Australia, China, Eurasia, Europe, Hong Kong, Macau, Israel, Japan, India, South Korea, and New Zealand, which claim, among other things, OLINVYK, compositions comprising OLINVYK and methods of making or using OLINVYK. The company has patent applications pending in the United States, Europe, Japan, Israel, Brazil, and Canada. The issued patents and patents that could issue in the future from these allowed or pending applications outside the United States are expected to expire no earlier than 2032, subject to any disclaimers or extensions. Following the FDA approval of OLINVYK, the FDA has added four issued U.S. patents to the Orange Book of Approved Drug Products with Therapeutic Equivalence Evaluations (U.S. Patent Nos. 8,835,488, 9,309,234, 9,642,842, and 11,077,098). In addition, the company has filed Patent Term Extension applications with the United States Patent and Trademark Office that could extend the life of one of the patents until 2034. Finally, the FDA has designated OLINVYK as a new chemical entity, or NCE, in the Orange Book and it will therefore receive the exclusivity and protections afforded to NCE’s. TRV045 (S1P Modulators) TRV045 is the company’s novel sphingosine-1-phosphate, or S1P, receptor modulator that may offer a new, non-opioid approach to managing chronic pain, as well as for treating epilepsy and seizure disorders. TRV045 has also demonstrated an anti-inflammatory effect in nonclinical studies that may have broad potential application in CNS disorders, autoimmune disease and inflammatory disease. TRV045 targets the S1P subtype 1 receptor and nonclinical data suggests that TRV045 effectively reverses neuropathic pain and reduces seizure risk without the immune-suppressing activity, or lymphopenia, observed with approved therapeutics targeting S1P receptors. In November 2022, the company announced Phase 1 data, with TRV045 demonstrating a favorable tolerability profile, no reported serious adverse events and no lymphopenia. The study had a three-part design, examining the PK profile, safety and tolerability of orally administered TRV045 in healthy volunteers. The company also conducted an additional nonclinical study that showed TRV045 has a potential anti-inflammatory effect on astrocytes. This suggests TRV045 may play a role as a disease-modifying treatment in epilepsy. In this study, primary astrocytes derived from mouse brains were isolated and studied in cell culture. In December 2022, the company initiated a new Phase 1 proof-of-concept study, the Target Engagement Study, for TRV045. This randomized, double-blind, placebo-controlled, four-way cross-over study is designed to test the mechanism of action and measure evidence of target engagement for TRV045. The study uses a validated set of analgesic tests to evaluate potential central and peripheral nervous system effects and to provide insight into the potential anti-inflammatory actions of TRV045. In March 2023, the company initiated a second Phase 1 proof-of-concept study, the TMS Study, for TRV045. The study will use transcranial magnetic stimulation, or TMS, to evaluate how TRV045 affects the ability of the brain cells to conduct electrical stimulation. The effects of TMS will be explored using both electromyography (EMG) and electroencephalography (EEG) to measure the effect of TRV045 on brain function. The study is a randomized, double-blind, placebo-controlled, two-way cross-over, multiple dose study. Approximately twenty-four healthy male volunteers will be enrolled and each subject will receive one of two treatment sequences in random order: TRV045 250 mg followed by placebo; or placebo followed by TRV045 250 mg, each treatment sequence given once daily for four consecutive days. Intellectual Property The company wholly owns the S1P patent portfolio, including one pending provisional application, one pending PCT application, and pending applications in the United States, Australia, Brazil, Canada, China, Europe, Israel, India, Japan, South Korea, Hong Kong, and New Zealand. The applications are directed to, amongst other things, compounds that modulate the S1P receptor and methods of using these compounds, including methods of treating pain, epilepsy, mood disorders, anxiety disorders, and trauma-and stressor-related disorders. The company is aware of a certain U.S. patent owned by a third party with claims that are broadly directed to a method of treating chemotherapy induced neuropathic pain with an S1P receptor agonist or an S1P receptor antagonist. TRV250 TRV250 is a G-protein biased ligand targeting the DOR agonist as a compound with potential first-in-class, novel mechanism for the treatment of acute migraine. TRV250 also may have utility in a range of other CNS indications. The company has completed a first-in-human Phase 1 trial of TRV250, which showed a favorable tolerability profile and pharmacokinetics. The company has initiated IND-enabling activities to evaluate the potential oral dosage formulation to support future clinical development. In June 2018, the company announced the completion of its first-in-human Phase 1 study of TRV250. Data from this healthy volunteer study showed a favorable tolerability profile and pharmacokinetics. The Phase 1 study was a two part, randomized, single-blind, placebo-controlled, single ascending dose study to evaluate the safety, tolerability, and pharmacokinetics of subcutaneous and oral TRV250 in healthy adults. Part A assessed single subcutaneous doses in 38 subjects. Four cohorts of nine or ten subjects were randomized to receive a single dose of up to 30mg TRV250 or placebo. Part B consisted of a single cohort of nine subjects administered either TRV250 as a single 6 mg oral dose (either as a capsule in the fed state or a capsule in the fasted state, n=7) or placebo (as a capsule in the fed or fasted state, n=2). Intellectual Property The company wholly owns the TRV250 patent portfolio, including two issued patents (U.S. Patent No. 10,246,436 and 11,465,980) in the United States directed to compounds that modulate the delta receptor, claiming, among other things, TRV250, compositions comprising TRV250, and methods of using TRV250. The patent is expected to expire no earlier than 2036, subject to any disclaimers or extensions. The company also has issued patents in Australia, Europe, Israel, Japan, and Hong Kong, which claim, among other things, TRV250, compositions comprising TRV250, and methods of using TRV250. The company also has patent applications pending in the United States, Australia, Brazil, Canada, China, Europe, Hong Kong, Israel, India, Japan, South Korea, and New Zealand. Any patents that may issue from these applications are expected to expire no earlier than 2036, subject to any disclaimers or extensions. The company also has two pending PCT patent applications that are, among other things, directed to the synthesis of TRV250, and crystalline forms of TRV250, compositions comprising crystalline forms of TRV250, and methods of using crystalline forms of TRV250. Any patents that may issue based on the provisional application and PCT application would be expected to expire no earlier than 2042 or 2041, respectively, subject to any disclaimers or extensions. TRV734 TRV734 is a small molecule G-protein biased ligand of the MOR that the company discovered and has developed through Phase 1 as a first-line, orally administered compound for the treatment of moderate-to-severe acute and chronic pain. Like OLINVYK, TRV734 utilizes a well-established mechanism of pain relief by targeting the MOR. Also, like OLINVYK, it does so with enhanced selectivity for the G-protein signaling pathway, which in nonclinical studies was linked to analgesia, as opposed to the beta-arrestin signaling pathway, which in nonclinical studies was associated with the development of side effects. The company intends to continue to focus its efforts for TRV734 on securing a development and commercialization partner for this asset. Clinical Development The company has completed three Phase 1 trials of TRV734 in healthy volunteers, including a single ascending dose study, a multiple ascending dose study, and a pharmacokinetic study. In these studies, a total of 127 healthy volunteers were exposed to TRV734 at doses between 2 mg and 250 mg. In collaboration with NIDA, the company intends to pursue a clinical study to determine whether TRV734 decreases symptoms of opioid withdrawal in patients with OUD. Intellectual Property The company wholly owns the TRV734 patent portfolio, including two issued U.S. patents (U.S. Patent No, 9,044,469 and 10,588,898) claiming TRV734, other compounds and/or methods of making or using the same. These patents are expected to expire no earlier than 2032, subject to any disclaimers or extensions. The company also has issued patents in Australia, China, Europe, Eurasia, Hong Kong, Macau, Israel, Japan, India, South Korea, and New Zealand claiming TRV734, other compounds and/or methods of making or using the same. The company also has patent applications pending in the United States, Europe, Brazil, and Canada. The issued patents and patents that could issue in the future from these allowed or pending applications outside the United States are expected to expire no earlier than 2032, subject to any disclaimers or extensions. Additionally, the TRV734 patent portfolio also includes one issued U.S. patent (U.S. Patent No. 10,588,898), which claims, among other things, methods of using TRV734 or compositions comprising TRV734 for treating drug abuse. The company also has issued patents in Israel, Japan, and South Korea, which claim, among other things, methods of using TRV734 or compositions comprising TRV734 for treating drug abuse. The issued patents (U.S. Patent No. 10,588,898) is expected to expire no earlier than 2032. The company has patent applications pending in Brazil and Canada. The issued patents and patents that could issue in the future from these allowed or pending applications outside the United States are expected to expire no earlier than 2032, subject to any disclaimers or extensions. Commercialization The company launched the customer-facing elements of its commercial team in the first quarter of 2021 with Syneos Health, a contract sales organization, to assist in the sourcing, training and deployment of a range of customer-facing roles. In 2022, the company transitioned to an in-house U.S. commercial team. Research and Development The company capitalized approximately $ 18.7 million of R&D expenses incurred as of December 31, 2022. Government Regulation and Product Approval OLINVYK has been classified as a Schedule II controlled substance under the Federal Controlled Substances Act of 1970, or CSA. To meet its responsibilities, the DEA conducts periodic inspections of registered establishments that handle controlled substances. OLINVYK has been designated as a new chemical entity in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations. In the European Union, the company must obtain authorization of a clinical trial application, or CTA, in each member state in which it intends to conduct a clinical trial. History The company was founded in 2007. It was incorporated under the laws of the state of Delaware in 2007. The company was formerly known as Parallax Therapeutics, Inc. and changed its name to Trevena, Inc. in 2008.