SLC33A1

-- 92% probability that TRV027 has a potential beneficial impact on primary endpoint of D-dimer levels, a biomarker associated with critical illness and mortality ~12 days lower average hospital length of stay in patients treated with TRV027 compared to placebo TRV027 is currently being evaluated in a randomized controlled study (NIH ACTIV-4) and a global adaptive platform study (REMAP-CAP) TRV027 is a novel AT1 receptor selective agonist with the potential to treat acute lung damage / abnormal blood clotting associated with COVID-19 -- Company to host conference call today, September 30th, 2021, at 8:00 a.m. ET -- CHESTERBROOK, Pa., Sept. 30, 2021 (GLOBE NEWSWIRE) -- Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced data from 30 patients enrolled in the proof-of-concept study of TRV027, the Company’s novel AT1 receptor selective agonist, in hospitalized COVID-19 patients. The results showed that TRV027 was well-tolerated and provided initial evidence of its potential to improve biomarker and clinical endpoints associated with COVID-19 disease severity and progression. The study was led and funded by Imperial College London, with additional support through the British Heart Foundation Imperial Centre for Research Excellence Award. “I am pleased to announce the results from this analysis, which provide initial evidence of the therapeutic potential of TRV027 to improve COVID-19 patient outcomes. With the ACTIV and REMAP-CAP COVID-19 platform trials currently evaluating TRV027, and data expected as early as mid-2022, we look forward to building upon these promising results,” said Carrie Bourdow, President and CEO of Trevena. “I would like to thank the patients and their families who participated, as well as Imperial College London for their partnership and interest in investigating our novel molecule.” The primary endpoint was mean change from baseline D-dimer levels at three days. D-dimer is a biomarker used to monitor the risk of abnormal clotting throughout the vascular system. In patients with COVID-19, elevations in circulating D-dimer are also known to be an accurate predictor of critical disease progression and death. Among TRV027 treated patients, 70% (7 of 10) experienced a reduction in circulating D-dimer, compared to 27% (3 of 11) of patients on placebo. TRV027 was associated with a 92% probability of a potential beneficial treatment effect, based on a Bayesian model analysis recommended by the study’s Data Monitoring and Safety Committee (DMSC). Notably, a post-hoc analysis indicated that patients receiving TRV027 experienced a 12 day reduction in average length of hospital stay compared to placebo (11.4 vs. 23.3 days), with a median reduction of 4 days (8 vs. 12). “The overall outcomes from this analysis showing a reduction of D-dimer and a reduced length of hospital stay suggest that TRV027 may effectively combat dysregulation of the renin angiotensin system caused by a COVID-19 infection and thereby improve clinical outcomes,” said David Owen, M.D., Ph.D., Faculty of Medicine, Imperial College London and Head of Clinical Studies, NIHR Imperial Clinical Research Facility. “I am pleased that our efforts yielded these exciting findings, and I look forward to continue investigating this novel compound in two global multi-site platform trials.” In March 2021, the study’s DMSC reviewed this data and unanimously found no safety or efficacy concerns, and it supported advancing TRV027 to a larger, more extensive study with clinical efficacy outcomes. As a result, the DMSC recommended closing enrollment at the interim analysis (~30 patients) prior to reaching the full study population number necessary to detect statistically significant treatment differences. The DMSC also recommended use of a Bayesian analysis on the primary endpoint to take full advantage of the accumulated data. TRV027 is now being evaluated in two larger efficacy studies: ACTIV-4 Host Tissue led by Vanderbilt University Medical Center / NIH in the U.S. (ClinicalTrials.gov Identifier: NCT04924660), with data expected as early as mid-2022, and REMAP-CAP in the U.K. These two global, multi-site, multi-arm COVID-19 platform trials are expected to generate extensive scientific data in up to 600 patients on the potential clinical impact of TRV027 to prevent critical illness progression, multiorgan failure, and mortality in hospitalized patients with COVID-19 infection. Conference Call and Webcast Information The Company will host a conference call and webcast with the investment community on September 30, 2021, at 8:00 a.m. Eastern Time featuring remarks by Carrie Bourdow, President and Chief Executive Officer and Mark Demitrack, M.D., Senior Vice President and Chief Medical Officer. Title: TRV027 Proof-of-Concept Data Presentation Date: Thursday, September 30, 2021 Time: 8:00 a.m. ET Conference Call Details: Toll-Free: (855) 465-0180 International: (484) 756-4313 Conference ID: 6687853 Webcast: About the TRV027 Proof-of-Concept COVID-19 Trial (COVRAS) This was a randomized, double-blind, placebo-controlled proof-of-concept study that enrolled 30 hospitalized, non-ventilated patients aged 18 or older with a confirmed COVID-19 infection. 21 patients (n=10 for TRV027, n=11 for placebo) received at least 3 days of their assigned infusion and were evaluable for primary analysis. The primary objective of the study was to determine whether the coagulopathy associated with COVID-19 infection was driven by overactivation of the renin angiotensin system (RAS). The secondary objective was to determine whether dysregulation of other organ systems associated with COVID-19 infection is driven by overactivation of the RAS. Among 28 patients who received treatment, 10 experienced at least one adverse event (AE) (n=5 for TRV027, n=5 for placebo), and 7 experienced at least one serious AE (SAE) (n=4 for TRV027, n=3 for placebo). All SAEs, including 3 deaths (n=2 for TRV027, n=1 for placebo), were assessed by the study clinician to be unrelated to study drug assignment or study procedures. At the 30 day follow-up, 24 patients survived (n = 12 for TRV027, n=12 for placebo). Imperial College London sponsored and funded the study, with additional support through the British Heart Foundation Imperial Centre for Research Excellence Award and the NIHR Imperial Clinical Research Facility. The Company provided TRV027 in support of the study. About TRV027 TRV027 is a novel AT1 receptor selective agonist that is currently being investigated by multiple institutions as a potential treatment for acute lung injury contributing to ARDS and abnormal blood clotting in COVID-19 patients. It has previously been studied in 691 individuals, has a well-characterized pharmacokinetic profile, and has demonstrated efficacy, potency, and selectivity at the AT1 receptor in nonclinical studies. In previous clinical trials, there was a low dropout rate associated with TRV027, and no significant safety issues were reported. In April 2021, the Company filed a non-provisional patent application and PCT application with the United States Patent and Trademark Office covering the use of TRV027 to treat ARDS and the prevention or treatment of abnormal clotting in COVID-19 patients. About Trevena Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative medicines for patients with CNS disorders. The Company has one approved product in the United States, OLINVYK® (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Company’s novel pipeline is based on Nobel Prize winning research and includes four differentiated investigational drug candidates: TRV250 for the acute treatment of migraine, TRV734 for maintenance treatment of opioid use disorder, TRV045 for diabetic neuropathic pain and epilepsy, and TRV027 for acute respiratory distress syndrome and abnormal blood clotting in COVID-19 patients. For more information, please visit 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 and trials of its therapeutic candidates, plans for potential future product candidates, commercialization of approved drug products and other statements containing the words “anticipate,” “believe,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “objective,” “predict,” “project,” “suggest,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue,” “ongoing,” or the negative of these terms or 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: the commercialization of any approved drug product, the status, timing, costs, results and interpretation of the Company’s clinical trials or any future trials of any of the Company’s investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including the Company’s assessment of the discussions with the FDA or other regulatory agencies about any and all of its programs; uncertainties related to the commercialization of OLINVYK; available funding; uncertainties related to the Company’s intellectual property; uncertainties related to the ongoing COVID-19 pandemic, 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. For more information, please contact: Investor Contact: Dan Ferry Managing Director LifeSci Advisors, LLC daniel@lifesciadvisors.com (617) 430-7576 PR & Media Contact: Sasha Bennett Associate Vice President Clyde Group Sasha.Bennett@clydegroup.com (239) 248-3409

CHESTERBROOK, Pa., July 26, 2021 (GLOBE NEWSWIRE) -- Trevena, Inc. (Nasdaq: TRVN), a biopharmaceutical company focused on the development and commercialization of novel medicines for patients with central nervous system (CNS) disorders, today announced that the first COVID-19 patient has been enrolled in the NIH-funded ACTIV-4 Host Tissue (Accelerating COVID-19 Therapeutic Interventions and Vaccines) trial. “There is no one solution to end COVID-19, and we are honored to play a role in the global effort to overcome this pandemic and mitigate its long-term impact on our communities,” said Carrie Bourdow, President and CEO of Trevena. “I am excited that patients are now being enrolled in this study and that TRV027 is the one of the first active treatment arms available for patient randomization.” The trial, known as ACTIV-4 Host Tissue, is testing four investigational agents that combat dysregulation of the renin-angiotensin-aldosterone system (RAAS) and the immune system caused by a COVID-19 infection. TRV027 is a novel AT1 receptor selective agonist that specifically binds to and rebalances AT1 receptor activation within the RAAS, blocking the damaging pathway that leads to acute lung damage and abnormal blood clotting, while activating the cellular pathway that selectively targets reparative actions that improve lung function and promote anti-inflammatory effects. The trial is enrolling approximately 1,600 patients at over 50 sites in the U.S. TRV027 is part of the initial trial launch, and additional study arms will be added to the trial over time. The study is evaluating the impact of each intervention on recovery, supplemental oxygen use, need for mechanical ventilation, organ failure, and mortality. “As the COVID-19 pandemic continues to evolve, the development of interventions that can combat the vascular, fibrotic, and inflammatory damage done by the coronavirus remains a top priority,” said Sean Collins, M.D., M.Sci., Principal Investigator of the ACTIV-4 Host Tissue trial, Co-Director of the Vanderbilt Coordinating Center and Professor of Emergency Medicine, Vanderbilt University Medical Center. “I am very pleased that we have enrolled our first patient in the ACTIV-4 Host Tissue trial, and I look forward to investigating the potential of TRV027 to modulate the RAAS and improve outcomes for patients hospitalized with COVID-19.” About ACTIV-4 Host Tissue This is a multi-site, randomized, placebo-controlled, clinical trial with multiple treatment arms, each enrolling approximately 300-400 COVID-19 patients ≥ 18 years old. Four trial arms are testing investigational agents, including TRV027, that target the RAAS or the immune system through distinct mechanisms of action. The objective of the trial is to determine whether modulation of these systems is an effective strategy for preventing progression to critical illness, multiorgan failure, or mortality in hospitalized COVID-19 patients. The trial is funded by the National Heart, Lung, and Blood Institute (NHLBI), part of the NIH. About the NIH ACTIV Initiative On April 17, 2020, the National Institutes of Health (NIH) announced the Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) public-private partnership to develop a coordinated research strategy for prioritizing and speeding development of the most promising treatments and vaccines.Coordinated by the Foundation for the National Institutes of Health (FNIH), ACTIV brings NIH together with its sibling agencies in the Department of Health and Human Services, including the Biomedical Advanced Research and Development Authority (BARDA), Centers for Disease Control and Prevention (CDC), and the U.S. Food and Drug Administration (FDA); other government agencies including the Department of Defense (DOD) and Department of Veterans Affairs (VA); The Operation; the European Medicines Agency (EMA); and representatives from academia, philanthropic organizations, and numerous biopharmaceutical companies. For more information about the ACTIV therapeutic trials, including ACTIV-4 Host Tissue, visit the ACTIV website: . About TRV027 TRV027 is a novel AT1 receptor selective agonist that is currently being investigated by multiple institutions as a potential treatment for acute lung injury contributing to ARDS and abnormal blood clotting in COVID-19 patients. It has previously been studied in 691 individuals, has a well-characterized pharmacokinetic profile, and has demonstrated efficacy, potency, and selectivity at the AT1 receptor in nonclinical studies. In previous clinical trials, there was a low dropout rate associated with TRV027, and no significant safety issues were reported. TRV027 is currently being evaluated in the REMAP-CAP COVID-19 ACE2 RAS Modulation Domain, an international, multi-site, randomized, Phase 2 / 3 adaptive clinical trial in hospitalized COVID-19 patients. In April 2021, the Company filed a non-provisional patent application and PCT application with the United States Patent and Trademark Office covering the use of TRV027 to treat ARDS and the prevention or treatment of abnormal clotting in COVID-19 patients. About Trevena Trevena, Inc. is a biopharmaceutical company focused on the development and commercialization of innovative medicines for patients with CNS disorders. The Company has one approved product in the United States, OLINVYK® (oliceridine) injection, indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. The Company’s novel pipeline is based on Nobel Prize winning research and includes four differentiated investigational drug candidates: TRV250 for the acute treatment of migraine, TRV734 for maintenance treatment of opioid use disorder, TRV045 for diabetic neuropathic pain and epilepsy, and TRV027 for acute respiratory distress syndrome and abnormal blood clotting in COVID-19 patients. 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 and trials 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: the status, timing, costs, results and interpretation of the Company’s clinical trials or any future trials of any of the Company’s investigational drug candidates; the uncertainties inherent in conducting clinical trials; expectations for regulatory interactions, submissions and approvals, including the Company’s assessment of the discussions with FDA, the timing of FDA’s decision on the oliceridine NDA; available funding ; uncertainties related to the Company’s intellectual property; uncertainties related to the ongoing COVID-19 pandemic, 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. For more information, please contact:Investor Contact:Dan FerryManaging DirectorLifeSci Advisors, LLCdaniel@lifesciadvisors.com(617) 430-7576 PR & Media Contact:Sasha BennettAssociate Vice PresidentClyde GroupSasha.Bennett@clydegroup.com(239) 248-3409

Colourised scanning electron micrograph of a cell (green) infected with SARS-CoV-2 virus particles (blue). Credit: NIAID / Flickr. TRV027 is an angiotensin II receptor type 1 (AT1 receptor) selective agonist and fights disruption within the renin-angiotensin-aldosterone system (RAAS) by attaching to and rebalancing AT1 receptor activation. It also hinders the damaging pathway that causes acute lung damage and abnormal blood clotting. Additionally, it stimulates the cellular pathway that targets reparative activities that enhance lung function and boost anti-inflammatory effects. Called ‘ACTIV-4d RAAS’, the multi-site, randomised, placebo-controlled trial has multiple treatment arms, each with 300 adult Covid-19 patients. Coordinated by the Vanderbilt University Medical Center (VUMC) in the US, ACTIV-4d RAAS is a part of the National Heart, Lung and Blood Institute of the NIH’s Collaborating Network of Networks for Evaluating Covid-19 and Therapeutic Strategies programme. The trial is assessing various therapies, including TRV027, that target the RAAS and will evaluate if its modulation could become a potential approach to prevent disease progression to critical illness, multiorgan failure or mortality in Covid-19 patients who are admitted to the hospital. It will analyse TRV027’s impact on recovery, use of supplemental oxygen, the requirement for mechanical ventilation and mortality. Trevena president and CEO Carrie Bourdow said: “The NIH’s ongoing ACTIV public-private partnership has facilitated the unprecedented development of cutting-edge vaccines and therapeutics to fight the Covid-19 pandemic. “Vanderbilt University Medical Center has emerged as a leader in Covid-19 research in the US, and I look forward to supporting their investigation of TRV027 as a potentially meaningful therapy for Covid-19 patients.” In April last year, the NIH announced the ACTIV public-private partnership for developing a research plan to prioritise and expedite the development of potential therapies and vaccines.