Status Epilepticus

Increase in visibility in its regulatory and commercialization prospects in the U.S. since latest interactions with the FDA Expectation to receive U.S. Emergency Use Authorization (EUA) for ZEPIZURE® in Q1 2025 Expectation to complete U.S. New Drug Application (NDA) for ZEPIZURE® in H1 2025 Reinforcement of supply chain [with addition of a second fill-and-finish CDMO] Reporting of a reduced Net loss of €8.5 million versus €11.2 million in 2022 Dijon, France April 2, 2024, 10:30am CET -- Crossject (ISIN: FR0011716265; Euronext: ALCJ), a specialty pharma company developing needle-free auto-injectors for emergency situations, announces progress on multiple fronts in its clinical development, registration and U.S. commercial strategy and reports its financial results for the year ending December 31, 2023. Patrick Alexandre, CEO of Crossject, announces: Crossject is approaching a number of important value inflection points, which have the potential to transform our company and deliver substantial shareholder value. Our $92 million contract with the Biomedical Advanced Research and Development Authority (BARDA) (up to $155 million if all options are exercised) is progressing. This contract, with the Department of Health and Human Services; Administration for Strategic Preparedness and Response; BARDA under contract number 75A50122C00031, includes up to $32 million for the advanced development of ZEPIZURE® through approval by the FDA for the treatment of status epilepticus seizures in adults and children over the age of 2. It also includes the procurement of $60 million of ZEPIZURE® to the U.S. Government once it has received Emergency Use Authorization (EUA) from the FDA. These proceeds will contribute in a timely fashion to the deployment of ZEPIZURE® in epilepsy markets. During recent interactions with the FDA, we have achieved better visibility on the next development steps for the U.S. regulatory pathway. We estimate that a response from FDA regarding the EUA will be received during Q1 2025. In parallel, we expect to H1 2025 for an NDA of ZEPIZURE®. We are firmly focused on the final development stages for epileptic crises, including an upcoming 505(b)(2) pivotal bioequivalence study, as part of the NDA that we anticipate to H1 2025. We are also working on activities related to its registration and pre-commercialization in the United States, since Crossject intends to retain U.S. commercial rights to ZEPIZURE®. We have been working in close collaboration with Syneos Health, a leading contract research, market access and commercialization services organization, which we engaged in January. Together, we are working with the aim to ensure a smooth and rapid launch of ZEPIZURE® upon receiving regulatory approval from the Food and Drug Administration (FDA). We intend to NDA application for the Status Epilepticus indication under FDA’s 505(b)(2) regulatory pathway.. This is a streamlined NDA process in which we can rely on investigations previously conducted by third parties for an FDA approved reference product, and where we will only need to demonstrate bioequivalence with such a product. In our upcoming pivotal study, we intend to replicate the comprehensive positive bioequivalence results already demonstrated in our precedent study released on 2 November 2022, which will be used for the EUA. In this randomized crossover study, ZEPIZURE® demonstrated bioequivalence to a predicate injectable marketed in Europe. Based on these and other data, we are confident that the ZENEO® platform will continue to demonstrate its ability to mimic intramuscular injections from traditional injectables with a high accuracy and low variability. These ZENEO features, now well validated, will be essential to limit development and regulatory risks. More importantly, we also expect them to drive market acceptance versus traditional injectables, and versus other delivery methods, including intranasals, which are known for their intrinsic transmucosal pharmacokinetic variability, compounding with the admnistration challenges customarily incurred during crises. Our market opportunity has been validated by the relative success of such intranasal products, promoted as “needle free”. We look forward to reaching the market with our first unique solution in epilepsy, that is dependable and addresses the limitations of currently marketed products. Our two main additional programs, ZENEO® Hydrocortisone and ZENEO® Adrenaline, are also progressing toward planned market authorization filings in 2025 and 2026 respectively. The supply chain organization, including our new partner Eurofins Scientific as fill-and-finish CDMO (Contract Development and Manufacturing Organization), was discussed with BARDA and the FDA. Although it has led to further delay, we firmly believe that, today, our level of automation will not only strengthen our supply chain but also further secure the anticipated volumes for all our programs. This combination of positive developments has served as a strong background for the continued strengthening of our balance-sheet, recently achieved through our €12 million financing with Heights Capital Management. As ZEPIZURE® progresses toward market authorizations, and as we also support our two main additional programs, we will continue to actively explore the best way to finance our maturing global operations throughout the rest of 2024. Philippe Monnot, CEO and one of the founders of Gemmes Venture, our reference shareholder, has confirmed his support : « With the recent evolutions in Crossject’s supply chain and the constructive interactions with the FDA we trust that the Company can market its revolutionary products; we renew our trust in the Company and its management. » I am grateful to you, our shareholders, for your unwavering attention and your continuing support of our efforts. Together, we have the opportunity to make a significant difference for patients and create value for our company. Financials for 2023 Key financial information as of December 31, 2023 In 2023, we continued the financing of the development ZEPIZURE® and of the rest of our pipeline and infrastructure through multiple sources: BARDA invoicing: $6.7 million were invoiced as reimbursements of research and development expenses incurred in 2023, versus $1.8 million in 2022; Invoicing to distributor: € 145 thousand were collected as upfront payment upon signing of the agreement with AFT Pharmaceuticals, Ltd; Research tax credit: €2.4 million were collected in 2023 versus €2.0 million in 2022. Real estate leaseback transaction : €4.7 million were raised through a sale and leaseback transaction for two of its buildings with leasing payments spread over the following 12 years; Borrowings: 8 million proceeds from loans contracted in 2022 were collected. Convertible Bonds: All outstanding convertible bonds had been converted as of 31/12/2023. In 2023, we accelerated our research and development and overall activities. As a result, we recorded a very substantial increase in operating income to €12.8 million, an increase of 32% over 2022. The table below summarizes our income statement for the years ending 31 December 2023 and 2022: € thousands, as of 31 December 2023 2022 Operating income 12 826 9 718 Operating expenses -25 126 -23 005 Purchase of raw materials and supplies -1 595 -498 Other purchases and external expenses -8 869 -8 116 Personal expenses -7 713 -7 424 Taxes and duties -267 -176 Depreciation, amortisation and provision -6 185 -6 358 Other expenses -494 -433 Operating profit/loss -12 300 -13 288 Financial income/expense -497 -319 Exceptional income/expense 1 463 228 Corporate tax 2 867 2 222 Net profit/loss -8 467 -11 157 The Operating expenses increased by 9% in 2023 over 2022, a very moderate rise in relation to the increase of our operating income. Such increase resulted from our advancing in the research and development of ZEPIZURE and of our other programs as well as from the initial steps in building our US team and operations. Other purchases and external expenses amounted to €8.9 million, compared with €8.1 million in 2022, as we have been maintaining the progress in our production work and third-party activities linked to the regulatory development of ZEPIZURE® as well as activities on other key programs in our pipeline. As of 31 December 2023, Crossject had approximately 111 employees, an 11% increase compared with 2022. Personnel expenses amounted to €7.7 million in 2023 compared to €7.4 million in 2022, the increase is due to these new recruitments in 2023. We reported an Operating loss of €12.3 million, compared with a loss of €13.3 million in 2022 with the relative stability reflecting our increased operating expenses and their partial offsetting by operating income. We recorded net financial expenses of €0.5 million for 2023, compared to an expense of €0.3 million for 2022. After taking into account an exceptional income of €1.5 million, provided primarily from the transaction of the real estate leaseback and a reversal of accounting provision, as well as the research tax credit for an amount of €2.9 million, we are reporting a Net loss for 2023 of €8.5 million versus a loss of €11.2 million in 2022. Treasury position As of 31 December 2023, we had a cash balance of €2.3 million. From the beginning of 2024 we have made it a priority to explore all types of financings to pursue our research and development and overall activities. As of 28 February 2024, we raised a first financing of up to €12 million from Heights Capital Management, in two tranches, with the first tranche of €7 million extended at closing. That tranche may be supplemented by a second tranche of a maximum amount of approximately €5 million on our initiative and subject to compliance with certain conditions. Based on our financial resources as of 31 March 2024 and taking into account ongoing historical relationships with our lenders and creditors, the Company is confident to be able to finance its business plan until September 2024. In 2024, the Company also intends to obtain material financings from its undisclosed European collaboration partner, for an amount of €0.5 million, €0.7 million from grants as well as from research tax credit payments related to the periods of 2023 and 2024. As the prospects for ZEPIZURE® improve and as we dedicate resources to the research and development of our two main additional ZENEO product candidates, ZENEO® Hydrocortisone and ZENEO® Adrenaline, we will continue to actively explore the best ways to finance our maturing global operations in equity, debt, public financings and other kinds of financings throughout 2024. Notable milestones in 2023 Non-dilutive financing Crossject completed a combined non-dilutive financial transaction of €14 million to accelerate the company's development. The transaction includes various loans granted by its long-standing banks (Caisse d'Epargne and BNP), Société Générale and BPI, with amortization periods ranging from 5 to 10 years and with nearly 85% of the total available. New licensing agreement on ZENEO® Midazolam epilepsy rescue therapy Crossject signed an Australia & New Zealand commercial agreement with AFT Pharmaceuticals for ZENEO® Midazolam, its innovative rescue therapy for epileptic seizures. AFT Pharmaceuticals is a particularly well-suited partner because of its strong regional presence and extensive experience with successful commercial launches. Commercialization agreement in northern Europe Under this agreement with an undisclosed strategic partner, Crossject will receive milestone payments of up to €1 million in total, upon marketing authorizations being granted in the partner’s territories. Crossject will manufacture and sell ZEPIZURE® to its strategic partner with a markup that is a share of the gross profit (defined as net sales minus cost of goods). Successful completion of European and U.S. audits Crossject's manufacturing sites in Dijon and Gray (France) passed an annual ISO certification audit, expanded their scope of certification by the French Health Agency, and received positive feedback after an audit by BARDA on compliance of manufacturing ZENEO® Midazolam for the U.S. market. Appointment of Daniel Teper as Director on the Supervisory Board With a PhD in Pharmacy from Paris-Saclay University and an MBA from INSEAD, Daniel Teper is a U.S.-based pharmaceuticals industry leader and entrepreneur with a compelling background spanning the fields of marketing, capital markets, strategy and development. hErOiSme early stage project The French Ministry of Armed Forces (Ministère des Armées) selected the project offered by a research consortium to develop a new molecule for rescue therapies for hemorrhagic shock treatment with ZENEO® auto-injector. Many civilian and military lives could be saved by promptly stabilizing the condition of a person suffering from hemorrhagic shocks. Crossject and IDD, its long-term regulatory partner, have officially joined this 3-year-long research program with a total budget of EUR 800,000. Initiation of coverage by ODDO-BHF In November 2023, ODDO-BHF analysts rated Crossject as “Outperform” with a price target of €7.10, citing the significant advantages associated with the company’s needle-free ZENEO® device. Significant improvement in Gaïa ESG rating Crossject’s new score of 73/100 is significantly up from 60 last year and 46 in 2021. Crossject's Gaïa rating, compiled by EthiFinance ESG Ratings, increased across all four themes: governance, social, environment and external stakeholders. There were particularly notable improvements in the ratings for environment and external stakeholders' performance. Events beyond the reporting period Convertible bond financing of up to €12 million The financing is in two tranches, from an entity managed by Heights Capital Management, in issued bonds convertible in new shares, with a conversion premium of 35%1, or repayable (in cash and/or stocks, according to the company’s options) over 36 months at a rate of 7%. Heights Capital Management, Inc. is an institutional investor specialized in financing growing companies. The financing is a sign of confidence in our industrial and market progress, particularly in North America. Engagement of Syneos Health for U.S. commercial launch of ZEPIZURE® Crossject engaged Syneos Health, a leading fully integrated biopharmaceutical solutions organization, to prepare for the commercial launch of ZEPIZURE® for epileptic seizures in the U.S. Under the agreement, Syneos Health will provide support in all pre-launch and launch activities for ZEPIZURE®. Syneos Health brings a strong U.S. presence and significant expertise in commercializing new therapies for Crossject. Gender equality score reaches 96/100 in 2024 This is the third successive year the score has been above 90%. The Gender Equality Index is a tool to measure the progress of gender equality in the EU and is assessed by a score from 1 to 100, with 100 meaning full equality between women and men. About Crossject Crossject SA (Euronext: ALCJ; ) is an emerging specialty pharma company. It is in advanced regulatory development for ZEPIZURE®, an epileptic rescue therapy, for which it has a $60 million contract with the U.S. Biomedical Advanced Research and Development Authority (BARDA). ZEPIZURE® is based on the Company’s award-winning needle-free autoinjector ZENEO®, designed to enable patients and untrained caregivers to easily and instantly deliver emergency medication via intramuscular injection on bare skin or even through clothing. The Company’s other products in development include rescue therapies for allergic shocks, adrenal insufficiencies, opioid overdose and asthma attacks. For further information, please contact: Investors Natasha Drapeau Cohesion Bureau +41 76 823 75 27 natasha.drapeau@cohesionbureau.com Media Sophie Baumont Cohesion Bureau +33 6 27 74 74 49 sophie.baumont@cohesionbureau.com Attachment Crossject_PR_FinResults_EN

TRV045, novel S1P receptor modulator for chronic pain and epilepsy, advances toward important milestones in both non-clinical and clinical studies Company announces reduction of OLINVYK commercial support and review of alternatives for OLINVYK CHESTERBROOK, Pa., April 01, 2024 (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 reported its financial results for the fourth quarter ended December 31, 2023 and provided an overview of its recent operational highlights. “Despite OLINVYK’s differentiated profile, the hospital environment continues to be challenging. Given performance to date, we are reducing commercial support and reviewing alternatives for OLINVYK to preserve capital,” said Carrie Bourdow, President and CEO of Trevena. “We will focus our resources on the continued development of TRV045 and we are pleased with the progress we have made toward potential Phase 2 readiness.” Fourth Quarter 2023 and Recent Corporate Highlights Company to focus resources on TRV045 development, reducing OLINVYK commercial support to preserve capital. The Company announced today that it plans to focus its resources on the continued development of TRV045, with several near-term milestones expected. Despite OLINVYK’s differentiated profile for patients and demonstrated savings to hospitals, based on its sales performance to date and other factors, the Company has reduced commercial support of OLINVYK to help preserve capital. OLINVYK will remain available for purchase by customers, who can continue to order the product through their normal channels. The Company will continue to comply with all regulatory requirements, including post-marketing surveillance and reporting obligations. The Company is conducting a review of strategic alternatives for OLINVYK, which may include a sale, license or divestiture of OLINVYK. There can be no assurance regarding the schedule for completion of the strategic review process, that this strategic review process will result in the Company pursuing any transaction or that any transaction, if pursued, will be completed.Previously, the Company reported data from two positive proof-of-concept studies demonstrating CNS target engagement for TRV045 and supporting further development in patients in neuropathic pain and epilepsy. In a target engagement POC study, TRV045 demonstrated statistically significant analgesic effect in a capsaicin-induced model of neuropathic pain. In the second study, a TMS POC study provided statistically significant evidence of CNS activity of TRV045 through day 4 as measured by resting-state EEG power spectral analysis. In a review of safety and tolerability across both studies, TRV045 was well tolerated with results generally consistent with prior first-in-human studies. There were no drug-related adverse events and no serious adverse events reported in the studies. Importantly, TRV045-treated subjects did not show any drug-related lymphopenia, bradycardia or change in blood pressure which have been reported with other S1P modulators.TRV045 progresses towards Phase 2 readiness with advances in formulation development and toxicology studies. The Company has successfully identified an optimized formulation of TRV045, which it believes is suitable for late-stage clinical studies and, if approved, commercialization. The modest food effect observed with the initial POC formulation has not been seen with the new formulation. TRV045 continues to demonstrate a favorable tolerability profile with the optimized formulation. In addition, the live phase of the reproductive toxicology and sub-chronic toxicology studies have been completed, with final reports expected in 2H 2024. The Company currently has an IND for TRV045 in diabetic neuropathic pain and may submit an IND application for TRV045 focused on epilepsy and seizure disorders.NIH-Supported Epilepsy Therapy Screening Program (ETSP) continues to study TRV045 as a potential disease-modifying agent for the prevention of seizures. Previous nonclinical studies indicate that TRV045’s action on astrocytes may modify their inflammatory signaling with a net action to potentially reduce neuroinflammation and thereby may play a role in how seizures develop (epileptogenesis). The NIH continues to study TRV045 for the prevention of seizures and is currently conducting a nonclinical study in a kainic acid-induced spontaneously-recurring seizure model. Following an induction phase of status epilepticus, rats are randomized and prophylactically treated with either TRV045 15mg/kg or vehicle, dosed twice daily for seven days starting one hour after cessation of status epilepticus. The Company expects results from the studies to be available by mid-2024. Financial Results for Fourth Quarter 2023For the fourth quarter of 2023, the Company reported a net loss attributable to common stockholders of $16.5 million, or $1.06 per share, compared to $7.0 million, or $0.73 per share in the fourth quarter of 2022. For the full year ended December 31, 2023, net loss attributable to common stockholders was $40.3 million, or $3.16 per share, compared to $53.7 million, or $7.59 per share. Cash and cash equivalents were $33.0 million as of December 31, 2023. 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 three differentiated investigational drug candidates: TRV045 for diabetic neuropathic pain and epilepsy, TRV250 for the acute treatment of migraine and TRV734 for maintenance treatment of opioid use disorder. For more information, please visit www.Trevena.com About TRV045 TRV045 is a novel, highly selective sphingosine-1-phosphate subtype 1 (S1P1) receptor modulator being developed as a potential treatment for acute and chronic neuropathic pain secondary to diabetic peripheral neuropathy. Through a collaboration with the National Institutes of Health, Trevena is also exploring TRV045 as a potential treatment for epilepsy. S1P receptors are located throughout the body, including the central nervous system, where they are believed to play a role in modulating neurotransmission and membrane excitability. Trevena's discovery efforts have identified a family of compounds that are highly selective for the S1P1 receptor. TRV045 reversed thermal hyperalgesia, a measure of neuropathic pain, in nonclinical models of diabetic peripheral neuropathy and chemotherapy-induced peripheral neuropathy. TRV045 was not associated with lymphopenia and produced no changes in blood pressure, heart rate, or respiratory function at or above pharmacologically active doses in nonclinical studies. TRV045 is an investigational product and is not yet approved by the FDA. Subjects in both studies referenced in this press release were enrolled outside of the United States, and the studies were not conducted under the Investigational New Drug Application for TRV045. About OLINVYK® (oliceridine) injection OLINVYK is a new chemical entity approved by the FDA in August 2020. OLINVYK contains oliceridine, an opioid, which is a Schedule II controlled substance with a high potential for abuse similar to other opioids. It is indicated 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 available in 1 mg/1 mL and 2 mg/2 mL single-dose vials, and a 30 mg/30 mL single-patient-use vial for patient-controlled analgesia (PCA). Approved PCA doses are 0.35 mg and 0.5 mg and doses greater than 3 mg should not be administered. The cumulative daily dose should not exceed 27 mg. Please see Important Safety Information, including the BOXED WARNING, and full prescribing information at www.OLINVYK.com. IMPORTANT SAFETY INFORMATION WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF OLINVYK Addiction, Abuse, and Misuse Because the use of OLINVYK exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of OLINVYK, especially during initiation or following a dosage increase. To reduce the risk of respiratory depression, proper dosing and titration of OLINVYK are essential. Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of OLINVYK and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate. Neonatal Opioid Withdrawal Syndrome If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery. INDICATIONS AND USAGE OLINVYK is an opioid agonist indicated in adults for the management of acute pain severe enough to require an intravenous opioid analgesic and for whom alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse with opioids, which can occur at any dosage or duration, reserve OLINVYK for use in patients for whom alternative treatment options [e.g., non-opioid analgesics or opioid combination products]: Have not been tolerated or are not expected to be tolerated.Have not provided adequate analgesia or are not expected to provide adequate analgesia. The cumulative total daily dose should not exceed 27 mg. CONTRAINDICATIONS OLINVYK is contraindicated in patients with: Significant respiratory depressionAcute or severe bronchial asthma in an unmonitored setting or in absence of resuscitative equipmentKnown or suspected gastrointestinal obstruction, including paralytic ileusKnown hypersensitivity to oliceridine (e.g. anaphylaxis) WARNINGS AND PRECAUTIONS OLINVYK contains oliceridine, a Schedule II controlled substance, that exposes users to the risks of addiction, abuse, and misuse. Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed OLINVYK. Assess risk, counsel, and monitor all patients receiving opioids.Serious, life-threatening respiratory depression has been reported with the use of opioids, even when used as recommended, especially in patients with chronic pulmonary disease, or in elderly, cachectic and debilitated patients. The risk is greatest during initiation of OLINVYK therapy, following a dose increase, or when used with other drugs that depress respiration. Proper dosing of OLINVYK is essential, especially when converting patients from another opioid product to avoid overdose. Management of respiratory depression may include close observation, supportive measures, and use of opioid antagonists, depending on the patient’s clinical status.Opioids can cause sleep-related breathing disorders including central sleep apnea (CSA) and sleep-related hypoxemia with risk increasing in a dose-dependent fashion. In patients who present with CSA, consider decreasing the dose of opioid using best practices for opioid taper.Profound sedation, respiratory depression, coma, and death may result from the concomitant use of OLINVYK with benzodiazepines and/or other CNS depressants (e.g., non-benzodiazepine sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, other opioids, or alcohol). Because of these risks, reserve concomitant prescribing of these drugs for use in patients for whom alternative treatment options are inadequate, prescribe the lowest effective dose, and minimize the duration.Use of OLINVYK for an extended period of time during pregnancy can result in withdrawal in the neonate that may be life-threatening. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available.OLINVYK was shown to have mild QTc interval prolongation in thorough QT studies where patients were dosed up to 27 mg. Total cumulative daily doses exceeding 27 mg per day were not studied and may increase the risk for QTc interval prolongation. Therefore, the cumulative total daily dose of OLINVYK should not exceed 27 mg.Increased plasma concentrations of OLINVYK may occur in patients with decreased Cytochrome P450 (CYP) 2D6 function or normal metabolizers taking moderate or strong CYP2D6 inhibitors; also in patients taking a moderate or strong CYP3A4 inhibitor, in patients with decreased CYP2D6 function who are also receiving a moderate or strong CYP3A4 inhibitor, or with discontinuation of a CYP3A4 inducer. These patients may require less frequent dosing and should be closely monitored for respiratory depression and sedation at frequent intervals. Concomitant use of OLINVYK with CYP3A4 inducers or discontinuation of a moderate or strong CYP3A4 inhibitor can lower the expected concentration, which may decrease efficacy, and may require supplemental doses.Opioid-Induced Hyperalgesia (OIH) occurs when an opioid analgesic paradoxically causes an increase in pain, or an increase in sensitivity to pain. This differs from tolerance where increasing doses are required to maintain the desired effect. Symptoms of OIH include, but may not be limited to, increased levels of pain upon dose increase, decreased levels of pain upon dose decrease, or pain from ordinarily non-painful stimuli (allodynia). These symptoms may suggest OIH only if there is no evidence of disease progression, opioid tolerance, withdrawal, or addictive behavior. If OIH is suspected, carefully consider appropriately decreasing the dose of the current opioid analgesic or opioid rotation.Cases of adrenal insufficiency have been reported with opioid use (usually greater than one month). Presentation and symptoms may be nonspecific and include nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If confirmed, treat with physiologic replacement doses of corticosteroids and wean patient from the opioid.OLINVYK may cause severe hypotension, including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics). Monitor these patients for signs of hypotension. In patients with circulatory shock, avoid the use of OLINVYK as it may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of OLINVYK in patients with impaired consciousness or coma. OLINVYK should be used with caution in patients who may be susceptible to the intracranial effects of CO2 retention, such as those with evidence of increased intracranial pressure or brain tumors, as a reduction in respiratory drive and the resultant CO2 retention can further increase intracranial pressure. Monitor such patients for signs of sedation and respiratory depression, particularly when initiating therapy.As with all opioids, OLINVYK may cause spasm of the sphincter of Oddi, and may cause increases in serum amylase. Monitor patients with biliary tract disease, including acute pancreatitis, for worsening symptoms.OLINVYK may increase the frequency of seizures in patients with seizure disorders and may increase the risk of seizures in vulnerable patients. Monitor patients with a history of seizure disorders for worsened seizure control.Do not abruptly discontinue OLINVYK in a patient physically dependent on opioids. Gradually taper the dosage to avoid a withdrawal syndrome and return of pain. Avoid the use of mixed agonist/antagonist (e.g., pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving OLINVYK, as they may reduce the analgesic effect and/or precipitate withdrawal symptoms.OLINVYK may impair the mental or physical abilities needed to perform potentially hazardous activities such as driving a car or operating machinery.Although self-administration of opioids by patient-controlled analgesia (PCA) may allow each patient to individually titrate to an acceptable level of analgesia, PCA administration has resulted in adverse outcomes and episodes of respiratory depression. Health care providers and family members monitoring patients receiving PCA analgesia should be instructed in the need for appropriate monitoring for excessive sedation, respiratory depression, or other adverse effects of opioid medications. ADVERSE REACTIONS Adverse reactions are described in greater detail in the Prescribing Information. The most common (incidence ≥10%) adverse reactions in Phase 3 controlled clinical trials were nausea, vomiting, dizziness, headache, constipation, pruritus, and hypoxia. MEDICAL INFORMATION For medical inquiries or to report an adverse event, other safety-related information or product complaints for a company product, please contact the Trevena Medical Information Contact Center at 1-844-465-4686 or email MedInfo@Trevena.com. You are encouraged to report suspected adverse events of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088. PLEASE see www.OLINVYK.com for full prescribing information including BOXED warning and important safety information 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 expectations surrounding the continued advancement of the Company’s product pipeline; the potential safety and efficacy of the Company’s product candidates and their regulatory and clinical development; the Company’s intention to pursue strategic alternatives for OLINVYK and the ability of any such strategic alternative to provide shareholder value; the expected financial and operational impacts of the Company’s decision to reduce commercial support for OLINVYK; 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 discussions with FDA; available funding; uncertainties related to the Company’s intellectual property; uncertainties related to other matters that could affect the availability or commercial potential of the Company’s therapeutic candidates and approved product; 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 Company Contact: Bob YoderSVP and Chief Business OfficerTrevena, Inc.(610) 354-8840 TREVENA, INC. Condensed Statements of Operations (Unaudited, in thousands except share and per share data) Three Months Ended Dec 31, Year Ended Dec 31, 2023 2022 2023 2022 Product revenue $(81) $- $(54) $(438) License revenue - - 3,179 20 Total revenue (81) - 3,125 (418) Operating expenses: Cost of goods sold 1,281 228 1,670 3,018 Selling, general and administrative 4,610 5,723 20,410 34,728 Research and development 4,174 3,396 16,333 18,211 Total operating expenses 10,065 9,347 38,413 55,957 Loss from operations (10,146) (9,347) (35,288) (56,375) Other income (6,381) 2,342 (5,001) 2,705 Loss before income tax expense (16,527) (7,005) (40,289) (53,670) Unrealized gain on marketable securities - - - 1 Net loss $(16,527) $(7,005) $(40,289) $(53,669) Per share information: Net loss per share of common stock, basic and diluted ($1.06) ($0.73) ($3.16) ($7.59) Weighted average shares outstanding, basic and diluted 15,649,160 9,594,072 12,735,010 7,072,362 TREVENA, INC.Condensed Balance Sheets(Unaudited, in thousands) December 31, 2023December 31, 2022Assets Current assets: Cash and cash equivalents $32,975 $38,320 Inventories - 906 Prepaid expenses and other current assets 2,230 1,782 Total current assets 35,205 41,008 Restricted cash 540 1,960 Property and equipment, net 1,195 1,488 Right-of-use lease assets 3,665 4,224 Total assets $40,605 $48,680 Liabilities and stockholders’ equity Current liabilities: Accounts payable, net $2,303 $2,372 Accrued expenses and other current liabilities 4,239 5,461 Current portion of lease liabilities 1,012 899 Total current liabilities 7,554 8,732 Loans payable, net 30,809 13,430 Leases, net of current portion 4,424 5,436 Warrant liability 5,475 5,483 Total liabilities 48,262 33,081 Common stock 17 8 Additional paid-in capital 580,387 563,362 Accumulated deficit (588,061) (547,772)Accumulated other comprehensive income (loss) - 1 Total stockholders’ equity (7,657) 15,599 Total liabilities and stockholders’ equity $40,605 $48,680

TOKYO and CAMBRIDGE, Mass., March 31, 2024 /PRNewswire/ -- Eisai Co., Ltd. (Headquarters: Tokyo, CEO: Haruo Naito, "Eisai") and Biogen Inc. (Nasdaq: BIIB, Corporate headquarters: Cambridge, Massachusetts, CEO: Christopher A. Viehbacher, "Biogen") announced today that Eisai submitted to the U.S. Food and Drug Administration (FDA) a Supplemental Biologics License Application (sBLA) for monthly lecanemab-irmb (U.S. brand name: LEQEMBI®) intravenous (IV) maintenance dosing. LEQEMBI is indicated for the treatment of Alzheimer's disease (AD) in patients with mild cognitive impairment or mild dementia stage of disease (collectively referred to as early AD). As part of the monthly IV maintenance regimen, the patients who have completed the biweekly IV initiation phase, exact period under discussion with the FDA, would receive a monthly IV dose that maintains effective drug concentration to sustain the clearance of highly toxic protofibrils* which can continue to cause neuronal injury even after the amyloid-beta (Aβ) plaque has been cleared from the brain. The sBLA is based on modeling of observed data from the Phase 2 study (Study 201) and its open-label extension (OLE) as well as Clarity AD study (Study 301) and its OLE study. Eisai had aimed to submit a Biologics License Application (BLA) for weekly maintenance therapy using subcutaneous (SC) administration in March 2024. To respond to the FDA's recent requirement of additional three-month immunogenicity data at the proposed maintenance dose of 360 mg weekly, Eisai planned to initiate a rolling BLA for lecanemab SC maintenance in March 2024, under the existing Fast Track and Breakthrough Therapy designations. However, Eisai was recently informed by the FDA that a Fast Track designation specific for the SC formulation is needed to receive rolling review. Following the guidance, Eisai submitted a request for Fast Track designation for the SC formulation and will initiate a rolling submission should the FDA grant this designation. The Fast Track designation will be determined within 60 days from the March 2024 submission. AD is an ongoing neurotoxic process that begins before and continues after plaque deposition. There is an urgency to treat early AD because early and ongoing treatment can slow the progression of AD and continuing treatment may prolong the benefit even after plaque is cleared from the brain. The earlier Mild Cognitive Impairment (MCI) due to AD and mild AD dementia are diagnosed and treated, the greater the opportunity for the patient to benefit. Continued maintenance dosing is intended to maintain the clinical and biomarker benefits with a dosing regimen that may be more convenient for some patients and their care partners. LEQEMBI is now approved in the U.S., Japan and China, and applications have been submitted for review in the European Union, Australia, Brazil, Canada, Hong Kong, Great Britain, India, Israel, Russia, Saudi Arabia, South Korea, Taiwan, Singapore, and Switzerland. Eisai serves as the lead for lecanemab's development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority. * Protofibrils are believed to contribute to the brain injury that occurs with AD and are considered to be the most toxic form of Aβ, having a primary role in the cognitive decline associated with this progressive, debilitating condition.1 Protofibrils cause injury to neurons in the brain, which in turn, can negatively impact cognitive function via multiple mechanisms, not only increasing the development of insoluble Aβ plaques but also increasing direct damage to brain cell membranes and the connections that transmit signals between nerve cells or nerve cells and other cells. It is believed the reduction of protofibrils may prevent the progression of AD by reducing damage to neurons in the brain and cognitive dysfunction. 2 U.S. INDICATION AND IMPORTANT SAFETY INFORMATION LEQEMBI (lecanemab-irmb) 100 mg/ml injection for intravenous (IV) use is indicated for the treatment of Alzheimer's disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. CONTRAINDICATION LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI. Reactions have included angioedema and anaphylaxis. WARNINGS AND PRECAUTIONS Amyloid Related Imaging Abnormalities LEQEMBI can cause ARIA-E and ARIA-H. ARIA-E can be observed on MRI as brain edema or sulcal effusions, and ARIA-H as microhemorrhage and superficial siderosis. ARIA can occur spontaneously in patients with Alzheimer's disease. ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E. ARIA-H and ARIA-E can occur together. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. Reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA usually resolve over time. ARIA Monitoring and Dose Management Guidelines Obtain recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. Obtain an MRI prior to the 5th, 7th and 14th infusions. Recommendations for dosing in patients with ARIA-E and ARIA-H depend on clinical symptoms and radiographic severity. Depending on ARIA severity, use clinical judgment in considering whether to continue dosing, temporarily discontinue treatment, or permanently discontinue LEQEMBI. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI if indicated. If ARIA is observed on MRI, careful clinical evaluation should be performed prior to continuing treatment. There is no experience in patients who continued dosing through symptomatic ARIA-E or through asymptomatic, but radiographically severe, ARIA-E. There is limited experience in patients who continued dosing through asymptomatic but radiographically mild to moderate ARIA-E. There are limited data in dosing patients who experienced recurrent ARIA-E. Incidence of ARIA In Study 2, symptomatic ARIA occurred in 3% (29/898) of LEQEMBI-treated patients. Serious symptoms associated with ARIA were reported in 0.7% (6/898) of patients treated with LEQEMBI. Clinical symptoms associated with ARIA resolved in 79% (23/29) of patients during the period of observation. Including asymptomatic radiographic events, ARIA was observed in LEQEMBI: 21% (191/898); placebo: 9% (84/897). ARIA-E was observed in LEQEMBI: 13% (113/898); placebo: 2% (15/897). ARIA-H was observed in LEQEMBI: 17% (152/898); placebo: 9% (80/897). There was no increase in isolated ARIA-H for LEQEMBI vs placebo. ApoE ε4 Carrier Status and Risk of ARIA In Study 2, 16% (141/898) of patients in the LEQEMBI arm were ApoE ε4 homozygotes, 53% (479/898) were heterozygotes, and 31% (278/898) were noncarriers. The incidence of ARIA was higher in ApoE ε4 homozygotes (LEQEMBI: 45%; placebo: 22%) than in heterozygotes (LEQEMBI: 19%; placebo: 9%) and noncarriers (LEQEMBI: 13%; placebo: 4%). Among patients treated with LEQEMBI, symptomatic ARIA-E occurred in 9% of ApoE ε4 homozygotes compared with 2% of heterozygotes and 1% noncarriers. Serious events of ARIA occurred in 3% of ApoE ε4 homozygotes, and approximately 1% of heterozygotes and noncarriers. The recommendations on management of ARIA do not differ between ApoE ε4 carriers and noncarriers. Radiographic Findings The majority of ARIA-E radiographic events occurred early in treatment (within the first 7 doses), although ARIA can occur at any time and patients can have more than 1 episode. The maximum radiographic severity of ARIA-E in patients treated with LEQEMBI was mild in 4% (37/898), moderate in 7% (66/898), and severe in 1% (9/898). Resolution on MRI occurred in 52% of ARIA-E patients by 12 weeks, 81% by 17 weeks, and 100% overall after detection. The maximum radiographic severity of ARIA-H microhemorrhage in LEQEMBI-treated patients was mild in 9% (79/898), moderate in 2% (19/898), and severe in 3% (28/898) of patients; superficial siderosis was mild in 4% (38/898), moderate in 1% (8/898), and severe in 0.4% (4/898). Among LEQEMBI-treated patients, the rate of severe radiographic ARIA-E was highest in ApoE ε4 homozygotes 5% (7/141), compared to heterozygotes 0.4% (2/479) or noncarriers 0% (0/278). Among LEQEMBI-treated patients, the rate of severe radiographic ARIA-H was highest in ApoE ε4 homozygotes 13.5% (19/141), compared to heterozygotes 2.1% (10/479) or noncarriers 1.1% (3/278). Intracerebral Hemorrhage Intracerebral hemorrhage >1 cm in diameter was reported in 0.7% (6/898) of patients in Study 2 after treatment with LEQEMBI compared to 0.1% (1/897) on placebo. Fatal events of intracerebral hemorrhage in patients taking LEQEMBI have been reported. Concomitant Antithrombotic Medication: In Study 2, baseline use of antithrombotic medication (aspirin, other antiplatelets, or anticoagulants) was allowed if the patient was on a stable dose. The majority of exposures to antithrombotic medications were to aspirin. Antithrombotic medications did not increase the risk of ARIA with LEQEMBI. The incidence of intracerebral hemorrhage was 0.9% (3/328 patients) in patients taking LEQEMBI with a concomitant antithrombotic medication at the time of the event compared to 0.6% (3/545 patients) in those who did not receive an antithrombotic. Patients taking LEQEMBI with an anticoagulant alone or combined with an antiplatelet medication or aspirin had an incidence of intracerebral hemorrhage of 2.5% (2/79 patients) compared to none in patients who received placebo. Because intracerebral hemorrhages >1 cm in diameter have been observed in patients taking LEQEMBI, additional caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g., tissue plasminogen activator) to a patient already being treated with LEQEMBI. Other Risk Factors for Intracerebral Hemorrhage: Patients were excluded from enrollment in Study 2 for findings on neuroimaging that indicated an increased risk for intracerebral hemorrhage. These included findings suggestive of cerebral amyloid angiopathy (prior cerebral hemorrhage >1 cm in greatest diameter, >4 microhemorrhages, superficial siderosis, vasogenic edema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of intracerebral hemorrhage. The presence of an ApoE ε4 allele is also associated with cerebral amyloid angiopathy, which has an increased risk for intracerebral hemorrhage. Caution should be exercised when considering the use of LEQEMBI in patients with factors that indicate an increased risk for intracerebral hemorrhage and in particular for patients who need to be on anticoagulant therapy. Hypersensitivity Reactions Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred in LEQEMBI-treated patients. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction, and initiate appropriate therapy. Infusion-Related Reactions In Study 2, infusion-related reactions were observed in LEQEMBI: 26% (237/898); placebo: 7% (66/897), and the majority of cases in LEQEMBI-treated patients (75%, 178/237) occurred with the first infusion. Infusion-related reactions were mostly mild (69%) or moderate (28%) in severity. Infusion-related reactions resulted in discontinuations in 1% (12/898) of LEQEMBI-treated patients. Symptoms of infusion-related reactions included fever and flu-like symptoms (chills, generalized aches, feeling shaky, and joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation. In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions may be considered. ADVERSE REACTIONS In Study 2, the most common adverse reactions leading to discontinuation of LEQEMBI was ARIA-H microhemorrhages that led to discontinuation in 2% (15/898) of patients treated with LEQEMBI compared to <1% (1/897) of patients on placebo. In Study 2, the most common adverse reactions reported in ≥5% of patients treated with LEQEMBI (N=898) and ≥2% higher than placebo (N=897) were infusion-related reactions (LEQEMBI: 26%; placebo: 7%), ARIA-H (LEQEMBI: 14%; placebo: 8%), ARIA-E (LEQEMBI: 13%; placebo: 2%), headache (LEQEMBI: 11%; placebo: 8%), superficial siderosis of central nervous system (LEQEMBI: 6%; placebo: 3%), rash (LEQEMBI: 6%; placebo: 4%), and nausea/vomiting (LEQEMBI: 6%; placebo: 4%). Please see full Prescribing Information f or LEQEMBI, including Boxed WARNING. Notes to Editors 1. About lecanemab (Leqembi®) Lecanemab is the result of a strategic research alliance between Eisai and BioArctic. It is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble (protofibril) and insoluble forms of amyloid-beta (Aβ).3 Lecanemab is approved in the U.S.,4 Japan,5 and China.6 In the U.S., Japan and China, the indications are as follows: U.S.: For the treatment of Alzheimer's disease (AD). It should be initiated in patients with mild cognitive impairment (MCI) or mild dementia stage of disease.4 Japan: For slowing progression of MCI and mild dementia due to AD.5 China: For the treatment of MCI due to AD and mild AD dementia.6 LEQEMBI's FDA approval was based on Phase 3 data from Eisai's, global Clarity AD clinical trial, in which it met its primary endpoint and all key secondary endpoints with statistically significant results.7 The primary endpoint was the global cognitive and functional scale, Clinical Dementia Rating Sum of Boxes (CDR-SB). In the Clarity AD clinical trial, treatment with lecanemab reduced clinical decline on CDR-SB by 27% at 18 months compared to placebo.7 The mean CDR-SB score at baseline was approximately 3.2 in both groups. The adjusted least-squares mean change from baseline at 18 months was 1.21 with lecanemab and 1.66 with placebo (difference, −0.45; 95% confidence interval [CI], −0.67 to −0.23; P<0.001).7 In addition, the secondary endpoint from the AD Cooperative Study-Activities of Daily Living Scale for Mild Cognitive Impairment (ADCS-MCI-ADL), which measures information provided by people caring for patients with AD, noted a statistically significant benefit of 37% compared to placebo.7 The adjusted mean change from baseline at 18 months in the ADCS-MCI-ADL score was −3.5 in the lecanemab group and −5.5 in the placebo group (difference, 2.0; 95% CI, 1.2 to 2.8; P<0.001).7 The ADCS MCI-ADL assesses the ability of patients to function independently, including being able to dress, feed themselves and participate in community activities. The most common adverse events (>10%) in the lecanemab group were infusion reactions, ARIA-H (combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis), ARIA-E (edema/effusion), headache, and fall.7 Eisai has also submitted applications for approval of lecanemab in 14 countries and regions, including the European Union (EU). 2. About the Collaboration between Eisai and Biogen for AD Eisai and Biogen have been collaborating on the joint development and commercialization of AD treatments since 2014. Eisai serves as the lead of lecanemab development and regulatory submissions globally with both companies co-commercializing and co-promoting the product and Eisai having final decision-making authority. 3. About the Collaboration between Eisai and BioArctic for AD Since 2005, Eisai and BioArctic have had a long-term collaboration regarding the development and commercialization of AD treatments. Eisai obtained the global rights to study, develop, manufacture and market lecanemab for the treatment of AD pursuant to an agreement with BioArctic in December 2007. The development and commercialization agreement on the antibody lecanemab back-up was signed in May 2015. 4. About Eisai Co., Ltd. Eisai's Corporate Concept is "to give first thought to patients and people in the daily living domain, and to increase the benefits that health care provides." Under this Concept (also known as human health care (hhc) Concept), we aim to effectively achieve social good in the form of relieving anxiety over health and reducing health disparities. With a global network of R&D facilities, manufacturing sites and marketing subsidiaries, we strive to create and deliver innovative products to target diseases with high unmet medical needs, with a particular focus in our strategic areas of Neurology and Oncology. In addition, we demonstrate our commitment to the elimination of neglected tropical diseases (NTDs), which is a target (3.3) of the United Nations Sustainable Development Goals (SDGs), by working on various activities together with global partners. For more information about Eisai, please visit (for global headquarters: Eisai Co., Ltd.), and connect with us on X, LinkedIn and Facebook. The website and social media channels are intended for audiences outside of the UK and Europe. For audiences based in the UK and Europe, please visit and Eisai EMEA LinkedIn. 5. About Biogen Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patient's lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. The company routinely posts information that may be important to investors on its website at . Follow Biogen on social media – Facebook, LinkedIn, X, YouTube. Biogen Safe Harbor This news release contains forward-looking statements, about the potential clinical effects of lecanemab; the potential benefits, safety and efficacy of LEQEMBI; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Alzheimer's disease; the anticipated benefits and potential of Biogen's collaboration arrangements with Eisai; the potential of Biogen's commercial business and pipeline programs, including LEQEMBI; and risks and uncertainties associated with drug development and commercialization. These statements may be identified by words such as "aim," "anticipate," "believe," "could," "estimate," "expect," "forecast," "intend," "may," "plan," "possible," "potential," "will," "would" and other words and terms of similar meaning. Drug development and commercialization involve a high degree of risk, and only a small number of research and development programs result in commercialization of a product. Results in early-stage clinical studies may not be indicative of full results or results from later stage or larger scale clinical studies and do not ensure regulatory approval. You should not place undue reliance on these statements. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including without limitation unexpected concerns that may arise from additional data, analysis or results obtained during clinical studies; the occurrence of adverse safety events; risks of unexpected costs or delays; the risk of other unexpected hurdles; regulatory submissions may take longer or be more difficult to complete than expected; regulatory authorities may require additional information or further studies, or may fail or refuse to approve or may delay approval of Biogen's drug candidates, including lecanemab; actual timing and content of submissions to and decisions made by the regulatory authorities regarding lecanemab; uncertainty of success in the development and potential commercialization of lecanemab; failure to protect and enforce Biogen's data, intellectual property and other proprietary rights and uncertainties relating to intellectual property claims and challenges; product liability claims; and third party collaboration risks, results of operations and financial condition. The foregoing sets forth many, but not all, of the factors that could cause actual results to differ from Biogen's expectations in any forward-looking statement. Investors should consider this cautionary statement as well as the risk factors identified in Biogen's most recent annual or quarterly report and in other reports Biogen has filed with the U.S. Securities and Exchange Commission. These statements speak only as of the date of this news release. Biogen does not undertake any obligation to publicly update any forward-looking statements. References Amin L, Harris DA. Aβ receptors specifically recognize molecular features displayed by fibril ends and neurotoxic oligomers. Nat Commun. 2021;12:3451. doi:10.1038/s41467-021-23507-z Ono K, Tsuji M. Protofibrils of Amyloid-β are Important Targets of a Disease-Modifying Approach for Alzheimer's Disease. Int J Mol Sci. 2020;21(3):952. doi: 10.3390/ijms21030952. PMID: 32023927; PMCID: PMC7037706. LEQEMBI. Prescribing information. Eisai Inc. 2023. US Food and Drug Administration. FDA Grants Accelerated Approval for Alzheimer's Disease Treatment. Available at: . Last accessed: March 2024. Eisai Global. 2023. "LEQEMBI® Intravenous Infusion" (Lecanemab) Approved for the Treatment of Alzheimer's Disease in Japan Available at: . Last accessed: March 2024. Eisai Global. 2024. "LEQEMBI®" (Lecanemab) Approved for the Treatment of Alzheimer's Disease in China. Available at: . Last accessed: March 2024. van Dyck, H., et al. Lecanemab in Early Alzheimer's Disease. New England Journal of Medicine. 2023;388:9-21. . SOURCE Eisai Inc.