Oligohydramnios

BIZENGRI® is the first and only FDA-approved therapy specifically for patients with advanced unresectable or metastatic pancreatic adenocarcinoma or non-small cell lung cancer (NSCLC) who harbor NRG1 gene fusions1 NRG1 gene fusions are best detected by tissue-based RNA next generation sequencing (NGS)3 LEXINGTON, Mass., Feb. 5, 2025 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company announced today that the New England Journal of Medicine (NEJM) published results of the 204-patient, global, multicenter, single-arm, Phase 2 clinical trial of zenocutuzumab-zbco (BIZENGRI®) (eNRGy trial; NCT02912949).2 The eNRGy trial evaluated overall response rate to zenocutuzumab-zbco in patients with NRG1 gene fusions across multiple tumor types. Responses by tumor type and safety data are detailed in the NEJM manuscript. Continue Reading "Zenocutuzumab helps fill an important need for patients with advanced pancreatic cancer and NSCLC with NRG1 gene fusions," said Alison Schram M.D., an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, a principal investigator for the eNRGy trial, and lead author on the NEJM manuscript. "The overall response rate and durability of responses we observed in the eNRGy trial are noteworthy. I strongly encourage my colleagues to obtain tissue-based RNA NGS to identify NRG1 rearrangements and other oncogenic gene alterations, particularly in otherwise driver-negative tumors, as fusions often are missed by DNA-based NGS techniques." New England Journal of Medicine Publishes eNRGy Trial Evaluating Zenocutuzumab-zbco (BIZENGRI®) in NRG1+ cancer Post this "The eNRGy study highlights that NRG1 fusions are an actionable therapeutic target and the importance of developing biomarker driven therapies like zenocutuzumab," said Debasish Roychowdhury, MD, Chief Technology Officer at PTx. "We are deeply grateful to the Merus team that designed, researched and developed zenocutuzumab, the eNRGy trial investigators, and the dedicated study participants who helped advance this important research." A subset of data from the eNRGy trial reported in the NEJM publication supported the recent FDA approval of BIZENGRI in adult patients with pancreatic adenocarcinoma or NSCLC that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression on or after prior systemic therapy. These indications are approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). BIZENGRI® has a Boxed WARNING for Embryo-Fetal Toxicity and warnings for infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions, interstitial lung disease (ILD)/pneumonitis, and left ventricular dysfunction.1 See Important Safety Information below. Under an agreement with Merus, PTx has exclusive rights to develop, manufacture, and commercialize zenocutuzumab-zbco for the treatment of NRG1+ cancer in the U.S. and provide the product on a named-patient basis for this use outside of the U.S. pending future regulatory developments. The companies are working to provide BIZENGRI for commercial distribution as quickly as possible. About NRG1 Gene Fusions NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activating downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. About BIZENGRI ( zenocutuzumab-zbco) INDICATIONS BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Important Safety Information BOXED WARNING: EMBRYO-FETAL TOXICITY Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception. WARNINGS AND PRECUATIONS Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough. In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion. Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions. Interstitial Lung Disease/Pneumonitis BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis. In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated. Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed. Left Ventricular Dysfunction BIZENGRI can cause left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment. In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 - 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event. Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI. Embryo-Fetal Toxicity Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose. ADVERSE REACTIONS NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC Serious adverse reactions occurred in 25% of patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each). In patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI, the most common (>20%) Adverse Reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%) diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%). NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma Serious adverse reactions occurred in 23% of patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI. There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%) musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%),vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%). Please see full Prescribing Information, including Boxed Warning About Partner Therapeutics Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of therapeutics to improve health outcomes in cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit the PTx website and LinkedIn. References: BIZENGRI® (zenocutuzumab-zbco) injection [package insert]. Available at: Schram AM, Goto K, Kim DW, et al. Efficacy of Zenocutuzumab in NRG1 Fusion–Positive Cancer. N Engl J Med. 2025;392:566-76. doi: 10.1056/NEJMoa2405008 Drilon A, Duruisseaux M, Han JY, et al. Clinicopathologic Features and Response to Therapy of NRG1 Fusion-Driven Lung Cancers: The eNRGy1 Global Multicenter Registry. J Clin Oncol. 2021;39(25):2791-2802. doi:10.1200/JCO.20.03307 BIZENGRI® is a registered trademark of Merus N.V. PARTNER THERAPEUTICS® is a registered trademark owned by Partner Therapeutics, Inc. ©2025 Partner Therapeutics, All rights reserved. Investor and Media Inquiries: Partner Therapeutics Media Relations 781-786-2405 [email protected] SOURCE Partner Therapeutics, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

UTRECHT, The Netherlands and CAMBRIDGE, Mass., Feb. 05, 2025 (GLOBE NEWSWIRE) -- Merus N.V. (Nasdaq: MRUS) (Merus, the Company, we, or our), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics® and Triclonics®), today announced that the New England Journal of Medicine (NEJM) published results of the registrational phase 2 eNRGy trial for Bizengri® (zenocutuzumab), the first and only treatment indicated for adults with pancreatic adenocarcinoma or non–small cell lung cancer (NSCLC) that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression on or after prior systemic therapy. “This manuscript provides comprehensive data on the safety and efficacy of Bizengri® and demonstrates the meaningful results observed in the eNRGy trial,” said Bill Lundberg, M.D., President, Chief Executive Officer of Merus. “We continue to make significant progress across our clinical pipeline of important and new cancer therapeutic candidates, all from our own Biclonics® antibody technologies.” NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (TRK, RET, ROS1, ALK, and FGFR fusions). This is the first reported prospective clinical trial targeting cancers with this rare genomic alteration, a population enriched for cancer types with limited effective treatment options.1, 2, 3 The publication reviews the results of 204 patients with 12 tumor types enrolled and treated on the eNRGy study, concluding “Zenocutuzumab demonstrated durable efficacy in patients with advanced NRG1+ cancer, notably NSCLC and pancreatic adenocarcinoma, with a favorable safety profile.” “This medicine fills an important need among patients with NRG1 fusion pancreatic adenocarcinoma and lung cancer who have not previously had targeted treatment options,” said Alison Schram M.D., an attending medical oncologist in the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, a principal investigator for the eNRGy trial, and lead author on the NEJM manuscript. In December, Merus announced it had entered into an agreement with Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company with a focus in hematology and oncology, in which Merus has exclusively licensed to PTx the right to commercialize zenocutuzumab (Zeno, tradename Bizengri®) for the treatment of NRG1 fusion-positive (NRG1+) cancer in the United States (U.S.). Indications: BIZENGRI® (zenocutuzumab-zbco) is indicated for adults with pancreatic adenocarcinoma or non–small cell lung cancer (NSCLC) that are advanced unresectable or metastatic and harbor a neuregulin 1 (NRG1) gene fusion who have disease progression on or after prior systemic therapy. These indications are approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). IMPORTANT SAFETY INFORMATION BOXED WARNING: EMBRYO-FETAL TOXICITY Embryo-Fetal Toxicity: Exposure to BIZENGRI® during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception. WARNINGS AND PRECAUTIONS Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions BIZENGRI® can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough. In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion. Administer BIZENGRI® in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI® infusion and as clinically indicated. Interrupt BIZENGRI® infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI® for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions. Interstitial Lung Disease/Pneumonitis BIZENGRI® can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis. In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI®. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI® occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI® in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated. Permanently discontinue BIZENGRI® if ILD/pneumonitis ≥ Grade 2 is confirmed. Left Ventricular Dysfunction BIZENGRI® can cause left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI®. Treatment with BIZENGRI® has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment. In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 - 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event. Before initiating BIZENGRI®, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI®. Embryo-Fetal Toxicity Based on its mechanism of action, BIZENGRI® can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI®. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI®. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI® and for 2 months after the last dose. ADVERSE REACTIONS NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma Serious adverse reactions occurred in 23% of patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI®. There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 Gene Fusion Positive Pancreatic Adenocarcinoma who received BIZENGRI® the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%) musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%). NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC Serious adverse reactions occurred in 25% of patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI®. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI® due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI® included dyspnea, pneumonitis and sepsis (n=1 each). In patients with NRG1 Gene Fusion Positive NSCLC who received BIZENGRI®, the most common (>20%) Adverse Reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27%), decreased phosphate (26%) diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%). Please see full Prescribing Information, including Boxed WARNING, at BIZENGRI.com/pi. About BIZENGRI® BIZENGRI® is a bispecific antibody that binds to the extracellular domains of HER2 and HER3 expressed on the surface of cells, including tumor cells, inhibiting HER2:HER3 dimerization and preventing NRG1 binding to HER3. BIZENGRI® decreased cell proliferation and signaling through the phosphoinositide 3-kinase-AKT-mammalian target of rapamycin pathway. In addition, BIZENGRI® mediates antibody-dependent cellular cytotoxicity. BIZENGRI® showed antitumor activity in mouse models of NRG1+ lung and pancreatic cancers.4 About the eNRGy Trial The eNRGy trial (Clinicaltrials.gov NCT02912949) is a multicenter, open-label clinical trial that includes patients with advanced unresectable or metastatic NRG1+ pancreatic adenocarcinoma or NRG1+ NSCLC who have disease progression on or after prior systemic therapy. There were 30 patients in the NRG1+ pancreatic adenocarcinoma group and 64 patients in the NRG1+ NSCLC group. The main outcome measures were ORR and DOR, as determined by BICR according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.4 In the NRG1+ pancreatic adenocarcinoma group, the median age was 49 years (range, 21-72 years); 43% were female; 87% were White, 7% were Asian, and 3.3% were Black or African American. All patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and all patients had metastatic disease. Patients received a median of 2 prior systemic therapies (range, 0-5); 97% had prior systemic therapy with prior chemotherapy.4 In the NRG1+ NSCLC group, the median age was 64 years (range, 32-86 years); 64% were female, 33% were White, 56% were Asian, and 3.4% were Black or African American. ECOG performance status was 0 or 1 in 97% of patients or 2 in 3% of patients, and 98% of patients had metastatic disease. Patients received a median of 2 prior systemic therapies (range, 1-6).4 Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation, benefits of a license between PTx and Merus; whether and when Merus will receive any future payment under the license agreement, including milestones or royalties, and the amounts of such payments; our progress across our clinical pipeline of important and new cancer therapeutic candidates, all from our own Biclonics® antibody technologies; the belief that this medicine fills an important need among patients with NRG1 fusion pancreatic adenocarcinoma and lung cancer who have not previously had targeted treatment options. These forward-looking statements are based on management’s current expectations. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our need for additional funding, which may not be available and which may require us to restrict our operations or require us to relinquish rights to our technologies or antibody candidates; potential delays in regulatory approval, which would impact our ability to commercialize our product candidates and affect our ability to generate revenue; the lengthy and expensive process of clinical drug development, which has an uncertain outcome; the unpredictable nature of our early stage development efforts for marketable drugs; potential delays in enrollment of patients, which could affect the receipt of necessary regulatory approvals; our reliance on third parties to conduct our clinical trials and the potential for those third parties to not perform satisfactorily; impacts of the volatility in the global economy, including global instability, including the ongoing conflicts in Europe and the Middle East; we may not identify suitable Biclonics® or bispecific antibody candidates under our collaborations or our collaborators may fail to perform adequately under our collaborations; our reliance on third parties to manufacture our product candidates, which may delay, prevent or impair our development and commercialization efforts; protection of our proprietary technology; our patents may be found invalid, unenforceable, circumvented by competitors and our patent applications may be found not to comply with the rules and regulations of patentability; we may fail to prevail in potential lawsuits for infringement of third-party intellectual property; and our registered or unregistered trademarks or trade names may be challenged, infringed, circumvented or declared generic or determined to be infringing on other marks. These and other important factors discussed under the caption “Risk Factors” in our Quarterly Report on Form 10-Q for the period ended September 30, 2024, filed with the Securities and Exchange Commission, or SEC, on October 31, 2024, and our other reports filed with the SEC, could cause actual results to differ materially from those indicated by the forward-looking statements made in this press release. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change, except as required under applicable law. These forward-looking statements should not be relied upon as representing our views as of any date subsequent to the date of this press release. References: 1Chang JC, Offin M, Falcon C, et al. Comprehensive molecular and clinicopathologic analysis of 200 pulmonary invasive mucinous adenocarcinomas identifies distinct characteristics of molecular subtypes. Clin Cancer Res 2021;27:4066-76. 2Drilon A, Duruisseaux M, Han JY, et al. Clinicopathologic features and response to therapy of NRG1 fusion-driven lung cancers: the eNRGy1 global multicenter registry. J Clin Oncol 2021;39:2791-802. 3Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet 2014;384:665-73. 4BIZENGRI. Prescribing information. Merus N.V.; 2024. About Merus Merus is a clinical stage oncology company developing innovative full-length human bispecific and trispecific antibody therapeutics, referred to as Multiclonics®. Multiclonics® are manufactured using industry standard processes and have been observed in preclinical and clinical studies to have several of the same features of conventional human monoclonal antibodies, such as long half-life and low immunogenicity. For additional information, please visit Merus’ website, and LinkedIn. Multiclonics®, Biclonics®, Triclonics®, and Bizengri® are registered trademarks of Merus N.V. Source: Merus N.V.

A single oral dose of SYMBRAVO provided rapid migraine pain freedom and return to normal functioning within 2 hours, and sustained efficacy through 24 and 48 hours 85% and 77% of patients treated with a single dose of SYMBRAVO did not require migraine rescue medication within 24 hours in two Phase 3 studies SYMBRAVO demonstrated superior efficacy across a broad range of migraine severity (mild, moderate, and severe), and in head-to-head evaluation SYMBRAVO incorporates Axsome’s rapid absorption technology and mechanisms that target multiple migraine attack pathways Company to host conference call and webcast Friday, January 31, at 8:00 AM Eastern NEW YORK, Jan. 30, 2025 (GLOBE NEWSWIRE) -- Axsome Therapeutics, Inc. (NASDAQ: AXSM), a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) disorders, today announced that the U.S. Food and Drug Administration (FDA) has approved SYMBRAVO® (meloxicam and rizatriptan) for the acute treatment of migraine with or without aura in adults.1 SYMBRAVO represents a novel multi-mechanistic approach to treating migraine that targets multiple pathways underlying a migraine attack. SYMBRAVO can rapidly eliminate migraine pain and return patients to normal functioning, with efficacy sustained through 24 and 48 hours in some patients after a single dose. The efficacy of SYMBRAVO was demonstrated across a broad range of settings including at the earliest onset of migraine when the pain was mild, in patients with moderate and severe migraine pain, and in those with a history of various responses to prior acute treatments. The Company expects SYMBRAVO to be commercially available in the U.S. in approximately four months. Richard B. Lipton, MD, Professor of Neurology and Director of the Montefiore Headache Center, Albert Einstein College of Medicine, commented, “A significant proportion of migraine patients experience inadequate efficacy with currently available acute treatments, leading to even greater suffering, and an increased risk of worsening of migraine pain and attack frequency. Results of multiple clinical trials demonstrate that SYMBRAVO can provide rapid and long-lasting freedom from migraine pain, whether treatment is taken early in the attack while the pain is mild, or later in the attack when the pain may be severe. The approval of SYMBRAVO is a long awaited and much welcomed advancement for clinicians and our patients, providing a new, meaningful treatment option.” Stewart Tepper, MD, Clinical Professor of Neurology at the Geisel School of Medicine at Dartmouth and Vice President of the New England Institute for Neurology and Headache, said, “Migraine is a debilitating condition that affects millions of Americans. Unfortunately, many patients still struggle to find an option that effectively treats their attacks and is both safe and well tolerated, which creates a great need for new migraine medicines. SYMBRAVO’s approval by the FDA provides a new medicine for physicians and patients that was designed to target key unmet needs in the migraine treatment space. The clinical data supporting its approval validates the additive benefit of SYMBRAVO’s multi-mechanistic design and demonstrates its potential to make a meaningful difference for the migraine community.” Susan Doughty, Executive Director of the Coalition for Headache and Migraine Patients (CHAMP), added, “Migraine is one of the most misunderstood and stigmatized neurological diseases, despite the fact that one in four households in the U.S. includes someone living with it. This widespread lack of understanding creates unnecessary barriers for individuals seeking proper diagnosis, care, and treatment. CHAMP, alongside our 20 plus dedicated coalition organizations and patient advocates, is committed to empowering the migraine community by providing education, reducing stigma, and advocating for fair and equitable access to treatment options. The approval of SYMBRAVO as a new acute treatment for migraine is an important step forward, offering a new option for people seeking relief. We also see this moment as an opportunity to continue to shine a bright light on migraine, fostering greater awareness and helping to dismantle the stigma that so often surrounds this disease.” The FDA approval of SYMBRAVO is based on the results of the Phase 3 MOMENTUM trial that treated migraine of moderate and severe pain intensity, the Phase 3 INTERCEPT trial that treated migraine when the initial pain was mild, and the Phase 3 MOVEMENT long-term open label safety trial. In this comprehensive clinical program, over 21,000 migraine attacks were treated with SYMBRAVO. In the MOMENTUM trial, SYMBRAVO demonstrated a statistically significantly greater percentage of patients achieving pain freedom and freedom from their most bothersome symptom (photophobia, phonophobia, nausea) 2 hours after dosing compared to placebo. SYMBRAVO also demonstrated statistical superiority for pain relief (reduction of moderate or severe pain to no pain or mild pain) and the ability to perform normal daily activities. The benefits of pain freedom at 2 hours were sustained through 24 and 48 hours for many patients. In a head-to-head comparison, SYMBRAVO demonstrated statistically significant superiority compared to rizatriptan on sustained pain freedom from 2 to 24 hours. Notably, these benefits were seen with only a single dose of SYMBRAVO. In the MOMENTUM trial, 77% of patients treated with SYMBRAVO did not require rescue medication within 24 hours post dose. In the INTERCEPT trial, SYMBRAVO demonstrated a statistically significantly greater percentage of patients achieving pain freedom and freedom from their most bothersome symptom (photophobia, phonophobia, nausea) 2 hours after dosing compared to placebo. The benefits of pain freedom at 2 hours were sustained through 24 and 48 hours for many patients. Notably, these benefits were seen with only a single dose of SYMBRAVO. In the INTERCEPT trial, 85% of patients treated with SYMBRAVO did not require rescue medication within 24 hours post dose. The most common adverse reactions (≥1% and greater than placebo) in the controlled studies were somnolence and dizziness, being reported each in 2% and 1% of patients in the SYMBRAVO and placebo arms, respectively. The long-term safety of SYMBRAVO was demonstrated in the MOVEMENT trial, which assessed 706 patients dosing intermittently for up to 12 months and treating at least 2 migraines per month with SYMBRAVO. SYMBRAVO is engineered with Axsome’s patented MoSEICTM (Molecular Solubility Enhanced Inclusion Complex) rapid absorption technology. MoSEIC results in a five times faster median time to maximum plasma concentration for meloxicam while maintaining a long plasma half-life, enabling meloxicam’s use as a new molecular entity for the acute treatment of migraine. SYMBRAVO is protected by a robust patent estate extending out to at least 2040. Herriot Tabuteau, MD, Chief Executive Officer of Axsome Therapeutics, said, “Today’s approval of SYMBRAVO marks an important milestone for the migraine community by providing a rationally designed novel acute treatment for this debilitating condition. Migraine attacks strike without warning, and disrupt the lives of estimated more than 39 million patients in the U.S. alone. SYMBRAVO provides patients and clinicians an important new option which can quickly stop a migraine attack, keep it away, and allow patients to resume their normal activities, with just a single dose. SYMBRAVO demonstrates Axsome’s commitment to developing and delivering differentiated new treatments to improve the lives of patients living with difficult to treat central nervous system disorders.” Conference Call Information Axsome will host a conference call and webcast on Friday, January 31, at 8:00 a.m. Eastern Time to discuss the approval of SYMBRAVO. Dr. Stewart Tepper, Clinical Professor of Neurology at the Geisel School of Medicine at Dartmouth and Vice President of the New England Institute for Neurology and Headache, will join the call and will be available to answer questions during the Q&A session. To participate in the live conference call, please dial (877) 405-1239 (toll-free domestic) or +1 (201) 389-0851 (international). A live webcast can be accessed on the “Webcasts & Presentations” page of the “Investors” section of the Company’s website at axsome.com. A replay of the webcast will be available for approximately 30 days following the live event. About Migraine Migraine is a serious neurological condition characterized by recurrent attacks of pulsating, often severe and disabling head pain associated with nausea, sensitivity to light, and sensitivity to sound.2 It is estimated that over 39 million Americans suffer from migraine, and it is the leading cause of disability among neurological disorders in the United States according to the American Migraine Foundation.3-5 Extensive surveys of migraine sufferers underscore the unmet need for therapies that work faster, more consistently, and result in less symptom recurrence.6,7 Over 70% of patients report experiencing an inadequate response to their oral, acute migraine treatment.8 About SYMBRAVO SYMBRAVO is a novel, oral, single-dose medicine approved for the acute treatment of migraine with or without aura in adults. SYMBRAVO consists of MoSEIC™ meloxicam and rizatriptan. Meloxicam is a new molecular entity for migraine enabled by Axsome’s MoSEIC (Molecular Solubility Enhanced Inclusion Complex) technology, which enables the rapid absorption of meloxicam while maintaining a long plasma half-life. Meloxicam is a COX-2 preferential non-steroidal anti-inflammatory drug (NSAID) and rizatriptan is a 5-HT1B/1D agonist. SYMBRAVO is designed to provide rapid, enhanced, and consistent migraine pain relief, and reduced symptom recurrence. The exact mechanism of action of SYMBRAVO in the treatment of acute migraine is unknown. For more information, visit www.symbravo.com. INDICATION SYMBRAVO® (meloxicam and rizatriptan) is indicated for the acute treatment of migraine with or without aura in adults. IMPORTANT SAFETY INFORMATION Limitations of Use SYMBRAVO is not indicated for the preventative treatment of migraine or for the treatment of cluster headache. CONTRAINDICATIONS SYMBRAVO is contraindicated in patients with: Ischemic coronary artery disease or other significant underlying cardiovascular disease Coronary artery vasospasm In the setting of CABG surgery History of stroke or transient ischemic attack Hemiplegic or basilar migraine Peripheral vascular disease Ischemic bowel disease Uncontrolled hypertension Concomitant use of propranolol Recent (within 24 hours) use of an ergotamine-containing medication, ergot-type medication (such as dihydroergotamine or methysergide), another 5-HT1 agonist (e.g., another triptan) Concurrent administration or recent discontinuation (i.e., within the past 2 weeks) of a MAO-A inhibitor Known hypersensitivity to SYMBRAVO, meloxicam, rizatriptan, NSAIDs, triptans, or any of the excipients in SYMBRAVO History of asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs Moderate to severe renal insufficiency in patients who are at risk for renal failure due to volume depletion or who are on dialysis WARNINGS AND PRECAUTIONS Cardiovascular Thrombotic Events, Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors. Arrhythmias: Discontinue dosing if arrhythmia occurs. Cerebral Hemorrhage, Subarachnoid Hemorrhage, and Stroke: Discontinue dosing if occurs. Anaphylactic Reactions: Seek emergency help if an anaphylactic reaction occurs. Chest/Throat/Neck/Jaw Pain, Tightness, Pressure, or Heaviness: Generally not associated with myocardial ischemia; evaluate patients at high risk. Gastrointestinal Ischemic Events, Peripheral Vasospastic Reactions: Discontinue dosing if occurs. Hepatotoxicity: Inform patients of warning signs and symptoms of hepatotoxicity. Discontinue if abnormal liver tests persist or worsen or if clinical signs and symptoms of liver disease develop. Hypertension: Patients taking some antihypertensive medications may have impaired response to these therapies when taking NSAIDs. Monitor blood pressure. Heart Failure and Edema: Avoid use of SYMBRAVO in patients with severe heart failure unless benefits are expected to outweigh risk of worsening heart failure. Renal Toxicity and Hyperkalemia: Monitor renal function in patients with renal or hepatic impairment, heart failure, dehydration, or hypovolemia. Use is not recommended in patients with moderate to severe renal insufficiency; avoid the use in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function. Serious Skin Reactions: Discontinue SYMBRAVO at first appearance of skin rash or other signs of hypersensitivity. Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Discontinue SYMBRAVO and evaluate clinically. Fetal Toxicity: Limit use of NSAIDs, including SYMBRAVO, between about 20 to 30 weeks in pregnancy due to the risk of oligohydramnios/fetal renal dysfunction. Avoid use of NSAIDs in women at about 30 weeks gestation and later in pregnancy due to the risks of oligohydramnios/fetal renal dysfunction and premature closure of the fetal ductus arteriosus. Hematologic Toxicity: Monitor hemoglobin or hematocrit in patients with any signs or symptoms of anemia. Exacerbation of Asthma Related to Aspirin Sensitivity: SYMBRAVO is contraindicated in patients with aspirin-sensitive asthma. Monitor patients with preexisting asthma (without aspirin sensitivity). Medication Overuse Headache: Detoxification may be necessary. Serotonin Syndrome: Discontinue dosing if occurs. Most common adverse reactions (≥1% and greater than placebo): dizziness and somnolence. Use in specific populations: Infertility: NSAIDs are associated with reversible infertility. Consider withdrawal of SYMBRAVO in women who have difficulties conceiving. SYMBRAVO is available in 20 mg meloxicam / 10 mg rizatriptan tablets. Please see full Prescribing Information, including Boxed Warning for risk of serious cardiovascular and gastrointestinal adverse events, and Medication Guide. About Axsome Therapeutics Axsome Therapeutics is a biopharmaceutical company leading a new era in the treatment of central nervous system (CNS) conditions. We deliver scientific breakthroughs by identifying critical gaps in care and develop differentiated products with a focus on novel mechanisms of action that enable meaningful advancements in patient outcomes. Our industry-leading neuroscience portfolio includes FDA-approved treatments for major depressive disorder and excessive daytime sleepiness associated with narcolepsy and obstructive sleep apnea and multiple late-stage development programs addressing a broad range of serious neurological and psychiatric conditions that impact over 150 million people in the United States. Together, we are on a mission to solve some of the brain’s biggest problems so patients and their loved ones can flourish. For more information, please visit the Company’s website at www.axsome.com. Forward Looking Statements Certain matters discussed in this press release are “forward-looking statements”. The Company may, in some cases, use terms such as “predicts,” “believes,” “potential,” “continue,” “estimates,” “anticipates,” “expects,” “plans,” “intends,” “may,” “could,” “might,” “will,” “should” or other words that convey uncertainty of future events or outcomes to identify these forward-looking statements. In particular, the Company’s statements regarding trends and potential future results are examples of such forward-looking statements. The forward-looking statements include risks and uncertainties, including, but not limited to, the commercial success of the Company’s Sunosi®, Auvelity®, and Symbravo® products and the success of the Company’s efforts to obtain any additional indication(s) with respect to solriamfetol and/or AXS-05; the Company’s ability to maintain and expand payer coverage; the success, timing and cost of the Company’s ongoing clinical trials and anticipated clinical trials for the Company’s current product candidates, including statements regarding the timing of initiation, pace of enrollment and completion of the trials (including the Company’s ability to fully fund the Company’s disclosed clinical trials, which assumes no material changes to the Company’s currently projected revenues or expenses), futility analyses and receipt of interim results, which are not necessarily indicative of the final results of the Company’s ongoing clinical trials, and/or data readouts, and the number or type of studies or nature of results necessary to support the filing of a new drug application (“NDA”) for any of the Company’s current product candidates; the Company’s ability to fund additional clinical trials to continue the advancement of the Company’s product candidates; the timing of and the Company’s ability to obtain and maintain U.S. Food and Drug Administration (“FDA”) or other regulatory authority approval of, or other action with respect to, the Company’s product candidates, including statements regarding the timing of any NDA submission; the Company’s ability to successfully defend its intellectual property or obtain the necessary licenses at a cost acceptable to the Company, if at all; the successful implementation of the Company’s research and development programs and collaborations; the success of the Company’s license agreements; the acceptance by the market of the Company’s products and product candidates, if approved; the Company’s anticipated capital requirements, including the amount of capital required for the commercialization of Sunosi, Auvelity, and Symbravo and for the Company’s commercial launch of its other product candidates, if approved, and the potential impact on the Company’s anticipated cash runway; the Company’s ability to convert sales to recognized revenue and maintain a favorable gross to net sales; unforeseen circumstances or other disruptions to normal business operations arising from or related to domestic political climate, geo-political conflicts or a global pandemic and other factors, including general economic conditions and regulatory developments, not within the Company’s control. The factors discussed herein could cause actual results and developments to be materially different from those expressed in or implied by such statements. The forward-looking statements are made only as of the date of this press release and the Company undertakes no obligation to publicly update such forward-looking statements to reflect subsequent events or circumstance. Investors: Mark Jacobson Chief Operating Officer (212) 332-3243 mjacobson@axsome.com Media: Darren Opland Director, Corporate Communications (929) 837-1065 dopland@axsome.com References Source: Axsome Therapeutics, Inc.