The Massachusetts General Hospital

By combining non-invasive imaging techniques, investigators have created a comprehensive cellular atlas of a region of the human brain known as Broca's area. The brain is made up of numerous types of cells that are organized into different structures and regions. Although several important steps have been made towards building models of the human brain, the advances have not produced undistorted 3D images of cellular architecture that are needed to build accurate and detailed models. In new research published in Science Advances, a team led by investigators at Massachusetts General Hospital (MGH), a founding member of Mass General Brigham (MGB), has overcome this challenge to offer scientists and clinicians a comprehensive cellular atlas of a part of the human brain known as Broca's area, with detailed resolution to study brain function and health. By combining different sophisticated imaging techniques -- including magnetic resonance imaging, optical coherence tomography, and light-sheet fluorescence microscopy -- the researchers were able to overcome the limitations associated with any single method to create a high-resolution cell census atlas of a specific region of the human cerebral cortex, or the outer layer of the brain's surface. The team created such an atlas for a human postmortem specimen and integrated it within a whole-brain reference atlas. "We built the technology needed to integrate information across many orders of magnitude in spatial scale from images in which pixels are a few microns to those that image the entire brain," says co-senior author Bruce Fischl, PhD, director of the Computational Core at the Athinoula A. Martinos Center for Biomedical Imaging at MGH and a professor in Radiology at Harvard Medical School. Ultimately, the methods in this study could be used to reconstruct undistorted 3D cellular models of particular brain areas as well as of the whole human brain, enabling investigators to assess variability between individuals and within a single individual over time. This will provide insights into the presence and spread of pathologic changes that occur in neurodegenerative and psychiatric illnesses. "These advances will help us understand the mesoscopic structure of the human brain that we know little about. Structures that are too large and geometrically complicated to be analyzed by looking at 2D slices on the stage of a standard microscope, but too small to see routinely in living human brains, says Fischl. "Currently we don't have rigorous normative standards for brain structure at this spatial scale, making it difficult to quantify the effects of disorders that may impact it such as epilepsy, autism, and Alzheimer's disease."

Presentations include new data from clinical and real-world evaluations of RADICAVA ORS® (edaravone) and RADICAVA® (edaravone) JERSEY CITY, N.J., Oct. 4, 2023 /PRNewswire/ -- Mitsubishi Tanabe Pharma America, Inc. (MTPA) today announced that eight presentations in amyotrophic lateral sclerosis (ALS) will be shared at the 22nd Annual Northeast Amyotrophic Lateral Sclerosis (NEALS) Meeting, being held in Clearwater, Fla., from October 4-6. "We look forward to sharing several presentations at NEALS that demonstrate our progress in ALS research and underscore our commitment to understanding treatment outcomes for people living with this disease," said Gustavo A. Suarez Zambrano, M.D., Vice President of Medical Affairs at MTPA. "From the continued evaluation of RADICAVA ORS® (edaravone) and RADICAVA® (edaravone) with real-world and patient-reported insights to exploration of home-based respiratory monitoring, we remain steadfast in our efforts to deepen our understanding of ALS and the impact of our treatment options." MTPA's posters will be viewable throughout the conference. Presentations include: RADICAVA ORS A preliminary analysis of demographics and clinical characteristics in people with ALS being treated with RADICAVA ORS, utilizing U.S.-based administrative claims data from Optum's Clinformatics® Data Mart (CDM), will be presented. Additional presentations include results from a pre-planned futility analysis – conducted by an independent data monitoring committee (IDMC) – of the global, multi-center, double-blind, Phase 3b MT-1186-A02 study of oral edaravone, as well as study design details from its extension study, MT-1186-A04, comparing two dosing regimens for oral edaravone to evaluate its continued efficacy and safety in ALS. A Preliminary Analysis of Oral Edaravone-Treated Patients With Amyotrophic Lateral Sclerosis Enrolled in a US-Based Administrative Claims Database (Malgorzata Ciepielewska, M.S.; MTPA) Phase 3b Study MT-1186-A02 of a Daily Dosing Regimen of Oral Edaravone Compared With the FDA-approved On/Off Regimen, Over 48 Weeks in Patients With Amyotrophic Lateral Sclerosis: An Update on a Pre-specified Futility Analysis (Steve Apple, M.D.; MTPA) Phase 3b Extension Study Evaluating Superiority of Daily vs Approved On/Off Oral Edaravone Dosing in Patients With Amyotrophic Lateral Sclerosis (Alejandro Salah, M.D., Ph.D., MBA, MHA; MTPA) Phase 4 REFINE-ALS Biomarker Study Results from an interim analysis of the prospective, observational, longitudinal, multi-center Phase 4 REFINE-ALS study, designed to identify predictive and pharmacodynamic biomarkers to measure the effect of intravenous (IV) RADICAVA in ALS, as well as evaluate clinical outcomes in real-world settings, will be presented. REFINE-ALS is a NEALS-affiliated clinical trial sponsored by MTPA and conducted in collaboration with the Neurological Clinical Research Institute (NCRI) at Massachusetts General Hospital (MGH). Interim Analysis of the Radicava/Edaravone Findings in Biomarkers from ALS (REFINE-ALS) Study (Steve Apple, M.D.; MTPA) Additional Real-World Data Presentations include an interim analysis of treatment patterns and clinical and patient-reported outcomes with RADICAVA, based on data from the ALS/Motor Neuron Disease (MND) Natural History Consortium (NHC) multidisciplinary, clinic-based registry. Additionally, updates from a prospective study evaluating slow vital capacity (SVC) in erect-seated (eSVC) and supine (sSVC) positions using in-clinic conventional and in-home, portable spirometry will be presented. Real-World Evidence on Treatment Patterns, Clinical Outcomes, and Patient-Reported Outcomes of Intravenous Edaravone–Treated People With Amyotrophic Lateral Sclerosis in the ALS/MND Natural History Consortium Registry Database (Malgorzata Ciepielewska, M.S.; MTPA) Internet-Supervised Home-Based Spirometry through Telemedicine in Amyotrophic Lateral Sclerosis (Eufrosina Young, M.D.; State University of New York Upstate Medical University) Additionally, study design details from two studies sponsored by Mitsubishi Tanabe Pharma Canada, Inc. (MTP-CA) will be presented, including a real-world survival analysis evaluating the effectiveness of edaravone on tracheostomy-free survival in people with ALS and a real-world evidence study assessing treatment retention, safety and tolerability in edaravone-treated individuals, based on de-identified data from the Mitsubishi Tanabe Pharma-Patient Support™ (MTP-PS) program. Real-World Survival Effectiveness of Edaravone in Amyotrophic Lateral Sclerosis: A Propensity Score Weighted, Registry-based, Canada-wide Cohort Study (Agessandro Abrahao, M.D., M.S.; Sunnybrook Health Sciences Centre and University of Toronto) Real-World Evidence on Treatment Retention, Safety, and Tolerability of Edaravone in Canadian Patients With Amyotrophic Lateral Sclerosis (Dung Pham, Ph.D.; MTP-CA) About RADICAVA® (edaravone) and RADICAVA ORS® (edaravone) The U.S. Food and Drug Administration (FDA) approved RADICAVA® (edaravone) on May 5, 2017, and the oral formulation RADICAVA ORS® (edaravone) on May 12, 2022, for the treatment of amyotrophic lateral sclerosis (ALS). RADICAVA is administered in 28-day cycles by intravenous (IV) infusion. It takes 60 minutes to receive each 60 mg dose. For the initial cycle, the treatment is infused daily for 14 consecutive days, followed by a two-week drug-free period. All cycles thereafter are infused daily for 10 days within a 14-day period, followed by a two-week drug-free period. RADICAVA ORS is taken daily for 14 consecutive days followed by a 14-day drug-free period for the initial treatment cycle. For subsequent treatment cycles, RADICAVA ORS is taken for 10 days within a 14-day period followed by a 14-day drug-free period. RADICAVA ORS should be taken in the morning after overnight fasting. Patients should not eat or drink (except water) within one hour after taking RADICAVA ORS.1 Edaravone was discovered and developed for ALS by Mitsubishi Tanabe Pharma Corporation (MTPC) and commercialized in the U.S. by Mitsubishi Tanabe Pharma America, Inc. (MTPA). The MTPC group companies began researching ALS in 2001 through an iterative clinical platform over a 13-year period. In 2015, edaravone was approved as RADICUT® for the treatment of ALS in Japan and South Korea. Marketing authorizations were subsequently granted in Canada (October 2018), Switzerland (January 2019), Indonesia (July 2020), Thailand (April 2021) and Malaysia (December 2021). Marketing authorization for RADICAVA® Oral Suspension was granted in Canada (November 2022) and Switzerland (May 2023), and RADICUT® Oral Suspension 2.1% was granted regulatory approval in Japan in December 2022. To date, in the U.S., RADICAVA and RADICAVA ORS have been used to treat over 12,000 people with ALS, with over 1.45-million days of therapy, and have been prescribed by over 2,100 HCPs.2-4 IMPORTANT SAFETY INFORMATION Hypersensitivity Reactions RADICAVA (edaravone) and RADICAVA ORS (edaravone) are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients of this product. Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have occurred with RADICAVA. Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA or RADICAVA ORS, treat per standard of care, and monitor until the condition resolves. Sulfite Allergic Reactions RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown but occurs more frequently in asthmatic people. Adverse Reactions The most common adverse reactions (≥10%) reported in RADICAVA-treated patients were contusion (15%), gait disturbance (13%), and headache (10%). In an open label study, fatigue was also observed in 7.6% of patients receiving RADICAVA ORS. Pregnancy Based on animal data, RADICAVA and RADICAVA ORS may cause fetal harm. To report suspected adverse reactions or product complaints, contact Mitsubishi Tanabe Pharma America, Inc., at 1-888-292-0058. You may also report suspected adverse reactions to the FDA at 1-800-FDA-1088 or . INDICATION RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). For more information, including full Prescribing Information , please visit . About Mitsubishi Tanabe Pharma America, Inc. Based in Jersey City, N.J., Mitsubishi Tanabe Pharma America, Inc. (MTPA) is a wholly-owned subsidiary of Mitsubishi Tanabe Pharma Corporation (MTPC). It was established by MTPC to develop and advance our pipeline as well as commercialize approved pharmaceutical products in North America. For more information, please visit or follow us on X (formerly Twitter), Facebook and LinkedIn. About Mitsubishi Tanabe Pharma Corporation Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of Mitsubishi Chemical Group (MCG), is one of the oldest pharmaceutical companies in the world, founded in 1678. MTPC is headquartered in Doshomachi, Osaka, the birthplace of Japan's pharmaceutical industry. MCG has positioned health care as its strategic focus in its management policy, "Forging the future". MTPC sets the MISSION of "Creating hope for all facing illness". To that end, MTPC is working on the disease areas of central nervous system, immuno-inflammation, diabetes and kidney, and cancer. MTPC is focusing on "precision medicine" to provide drugs with high treatment satisfaction and additionally working to develop "around the pill solutions" to address specific patient concerns based on therapeutic medicine, including prevention of diseases, pre-symptomatic disease care, prevention of aggravation and prognosis. For more information, go to . Media inquiries: [email protected] 1 RADICAVA and RADICAVA ORS Prescribing Information. Jersey City, NJ: Mitsubishi Tanabe Pharma America, Inc.; 2022. 2 Data on file. Mitsubishi Tanabe Pharma America, Inc. 3 Data on file. Mitsubishi Tanabe Pharma America, Inc. 4 Data on file. Mitsubishi Tanabe Pharma America, Inc. SOURCE Mitsubishi Tanabe Pharma America, Inc.

Company plans to host a conference call on October 13, 2023 CAMBRIDGE, Mass., Sept. 18, 2023 /PRNewswire/ -- Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, today announced it will present preliminary dose-escalation data from its ongoing ALKOVE-1 Phase 1/2 clinical trial of NVL-655 at the 35th AACR-NCI-EORTC (ANE) Symposium taking place October 11-15, 2023, in Boston, Massachusetts. The presentation marks the first disclosure of data characterizing the safety and clinical activity of NVL-655 from the Phase 1 dose-escalation portion of the ongoing ALKOVE-1 Phase 1/2 clinical trial evaluating NVL-655 in patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors. NVL-655 has been designed with the aim to address challenges that limit clinical use of existing ALK tyrosine kinase inhibitors (TKIs), including treatment emergent resistance mutations, lack of brain penetrance, and off-target CNS adverse events. The ALKOVE-1 clinical trial is continuing to enroll patients in the Phase 1 portion of the trial. Nuvalent plans to host a conference call and webcast on October 13, 2023. Details for the conference call will be provided at a future date and available on the Nuvalent website at . Details for the presentation are as follows: Title: Safety and preliminary activity of the selective ALK inhibitor NVL-655 in patients with ALK fusion-positive solid tumors Abstract Number: 35177 Poster Number: B154 Session: Poster Session B Session Date and Time: Friday, October 13, 12:30 pm-4:00 pm Presenting Author: Jessica J Lin, Massachusetts General Hospital (MGH), Boston, MA About NVL-655 NVL-655 is a novel brain-penetrant ALK-selective inhibitor created to overcome limitations observed with currently available ALK inhibitors. NVL-655 is designed to remain active in tumors that have developed resistance to first-, second-, and third-generation ALK inhibitors, including tumors with the solvent front G1202R mutation or compound mutations G1202R / L1196M ("GRLM"), G1202R / G1269A ("GRGA"), or G1202R/L1198F ("GRLF"). NVL-655 has been optimized for CNS penetrance to improve treatment options for patients with brain metastases. NVL-655 has been observed in preclinical studies to selectively inhibit wild-type ALK and its resistance variants over the structurally related tropomyosin receptor kinase (TRK) family to potentially avoid TRK-related CNS adverse events seen with dual TRK/ALK inhibitors and drive more durable responses for patients. NVL-655 is currently being investigated in the ALKOVE-1 clinical trial (NCT05384626), a first-in-human Phase 1/2 clinical trial for patients with advanced ALK-positive non-small cell lung cancer (NSCLC) and other solid tumors. About Nuvalent Nuvalent, Inc. (Nasdaq: NUVL) is a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for patients with cancer, designed to overcome the limitations of existing therapies for clinically proven kinase targets. Leveraging deep expertise in chemistry and structure-based drug design, we develop innovative small molecules that have the potential to overcome resistance, minimize adverse events, address brain metastases, and drive more durable responses. Nuvalent is advancing a robust pipeline with parallel lead programs in ROS1-positive and ALK-positive non-small cell lung cancer (NSCLC), a program in HER2 Exon 20 Insertion positive cancers, and multiple discovery-stage research programs. We routinely post information that may be important to investors on our website at . Follow us on Twitter (@nuvalent) and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, implied and express statements regarding Nuvalent's strategy, business plans, and focus; the expected timing of data announcements; the preclinical and clinical development programs for NVL-655; the potential clinical effect of NVL-655; the design and enrollment of the ALKOVE-1 clinical trial; the potential of NVL-655; Nuvalent's research and development programs for the treatment of cancer; and risks and uncertainties associated with drug development. The words "may," "might," "will," "could," "would," "should," "expect," "plan," "anticipate," "aim," "goal," "intend," "believe," "expect," "estimate," "seek," "predict," "future," "project," "potential," "continue," "target" or the negative of these terms and similar words or expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. 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. You should not place undue reliance on these statements or the scientific data presented. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks, uncertainties, and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation: risks that Nuvalent may not fully enroll the ALKOVE-1 clinical trial or that enrollment will take longer than expected; unexpected concerns that may arise from additional data, analysis, or results obtained during preclinical studies or clinical trials, including ALKOVE-1; the occurrence of adverse safety events; risks of unexpected costs, delays, or other unexpected hurdles; risks that Nuvalent may not be able to nominate drug candidates from its discovery programs; the direct or indirect impact of public health emergencies or global geopolitical circumstances on the timing and anticipated timing and results of Nuvalent's clinical trials, strategy, and future operations, including the ALKOVE-1 clinical trial; the timing and outcome of Nuvalent's planned interactions with regulatory authorities; and risks related to obtaining, maintaining, and protecting Nuvalent's intellectual property. These and other risks and uncertainties are described in greater detail in the section entitled "Risk Factors" in the Company's Quarterly Report on Form 10-Q for the quarterly period ended June 30, 2023, as well as any prior and subsequent filings with the Securities and Exchange Commission. In addition, any forward-looking statements represent Nuvalent's views only as of today and should not be relied upon as representing its views as of any subsequent date. Nuvalent explicitly disclaims any obligation to update any forward-looking statements. View original content to download multimedia: SOURCE Nuvalent, Inc. Company Codes: NASDAQ-NMS:NUVL