Venoocclusive disease

MELBOURNE, Australia and PRINCETON, N.J., March 19, 2024 (GLOBE NEWSWIRE) -- Opthea Limited (ASX:OPT; NASDAQ:OPT; “Opthea”), a clinical-stage biopharmaceutical company developing novel therapies to treat highly prevalent and progressive retinal diseases, today announced it will host a virtual key opinion leader (KOL) event on Wednesday, April 3, 2024, from 10:00 to 11:30 am ET, featuring presentations from global retina experts: Arshad M. Khanani, MD, MA, FASRS, Sierra Eye Associates and University of Nevada, Reno School of Medicine Charles C. Wykoff, MD, PhD, Retina Consultants of Texas and Blanton Eye Institute, Houston Methodist Hospital Veeral S. Sheth, MD, MBA, FASRS, FACS, University Retina and Macula Associates, University of Illinois at Chicago This event will focus on the potential of sozinibercept to transform patient outcomes by delivering superior vision gains in wet age-related macular degeneration (wet AMD), with KOL perspectives on (1) the wet AMD treatment landscape and unmet medical need addressed by sozinibercept’s novel mechanism of action, (2) the Phase 2b data demonstrating superiority in combination with standard-of-care therapy, and (3) the company's two ongoing global Phase 3 registrational trials (COAST and ShORe) evaluating sozinibercept in combination with standard-of-care VEGF-A inhibitors. Additionally, Opthea will provide a strategic outlook. A live question and answer session will follow the formal presentations. To register for this live webcast, click here. A replay of the webcast will be made available on the Company’s website. About Arshad M. Khanani, MD, MA, FASRS Arshad M. Khanani, MD, MA, FASRS is dedicated to advancing innovative treatment options for patients suffering from retinal diseases. Over a decade ago, he established the clinical research department at Sierra Eye Associates, which has since evolved into one of the foremost clinical research sites nationwide. With a wealth of experience, he has assumed the role of principal investigator for more than 120 clinical trials, consistently ranking as a top enroller in the nation across multiple Phase 1-3 trials. Notably, Dr. Khanani recently chaired the Phase 3 GATHER2 steering committee for IZERVAY™, playing a pivotal role in IZERVAY's approval for geographic atrophy. His contributions extend to over 100 authored or contributed scientific publications in prominent ophthalmology journals. Dr. Khanani actively participates as a member of national and international clinical trial steering committees, in addition to serving on scientific advisory boards. Dr. Khanani also serves as the lead principal investigator for multiple national and global clinical trials. He is often sought after as a guest speaker and lecturer at prestigious national and international gatherings. In pursuit of advancements in vitreoretinal care, Dr. Khanani initiated the Clinical Trials at the Summit (CTS) meeting, aiming to foster dialogue on clinical trial execution, design, and data analysis. Dr. Khanani holds elected membership in esteemed organizations such as the Macula Society and Retina Society, in addition to being the recipient of numerous distinguished awards. In 2019, he was honored with the Nevada Business Magazine Healthcare Heroes Physician of the Year award in recognition of his unwavering commitment to the field of ophthalmology. Dr. Khanani has been bestowed with the Senior Honor Award from the American Society of Retina Specialists (ASRS) and was also awarded the prestigious ASRS Presidents’ Young Investigator Award in 2021. Furthermore, in 2023, he was invited to deliver the esteemed Ernst Bodenheimer Memorial Lecture at the Wilmer Eye Institute at Johns Hopkins University. In February 2024, Dr. Khanani joined Opthea as its Chief Medical Advisor, while retaining his practice, sponsorship, and research activities. Prior to his new role at Opthea, Dr. Khanani served as a principal investigator for Opthea’s ShORe Phase 3 pivotal trial. About Charles C. Wykoff, MD, PhD Charles C. Wykoff, MD, PhD is a board-certified Medical and Surgical Retina Specialist and ophthalmologist with Retina Consultants of Texas (RCTX). Leading a top international research facility for vitreoretinal diseases, Dr. Wykoff serves as Director of Research at RCTX and the Greater Houston Retina Research Foundation (GHRRF), and Chairman of the Research and Clinical Trials Subcommittee, Retina Consultants of America. In addition, he serves as the elected Deputy Chair of Ophthalmology for the Blanton Eye Institute, Houston Methodist Hospital. Dr. Wykoff has been awarded the American Academy of Ophthalmology Secretariat and Achievement Awards as well as the American Society of Retina Specialists Senior Honor and Young Investigator Awards. Dr. Wykoff serves as the Chief Investigator for Opthea’s COAST Phase 3 pivotal trial and is on Opthea’s Clinical Advisory Board. About Veeral S. Sheth, MD, MBA, FASRS, FACS Veeral Sheth, MD, MBA, FACS, is a native Chicagoan that specializes in diseases of the retina and vitreous. He also is a Clinical Assistant Professor at the University of Illinois at Chicago. Dr. Sheth completed his ophthalmology residency at the Illinois Eye and Ear Infirmary where he served as Chief Resident. After residency, Dr. Sheth completed his fellowship at the University of Chicago in Retinal Surgery. He completed his MBA at Northwestern University’s Kellogg School of Management. Dr. Sheth is a Partner at University Retina and Macula Associates. He is Director of Clinical Trials at one of the busiest clinical trial sites in the country. He has been principal investigator for over 60 clinical trials and has research interests in macular degeneration, diabetic retinopathy, vein occlusion, as well as surgical pathology. He is involved in clinical trials developing new drugs, delivery devices, and gene therapy. Dr. Sheth is an active member of the American Society of Retina Specialists, Retina Society, American Academy of Ophthalmology, The Association for Research in Vision and Ophthalmology, and the European Society of Retina Specialists. He is the Chairman Emeritus of the Board of Directors for Meals on Wheels Chicago. Dr. Sheth is fluent in English, Spanish, and Gujarati. Dr. Sheth is a principal investigator for Opthea’s ShORe Phase 3 pivotal trial. About Sozinibercept Sozinibercept (OPT-302) is a soluble form of vascular endothelial growth factor receptor 3 (VEGFR-3) expressed as an immunoglobulin G1 (IgG1) Fc-fusion protein. It binds and neutralizes the activity of VEGF-C and VEGF-D on their endogenous receptors, VEGFR-2 and VEGFR-3. Research indicates that targeted inhibition of VEGF-C and VEGF-D can prevent blood vessel growth and vascular leakage, which contribute to the pathophysiology of retinal diseases including wet AMD. Sozinibercept has received Fast Track Designation from the U.S. FDA for the treatment of wet AMD. Positive results from the Phase 2b study of sozinibercept, administered in combination with standard of care, LUCENTIS® (ranibizumab), for the treatment of wet AMD, published in Ophthalmology, met the pre-specified primary efficacy endpoint of a statistically superior gain in visual acuity at 24 weeks, compared to ranibizumab alone. In addition, secondary outcomes were positive for the combination therapy with sozinibercept, including more participants with gains in vision of 10 or more letters and improved anatomy, with a reduction in swelling and vascular leakage, with a favorable safety profile. About Opthea Opthea (ASX:OPT; NASDAQ:OPT) is a biopharmaceutical company developing novel therapies to address the unmet need in the treatment of highly prevalent and progressive retinal diseases, including wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME). Opthea’s lead product candidate, sozinibercept, is being evaluated in two pivotal Phase 3 clinical trials (COAST, NCT04757636, and ShORe, NCT04757610,) for use in combination with standard-of-care anti-VEGF-A monotherapies to improve overall efficacy and deliver superior vision gains compared to the standard-of-care anti-VEGF-A agents. To learn more, visit our website and follow us on X and LinkedIn. IZERVAY™ is a registered trademark of Astellas Pharma Inc. LUCENTIS® is a registered trademark of Genentech USA, Inc. A member of the Roche Group. Authorized for release to ASX by Fred Guerard, CEO Investor Enquiries PJ Kelleher LifeSci Advisors Email: pkelleher@lifesciadvisors.com Phone: 617-430-7579 Media Silvana Guerci-Lena NorthStream Global Partners Email: silvana@nsgpllc.com Join our email database to receive program updates: Tel: +61 (0) 3 9826 0399 Email: info@opthea.com Source: Opthea Limited

One-time treatment with Lenmeldy has shown the potential to restore enzymatic function to stop or slow disease progression, with up to 12 years of follow-up (median 6.76 years)TOKYO and LONDON and BOSTON, March 18, 2024 (GLOBE NEWSWIRE) -- Orchard Therapeutics, recently acquired by Kyowa Kirin with the goal of accelerating the delivery of new gene therapies to patients around the globe, today announced the U.S. Food and Drug Administration (FDA) has approved Lenmeldy™ (atidarsagene autotemcel), formerly known as OTL-200, for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early symptomatic early juvenile (ESEJ)—collectively referred to as early-onset—metachromatic leukodystrophy (MLD). “The FDA approval of Lenmeldy opens up tremendous new possibilities for children in the U.S. with early-onset MLD who previously had no treatment options beyond supportive and end-of-life care,” said Bobby Gaspar, M.D., Ph.D., co-founder and chief executive officer of Orchard Therapeutics. “MLD is a rapidly progressing, life-limiting and ultimately fatal rare disease that has a devastating impact on afflicted children and their families. This achievement is the culmination of decades of research and development in partnership with our academic and clinical collaborators at the San Raffaele-Telethon Institute for Gene Therapy. I want to express my sincere gratitude to the patients and families who participated in our clinical trials as well as to the broader MLD community—we would not be here today without your contributions and support.” Dr. Gaspar continued, “I am also incredibly proud of the entire team at Orchard for their tireless effort to make this moment possible, and we look forward to ensuring broad and sustainable access to this remarkable innovation for eligible patients in need.” MLD is a rare, fatal genetic disorder caused by a mutation in the gene responsible for encoding the enzyme arylsulfatase A (ARSA) leading to neurological damage and developmental regression due to the accumulation of fats called sulfatides in the brain and other areas of the body which, when not broken down, damage the central nervous system over time. In its most severe form, babies develop normally but in late infancy start to rapidly lose the ability to walk, talk and interact with the world around them. These children eventually deteriorate into a vegetative state, which may require 24-hour intensive care, and the majority pass away within five years of disease onset, creating an enormous emotional and financial burden on the family. Lenmeldy aims to correct the underlying genetic cause of MLD by inserting one or more functional copies of the human ARSA gene ex vivo (outside the body) into the genome of a patient’s own hematopoietic stem cells (HSCs) using a lentiviral vector. The genetically repaired cells are infused back into the patient, where, once engrafted, they differentiate into multiple cell types, some of which migrate across the blood-brain barrier into the central nervous system and express the functional enzyme. This approach has the potential to restore enzymatic function to stop or slow disease progression with a single treatment. “This is a momentous occasion and I commend the FDA for recognizing the clinical impact Lenmeldy has on this cruel disease,” said Barbara Burton, M.D., attending physician, genetics, genomics and metabolism at the Ann & Robert H. Lurie Children’s Hospital of Chicago. “For too long, my colleagues and I have consoled families at their most vulnerable times—usually following an arduous diagnostic odyssey, coping with a dire prognosis and being told there were no treatments, and then having to watch their young child slip away. With this approval, we are now one significant step closer to ensuring future generations of children, families and healthcare professionals no longer need to experience first-hand the terrible manifestations this disease has on untreated patients.” “As a mother who lost a child to MLD, it is difficult to articulate how much of a watershed moment this is for patients, families and advocates,” said Maria Kefalas, Ph.D., co-founder of the Calliope Joy Foundation and a founding member of Cure MLD. “I, and so many others in our community, have made it our life’s work to end the horror caused by MLD so other families may not have to face the same terrible fate as ours. Today, we are closer than ever to making that vision a reality, but there’s still more work to be done. With the first therapy for this childhood disease now approved, we must act urgently and collaboratively to enable universal newborn screening for MLD in the U.S. so babies with these pathogenic mutations can be diagnosed and referred for appropriate treatment before the onset of symptoms.” Lenmeldy was granted Priority Review in September 2023. It was previously given both Rare Pediatric Disease (RPD) and Regenerative Medicine Advanced Therapy (RMAT) designations from FDA. In connection with the approval, Orchard Therapeutics received a Priority Review Voucher (PRV), which will be transferred to GSK in accordance with the terms of the original licensing agreement. Orchard Therapeutics will provide more details about the launch of Lenmeldy in the U.S. through a separate announcement this week. Overview of Clinical Development Program and Results The FDA approval of Lenmeldy is based on data from 37 pediatric patients with early-onset MLD, enrolled in two single-arm, open-label clinical studies or treated under European expanded access frameworks, who received a one-time administration of the gene therapy and compared with natural history data. All treated patients were administered Lenmeldy and subsequently monitored at Ospedale San Raffaele in Milan, Italy. With more than 12 years of follow-up in the earliest treated patients (median 6.76 years), treatment with Lenmeldy significantly extended overall survival and resulted in the preservation of motor function and cognitive skills in most late infantile MLD patients past ages at which untreated patients showed severe cognitive and motor impairments. Lenmeldy also resulted in the preservation of motor function and cognitive skills in some early juvenile MLD patients which is not expected when compared to untreated patients. The most common non-laboratory adverse reactions (incidence ≥ 10%) were: febrile neutropenia (85%), stomatitis (77%), respiratory tract infections (54%), rash (33%), device related infections (31%), other viral infections (28%), pyrexia (21%), gastroenteritis (21%), and hepatomegaly (18%). The most common laboratory abnormalities were: elevated D-dimer (67%), neutropenia (28%), and elevated liver enzymes (23%). Please see below for additional details and Important Safety Information. About MLDMLD is a rare and life-threatening inherited disease of the body’s metabolic system estimated to occur in approximately one in every 100,000 live births based on existing literature. MLD is caused by a mutation in the arylsulfatase-A (ARSA) gene that results in the accumulation of sulfatides in the brain and other areas of the body, including the liver, gallbladder, kidneys, and/or spleen. Over time, the nervous system is damaged, leading to neurological problems such as motor, behavioral and cognitive regression, severe spasticity and seizures. Patients with MLD gradually lose the ability to move, talk, swallow, eat and see. In its late infantile form, mortality at five years from onset is estimated at 50 percent and 44 percent at 10 years for juvenile patients.i About LenmeldyLenmeldy™ (atidarsagene autotemcel), formerly known as OTL-200, is the only approved therapy in the U.S. for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ) or early-symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). For additional details about Lenmeldy, please refer to the full Prescribing Information. In Europe, Lenmeldy is known as Libmeldy®, where it has been approved by the European Commission (EC), UK Medicines and Healthcare products Regulatory Agency (MHRA), and Swiss Agency for Therapeutic Products (Swissmedic). For more information about Libmeldy, please see the Summary of Product Characteristics (SmPC) available on the EMA website. The program was originated by and developed in partnership with the San Raffaele-Telethon Institute for Gene Therapy (SR-Tiget) in Milan, Italy. It was licensed by Orchard Therapeutics from GSK in 2018. INDICATION LENMELDYTM (atidarsagene autotemcel) is an autologous hematopoietic stem cell-based gene therapy indicated for the treatment of children with pre-symptomatic late infantile (PSLI), pre-symptomatic early juvenile (PSEJ), or early symptomatic early juvenile (ESEJ) metachromatic leukodystrophy (MLD). IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS Thrombosis and Thromboembolic Events:Treatment with LENMELDY may increase the risk of thrombosis and thromboembolic events. A child with PSEJ MLD died after experiencing a left hemisphere cerebral infarction secondary to a thrombotic event in a large blood vessel approximately 1 year after treatment with LENMELDY. Evaluate the risk factors for thrombosis prior to and after LENMELDY infusion according to best clinical practice. Consider monitoring D-dimer levels after LENMELDY treatment. Encephalitis:Treatment with LENMELDY may increase the risk of encephalitis. A child with ESEJ developed a serious event of encephalitis after treatment with LENMELDY. The etiology of this event is unclear but attribution to LENMELDY cannot be ruled out. Treatment with LENMELDY may trigger a relapsing-remitting pattern of disease progression. No other events related to encephalitis have been reported during the clinical development of LENMELDY. Monitor children for signs or symptoms of encephalitis after LENMELDY treatment. Serious Infection:In the period between start of conditioning and within 1 year after LENMELDY treatment, severe Grade 3 infections occurred in 39% of all children (21% bacterial, 5% viral, 5% bacterial and viral or bacterial and fungal, and 8% unspecified). Grade 3 febrile neutropenia developed within 1 month after LENMELDY infusion in 82% of children. In the event of febrile neutropenia, monitor for signs and symptoms of infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated. Monitor children for signs and symptoms of infection after myeloablative conditioning and LENMELDY infusion and treat appropriately. Administer prophylactic antimicrobials according to best clinical practice. Veno-Occlusive Disease:Three children (8%) treated in clinical trials of LENMELDY developed veno-occlusive disease (VOD) with one Grade 4 SAE and two Grade 3 AEs. None of these three events met Hy’s Law criteria. Monitor children for signs and symptoms of VOD including liver function tests in all children during the first month after LENMELDY infusion. Consider prophylaxis for VOD with an anti-thrombotic such as defibrotide or ursodeoxycholic acid based on risk factors for VOD and best clinical practice. Delayed Platelet Engraftment (DPE):DPE has been observed with LENMELDY treatment. Bleeding risk is increased prior to platelet engraftment and may continue after engraftment in children with prolonged thrombocytopenia. In clinical trials of LENMELDY, 4 (10%) children had delayed platelet engraftment after day 60 (range day 67-109), with 3 children requiring platelet transfusions until engraftment occurred. Patients should be informed of the risk of bleeding until platelet recovery has been achieved. Monitor patients for thrombocytopenia and bleeding until platelet engraftment and recovery are achieved. Neutrophil Engraftment Failure: There is a potential risk of neutrophil engraftment failure after treatment with LENMELDY. Monitor neutrophil counts until engraftment has been achieved. If neutrophil engraftment failure occurs in a child treated with LENMELDY, provide rescue treatment with the unmanipulated back-up collection of CD34+ cells. Insertional Oncogenesis: There is a potential risk of LVV-mediated insertional oncogenesis after treatment with LENMELDY. Children treated with LENMELDY may develop hematologic malignancies and should be monitored lifelong. Monitor for hematologic malignancies with a complete blood count (with differential) annually and integration site analysis as warranted for at least 15 years after treatment with LENMELDY. In the event that a malignancy occurs, contact Orchard Therapeutics at 1-888-878-0185 for reporting and to obtain instructions on collection of samples for testing. Hypersensitivity Reactions: The dimethyl sulfoxide (DMSO) in LENMELDY may cause hypersensitivity reactions, including anaphylaxis which is potentially life-threatening and requires immediate intervention. Hypersensitivity including anaphylaxis can occur in children with and without prior exposure to DSMO. Monitor for hypersensitivity reactions during infusion and after infusion. Anti-Retroviral Use: Children should not take prophylactic HIV anti-retroviral medications for at least one month prior to mobilization, or for the expected duration of time needed for the elimination of the medications. Anti-retroviral medications may interfere with the manufacturing of LENMELDY. If a child requires antiretrovirals for HIV prophylaxis, initiation of LENMELDY treatment should be delayed until confirmation of a negative test for HIV. Interference With Serology Testing: Due to the likelihood of a false-positive test for HIV, children who have received LENMELDY should not be screened for HIV infection using a PCR-based assay. USE IN SPECIFIC POPULATIONS Females and Males of Reproductive Potential Pregnancy TestingAs a precautionary measure, a negative serum pregnancy test must be confirmed prior to the start of mobilization, and reconfirmed prior to conditioning procedures, and before administration of LENMELDY in females of childbearing potential. Contraception Consult the Prescribing Information of the mobilization and conditioning agents for information on the need for effective contraception. Males capable of fathering a child and females of childbearing age should use an effective method of contraception from start of mobilization through at least 6 months after administration of LENMELDY. InfertilityThere are no data on the effects of LENMELDY on fertility. Data are available on the risk of infertility with myeloablative conditioning. In clinical trials of LENMELDY, seven children (50% of females) developed ovarian failure. Advise children of the option to cryopreserve semen or ova before treatment, if appropriate. For additional safety information, please see the full Prescribing Information. About Orchard TherapeuticsOrchard Therapeutics, a Kyowa Kirin company, is a global gene therapy leader focused on ending the devastation caused by genetic and other severe diseases by discovering, developing, and commercializing new treatments that tap into the curative potential of hematopoietic stem cell (HSC) gene therapy. In this approach, a patient’s own blood stem cells are genetically modified outside of the body and then reinserted, with the goal of correcting the underlying cause of disease with a single treatment. Founded in 2015, Orchard’s roots go back to some of the first research and clinical developments involving HSC gene therapy. Our team has played a central role in the evolution of this technology from a promising scientific idea to a potentially life-transforming reality. Today, Orchard is advancing a pipeline of HSC gene therapies designed to address serious diseases where the burden is immense for patients, families and society and current treatment options are limited or do not exist. For more information, please visit www.orchard-tx.com. About Kyowa KirinKyowa Kirin aims to discover novel medicines with life-changing value. As a Japan-based Global Specialty Pharmaceutical Company, we have invested in drug discovery and biotechnology innovation for more than 70 years and are currently working to engineer the next generation of antibodies and cell and gene therapies with the potential to help patients affected by a severe or rare disease. A shared commitment to our values, to sustainable growth, and to making people smile unites us across our four regions – Japan, Asia Pacific, North America, and EMEA/International. You can learn more about the business of Kyowa Kirin at www.kyowakirin.com.______________________________iMahmood et al. Metachromatic Leukodystrophy: A Case of Triplets with the Late Infantile Variant and a Systematic Review of the Literature. Journal of Child Neurology 2010, DOI: http://doi.org.libproxy1.nus.edu.sg/10.1177/0883073809341669

Pivekimab Triplet Demonstrates Encouraging CR, Composite CR, and MRD Negativity Rates; Broad Anti-Leukemia Activity Observed Across All Molecular Subsets Evaluated Pivekimab-Containing Triplet Well-Tolerated with Manageable Safety Pro > Data Support Continued Development of Triplet; Enrollment and Follow-Up Ongoing WALTHAM, Mass.--(BUSINESS WIRE)-- ImmunoGen Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced new safety and efficacy findings from the newly diagnosed (ND) cohorts of the Phase 1b/2 study of pivekimab sunirine (pivekimab) in combination with azacitidine (Vidaza®) and venetoclax (Venclexta®), (pivekimab triplet) in patients with ND acute myeloid leukemia (AML). These findings will be presented in a poster session at the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California. “We are pleased to share these new findings at ASH, which demonstrate encouraging anti-leukemia activity of the pivekimab triplet in newly diagnosed AML, a disease in which long-term survival unfortunately remains limited,” said Naval Daver, MD, Associate Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “The MRD negativity rates, which are indicative of a deep remission, are particularly promising in the treated patient population. This encouraging activity, along with a manageable safety profile, support the continued evaluation of this novel triplet in this setting.” PIVEKIMAB SUNIRINE, A CD123-TARGETING ANTIBODY-DRUG CONJUGATE, IN COMBINATION WITH AZACITIDINE AND VENETOCLAX IN PATIENTS WITH NEWLY DIAGNOSED ACUTE MYELOID LEUKEMIA Lead Author: Navel Daver, MD Poster Session: 616 (Acute Myeloid Leukemias: Investigational Therapies, Excluding Transplantation and Cellular Immunotherapies: Poster II) Date and Time: Sunday, December 10, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET Publication Number: 2906 In the open-label, multicenter, Phase 1b/2 study of pivekimab in combination with azacitidine and venetoclax in patients with ND CD123-positive AML, patients received the recommended Phase 2 dose of pivekimab at 0.045 mg/kg on day 7, azacitidine at 75 mg/m2 daily on days 1-7, and venetoclax at up to 400 mg for at least 14 days or up to 28 days, based on cohort assignment, in a 28-day cycle. The primary endpoints are complete remission (CR) rate, composite CR rate (CCR [CR+CRh+CRp+CRi]), minimal residual disease (MRD) negativity rate, and duration of remission. Key secondary endpoints are safety, pharmacokinetics, and immunogenicity. Key findings for 50 ND patients (n=25 per cohort) as of September 29, 2023 (data cut-off) include: Anti-Leukemia Activity In the overall population, CCR rate was 68% (34/50), CR rate was 54% (27/50), and MRD negativity rate among evaluable patients achieving CCR was 76% (22/29). MRD was assessed centrally by flow cytometry with <0.1% considered negative. Response rates and MRD negativity were numerically comparable between cohorts 1 and 2, despite differences in the venetoclax schedule. In a post hoc subset analysis of patients unfit for intensive chemotherapy (i.e. patients >75 years of age, and/or with pre-specified comorbidities) (n=23), CCR rate was 78% (18/23), CR rate was 61% (14/23), and MRD negativity rate was 79% (11/14). In patients known to be TP53wt (n=25), CCR rate was 88% (22/25), CR rate was 84% (21/25), and MRD negativity rate was 80% (16/20). CCR and MRD negativity rates, respectively, were high across other major molecular subsets, including: FLT3 (ITD or TKD): 100% (6/6) and 100% (6/6) IDH1 mutant: 100% (4/4) and 67% (2/3) IDH2 mutant: 100% (6/6) and 83% (5/6) NPM1 mutant: 100% (8/8) and 86% (6/7) K/NRAS mutant: 50% (3/6) and 67% (2/3) TP53 mutant: 50% (7/14) and 50% (3/6) Among all MRD negative patients, the median time to MRD negativity was 1.87 months (range: 0.79-5.16 months). Although follow-up duration was short (median 5.2 months), landmark overall survival estimate at 6 months is 86%. The study is continuing to enroll newly diagnosed unfit AML patients. Safety The triplet displayed a manageable safety profile; no new safety signals were observed compared to previously reported data. The most common non-hematologic treatment-emergent adverse events (TEAEs) (all grades [grade 3+]) seen in ≥20% of all patients were constipation (48% [2%]), peripheral edema (44% [4%]), diarrhea (40% [2%]), hypophosphatemia (34% [2%]), nausea (32% [4%]), hypokalemia (28% [4%]), fatigue (24% [6%]), hypotension (24% [2%]), and pyrexia (24% [0%]). In the overall population: Rates of cytopenias were similar to those observed with azacitidine and venetoclax, with a median neutrophil recovery to ≥500/µL and platelet recovery to ≥50,000/µL by day 34 and day 22, respectively. No veno-occlusive disease, capillary leak syndrome, or sinusoidal obstruction syndrome were observed. Infusion-related reactions (IRRs) occurred in 16% of patients (0 grade 3+ IRRs). Discontinuations due to an adverse event (AE) were 4% (2 patients). 30-day mortality was 0%. 60-day mortality was 4% (2 patients; due to pneumonia and early disease progression). "Building upon our initial findings in frontline AML presented last year, these data show broad and consistent response rates in a larger study population and across major molecular subsets of interest, including those patients with biological mutations making them high-risk," said Michael Vasconcelles, MD, ImmunoGen's Executive Vice President, Research, Development, and Medical Affairs. "We are pleased with the low early mortality and manageable safety pro in particular the lack of prolonged cytopenias. We look forward to continuing to expand our cohort of newly diagnosed unfit patients to inform the development path for pivekimab in AML.” PRECLINICAL POSTERS ImmunoGen is also presenting two preclinical posters at ASH. Title: Venetoclax Synergizes with IMGN632, a Novel CD123-Targeting Antibody Conjugated to a DNA Alkylating Payload, By Suppressing DNA Damage Response and Potentiating Apoptosis in Acute Myeloid Leukemia in Vitro Models Presenter: Anna Skwarska Session: 604 (Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster III) Date and Time: Monday, December 11, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET Publication Number: 4155 Title: Spatial Response to Pivekimab Sunirine In Vivo in a BPDCN Model Presenter: Margaux Poussard Session: 604 (Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Poster II) Date and Time: Sunday, December 10, 2023, 6:00-8:00 p.m. PT / 9:00-11:00 p.m. ET Publication Number: 2791 Additional information can be found at , including abstracts. ABOUT PIVEKIMAB SUNIRINE Pivekimab sunirine is a CD123-targeting ADC in clinical development for hematological malignancies, including blastic plasmacytoid dendritic cell neoplasm (BPDCN), acute myeloid leukemia (AML), and other CD123+ hematologic malignancies. Pivekimab is currently being evaluated as monotherapy for patients with BPDCN and in combination with azacitidine (Vidaza®) and venetoclax (Venclexta®) for patients with untreated and relapsed/refractory AML. Pivekimab uses one of ImmunoGen's novel indolinobenzodiazepine (IGN) payloads, which alkylate DNA and cause single-strand breaks without crosslinking. IGNs are designed to have high potency against tumor cells, while demonstrating less toxicity to normal marrow progenitors than other DNA-targeting payloads. The European Medicines Agency (EMA) granted orphan drug designation to pivekimab for the treatment of BPDCN in June 2020. Pivekimab also holds this designation in the US. In October 2020, the FDA granted pivekimab Breakthrough Therapy designation in relapsed/refractory BPDCN. ABOUT ACUTE MYELOID LEUKEMIA (AML) AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems, and anemia. It is estimated that, in the US alone, more than 20,000 people will be diagnosed with AML and more than 11,000 will die from the disease this year. ABOUT CD123 CD123, the interleukin-3 alpha chain, is expressed on multiple myeloid and lymphoid cancers including AML, BPDCN, ALL, chronic myeloid leukemia, and myeloproliferative neoplasms. With limited expression on normal hematopoietic cells, rapid internalization, and expression on AML leukemia stem cells, CD123 is a clinically validated therapeutic target. ABOUT IMMUNOGEN ImmunoGen is developing the next generation of antibody-drug conjugates (ADCs) to improve outcomes for cancer patients. By generating targeted therapies with enhanced anti-tumor activity and favorable tolerability pro we aim to disrupt the progression of cancer and offer our patients more good days. We call this our commitment to TARGET A BETTER NOW™. Learn more about who we are, what we do, and how we do it at . Vidaza® and Venclexta® are registered trademarks of their respective owners. FORWARD-LOOKING STATEMENTS This press release includes forward-looking statements. These statements include, but are not limited to, the potential efficacy and safety of pivekimab. Various factors could cause ImmunoGen's actual results to differ materially from those discussed or implied in the forward-looking statements, and you are cautioned not to place undue reliance on these forward-looking statements, which are current only as of the date of this release. Factors that could cause future results to differ materially from such expectations include, but are not limited to: the timing and outcome of the Company's clinical development processes; the difficulties inherent in the development of novel pharmaceuticals, including uncertainties as to the timing, expense, and results of clinical trials and regulatory processes; and other factors as set forth in the Company's Annual Report on Form 10-K filed with the Securities and Exchange Commission on March 1, 2023, the Company's Quarterly Reports on Form 10-Q filed with the Securities and Exchange Commission on April 28, 2023 and July 31, 2023 and November 2, 2023, and other reports filed with the Securities and Exchange Commission. The forward-looking statements in this press release speak only as of the date of this press release. ImmunoGen undertakes no obligation to update any forward-looking statement, whether as a result of new information, future developments, or otherwise, except as may be required by applicable law. View source version on businesswire.com: Contacts INVESTOR RELATIONS ImmunoGen Anabel Chan 781-895-0600 anabel.chan@immunogen.com MEDIA ImmunoGen Courtney O'Konek 781-895-0600 courtney.okonek@immunogen.com OR FTI Consulting Robert Stanislaro 212-850-5657 robert.stanislaro@fticonsulting.com Source: ImmunoGen Inc. View this news release online at: