EMBRACE is a double-blind, randomized, placebo-controlled, phase IIa study that will be conducted in multiple Intensive Care Units (ICUs) and departments of Internal Medicine across Greece. It aims to investigate if treatment with emapalumab, a monoclonal antibody which blocks IFNγ, may improve the outcome of patients with sepsis driven by the IDS (endotype of IFNγ-driven sepsis) endotype. EMBRACE also aims to identify the best dosing regimen of emapalumab for the management of IDS.

Start Date01 Jan 2025

Sponsor / Collaborator

Hellenic Institute for the Study of Sepsis

NCT06550141 / RecruitingPhase 2IIT

A Phase 2 Trial of Emapalumab for the Prevention of CAR-T Cell Associated Toxicities

This research study involves assessing the impact of emapalumab as preventative management of CAR-T related cytokine release syndrome in participants with Non-Hodgkin's lymphoma (NHL).
The research study involves the following study interventions:
* Fludarabine and cyclophosphamide (Lymphodepleting Chemotherapy)
* Axicabtagene Ciloleucel
* Emapalumab

Start Date18 Sep 2024

Sponsor / Collaborator

The General Hospital Corp.

[+1]

NCT06285825 / RecruitingPhase 2IIT

A Pilot Study of Emapalumab for the Treatment of CAR T-Cell Therapy-Associated Prolonged Cytopenia

To look at the safety and effectiveness of emapalumab for the treatment of prolonged severe cytopenia in participants with LBCL who receive CART.

Start Date05 Jul 2024

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

[+1]

100 Clinical Results associated with Emapalumab-LZSG

100 Translational Medicine associated with Emapalumab-LZSG

100 Patents (Medical) associated with Emapalumab-LZSG

Literatures (Medical) associated with Emapalumab-LZSG

19 Dec 2024·BLOOD

Emapalumab therapy for hemophagocytic lymphohistiocytosis before reduced-intensity transplantation improves chimerism

Article

Author: Marsh, Rebecca ; Jordan, Michael B. ; Jodele, Sonata ; Verkamp, Bethany ; Sabulski, Anthony ; Kieser, Pearce

Abstract:

Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory disorder driven by interferon gamma (IFN-γ). Emapalumab, an anti–IFN-γ antibody, is approved for the treatment of patients with primary HLH. Hematopoietic stem cell transplantation (HSCT) is required for curing HLH. Reduced-intensity conditioning (RIC) HSCT is associated with improved survival but higher incidences of mixed chimerism and secondary graft failure. To understand the potential impact of emapalumab on post-HSCT outcomes, we conducted a retrospective study of pediatric patients with HLH receiving a first RIC-HSCT at our institution between 2014 and 2022 after treatment for HLH, with or without this agent. Mixed chimerism was defined as <95% donor chimerism and severe mixed chimerism as <25% donor chimerism. Intervention-free survival (IFS) included donor lymphocyte infusion, infusion of donor CD34-selected cells, second HSCT, or death within 5 years after HSCT. Fifty patients met the inclusion criteria; 22 received emapalumab within 21 days before the conditioning regimen, and 28 did not. The use of emapalumab was associated with a markedly lower incidence of mixed chimerism (48% vs 77%; P = .03) and severe mixed chimerism (5% vs 38%; P < .01). IFS was significantly higher in patients receiving emapalumab (73% vs 43%; P = .03). Improved IFS was even more striking in infants aged <12 months, a group at the highest risk for mixed chimerism (75% vs 20%; P < .01). Although overall survival was higher with emapalumab, this difference was not significant (82% vs 71%; P = .39). We show that the use of emapalumab for HLH before HSCT mitigates the risk of mixed chimerism and graft failure after RIC-HSCT.

27 Sep 2024·MEDICINE

Emapalumab as a therapeutic intervention for Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis: A case series

Article

Author: Yu, Li ; Pei, Fuyu ; Yuan, Xiao ; Wang, Wen

Rationale::

Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is characterized by a severe cytokine storm, heightened inflammatory response, and immune-mediated damage to tissues and organs. Standard treatment protocols for hemophagocytic lymphohistiocytosis often fall short in effectively controlling EBV-HLH, leading to a need for novel therapeutic options. Emapalumab, a monoclonal antibody targeting interferon-gamma, has shown promise due to its targeted cytokine modulation capabilities and favorable safety profile. This study aimed to evaluate the efficacy and safety of emapalumab in pediatric patients with EBV-HLH.

Patient concerns::

The case series involved 4 pediatric patients diagnosed with EBV-HLH who did not achieve disease control despite receiving comprehensive treatment.

Diagnoses::

All 4 pediatric patients were diagnosed with EBV-HLH.

Interventions::

Emapalumab was introduced as an adjunctive therapeutic intervention alongside the HLH-94 or L-DEP regimens for these patients.

Outcomes::

Among the 4 patients, 1 experienced severe multiorgan dysfunction and opted to discontinue therapy. The remaining 3 patients showed controlled disease progression with significant clinical improvements following emapalumab administration. These improvements included reduced levels of inflammatory markers, normalization of blood counts and liver function, and decreased Epstein–Barr virus viral load.

Lessons::

The findings suggest that emapalumab may be an effective and safe treatment option for pediatric EBV-HLH. However, further research is necessary to confirm these outcomes, especially in critically ill patients.

01 Sep 2024·JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

Systemic T-cell activation and IFN-γ activity in indeterminate severe hepatitis are reminiscent of hemophagocytic lymphohistiocytosis: Implications for T-cell– and IFN-γ–directed therapies

Article

Author: Kapoor, Urvi ; Montminy, Taylor ; Chandrakasan, Shanmuganathan ; Prince, Chengyu ; Rytting, Heather B ; Goldner, Dana ; Satwani, Prakash ; Malik, Sakshi ; Remotti, Helen E. ; Nguyen, Thinh H. ; Marsh, Rebecca ; Fazlollahi, Ladan ; Romero, Rene ; Rytting, Heather B. ; Remotti, Helen E ; Nguyen, Thinh H ; Martinez, Mercedes ; Smiley, Kristi ; Kumar, Deepak

BACKGROUND:

Severe hepatitis cases in children are increasingly recognized, but the exact etiology remains unknown in a significant proportion of patients. Cases of indeterminate severe hepatitis (iSH) may progress to indeterminate pediatric acute liver failure (iPALF), so understanding its immunobiology is critical to preventing disease progression. Hemophagocytic lymphohistiocytosis (HLH) is a systemic hyperinflammatory disorder associated with T-cell and macrophage activation with liver injury.

OBJECTIVES:

We hypothesized that a high proportion of patients with iSH demonstrate systemic T-cell activation similar to HLH before developing iPALF and that the degree of T-cell activation in iSH might correlate with outcomes.

METHODS:

From 2019 to 2022, 14 patients with iSH and 7 patients with PALF of known, nonimmune etiology were prospectively enrolled. We compared immune signatures of iSH, HLH, known PALF, and healthy controls.

RESULTS:

We found that patients with iSH have increased CD8⁺ T-cell activation and high IFN-γ activity similar to HLH. The amplitude of CD8⁺ T-cell activation was predictive of iSH progression to iPALF. We also found that in patients with iSH, ferritin had only modest elevation. However, the ratio of age-normalized plasma soluble IL-2 receptor to ferritin level can distinguish iSH from known PALF and HLH. As proof of concept, we report that in 3 patients with steroid-refractory iSH, emapalumab, an IFN-γ blocking antibody used in combination with steroids, improved liver function and may have prevented progression to PALF.

CONCLUSIONS:

Flow-based T-cell activation markers could help in early identification and risk stratification for targeted intervention in patients with iSH.

News (Medical) associated with Emapalumab-LZSG

03 Dec 2024

·www.prnewswire.com

Sobi's strength in haematology to be showcased at ASH 2024

STOCKHOLM, Dec. 3, 2024 /PRNewswire/ -- New data from Sobi® and partners will be presented at the 66th Annual Meeting of the American Society of Hematology (ASH) in San Diego, CA (USA) from the 7th - 10th of December 2024. During the meeting several analyses will be presented on haemophilia A, haemophagocytic lymphohistiocytosis (HLH), myelofibrosis, paroxysmal nocturnal haemoglobinuria (PNH), and immune thrombocytopenia (ITP). "Haemophilia A has a lasting impact on joint health and quality of life. At ASH 2024, three oral presentations will reveal important new data about long-term outcomes with ALTUVOCT® prophylaxis," said Lydia Abad-Franch, MD, MBA, Head of Research, Development, and Medical Affairs (RDMA), and Chief Medical Officer at Sobi. "We will also present new data spanning different severe and debilitating rare diseases, including an oral presentation on the real-world effectiveness of Doptelet® in treating people with ITP, demonstrating our broader commitment to advancing innovative treatments for people with rare haematological diseases. We look forward to sharing these findings in San Diego." Key data to be presented at ASH 2024 About ALTUVOCT® ALTUVOCT® (efanesoctocog alfa) [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein] (formerly BIVV001) is the first high-sustained FVIII replacement therapy with the potential to deliver near-normal factor activity levels for a significant part of the week, improving bleed protection in a once-weekly dose for people with haemophilia A. ALTUVOCT builds on the established Fc fusion technology by innovatively adding a region of von Willebrand factor and XTEN® polypeptides to extend its time in circulation. It is the only therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on current factor VIII therapies. The European Commission granted Orphan Drug designation in June 2019. It is approved and marketed as ALTUVOCT by Sobi in Europe. It is approved and marketed as ALTUVIIIO™ [Antihemophilic Factor (Recombinant), Fc-VWF-XTEN Fusion Protein-ehtl] by Sanofi in the United States, Japan, and Taiwan. About the Sanofi and Sobi collaboration Sobi and Sanofi collaborate on the development and commercialisation of Alprolix® and Elocta®/Eloctate®. The companies also collaborate on the development and commercialisation of ALTUVOCT® (efanesoctocog alfa), or ALTUVIIIO™ in the US. Sobi has final development and commercialisation rights in the Sobi territory (essentially Europe, North Africa, Russia, and most Middle Eastern markets). Sanofi has final development and commercialisation rights in North America and all other regions in the world excluding the Sobi territory. About Gamifant® Gamifant (emapalumab) is an anti-interferon gamma (IFNγ) monoclonal antibody that binds to and neutralises IFNγ. In the USA, Gamifant is indicated for the treatment of adult and paediatric (newborn and older) patients with primary haemophagocytic lymphohistiocytosis (HLH) with refractory, recurrent or progressive disease or intolerance with conventional HLH therapy. Primary HLH is a rare syndrome of hyperinflammation that usually occurs within the first year of life and can rapidly become fatal unless diagnosed and treated. The FDA approval is based on data from the phase 2/3 studies (NCT01818492 and NCT02069899). Gamifant is indicated for administration through intravenous infusion over one hour twice per week until haematopoietic stem cell transplantation (HSCT). About Vonjo® Vonjo (pacritinib), a JAK-1 sparing JAK2/IRAK1/ACVR1 inhibitor, is approved for the treatment of adults with intermediate- or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L in the United States. This indication is approved under FDA accelerated approval based on spleen volume reduction. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Currently, a Phase 3 study (PACIFICA) is being conducted to assess pacritinib in patients with myelofibrosis and severe thrombocytopenia as a post-marketing requirement. About Aspaveli®/ Empaveli® Aspaveli/Empaveli (pegcetacoplan) is a targeted C3 and C3b inhibitor designed to regulate excessive activation of the complement cascade, part of the body's immune system, which can lead to the onset and progression of many serious diseases. Pegcetacoplan is approved for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) as Aspaveli/Empaveli in the United States, European Union, and other countries globally. Currently, a Phase 3 trial (VALIANT) is being conduted to assess the efficacy and safety of pegcetacoplan in patients with C3G and primary IC-MPGN. Aspaveli/Empaveli is also under investigation for several other rare diseases across haematology and nephrology. About the Sobi and Apellis collaboration Sobi and Apellis have global co-development rights for systemic pegcetacoplan. Sobi has exclusive ex-U.S. commercialisation rights for systemic pegcetacoplan, and Apellis has exclusive U.S. commercialisation rights for systemic pegcetacoplan and worldwide commercial rights for ophthalmological pegcetacoplan, including for geographic atrophy. About Doptelet® Doptelet (avatrombopag) is an orally administered thrombopoietin receptor agonist (TPO-RA) that mimics the biologic effects of TPO in stimulating the development and maturation of megakaryocytes, resulting in increased platelet count. It is approved in over 30 countries worldwide, including the EU and the US, for the treatment of severe thrombocytopenia in adult patients with chronic liver disease who are scheduled to undergo an invasive procedure, and for the treatment of thrombocytopenia in adult patients with primary chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment. Chronic ITP is a rare autoimmune bleeding disorder characterised by low number of platelets. The incidence of primary ITP in adults is 3.3/100,000 adults per year with a prevalence of 9.5 per 100,000 adults. About Sobi® Sobi® is a specialised international biopharmaceutical company transforming the lives of people with rare and debilitating diseases. Providing reliable access to innovative medicines in the areas of haematology, immunology, and specialty care, Sobi has approximately 1,800 employees across Europe, North America, the Middle East, Asia, and Australia. In 2023, revenue amounted to SEK 22.1 billion. Sobi's share (STO:SOBI) is listed on Nasdaq Stockholm. More about Sobi at sobi.com and LinkedIn. Contacts For details on how to contact the Sobi Investor Relations Team, please click here. For Sobi Media contacts, click here. This information was brought to you by Cision The following files are available for download: WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Drug ApprovalPhase 3ASHOrphan DrugLicense out/in

28 Nov 2024

·www.prnewswire.com

Follicular Lymphoma Clinical Trial Pipeline Appears Robust With 50+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

Advances in immunotherapy have ushered in a new era of treatment for follicular lymphoma (FL), particularly for patients who have experienced relapse after conventional chemotherapy regimens. This paradigm shift is characterized by the emergence of innovative therapies like CAR T-cell therapy and bispecific antibodies, which have demonstrated remarkable efficacy in targeting and eradicating lymphoma cells. CAR T-cell therapy represents a groundbreaking approach where a patient's own T-cells are genetically engineered to recognize and attack cancer cells. This personalized treatment has shown significant promise, especially for individuals who have undergone extensive previous therapies. One notable example is Axicabtagene ciloleucel (Yescarta), a CAR T-cell therapy approved for use in patients with relapsed or refractory follicular lymphoma. Clinical trials have highlighted its ability to induce durable remissions, with some patients experiencing long-term remission even after multiple prior therapies. LAS VEGAS, Nov. 28, 2024 /PRNewswire/ -- DelveInsight's ' Follicular Lymphoma Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline follicular lymphoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the follicular lymphoma pipeline domain. Key Takeaways from the Follicular Lymphoma Pipeline Report DelveInsight's follicular lymphoma pipeline report depicts a robust space with 50+ active players working to develop 55+ pipeline therapies for follicular lymphoma treatment. Key follicular lymphoma companies such as Chia Tai Tianqing Pharmaceutical Group, Incyte Corporation, Mabworks, Johnson & Johnson Innovative Medicine, Nektar Therapeutics, Xynomic Pharmaceuticals, Merck Sharp & Dohme, Jiangsu HengRui Medicine Co., Ltd., ADC Therapeutics, Bristol-Myers Squibb, Swedish Orphan Biovitrum, Zhejiang DTRM Biopharma, Immpact Bio, Galapagos, Immunitas Therapeutics, Enterome, CRISPR Therapeutics, CHO Pharma, Shanghai Blueray Biopharma, BeiGene, AstraZeneca, AVM Biotechnology, Mustang Bio, Merck, Pell Bio-Med Technology, Schrodinger Inc., Sana Biotechnology, Poseida Therapeutics, OncoNano Medicine, Inc., Nurix Therapeutics, Inc., NovalGen, Pfizer, Xencor, Wellington Zhaotai Therapies, MEI Pharma, Sutro Biopharma, Synthekine, Verismo Therapeutics, Vincerx Pharma, Novartis, Century Therapeutics, Newave Pharmaceuticals, Bio-Path Holdings, Affimed GmbH, Iksuda Therapeutics, Allogene Therapeutics, Adicet Bio, Carna Biosciences, Inc., BeiGene, Boryung Pharmaceutical, Accutar Biotechnology, Atara Biotherapeutics, AbbVie, InnoCare Pharma, NeoImmuneTech, and others are evaluating new follicular lymphoma drugs to improve the treatment landscape. Promising follicular lymphoma pipeline therapies such as Parsaclisib, TQ-B3525, Tafasitamab, MIL62, Ibrutinib, AZD0486, NKTR-255, Abexinostat, Acalabrutinib, Zilovertamab vedotin, SHR2554, Nivolumab, Loncastuximab tesirine, Golcadomide, Emapalumab, DTRM-555, Capivasertib, IMPT 314, GLPG5101, IMT-009, EO2463, CTX112, CHO-H01, BR1733, BGB-16673, BGB-10188, AZD5492, AVM0703, MB106, MK-1026, PL001, SGR-1505, SC291, SC262, P-CD19CD20-ALLO1, ONM 501, NX-5948, NX 2127, NVG-111, Mevrometostat, Plamotamab, WZTL-002, Voruciclib, STRO001, SYNCAR-001 + STK-009, SynKIR-310, VIP-152, VAY736, CNTY-101, LP-168, BP1002, IOA-244, IKS 03, ALLO-501, ADI-001, AS-1763, BGB-21447, BR101801, AC676, ATA3219, ABBV-319, ABBV-101, ICP-B02, ICP-B05, C-CAR039, Efineptakin Alfa, and others are under different phases of follicular lymphoma clinical trials. In August 2024, the company expects to file a supplemental Biologics License Application for tafasitamab for the treatment of patients with FL who have failed at least one prior systemic anti-CD20 immunotherapy or chemo-immunotherapy by the end of 2024 based on the positive Phase III results. In June 2024, a consortium of Eugene Private Equity and Korea Development Bank Private Equity announced that they would acquire 80% of South Korean vaccine maker Boryung Biopharma Co. for 320 billion won (USD 231 million). In February 2024, Incyte announced that it had entered into an asset purchase agreement with MorphoSys AG, which gives Incyte exclusive global rights for tafasitamab. Incyte will now recognize revenue and cost for all US commercialization and clinical development and MorphoSys will no longer be eligible to receive future milestone, profit split and royalty payments. In September 2023, OncoNano Medicine, Inc. announced a clinical trial supply agreement with Regeneron for the use of Libtayo (cemiplimab), a PD-1 inhibitor, in the combination stage of the first human trial of ONM-501, a dual-activating STING (STimulator of INterferon Genes) agonist and lead therapeutic development candidate. The ONM-501 first-in-human trial is a multicenter Phase Ia/b dose escalation and dose expansion study of intratumoral ONM-501 as monotherapy and in combination with Libtayo in patients with advanced solid tumors and lymphomas. OncoNano is the sponsor of the clinical trial, and Regeneron will supply cemiplimab. In May 2023, Janssen Pharmaceutical Companies of Johnson & Johnson announced that it had entered into a worldwide collaboration and license agreement with Cellular Biomedicine Group Inc. (CBMG) to develop, manufacture, and commercialize next-generation chimeric antigen receptor (CAR) T-cell therapies for the treatment of B-cell malignancies. Under the terms of the agreement, CBMG will grant Janssen a worldwide license to develop and commercialize the CAR-T assets, except in Greater China. Janssen and CBMG will negotiate an option for Janssen to commercialize the products in the Chinese territory. Janssen will make an upfront payment of USD 245 million that will be accounted for in the second quarter as a research and development expense. Additional future payments will be based upon achieving certain development, regulatory, and sales milestones, as well as tiered royalty payments on worldwide net trade sales, excluding Greater China. Request a sample and discover the recent advances in follicular lymphoma treatment drugs @ Follicular Lymphoma Pipeline Report The follicular lymphoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage follicular lymphoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the follicular lymphoma clinical trial landscape. Follicular Lymphoma Overview Follicular lymphoma is a common type of non-Hodgkin lymphoma (NHL) that originates from B-cells, a kind of white blood cell responsible for producing antibodies. This cancer is characterized by the growth of abnormal lymphoid follicles, which can disrupt normal lymphatic function. While the exact causes of follicular lymphoma are not fully understood, certain factors may increase the risk, including age (most commonly affecting adults over 60), a family history of lymphoma, and potential environmental factors such as exposure to pesticides or chemicals. Symptoms of follicular lymphoma can vary widely but may include painless swelling of lymph nodes in the neck, armpit, or groin, unexplained weight loss, night sweats, fatigue, and fever. Some patients may remain asymptomatic for extended periods, as this type of lymphoma can progress slowly. Diagnosis typically involves a combination of physical examinations, blood tests, imaging studies (like CT scans), and a biopsy of affected lymph nodes. The biopsy helps determine the subtype and stage of the lymphoma, which is crucial for planning treatment. Treatment for follicular lymphoma depends on the stage of the disease and the patient's overall health. Options may include watchful waiting for asymptomatic cases, chemotherapy, immunotherapy (such as monoclonal antibodies), and targeted therapies. In some cases, stem cell transplants may be considered for patients with more aggressive forms or those who do not respond to initial treatments. Given the indolent nature of follicular lymphoma, ongoing management, and regular monitoring are vital for achieving the best possible outcomes. Find out more about follicular lymphoma treatment drugs @ Drugs for Follicular Lymphoma Treatment A snapshot of the Follicular Lymphoma Pipeline Drugs mentioned in the report: Learn more about the emerging follicular lymphoma pipeline therapies @ Follicular Lymphoma Clinical Trials Follicular Lymphoma Therapeutics Assessment The follicular lymphoma pipeline report proffers an integral view of the follicular lymphoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Follicular Lymphoma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-articular, Intraocular, Intrathecal, Intravenous, Oral, Parenteral, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: Phosphatidylinositol 3 kinase delta inhibitors, Phosphatidylinositol 3 kinase gamma inhibitors, Emt protein-tyrosine kinase inhibitors, Interleukin 15 receptor agonists, Histone deacetylase inhibitors, Rad51 recombinase inhibitors, Agammaglobulinaemia tyrosine kinase inhibitors, Apoptosis stimulants, Cell cycle inhibitors, Tubulin inhibitors, Tubulin polymerisation inhibitors, Enhancer of zeste homolog 2 protein inhibitors, Antibody-dependent cell cytotoxicity, Programmed cell death 1 receptor antagonists, T lymphocyte stimulants, Alkylating agents, DNA cross-linking agents Key Follicular Lymphoma Companies: Chia Tai Tianqing Pharmaceutical Group, Incyte Corporation, Mabworks, Johnson & Johnson Innovative Medicine, Nektar Therapeutics, Xynomic Pharmaceuticals, Merck Sharp & Dohme, Jiangsu HengRui Medicine Co., Ltd., ADC Therapeutics, Bristol-Myers Squibb, Swedish Orphan Biovitrum, Zhejiang DTRM Biopharma, Immpact Bio, Galapagos, Immunitas Therapeutics, Enterome, CRISPR Therapeutics, CHO Pharma, Shanghai Blueray Biopharma, BeiGene, AstraZeneca, AVM Biotechnology, Mustang Bio, Merck, Pell Bio-Med Technology, Schrodinger Inc., Sana Biotechnology, Poseida Therapeutics, OncoNano Medicine, Inc., Nurix Therapeutics, Inc., NovalGen, Pfizer, Xencor, Wellington Zhaotai Therapies, MEI Pharma, Sutro Biopharma, Synthekine, Verismo Therapeutics, Vincerx Pharma, Novartis, Century Therapeutics, Newave Pharmaceuticals, Bio-Path Holdings, Affimed GmbH, Iksuda Therapeutics, Allogene Therapeutics, Adicet Bio, Carna Biosciences, Inc., BeiGene, Boryung Pharmaceutical, Accutar Biotechnology, Atara Biotherapeutics, AbbVie, InnoCare Pharma, NeoImmuneTech, and others. Key Follicular Lymphoma Pipeline Therapies: Parsaclisib, TQ-B3525, Tafasitamab, MIL62, Ibrutinib, AZD0486, NKTR-255, Abexinostat, Acalabrutinib, Zilovertamab vedotin, SHR2554, Nivolumab, Loncastuximab tesirine, Golcadomide, Emapalumab, DTRM-555, Capivasertib, IMPT 314, GLPG5101, IMT-009, EO2463, CTX112, CHO-H01, BR1733, BGB-16673, BGB-10188, AZD5492, AVM0703, MB106, MK-1026, PL001, SGR-1505, SC291, SC262, P-CD19CD20-ALLO1, ONM 501, NX-5948, NX 2127, NVG-111, Mevrometostat, Plamotamab, WZTL-002, Voruciclib, STRO001, SYNCAR-001 + STK-009, SynKIR-310, VIP-152, VAY736, CNTY-101, LP-168, BP1002, IOA-244, IKS 03, ALLO-501, ADI-001, AS-1763, BGB-21447, BR101801, AC676, ATA3219, ABBV-319, ABBV-101, ICP-B02, ICP-B05, C-CAR039, Efineptakin Alfa, and others. Dive deep into rich insights for new drugs for follicular lymphoma treatment, visit @ Follicular Lymphoma Drugs Table of Contents For further information on the follicular lymphoma pipeline therapeutics, reach out @ Follicular Lymphoma Treatment Drugs Related Reports Follicular Lymphoma Market Follicular Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key follicular lymphoma companies including Epizyme, Eisai, Bayer Healthcare Pharmaceuticals, Verastem Oncology, Gilead Sciences, TG Therapeutics, Bristol-Myers-Squibb, Roche, Incyte Corporation, Bristol Myers Squibb, ADC Therapeutics, MorphoSys, Nordic Nanovector, AbbVie, Regeneron Pharmaceuticals, Janssen Research & Development, Novartis, MEI Pharma, and BeiGene, among others. Non-Hodgkin Lymphoma Market Non-Hodgkin Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key Non-Hodgkin lymphoma companies, including Roche, Pfizer, Amgen, Novartis, Teva Pharmaceuticals, Genentech, ACD Therapeutics, among others. Non-Hodgkin Lymphoma Pipeline Non-Hodgkin Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Non-Hodgkin lymphoma companies, including Novartis, AstraZeneca, Genentech, BioInvent, Genmab, SystImmune, Nordic Nanovector, Pacylex Pharmaceuticals, Artiva Biotherapeutics, Inc., Chipscreen Biosciences, Ltd., Timmune Biotech Inc., Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Gilead Sciences, Acerta Pharma BV, Adagene Inc, Conjupro Biotherapeutics, Inc., Rhizen Pharmaceuticals, Juventas Cell Therapy Ltd., Incyte Corporation, HUYA Bioscience International, SecuraBio, Genor Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Antengene Therapeutics Limited, Regeneron Pharmaceuticals, Jiangsu HengRui Medicine Co., Ltd., Xynomic Pharmaceuticals, Inc., BioTheryX, Inc., UWELL Biopharma, Kronos Bio, Bio-Thera Solutions, Spectrum Pharmaceuticals, Inc., Aptose Biosciences Inc., Miltenyi Biomedicine GmbH, Precision BioSciences, Inc., Teneobio, Inc., TCR2 Therapeutics, IGM Biosciences, Inc, among others. Diffuse Large B-cell Lymphoma Market Diffuse Large B-cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key DLBCL companies, including AbbVie, Genmab, Merck, Roche, Xencor, Janssen, Denovo Biopharma, Calithera Biosciences IMV, Biogen, Autolus Therapeutics, Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Regeneron Pharmaceuticals, Debiopharm, Seagen, Takeda, AstraZeneca, Gilead Sciences, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

ImmunotherapyLicense out/inPhase 3VaccineCell Therapy

27 Nov 2024

·www.lightchainbio.com

ASH-2024 generation of FcRH5xCD28 bispecific antibodies

Light Chain Bioscience is leveraging its proprietary bispecific antibody format to advance immune therapies in oncology and beyond. The Swiss biopharmaceutical company Light Chain Bioscience has developed a novel and unique class of human, bispecific antibodies dubbed κλ bodies, so-called because they combine a κ light chain that recognizes a first target and a λ light chain that recognizes a second one, into a native human antibody structure. In collaboration with TG Therapeutics, Light Chain has brought one internally developed κλ body, TG-1801 (formerly NI-1701), into clinical trials for relapsed/refractory B cell lymphoma, and has a number of others in the pipeline for the treatment of various tumors and blood disorders. Light Chain emerged from Novimmune, which over the past 20 years has developed monoclonal antibodies (mAbs) in inflammatory and autoimmune diseases, with seven reaching clinical trials and one, the anti-interferon mAb Gamifant (emapalumab), gaining approval by the US Food and Drug Administration (FDA) in 2018 as the first treatment for hemophagocytic lymphohistiocytosis. In July 2019, Novimmune divested Gamifant and related activities, and rebranded as Light Chain Bioscience with a focus on bispecific antibodies. Light Chain, which draws on decades of experience in immunology and antibody-based therapies gained as Novimmune, is now seeking partners to take forward candidates identified by Light Chain, as well as partners seeking to apply Light Chain’s expertise and technology platform to their own projects. “Building on Novimmune’s long experience in antibody discovery and development, Light Chain Bioscience now focuses on leveraging the unique features of its bispecific antibody format”, said Erich Hunziker, Chairman of Light Chain Bioscience. Bispecific antibodies represent a rapidly growing therapeutic approach, and many methods have been devised for their production. Often this has required extensive engineering of antibodies at their interfaces, or addition of linkers and other foreign sequences, to facilitate assembly and allow the cells expressing the antibodies to produce the bispecific product in sufficient quantities. LightChain’s approach is different, creating bispecific antibodies that are essentially fully human, with no engineering required. The method for creating bispecific κλ bodies is simple: a production cell expresses a single heavy chain, alongside κ and λ light chains, which self-assemble into functional antibodies. This process creates a mixture of antibodies, 25% of which are monospecific containing two κ identical chains, 25% are monospecific with two identical λ chains and 50% are bispecific κλ bodies, which can be very effectively purified from the supernatant using affinity reagents binding to the two different light chains. Light Chain’s bispecific platform not only bypasses engineering challenges but also offers a simple and scalable manufacturing process. Working with contract manufacturing company Lonza Pharma & Biotech, Light Chain has already manufactured κλ bodies under good manufacturing practice (GMP) on a 1,000-litre scale in several runs, with high yields (Fig. 1). «Building on Novimmune’s long experience in antibody discovery and development, Light Chain Bioscience now focuses on leveraging the unique features of its bispecific antibody format» Erich Hunziker, Chairman, Light Chain Bioscience As more and more bispecific antibodies have entered clinical trials, immunogenicity potentially associated with engineered or foreign elements in the antibodies is emerging as a significant concern. Light Chain’s κλ bodies have no modifications, except for the loops present in the extremities of the light chains that create the desired target specificity, as in any normal human antibody. “Over the last decade challenges linked to bispecific antibodies engineering and manufacturing have been overcome. The field is now beginning to face the issue of immunogenicity,” said Nicolas Fischer, CEO of Light Chain Bioscience. “The native structure of κλ bodies is likely to represent a significant advantage.” Targeting innate immune checkpoints Light Chain’s most advanced bispecific κλ body candidate is TG-1801, which has binding moieties for CD47 and the B cell surface antigen CD19, and is in phase 1 trials for relapsed/refractory B cell lymphoma. CD47 is an immune checkpoint protein that functions as a regulator of phagocytosis. Cancer immunotherapies that target adaptive immune checkpoints have demonstrated clinical benefits in a range of cancers, and in recent years the idea of targeting innate immune checkpoints has emerged as a hot topic, with CD47 widely seen as an exciting new innate checkpoint molecule. CD47 is a membrane-bound protein expressed on tumor cells, as well as all normal cells in the body, where it acts as a ‘don’t eat me!’ signal. CD47 communicates this message by binding to signal-regulatory protein-α (SIRPα) on phagocytic cells, particularly macrophages; this binding in turn inhibits phagocytosis. Tumor cells frequently hijack this system and overexpress CD47, which translates clinically into worse prognoses across several cancer indications. Blocking the signalling between CD47 and SIRPα with anti-CD47 mAbs increases the phagocytosis and killing of tumor cells. However, early examples of this approach contained a fully functional Fc portion that led to indiscriminate binding and killing of normal cells, including red blood cells (RBCs) and platelets,which resulted in dangerous thrombocytopenia. To overcome the challenge of hemotoxicity, anti- CD47 mAbs that carry a silenced Fc portion have been developed, but these have to be administered alongside a second mAb directed against a tumorassociated antigen (TAA) such as HER2 (also known as ERBB2), CD19 or CD20. Light Chain’s TG-1801 combines the functions of two antibodies, with one light chain binding to CD47 and the other to CD19. The CD47-binding domain has been optimized so that it binds with relatively low affinity, which ensures that it does not remain bound to normal cells, including RBCs and platelets. The CD19- binding domain, however, binds to its ligand tightly and anchors TG-1801 on the surface of B cells, where it can then co-bind to CD47. Because TG-1801 only binds strongly to CD47 in the presence of CD19 on B cells, it is able to retain a fully functional Fc portion without causing hemotoxicity (Fig. 2). Crucially, because the Fc portion is fully functional in TG-1801, it can recruit macrophages as well as other effector cells in the tumor microenvironment to eat and kill tumor cells that they would otherwise ignore. Studies with non-human primates have shown that in a model system in which CD47 is ubiquitously expressed, TG-1801 has good pharmacokinetic properties and does not cause hemotoxicity. TG-1801 is being jointly developed with TG Therapeutics and is currently in a phase 1 trial for B cell lymphoma. TG-1801 established proof of principle for the bispecific κλ body approach, and Light Chain has six other bispecific candidates coming through the pipeline, developed internally or in collaboration with partners. NI-1801, a follow-on molecule, also contains a CD47-binding light chain and has the same mechanism of action as TG-1801. However, instead of co-binding with CD19, NI-1801 binds to mesothelin. Light Chain anticipates that NI-1801, which is being developed to target a range of solid tumors, will be ready to enter the clinic in 2021. In addition, Light Chain has developed candidates for indications beyond oncology, including NI-2101 for Takeda, which targets factor IX and factor X for the treatment of hemophilia. «Our dual targeting strategy has the potential of combining CD47 inhibition with an improved safety and pharmacokinetic profile, allowing for more drug to reach and target the tumor» Walter Ferlin, CSO, Light Chain Bioscience “Emerging clinical data put CD47 under the spotlight. Our dual targeting strategy has the potential of combiningCD47 inhibition with an improved safety and pharmacokinetic profile, allowing for more drug to reach and target the tumor,” said Walter Ferlin, CSO of Light Chain Bioscience. Light Chain is also developing T cell retargeting therapies using bispecific antibodies. This approach was first validated by the approval of Blincyto (blinatumomab; Amgen) for the treatment of refractory acute lymphoblastic leukemia. Since then, T cell retargeting has been widely developed and represents one of the main applications of bispecific antibodies in oncology. This mechanism of action can readily be achieved with bodies and several programs are being developed with partners for the treatment of solid cancers. Beyond bispecifics Looking into the future, Light Chain is leveraging a feature of its technology platform that enables the production from a single cell of well-controlled mixtures of monospecific and/or bispecific antibodies. Subsets composed of a few bispecific antibodies can be readily purified using affinity chromatography. The combination of therapeutic modalities is clearly the way forward to achieve responses in cancer patients. As more and more combinations of antibodies are being developed to treat complex diseases, the generation of a product consisting of several mono- or bispecific antibodies represents an attractive possibility for next-generation therapeutics. Today Light Chain seeks partners to work on projects in immuno-oncology and other therapeutic areas. Light Chain would like to hear from companies with the skills and expertise to co-develop internally discovered candidates such as NI-1801 and take them into the clinical stages of development. In addition, Light Chain welcomes discussions with prospective partners who want to draw on Light Chain’s deep well of expertise in bispecific antibodies for CD47 targeting and T cell retargeting, as well as other approaches outside oncology. Next-generation immunotherapy with native bispecific antibodies (PDF Download)

ImmunotherapyPhase 1Drug Approval

100 Deals associated with Emapalumab-LZSG

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KEGG	Wiki	ATC	Drug Bank
-	Emapalumab-LZSG	L04AA39	DB14724

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Lymphohistiocytosis, Hemophagocytic	US	Novimmune SA	20 Nov 2018

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Immune System Diseases	NDA/BLA	EU	Swedish Orphan Biovitrum AB	23 Jul 2020
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	US	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	JP	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	BE	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	CA	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	CZ	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	FR	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	DE	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	IT	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022
Polyarticular Juvenile Idiopathic Arthritis	Phase 3	NL	Supi Pharmaceutical (Guangzhou) Co., Ltd.	14 Jan 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Tandem Meetings ASTCT and CIBMTR2024	Not Applicable	-	-	Emapalumab	tmkftcgvpq(sbnuchqmis) = jodwmufugp utokesptph (tafwcmdqyv )	-	01 Feb 2024
NCT04765553 (CTgov)	Phase 1	Rare Diseases	8	NI-0501 (Emapalumab)	sqgvtwuzuo(bqtqoypnrw) = qodzqapftz exwovixyps (qhccwgtqjf, btzmalxiea - zejiubxeeg) View more	-	24 Nov 2023
NCT04765553 (CTgov)	Phase 1	Rare Diseases	8	Saline (Placebo)	pklyurvzjx(spbyrdmoak) = dkartqcerf enbgttzdxw (dmohsynpli, kabkjspzax - fvlagrcycb) View more	-	24 Nov 2023
NCT03985423 (CTgov)	Phase 2/3	Lymphohistiocytosis, Hemophagocytic	7	Emapalumab-Lzsg	zyudubvfha(ipxhevzvcf) = bdcieuajii viymttroxd (fqoufsxrcu, gfowumvlax - uwsnkasoux) View more	-	06 Oct 2023
P353 (EBMT2023)	Phase 2	IFNÎ³ \| CXCL9	1	Emapalumab 3 mg/kg	ueyopwkrus(jjwcvwkhwf) = tjqegatreq enpcyjvlil (igfejtbejf ) View more	Positive	23 Apr 2023
NCT02069899 (NI-0501-04 and NI-0501-05 \| ###DELETE, CTgov)	Phase 2/3	Lymphohistiocytosis, Hemophagocytic	58	Emapalumab (Enrolled-04 Cohort)	gxyhdxeanw(pcqqthosqu) = ymjppstquh fbpecaxzby (vabdygyabz, rtofitdpre - wtuihmizur) View more	-	28 Jun 2022
NCT02069899 (NI-0501-04 and NI-0501-05 \| ###DELETE, CTgov)	Phase 2/3	Lymphohistiocytosis, Hemophagocytic	58	emapalumab (Enrolled-06 Cohort)	gxyhdxeanw(pcqqthosqu) = wrmbeywtwy fbpecaxzby (vabdygyabz, suapiasdch - qktrypumgh) View more	-	28 Jun 2022
NCT04731298 (P449, EBMT2022)	Phase 2	Primary Graft Dysfunction CXCL9	10	Emapalumab	bmcblsiisn(clpapfzbdy) = aqsrinizfs qqxhvaicyi (yyqtouaugd ) View more	Positive	19 Mar 2022
NCT02069899 \| NCT01818492 (Tandem Meetings ASTCT and CIBMTR2021)	Phase 2/3	Lymphohistiocytosis, Hemophagocytic Second line	45	Emapalumab 1 mg/kg	dnphihozdf(dqvcgkgudb) = pvnscpcqke ygefjvwacy (nicipoziao, 68.3 - 97.6) View more	Positive	01 Mar 2021
	Phase 2/3	Lymphohistiocytosis, Hemophagocytic Second line	45	Background dexamethasone 5-10 mg/m2	dnphihozdf(dqvcgkgudb) = tcmhoxjqok ygefjvwacy (nicipoziao, 62.1 - 92.1) View more	Positive	01 Mar 2021
NCT02069899 \| NCT01818492 (NI-0501-04 \| NI-0501-05, Pubmed \| Br Dent J \| N Engl J Med) Manual	Phase 2/3	Lymphohistiocytosis, Hemophagocytic First line	34	Emapalumab (previously treated)	ixxwslzsyv(wrdoalspbx) = dvaommxwcz jdccnvzryv (eqejqglcyh ) View more	Positive	07 May 2020
	Phase 2/3	Lymphohistiocytosis, Hemophagocytic First line	34	Emapalumab (previously untreated)	ixxwslzsyv(wrdoalspbx) = rdkzdrgjdf jdccnvzryv (eqejqglcyh ) View more	Positive	07 May 2020
NI-0501 (ACR2015)	Not Applicable	Lymphohistiocytosis, Hemophagocytic \| Autoinflammation With Infantile Enterocolitis IL-18 \| IFNγ \| CXCL9 ... View more	1	NI-0501	uqzpsmmdak(mtmuwpuubv) = jbrjhqashr ihcfsnlerh (ccqeqhlnad )	Positive	10 Nov 2015
NI-0501 (ACR2015)	Not Applicable	Lymphohistiocytosis, Hemophagocytic IFNg	10	NI-0501 1 mg/kg	ckpsymgwzb(cgpgsnklim) = All infusions were well tolerated and no safety concerns emerged xigxtdijfb (mhrcjewvsg )	Positive	10 Nov 2015

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