Bi-Specific and Tri-Specific Antibodies- the Next Big Thing in Solid Tumor Therapeutics Karie Runcie1, Daniel R
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Polatuzumab Vedotin - R/R DLBCL RG7769 PD1-TIM3 Bimab - Solid Tumors NSCLC RG7446 Tecentriq – Her2-Pos
Pipeline summary Marketed products additional indications Global Development late-stage trials pRED (Roche Pharma Research & Early Development) gRED (Genentech Research & Early Development) 1 Changes to the development pipeline FY 2018 update New to phase I New to phase II New to phase III New to registration 3 NMEs: 2 NMEs transitioned from Ph1 1 NME transitioned from Ph2: 2 NMEs + 1 AI transitioned from Ph2 RG6217 - HBV RG7906 - psychiatric disorders RG6042 HTT ASO - Huntington’s following filing in EU and US: RG6237 - neuromuscular disorders RG6058 tiragolumab + Tecentriq - 6 AIs: RG7596 polatuzumab vedotin - r/r DLBCL RG7769 PD1-TIM3 biMAb - solid tumors NSCLC RG7446 Tecentriq – Her2-pos. BC neoadj RG6268 entrectinib - NSCLC ROS1+ 1 AI: 1 NME starting Ph2 RG7446 Tecentriq – high risk NMIBC RG6268 entrectinib – NTRK1 pan-tumor RG7601 Venclexta + gilteritinib – r/r RG6180 iNeST (personalized cancer RG6152 Xofluza - influenza hosp. patients 3 AIs transitioned from Ph3 following AML vaccine) + pembrolizumab - malignant RG6152 Xofluza – influenza pediatric filing in EU and US: melanoma patients RG7446 Tecentriq + nab-paclitaxel 1L 1 NME following termination of Ph3 RG7601 Venclexta - r/r MM t(11:14) non sq NSCLC RG7412 crenezumab – familial RG7601 Venclexta + HMA/LDAC - 1L RG7446 Tecentriq + nab-paclitaxel Alzheimer’s disease healthy individuals AML* 1LTNBC RG7446 Tecentriq + chemo - 1L extensive 1 AI: stage SCLC RG7446 Tecentriq SC – NSCLC Removed from phase I Removed from phase II Removed from phase III Removed from registration 2 NMEs: -
Prescribing Information: Gazyvaro® (Obinutuzumab)
Prescribing information: Gazyvaro®▼ (obinutuzumab) PRESCRIBING INFORMATION Gazyvaro maintenance as a single agent, 1000 mg 70 mL/min are more at risk of IRRs, including severe Gazyvaro® (obinutuzumab) 1000 mg once every 2 months for 2 years or until disease IRRs. Do not administer further infusions if patient concentrate for solution for infusion progression (whichever occurs first). Administration: experiences acute life-threatening respiratory Refer to Gazyvaro Summary of Product Monitor closely for infusion related reactions (IRRs). symptoms, a Grade 4 (life threatening) IRR or, a Characteristics (SmPC) for full prescribing CLL: Cycle 1: Day 1(100 mg): Administer at 25 mg/hr second occurrence of a Grade 3 (prolonged/recurrent) information. over 4 hours. Do not increase the infusion rate. Day 2 IRR (after resuming the first infusion or during a (or Day 1 continued) (900 mg): If no IRR occurred subsequent infusion). Carefully monitor patients who Indications: Previously-untreated chronic lymphocytic during prior infusion administer at 50 mg/hr. Infusion have pre-existing cardiac or pulmonary conditions leukaemia (CLL), in combination with chlorambucil, in rate can be escalated in 50 mg/hr increments every 30 throughout the infusion and post-infusion period. For patients with co-morbidities making them unsuitable for minutes to 400 mg/hr. – All subsequent infusions: If no patients at acute risk of hypertensive crisis evaluate full-dose fludarabine-based therapy. Follicular IRR occurred during prior infusion when final rate was the benefit and risks of withholding anti-hypertensive lymphoma (FL), in combination with bendamustine 100 mg/hr or faster, start at 100 mg/hr and increase by medicine. -
Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies
Review Taking up Cancer Immunotherapy Challenges: Bispecific Antibodies, the Path Forward? Joanie Del Bano 1,2,3,4,†, Patrick Chames 1,2,3,4, Daniel Baty 1,2,3,4 and Brigitte Kerfelec 1,2,3,4,*,† Received: 12 November 2015; Accepted: 18 December 2015; Published: 26 December 2015 Academic Editor: Christian Klein 1 Inserm, U1068, CRCM, Marseille F-13009, France; [email protected] (J.D.B.); [email protected] (P.C.); [email protected] (D.B.) 2 Aix-Marseille University, Marseille F-13284, France 3 CNRS, UMR7258, CRCM, Marseille F-13009, France 4 Institut Paoli-Calmettes, Marseille F-13009, France * Correspondence: [email protected]; Tel.: +33-491-828-833; Fax: +33-491-828-840 † These authors contributed equally to this work. Abstract: As evidenced by the recent approvals of Removab (EU, Trion Pharma) in 2009 and of Blincyto (US, Amgen) in 2014, the high potential of bispecific antibodies in the field of immuno-oncology is eliciting a renewed interest from pharmaceutical companies. Supported by rapid advances in antibody engineering and the development of several technological platforms such as Triomab or bispecific T cell engagers (BiTEs), the “bispecifics” market has increased significantly over the past decade and may occupy a pivotal space in the future. Over 30 bispecific molecules are currently in different stages of clinical trials and more than 70 in preclinical phase. This review focuses on the clinical potential of bispecific antibodies as immune effector cell engagers in the onco-immunotherapy field. We summarize current strategies targeting various immune cells and their clinical interests. -
Scientific Annual Report 2019
Scientific Annual Report 2019 Scientific Annual Report 2019 Contents 2 Introduction 14 Board members Director of Research 18 Group leaders 18 Neil Aaronson 37 Kees Jalink 56 Hein te Riele 19 Reuven Agami 38 Jos Jonkers 57 Lonneke van de Poll 20 Leila Akkari 39 Marleen Kok 58 Winette van der Graaf 21 Regina Beets-Tan 40 Pia Kvistborg and Olga Husson 22 Roderick Beijersbergen 41 Tineke Lenstra 60 Uulke van der Heide 23 Jos Beijnen 42 Sabine Linn 61 Michiel van der Heijden 24 André Bergman 43 René Medema 62 Wim van Harten 25 René Bernards 44 Gerrit Meijer and 63 Flora van Leeuwen and 26 Christian Blank Remond Fijneman Matti Rookus 27 Eveline Bleiker 46 Daniel Peeper 65 Fred van Leeuwen 28 Gerben Borst 47 Anastassis Perrakis 66 Maarten van Lohuizen 29 Thijn Brummelkamp 48 Benjamin Rowland 67 Jacco van Rheenen 30 Karin de Visser 49 Sanne Schagen 68 Bas van Steensel 31 Elzo de Wit 50 Alfred Schinkel 69 Olaf van Tellingen 32 William Faller 51 Marjanka Schmidt 70 Emile Voest 33 John Haanen 52 Ton Schumacher 71 Jelle Wesseling 34 Hugo Horlings 53 Titia Sixma 72 Lodewyk Wessels 35 Heinz Jacobs 54 Jan-Jakob Sonke 73 Lotje Zuur 36 Jacqueline Jacobs 55 Arnoud Sonnenberg 74 Wilbert Zwart 78 Division of 84 Division of 90 Division of Diagnostic Oncology Medical Oncology Surgical Oncology 96 Division of 102 Division of 110 Technology Radiation Oncology Pharmacology Transfer Office and Biometrics 112 Research Facilities 126 Education in 134 Clinical Oncology trials 164 Invited 166 Research 194 Personnel speakers projects index Netherlands Cancer Institute Plesmanlaan 121 1066 CX Amsterdam The Netherlands www.nki.nl Scientific Annual Report 2019 Introduction It is my pleasure to present the 2019 Scientific Annual Report of the Netherlands Cancer Institute. -
Assessment of Overall Survival, Quality of Life, And
Supplementary Online Content Salas-Vega S, Iliopoulos O, Mossialos E. Assesment of overall survival, quality of life, and safety benefits associated with new cancer medicines [published online December 29, 2016]. JAMA Oncol. doi:10.1001/jamaoncol.2016.4166 eTable 1. Therapeutic profile of all cancer medicines approved by the FDA between 2003- 2013 eTable 2. Regulatory evidence in support of classification of drug clinical benefits eFigure 1. Number of cancer drugs that were evaluated by all three HTA agencies, sorted by magnitude of clinical benefits eTable 3. Interagency agreement–Krippendorff’s alpha coefficients eMethods This supplementary material has been provided by the authors to give readers additional information about their work. Online-Only Supplement © 2016 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/25/2021 Clinical value of cancer medicines Contents eExhibits ......................................................................................................................................................... 3 eTable 1. Therapeutic profile of all cancer medicines approved by the FDA between 2003- 2013 (Summary of eTable 2) ................................................................................................................... 3 eTable 2. Regulatory evidence in support of classification of drug clinical benefits ....................... 6 eFigure 1. Number of cancer drugs that were evaluated by all three HTA agencies, sorted by magnitude of clinical benefits -
Press Release Corporate Communications
Matthias Link Press Release Corporate Communications Fresenius SE & Co. KGaA Else-Kröner-Strasse 1 61352 Bad Homburg Germany T +49 6172 608-2872 F +49 6172 608-2294 [email protected] www.fresenius.com June 22, 2011 Fresenius Biotech obtains reimbursement approval for Removab® antibody in Italy The Italian Medicines Agency, AIFA, has added Fresenius Biotech’s antibody Removab® to its list of reimbursable medications. As of June 25, 2011, use of Removab® for the treatment of malignant ascites in patients with EpCAM-positive carcinomas will be fully reimbursed. Removab® is a trifunctional monoclonal antibody approved throughout the European Union. It has been launched in Austria, France, Germany, Scandinavia and the UK. “The positive decision concerning reimbursement is another step in the successful implementation of our European marketing strategy for Removab®,” said Dr. Christian Schetter, CEO of Fresenius Biotech. “It enables patients in Italy to benefit from treatment with Removab® quickly and without bureaucratic hurdles.” Follow-up results for the pivotal study, recently presented at the 47th Annual Meeting of the American Society of Clinical Oncology (ASCO), showed a statistically significant benefit in overall survival for Removab®-treated patients. After six months, nearly 30% of all patients treated with Removab® were still alive, which is a fourfold increase compared to the control group (around 7%). In addition, Removab®-treated patients were shown to have an improved quality of life. ### Page 1/3 About Removab® (catumaxomab) Removab®, with its trifunctional mode of action, represents the first antibody of a new generation. The therapeutic objective of Removab® is to generate a stronger immune response to cancer cells that are the main cause of ascites. -
USAN Naming Guidelines for Monoclonal Antibodies |
Monoclonal Antibodies In October 2008, the International Nonproprietary Name (INN) Working Group Meeting on Nomenclature for Monoclonal Antibodies (mAb) met to review and streamline the monoclonal antibody nomenclature scheme. Based on the group's recommendations and further discussions, the INN Experts published changes to the monoclonal antibody nomenclature scheme. In 2011, the INN Experts published an updated "International Nonproprietary Names (INN) for Biological and Biotechnological Substances—A Review" (PDF) with revisions to the monoclonal antibody nomenclature scheme language. The USAN Council has modified its own scheme to facilitate international harmonization. This page outlines the updated scheme and supersedes previous schemes. It also explains policies regarding post-translational modifications and the use of 2-word names. The council has no plans to retroactively change names already coined. They believe that changing names of monoclonal antibodies would confuse physicians, other health care professionals and patients. Manufacturers should be aware that nomenclature practices are continually evolving. Consequently, further updates may occur any time the council believes changes are necessary. Changes to the monoclonal antibody nomenclature scheme, however, should be carefully considered and implemented only when necessary. Elements of a Name The suffix "-mab" is used for monoclonal antibodies, antibody fragments and radiolabeled antibodies. For polyclonal mixtures of antibodies, "-pab" is used. The -pab suffix applies to polyclonal pools of recombinant monoclonal antibodies, as opposed to polyclonal antibody preparations isolated from blood. It differentiates polyclonal antibodies from individual monoclonal antibodies named with -mab. Sequence of Stems and Infixes The order for combining the key elements of a monoclonal antibody name is as follows: 1. -
Monoclonal Antibody Playbook
Federal Response to COVID-19: Monoclonal Antibody Clinical Implementation Guide Outpatient administration guide for healthcare providers 2 SEPTEMBER 2021 1 Introduction to COVID-19 Monoclonal Antibody Therapy 2 Overview of Emergency Use Authorizations 3 Site and Patient Logistics Site preparation Patient pathways to monoclonal administration 4 Team Roles and Responsibilities Leadership Administrative Clinical Table of 5 Monoclonal Antibody Indications and Administration Indications Contents Preparation Administration Response to adverse events 6 Supplies and Resources Infrastructure Administrative Patient Intake Administration 7 Examples: Sites of Administration and Staffing Patterns 8 Additional Resources 1 1. Introduction to Monoclonal Therapy 2 As of 08/13/21 Summary of COVID-19 Therapeutics 1 • No Illness . Health, no infections • Exposed Asymptomatic Infected . Scope of this Implementation Guide . Not hospitalized, no limitations . Monoclonal Antibodies for post-exposure prophylaxis (Casirivimab + Imdevimab (RGN)) – EUA Issued. • Early Symptomatic . Scope of this Implementation Guide . Not hospitalized, with limitations . Monoclonal Antibodies for treatment (EUA issued): Bamlanivimab + Etesevimab1 (Lilly) Casirivimab + Imdevimab (RGN) Sotrovimab (GSK/Vir) • Hospital Adminission. Treated with Remdesivir (FDA Approved) or Tocilizumab (EUA Issued) . Hospitalized, no acute medical problems . Hospitalized, not on oxygen . Hospitlaized, on oxygen • ICU Admission . Hospitalized, high flow oxygen, non-invasive ventilation -
Enhancing Monocyte Effector Functions in Antibody Therapy Against Cancer
Enhancing monocyte effector functions in antibody therapy against cancer Dissertation Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Kavin Fatehchand, B.S. Biomedical Sciences Graduate Program The Ohio State University 2018 Dissertation Committee: Susheela Tridandapani, Ph.D., Advisor John C. Byrd, M.D. Larry Schlesinger, M.D. Tatiana Oberyszyn, Ph.D. Copyrighted by Kavin Fatehchand 2018 Abstract The immune system plays an important role in the clearance of pathogens and tumor cells. However, tumor cells can develop the ability to evade immune destruction, making the interaction between the immune system and the tumor an important area of research. The overall goal in my graduate studies, therefore, was to find different ways to enhance the innate immune response against cancer cells. First, I focused on monoclonal antibody therapy with reference to the role of monocytes/macrophages as immune effectors. Tumor-specific antibodies bind to cancer cells and create immune-complexes that are recognized by IgG receptors (FcγR) on these immune effector cells. FcγRIIb is the sole inhibitory FcγR that negatively regulates monocyte/macrophage effector responses. In the first part of this study, I examined the ability of the TLR4 agonist, LPS, to enhance macrophage FcγR function. I found that TLR4 activation led to the down-regulation of FcγRIIb through the activation of the March3 ubiquitin ligase. Although monocytes play an important role in tumor clearance, tumor cells can develop immune evasion. Acute Myeloid Leukemia (AML) is a hematologic malignancy caused by the proliferation of immature myeloid cells, which accumulate in the bone marrow, peripheral blood, and other tissues. -
REGENERON PHARMACEUTICALS, INC. (Exact Name of Registrant As Specified in Charter)
UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, DC 20549 FORM 8-K CURRENT REPORT Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 Date of Report (Date of earliest event reported): February 9, 2017 (February 9, 2017) REGENERON PHARMACEUTICALS, INC. (Exact Name of Registrant as Specified in Charter) New York 000-19034 13-3444607 (State or other jurisdiction (Commission (IRS Employer of Incorporation) File No.) Identification No.) 777 Old Saw Mill River Road, Tarrytown, New York 10591-6707 (Address of principal executive offices, including zip code) (914) 847-7000 (Registrant's telephone number, including area code) Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions: ☐ Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) ☐ Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) ☐ Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) ☐ Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) Item 2.02 Results of Operations and Financial Condition. On February 9, 2017, Regeneron Pharmaceuticals, Inc. issued a press release announcing its financial and operating results for the quarter and year ended December 31, 2016. A copy of the press release is being furnished to the Securities and Exchange Commission as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference to this Item 2.02. -
Classification Decisions Taken by the Harmonized System Committee from the 47Th to 60Th Sessions (2011
CLASSIFICATION DECISIONS TAKEN BY THE HARMONIZED SYSTEM COMMITTEE FROM THE 47TH TO 60TH SESSIONS (2011 - 2018) WORLD CUSTOMS ORGANIZATION Rue du Marché 30 B-1210 Brussels Belgium November 2011 Copyright © 2011 World Customs Organization. All rights reserved. Requests and inquiries concerning translation, reproduction and adaptation rights should be addressed to [email protected]. D/2011/0448/25 The following list contains the classification decisions (other than those subject to a reservation) taken by the Harmonized System Committee ( 47th Session – March 2011) on specific products, together with their related Harmonized System code numbers and, in certain cases, the classification rationale. Advice Parties seeking to import or export merchandise covered by a decision are advised to verify the implementation of the decision by the importing or exporting country, as the case may be. HS codes Classification No Product description Classification considered rationale 1. Preparation, in the form of a powder, consisting of 92 % sugar, 6 % 2106.90 GRIs 1 and 6 black currant powder, anticaking agent, citric acid and black currant flavouring, put up for retail sale in 32-gram sachets, intended to be consumed as a beverage after mixing with hot water. 2. Vanutide cridificar (INN List 100). 3002.20 3. Certain INN products. Chapters 28, 29 (See “INN List 101” at the end of this publication.) and 30 4. Certain INN products. Chapters 13, 29 (See “INN List 102” at the end of this publication.) and 30 5. Certain INN products. Chapters 28, 29, (See “INN List 103” at the end of this publication.) 30, 35 and 39 6. Re-classification of INN products. -
Tanibirumab (CUI C3490677) Add to Cart
5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor