Hensel F.,Patrys GmbH |
Timmermann W.,Allgemeines Krankenhaus |
Von Rahden B.H.A.,University of Würzburg |
Rosenwald A.,University of Würzburg |
And 2 more authors.
Oncology Reports | Year: 2014
The fully human monoclonal antibody PAT-SC1 is specific for an isoform of CD55 (decay-accelerating factor) designated CD55PAT-SC1. This antigen is expressed in the majority (80%) of gastric cancers (GCs), and the antibody induces tumour cell-specific apoptosis in vitro as well as in vivo. PAT-SC1, therefore, has been deemed promising as a therapeutic agent. Here, we describe the results of an academic clinical study performed in a neoadjuvant setting with resectable GC patients. Patients undergoing treatment for GC between 1997 and 2001 were tested for CD55PAT-SC1 expression. Fifty-one resectable patients that tested positively received a single administration of 20 mg PAT-SC1 48 h prior to surgery. They underwent standard surgery with either subtotal or total gastrectomy with bursectomy, omentectomy and a modi- fied D2-lymphadenectomy, aimed at R0 resection. Primary endpoints of the present study were to evaluate side-effects of the PAT-SC1 antibody treatment and to evaluate histopathological effects such as tumour regression and induction of apoptosis. Long-term survival was a secondary endpoint. Administration of PAT-SC1 appeared safe with only reversible side-effects according to WHO grade I and II. Despite the low-dose of the antibody, 81.6% of the patients showed signs of increased apoptosis within the primary tumour and 60% showed signs of tumour cell regression. Comparison of the 10-year survival rates of the R0-resected CD55PAT-SC1-positive patients treated with the PAT-SC1 antibody with a historical collective of R0-resected CD55PAT-SC1- positive patients not treated with PAT-SC1 indicated a survival benefit in the treated patients. Furthermore, comparison of the patient survival of CD55 PAT-SC1-positive vs. CD55PAT-SC1-negative groups suggested that CD55PAT-SC1 antigen expression is an independent predictor of poor survival in a Cox regression analysis. Antibody PAT-SC1 may be a useful additive therapeutic agent in the treatment of patients with CD55 PAT-SC1-expressing GCs. In combination with radical standard surgery, PAT-SC1 given as an adjuvant or neoadjuvant immunotherapeutic agent induces apoptosis in tumour cells which may improve survival of these patients. Because of the human origin and its specific binding to the CD55PAT-SC1 antigen, PAT-SC1 was well tolerated in this trial.
News Article | November 16, 2016
— Burkitt lymphoma is a form of non-Hodgkin's lymphoma in which cancer starts in immune cells called B-cells. Symptoms include fever, night sweats, swollen lymph nodes and weight loss. The disease is more common in males and people with compromised immune systems, such as those with HIV/AIDS. Treatment includes chemotherapy and radiation therapy. Report Highlights Pharmaceutical and Healthcare latest pipeline guide Burkitt Lymphoma – Pipeline Review, H2 2016, provides comprehensive information on the therapeutics under development for Burkitt Lymphoma (Oncology), complete with analysis by stage of development, drug target, mechanism of action (MoA), route of administration (RoA) and molecule type. The guide covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. The Burkitt Lymphoma (Oncology) pipeline guide also reviews of key players involved in therapeutic development for Burkitt Lymphoma and features dormant and discontinued projects. The guide covers therapeutics under Development by Companies /Universities /Institutes, the molecules developed by Companies in Phase II, Phase I and Preclinical stages are 1, 3 and 13 respectively. Similarly, the Universities portfolio in Phase II and Preclinical stages comprises 1 and 2 molecules, respectively.Burkitt Lymphoma. Burkitt Lymphoma (Oncology) pipeline guide helps in identifying and tracking emerging players in the market and their portfolios, enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. Additionally, various dynamic tracking processes ensure that the most recent developments are captured on a real time basis. Scope - The pipeline guide provides a snapshot of the global therapeutic landscape of Burkitt Lymphoma (Oncology). - The pipeline guide reviews pipeline therapeutics for Burkitt Lymphoma (Oncology) by companies and universities/research institutes based on information derived from company and industry-specific sources. - The pipeline guide covers pipeline products based on several stages of development ranging from pre-registration till discovery and undisclosed stages. - The pipeline guide features descriptive drug profiles for the pipeline products which comprise, product description, descriptive licensing and collaboration details, R&D brief, MoA & other developmental activities. - The pipeline guide reviews key companies involved in Burkitt Lymphoma (Oncology) therapeutics and enlists all their major and minor projects. - The pipeline guide evaluates Burkitt Lymphoma (Oncology) therapeutics based on mechanism of action (MoA), drug target, route of administration (RoA) and molecule type. - The pipeline guide encapsulates all the dormant and discontinued pipeline projects. - The pipeline guide reviews latest news related to pipeline therapeutics for Burkitt Lymphoma (Oncology) Reasons to buy - Procure strategically important competitor information, analysis, and insights to formulate effective R&D strategies. - Recognize emerging players with potentially strong product portfolio and create effective counter-strategies to gain competitive advantage. - Find and recognize significant and varied types of therapeutics under development for Burkitt Lymphoma (Oncology). - Classify potential new clients or partners in the target demographic. - Develop tactical initiatives by understanding the focus areas of leading companies. - Plan mergers and acquisitions meritoriously by identifying key players and it’s most promising pipeline therapeutics. - Formulate corrective measures for pipeline projects by understanding Burkitt Lymphoma (Oncology) pipeline depth and focus of Indication therapeutics. - Develop and design in-licensing and out-licensing strategies by identifying prospective partners with the most attractive projects to enhance and expand business potential and scope. - Adjust the therapeutic portfolio by recognizing discontinued projects and understand from the know-how what drove them from pipeline. Table of Contents Table of Contents 2 List of Tables 5 List of Figures 6 Introduction 7 Burkitt Lymphoma Overview 8 Therapeutics Development 9 Pipeline Products for Burkitt Lymphoma - Overview 9 Pipeline Products for Burkitt Lymphoma - Comparative Analysis 10 Burkitt Lymphoma - Therapeutics under Development by Companies 11 Burkitt Lymphoma - Therapeutics under Investigation by Universities/Institutes 13 Burkitt Lymphoma - Pipeline Products Glance 14 Clinical Stage Products 14 Early Stage Products 15 Burkitt Lymphoma - Products under Development by Companies 16 Burkitt Lymphoma - Products under Investigation by Universities/Institutes 17 Burkitt Lymphoma - Companies Involved in Therapeutics Development 18 AbbVie Inc 18 Arvinas, Inc. 19 bluebird bio, Inc. 20 Boehringer Ingelheim GmbH 21 Constellation Pharmaceuticals, Inc. 22 Immunomedics, Inc. 23 Karyopharm Therapeutics, Inc. 24 Millennium Pharmaceuticals Inc 25 Patrys Limited 26 Seattle Genetics, Inc. 27 Takeda Pharmaceutical Company Limited 28 Theravectys SA 29 Burkitt Lymphoma - Therapeutics Assessment 30 Assessment by Monotherapy Products 30 Assessment by Target 31 Assessment by Mechanism of Action 33 Assessment by Route of Administration 35 Assessment by Molecule Type 37 Drug Profiles 39 19-3s - Drug Profile 39 Product Description 39 Mechanism Of Action 39 R&D Progress 39 20-3s - Drug Profile 40 Product Description 40 Mechanism Of Action 40 R&D Progress 40 alisertib - Drug Profile 41 Product Description 41 Mechanism Of Action 41 R&D Progress 41 ARV-825 - Drug Profile 46 Product Description 46 Mechanism Of Action 46 R&D Progress 46 bb-2121 - Drug Profile 47 Product Description 47 Mechanism Of Action 47 R&D Progress 47 Cellular Immunotherapy to Target CD19 for ALL - Drug Profile 49 Product Description 49 Mechanism Of Action 49 R&D Progress 49 Cellular Immunotherapy to Target CD30 for Oncology - Drug Profile 50 Product Description 50 Mechanism Of Action 50 R&D Progress 50 denintuzumab mafodotin - Drug Profile 51 Product Description 51 Mechanism Of Action 51 R&D Progress 51 E1-3s - Drug Profile 54 Product Description 54 For more information, please visit http://www.wiseguyreports.com
News Article | November 2, 2016
The report provides comprehensive information on the therapeutics under development for Mantle Cell Lymphoma,complete with analysis by stage of development,drug target,mechanism of action (MoA),route of administration (RoA) and molecule type. The report also coversthe descriptive pharmacological action of the therapeutics,its complete research and development history and latest news and press releases. Additionally,the report provides an overview of key players involved in therapeutic development for Mantle Cell Lymphoma and features dormant and discontinued projects. The report helps in identifying and tracking emerging players in the market and their portfolios,enhances decision making capabilities and helps to create effective counter strategies to gain competitive advantage. Complete report on Mantle Cell Lymphoma Market - Pipeline Review,H2 2016 addition with 74 market data tables and 16 figures, spread across 426 pages is available at http://www.rnrmarketresearch.com/mantle-cell-lymphoma-pipeline-review-h2-2016-market-report.html This report features investigational drugs from across globe covering over 20 therapy areas and nearly 3,000 indications. The report is built using data and information sourced from Global Markets Direct's proprietary databases,company/university websites,clinical trial registries,conferences,SEC filings,investor presentations and featured press releases from company/university sites and industry-specific third party sources. Drug profiles featured in the report undergoes periodic review following a stringent set of processes to ensure that all the profiles are updated with the latest set of information. Additionally,various dynamic tracking processes ensure that the most recent developments are captured on a real time basis AB Science SA, AbbVie Inc, Acetylon Pharmaceuticals, Actinium Pharmaceuticals, Affimed GmbH , Amgen, Astellas Pharma, Bayer AG, BeiGene, Bristol-Myers Squibb Company, Eisai, EpiZyme Gilead Sciences, ImmunoGen, Immunomedics, Johnson & Johnson, Juno Therapeutics Inc, Karyopharm Therapeutics, Kite Pharma, MacroGenics, MedImmune, Merck & Co, Millennium Pharmaceuticals, MorphoSys AG, Nordic Nanovector ASA, Novartis AG, Onconova Therapeutics, Patrys Limited, Pharmacyclics, Inquire before buying http://www.rnrmarketresearch.com/contacts/inquire-before-buying?rname=688275(This is a premium report price at US$2000 for a single user PDF license).
Rasche L.,University of Würzburg |
Duell J.,University of Würzburg |
Castro I.C.,Patrys GmbH |
Dubljevic V.,Patrys Ltd |
And 9 more authors.
Haematologica | Year: 2015
The primary objective of this phase 1 study was to evaluate the safety and tolerability of the anti-glucose regulated protein 78 monoclonal immunoglobulin M antibody PAT-SM6 in subjects with relapsed or refractory multiple myeloma. Twelve heavily pretreated patients received four intravenous infusions of PAT-SM6 at doses of 0.3, 1, 3, and 6 mg/kg within 2 weeks. Efficacy, pharmacokinetics and immunogenicity were followed up until the end of the trial (day 36). In addition, immune cell patterns in peripheral blood were assessed by flow cytometry and glucose regulated protein 78 expression status was evaluated in bone marrow specimens by immunohistochemistry and flow cytometry at screening. All doses administered were found to be safe and well tolerated; the maximum tolerated dose was not reached. The most common treatment emergent adverse event was leukopenia (grades 1 and 2) in eight out of the 12 multiple myeloma patients. Pharmacokinetic analysis demonstrated dose-proportional increases in drug serum concentration. The terminal half-life ranged from 5.86 to 8.41 h, the apparent volume of distribution ranged from 101 to 150 mL/kg, and clearance ranged from 8.11 to 16.1 mL/h/kg. All patients showed glucose regulated protein 78 surface expression on multiple myeloma cells. Four out of the 12 patients (33.3%) had stable disease, according to the International Myeloma Working Group criteria, after PAT-SM6 treatment across the doses 1, 3 and 6 mg/kg. In summary, single-agent PAT-SM6 was well tolerated with modest clinical activity in relapsed or refractory multiple myeloma. Further trials exploring the combination of PAT-SM6 with existing myeloma therapies are planned. Trial registration: clinicaltrials.gov identifier:NCT01727778 © 2015 Ferrata Storti Foundation.
Rosenes Z.,University of Melbourne |
Mulhern T.D.,University of Melbourne |
Hatters D.M.,University of Melbourne |
Ilag L.L.,University of Melbourne |
And 6 more authors.
PLoS ONE | Year: 2012
The monoclonal IgM antibody PAT-SM6 derived from human tumours induces apoptosis in tumour cells and is considered a potential anti-cancer agent. A primary target for PAT-SM6 is the unfolded protein response regulator GRP78, over-expressed externally on the cell surface of tumour cells. Small angle X-ray scattering (SAXS) studies of human GRP78 showed a two-domain dumbbell-shaped monomer, while SAXS analysis of PAT-SM6 revealed a saucer-shaped structure accommodating five-fold symmetry, consistent with previous studies of related proteins. Sedimentation velocity analysis of GRP78 and PAT-SM6 mixtures indicated weak complex formation characterized by dissociation constants in the high micromolar concentration range. In contrast, enzyme-linked immunosorbant assays (ELISAs) showed strong and specific interactions between PAT-SM6 and immobilized GRP78. The apparent binding constant estimated from a PAT-SM6 saturation curve correlated strongly with the concentration of GRP78 used to coat the microtiter tray. Experiments using polyclonal antiGRP78 IgG antibodies or a monoclonal IgG derivative of PAT-SM6 did not show a similar dependence. Competition experiments with soluble GRP78 indicated more effective inhibition of PAT-SM6 binding at low GRP78 coating concentrations. These observations suggest an avidity-based binding mechanism that depends on the multi-point attachment of PAT-SM6 to GRP78 clustered on the surface of the tray. Analysis of ELISA data at high GRP78 coating concentrations yielded an apparent dissociation constant of approximately 4 nM. We propose that the biological action of PAT-SM6 in tumour cell apoptosis may depend on the multivalent nature of PAT-SM6 and the high avidity of its interaction with multiple GRP78 molecules clustered on the tumour cell surface. © 2012 Rosenes et al.
PubMed | Patrys GmbH, University of Würzburg and Patrys Ltd.
Type: Clinical Trial, Phase I | Journal: Haematologica | Year: 2015
The primary objective of this phase 1 study was to evaluate the safety and tolerability of the anti-glucose regulated protein 78 monoclonal immunoglobulin M antibody PAT-SM6 in subjects with relapsed or refractory multiple myeloma. Twelve heavily pretreated patients received four intravenous infusions of PAT-SM6 at doses of 0.3, 1, 3, and 6 mg/kg within 2 weeks. Efficacy, pharmacokinetics and immunogenicity were followed up until the end of the trial (day 36). In addition, immune cell patterns in peripheral blood were assessed by flow cytometry and glucose regulated protein 78 expression status was evaluated in bone marrow specimens by immunohistochemistry and flow cytometry at screening. All doses administered were found to be safe and well tolerated; the maximum tolerated dose was not reached. The most common treatment emergent adverse event was leukopenia (grades 1 and 2) in eight out of the 12 multiple myeloma patients. Pharmacokinetic analysis demonstrated dose-proportional increases in drug serum concentration. The terminal half-life ranged from 5.86 to 8.41 h, the apparent volume of distribution ranged from 101 to 150 mL/kg, and clearance ranged from 8.11 to 16.1 mL/h/kg. All patients showed glucose regulated protein 78 surface expression on multiple myeloma cells. Four out of the 12 patients (33.3 %) had stable disease, according to the International Myeloma Working Group criteria, after PAT-SM6 treatment across the doses 1, 3 and 6 mg/kg. In summary, single-agent PAT-SM6 was well tolerated with modest clinical activity in relapsed or refractory multiple myeloma. Further trials exploring the combination of PAT-SM6 with existing myeloma therapies are planned.clinicaltrials.gov identifier: NCT01727778.
Schatz N.,University of Würzburg |
Brandlein S.,University of Würzburg |
Ruckl K.,University of Würzburg |
Hensel F.,Patrys GmbH |
Vollmers H.P.,University of Würzburg
Cancer Research | Year: 2010
Human hybridoma technologies permit the cloning of patient antibodies that may have desirable qualities. In this study, we report the isolation of a natural IgG antibody from a stomach cancer patient that illustrates novel diagnostic and therapeutic uses. Human antibody PAT-BA4 recognizes a tumor-specific variant of the transcription factor TATA-binding protein-associated factor 15 (TAF15) that is expressed on the plasma membrane of stomach cancer and melanoma cells but not healthy tissues. TAF15 is a member of the multifunctional TET protein family involved in mRNA transcription, splicing, and transport that is normally expressed only in the cytoplasm and nucleus of fetal or adult tissue cells. However, in malignant cells, TET family members including TAF15 seem to be involved in cell adhesion and spreading. In support of this likelihood, we found that PAT-BA4 inhibited tumor cell motility and tumor cell adhesion. Our findings define a role for a tumor-specific TAF15 antigen in malignant processes. ©2010 AACR.
Hensel F.,Patrys GmbH |
Eckstein M.,University of Würzburg |
Rosenwald A.,University of Würzburg |
Brandlein S.,University of Würzburg
Melanoma Research | Year: 2013
Despite the recent development of novel therapies for patients with metastatic melanoma, this disease remains fatal in the majority of those who develop a relapse. Here, we report the preclinical and early clinical development of a novel IgM antibody PAT-SM6 that specifically binds to a cancer-specific isoform of glucose-regulated protein 78 (GRP78) and low-density lipoprotein. Finding a GRP78 cancer-specific form on the surface of cancer cells, but not normal cells in vivo, presents an opportunity for cancer-specific targeting. PAT-SM6 binding to the cell surface induces apoptosis in a variety of tumors, including melanoma. Recent studies show the specificity of PAT-SM6 binding to the surface of melanoma cells and primary tissue but not to normal tissue. They also confirm, for the first time, cell proliferation inhibition and apoptosis through classical apoptotic pathways as well as induction of lipid accumulation in melanoma cells. These in-vitro data are supported by positive in-vivo data using PAT-SM6 in a xenograft C8161 model. Furthermore, PAT-SM6 was well tolerated in pharmacokinetic/toxicology studies in monkeys. On the basis of these preclinical observations, a clinical study of PAT-SM6 was carried out in patients with 'in-transit' melanoma. Even with microdosing, histological analyses of tumor biopsies detected the presence of PAT-SM6 as well as apoptosis. Although there are many small molecules and monoclonal antibodies currently in clinical development for patients with melanoma, PAT-SM6 is the only therapeutic targeting the cancer-specific isoform of GRP78. These PAT-SM6 preclinical data and positive findings from the phase 1 safety study provide strong support for the further development of this novel antibody. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
Gagnon P.,Bioprocessing Technology Institute |
Hensel F.,Patrys GmbH |
Lee S.,Avid Bioservices |
Zaidi S.,Avid Bioservices
Journal of Chromatography A | Year: 2011
This study documents the presence of stable complexes between monoclonal IgM and genomic DNA in freshly harvested mammalian cell culture supernatants. 75% of the complex population elutes from size exclusion chromatography with the same retention volume as IgM. DNA comprises 24% of the complex mass, corresponding to an average of 347 base pairs per IgM molecule, distributed among fragments smaller than about 115 base pairs. Electrostatic interactions appear to provide most of the binding energy, with secondary stabilization by hydrogen bonding and metal affinity. DNA-dominant complexes are unretained by bioaffinity chromatography, while IgM-dominant complexes are retained and coelute with IgM. DNA-dominant complexes are repelled from cation exchangers, while IgM-dominant complexes are retained and partially dissociated. Partially dissociated forms elute in order of decreasing DNA content. The same pattern is observed with hydrophobic interaction chromatography. All complex compositions bind to anion exchangers and elute in order of increasing DNA content. A porous particle anion exchanger was unable to dissociate DNA from IgM. Monolithic anion exchangers, offering up to15-fold higher charge density, achieved nearly complete complex dissociation. The charge-dense monolith surface appears to outcompete IgM for the DNA. Monoliths also exhibit more than double the IgM dynamic binding capacity of the porous particle anion exchanger, apparently due to better surface accessibility and more efficient mass transfer. © 2011 Elsevier B.V.
Rasche L.,University of Würzburg |
Duell J.,University of Würzburg |
Morgner C.,University of Würzburg |
Chatterjee M.,Comprehensive Cancer Center Mainfranken |
And 5 more authors.
PLoS ONE | Year: 2013
In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM. © 2013 Rasche et al.