Intra-tumor Catabolites (fate of ADC) can Predict ADC Efficacy. Donglu Zhang, Ph.D. Genentech Feb 21, 2017 World ADC Berlin-2017
|
|
- Silas Gaines
- 6 years ago
- Views:
Transcription
1 Intra-tumor Catabolites (fate of ADC) can Predict ADC Efficacy Donglu Zhang, Ph.D. Genentech Feb 21, 2017 World ADC Berlin
2 Outline ADC structure and mechanism of action (MOA) Can we use PK or PK-PD (modeling) to predict ADC efficacy? Examples showing [tumor catabolite] efficacy correlation Implications in preclinical ADC discovery Discussion points 2
3 Basic ADC Structures Antibody (anti-her2, CD22 ) Antibody Linker Drug payload, Linker Drug (MMAE) catabolite, drug Val-Cit-PAB-MMAE A microtubule inhibitor Antibody Linker Disulfide-PBD A DNA alkylator Drug (pyrrolobenzodiazepine, PBD) LC HC THIOMAB MW 150,000 Da MMAE, DM1 are regular small molecules PBD are covalent binders They have different cell retention kinetics Different MOA Zhang_Genentech_World ADC 3
4 ADC Mechanism of Action Christina Peters and Stuart Brown. "Antibody drug conjugates as novel anticancer chemotherapeutics." Bioscience reports 35.4 (2015)(modified) 4
5 Which [ADC analyte] in Circulation Correlates with Efficacy or Toxicity? Multiple bioanalytical assays (ELISA, LC/MS) Kaur et al, Bioanalysis, 2013; Kamath & Iyer, Pharm Res, 2015; Xu et al, Anal Biochem 2011 ADC review:.additional work is still needed to better understand the best analytes to use for exposure-response correlations.. -Amrita Kamath Do ADC species in plasma reflect what are in the tumor or other tissues? AUC, Cmax, Cmin-dependent Prodrug PK does not drive efficacy It is important to note that till date there is no consensus on which analyte is the best one to correlate with ADC pharmacology. The process involved in plasma-to-tumor exchange of ADCs and released drug are complex and mostly nonlinear. Consequently, the plasma concentrations of these analytes do not accurately represent their concentrations inside the tumor. Khot A, Sharma S. Shah DK (2015) Bioanalysis Zhang_Genentech_World ADC 5
6 Is C min of Tab Really Correlated with ADC Efficacy? It is difficult to determine C min for a drug with long t 1/2 Trough concentrations (C min ) can not be predicted C min depends on payload class 6
7 What ADC Species Contribute to Efficacy? ADC species in circulation Unconjugated antibody no impact Unconjugated payload limited impact (often concentration too low, may contribute to toxicity) Conjugated antibody and conjugated drugs can carry payload to sites of action The correlation of exposure of any circulating ADC species with efficacy is not known The payload at the site of action is responsible for efficacy and at peripheral sites for toxicity Zhang_Genentech_World ADC 7
8 Example: Cyclopropyl- and Cyclobutyl-containing ADCs Show Distinct Efficacy in Xenograft Mouse Models General procedures: After a single IV dose, (1) plasma and tissues were taken, (2) DAR or total mab, and payload drugs were determined. Zhang et al. (2016) Drug Metab Dispos 8
9 Normalized Average DAR (%) Similar Systemic Exposures but Different Intra-tumor Catabolites From Cyclopropyl- and Cyclobutyl-ADCs in Mouse ADC Time (h) mab (nm) 5 mg/kg Plasma Liver Tumor Plasma Cyclobutyl- Cyclopropy l Similar exposure would predict similar efficacy Methyl Cyclopropyl Cyclobutyl Days after dose ADC Cyclobutyl- Cyclopropyl- Time (h) PBD-dimer (nm) Cyclopropyl-thiol (nm) Plasma Liver Tumor Plasma Liver Tumor <LLOQ <LLOQ <LLOQ But only intra-tumor catabolism analysis rationalizes efficacy difference 9
10 Absorbance, mau Did Cyclopropyl Thiol Bind to DNA Oligo Model? 4.0e4 3.6e4 3.2e4 2.8e4 2.4e4 2.0e4 1.6e4 1.2e4 Oligo 2 Oligo1 DNA Oligo 1: 5 TATAGAATCTATA 3 DNA Oligo 2: 3 ATATCTTAGATAT e4 3.8e4 3.0e4 2.2e4 1.4e4 Insert: charge Z = e4 2.6e4 2.2e4 1.8e4 1.4e4 1.0e4 Oligo 2 Oligo1 Minimal adducts HPLC Time (min) Prediction: ADCs prepared from cyclopropyl-containing PBD should be inactive. Zhang et al., 2016, ACS Med Chem Lett 10
11 Differentiation of Tumor from Organs and Between Organs A WSU-DLCL2 Xenograft Model Controls Vehicle B 12,000 PBD/cell or 140 ng PBD/cm 3 to sustain this efficacy! Tissue free [PBD] does not reflect cellular [PBD] (<1%). PBD was accumulated in tumor but not in normal tissues. DNA covalent-bound [PBD] differentiate tumor from normal tissues and between normal tissues. This analysis has potential utility in tox studies, what is the DNA binding threshold for organ toxicity? C DNA-bound PBD 41 PBDs/10 6 bp Free PBD from organic extraction 1 PBD/10 6 bp or ~300 PBD/cell in liver and lung Ma et al., 2016, Drug Metab Dipos 22
12 Intra-tumor [PBD] Correlates with efficacy of PBD-ADCs Zhang_Genentech_World ADC 12
13 Tumor Catabolites Have Different Kinetic Profiles From Circulating ADC Conjugates T-[3H]DM1 or T-SPP-[3H]DM1 concentrations in plasma/tumors of Xenograft mice Anti-CD70-[14C]MMAF concentrations in plasma/tumors of Xenograft mice Circulating ADCs DAR analysis Erickson et al., 2012, Mol Cancer Ther Alley et al., 2009, JPET DM1 and MMAF are different from DNA alkylators that have prolonged cellular retention times. 13
14 Points for Discussion for ADC Discovery and Development? The correlation of exposure of any circulating ADC species with efficacy (toxicity) is not known The payload at the site of action is responsible for efficacy and toxicity Questions: How does PK analysis help in understanding efficacy in ADC discovery and development? Why are we trying so hard to look for efficacy driver: systemic Cmax or AUC? Should we consider how systemic exposures affect payload delivery to the site of action? Is the method of calculation for therapeutic index valid? Systemic AUC or Cmax in tox/auc or Cmax in human Zhang_Genentech_World ADC 14
15 Summary For PBD, (1) [intratumor catabolite] correlated with tumor growth inhibition/reduction (2) Stability and concentrations of circulating ADC can not support the observed efficacy How can tumor catabolite analysis be routinely performed? In pre-clinic In clinic? Systemic PK can be used to ensure plasma stability of ADC 15
16 Acknowledgement Cyrus Khojasteh Yong Ma Buyun Chen Hoa Le Chenghong Zhang Sudheer Bobba Pingping Lu Liling Liu Peter Fan Emile Plise Jonathan Cheong Jonathan Wang Dewakar Sangaraju Xiao Ding Marcel Hop Pete Dragovich Tom Pillow Shang-Fan Yu Carter Fields Gail Phillips Hans Erickson Jack Sadowsky Dick Vandlen Keyang Xu Dian Su Surider Kaur Geoff Del Rosario Jeff Lau Zhonghua Pei Andy Polson 16
17 Thank You! 17
Impact of Payload Metabolism on Stability and Efficacy of ADCs
Impact of Payload Metabolism on Stability and Efficacy of ADCs Dian Su, Ph.D. 2017 Nanjing International DMPK meeting June 18,2017 Beijing, China Overview Introduction of ADCs ADC catabolites/biotransformations
More informationCreating Highly Efficacious ADCs for Low-Expression Targets While Improving Therapeutic Index TIM LOWINGER, PHD
Creating Highly Efficacious ADCs for Low-Expression Targets While Improving Therapeutic Index TIM LOWINGER, PHD CSO Mersana Therapeutics VC-backed Biotech in Cambridge, MA Investors: NEA, Pfizer, Fidelity,
More informationBench-to-Bedside Translation of ADCs using PK/PD M&S. Dhaval K. Shah, Ph.D.
Bench-to-Bedside Translation of ADCs using PK/PD M&S Dhaval K. Shah, Ph.D. dshah4@buffalo.edu 8/23/2016 Outline Overview: ADCs Prediction of Clinical Efficacy using a Multi-Scale Mechanistic PK/PD Model
More informationXpress CF+ : A Cell-Free Platform for the Rapid Screening and Production of Homogeneous ADCs
Xpress CF+ : A Cell-Free Platform for the Rapid Screening and Production of Homogeneous ADCs Alexander R. Steiner, M.S. Director, Protein Biochemistry Tuesday Feb 3 rd, 215 Making novel drugs is Pammolli
More informationWorkshop F: Linker Design: Why so complex?
Genomics Institute of the Novartis Research Foundation Workshop F: Linker Design: Why so complex? Bernhard Geierstanger October 10, 2016 Antibody Drug Conjugates Novel targets & Biology Diverse set of
More informationConjugation site modulates the in vivo stability and therapeutic activity of antibody conjugates
Conjugation site modulates the in vivo stability and therapeutic activity of antibody conjugates Ben-Quan Shen*, Keyang Xu*, Luna Liu, Helga Raab, Sunil Bhakta, Margaret Kenrick, Kathryn L. Parsons-Reponte,
More informationTowards an in vivo Stability Assay for ADCs and Their Metabolites in Serum by Affinity Capture LC-MS
Towards an in vivo Stability Assay for ADCs and Their Metabolites in Serum by Affinity Capture LC-MS mz (@Dr_mz13), PhD 11-Feb-2013 One of the challenges of ADCs includes the development of a method to
More informationDevelopment and Manufacture of a Novel Drug- Linker: Enabling High DAR ADCs. Michael J Kaufman, Ph.D. Senior Vice President, CMC
Development and Manufacture of a Novel Drug- Linker: Enabling High DAR ADCs Michael J Kaufman, Ph.D. Senior Vice President, CMC Legal Disclaimer This presentation contains forward-looking statements that
More informationThe SMARTag TM ADC Technology Platform
The SMARTag TM ADC Technology Platform 2 3 4 World Class Protein Production Capability New State of the Art Facility Madison, WI Expanded GPEx Cell Line Engineering capacity Flexible Non cgmp production
More informationADME and DDI Potential of Antibody-Drug Conjugates. Nagendra V. Chemuturi, Ph.D DDI, Seattle, WA
ADME and DDI Potential of Antibody-Drug Conjugates Nagendra V. Chemuturi, Ph.D. 2016 DDI, Seattle, WA Today s Presentation What are Antibody-Drug Conjugates (ADCs)? ADC technology ADME of ADCs Typical
More informationADCS, WHAT IS INDUSTRY DOING TODAY? AN OVERVIEW
ADCS, WHAT IS INDUSTRY DOING TODAY? AN OVERVIEW Johannes Stanta PhD Scientific Manager, Bioanalysis EBF ADC Training day June 2017 Copyright 2017 Covance. All Rights Reserved ADC Bioanalytical PK Assays
More informationAntibody-Drug Conjugates The Road to the Current State. Nila Das, Ph.D. American Drug Delivery & Formulation Summit San Diego, CA June 13, 2016
Antibody-Drug Conjugates The Road to the Current State Nila Das, Ph.D. American Drug Delivery & Formulation Summit San Diego, CA June 13, 2016 1 Current Status of ADCs C&E News. 2014, 92(3): 13-21 2 Current
More informationSubmission preparation what to watch out for
Submission preparation what to watch out for EBF 2017 Boris Gorovits AAPS BIOTEC section Pfizer June 2017 Analytes Commonly Assessed for ADC PK Unconjugated Drug analyte Total Antibody analyte Conjugated
More informationAbGn-107, an ADC Targets Gastrointestinal Tumors
AbGn-107, an ADC Targets Gastrointestinal Tumors For a Healthier Life Presented by Ron Lin Feb. 22, 2016 All Rights reserved AbGenomics International Inc. 4966 El Camino Real, Suite 200, Los Altos, CA
More informationSite-Specific ADC Generation Using SMARTag Technology
Site-Specific ADC Generation Using SMARTag Technology David Rabuka, PhD World ADC Summit San Diego, Oct 2015 SMARTag TM technology: Site-specific protein modification using bioorthogonal chemistry Site-Specific
More informationPreclinical to Clinical Translation of Antibody Drug Conjugates
Preclinical to Clinical Translation of Antibody Drug Conjugates Robert Lutz, PhD Crescendo Biopharma Consulting World ADC Summit Berlin 2016 1 Bio ImmunoGen 23 years Researcher in cell death and survival
More information6 th EBF Open meeting, Barcelona November 21st, 2013
Validation of an immunoassay to selectively quantify the naked antibody of a new Sanofi Antibody Drug Conjugate: an additional tool for improvement of PK interpretation 6 th EBF Open meeting, Barcelona
More informationLigand Binding Assays: Summary and Consensus from the Bioanalytical Workshop (CC V)
Ligand Binding Assays: Summary and Consensus from the Bioanalytical Workshop (CC V) Binodh DeSilva Executive Director Immunochemistry and Biomarker Development Bristol-Myers Squibb Contributors Lauren
More informationWhat s the difference? Challenges in pre-clinical development of biologics
Biologics vs Small MW NCEs What s the difference? Challenges in pre-clinical development of biologics Peter Lloyd Joint Conference of EU Human Pharmacological Societies and 20 th Anniversary of AGAH 31
More informationAntibody-drug Conjugates: Characterization and Control Strategies of Lysine-linked Products
Antibody-drug Conjugates: Characterization and Control Strategies of Lysine-linked Products Fred Jacobson Protein Analytical Chemistry Genentech, Inc. CASSS CMC Strategy Forum Japan 2013 December 9-10,
More informationOncology Product and Platform Partnering Opportunity
Protein Medicinal Chemistry with an Expanded Genetic Code Oncology Product and Platform Partnering Opportunity April 2017 Ambrx has Made Advances in Proprietary Platform and Titer while Achieving Clinical
More informationANTIBODY DRUG CONJUGATES AND BISPECIFIC ANTIBODIES: SCIENTIFIC & REGULATORY CHALLENGES AND OPPORTUNITIES
ANTIBODY DRUG CONJUGATES AND BISPECIFIC ANTIBODIES: SCIENTIFIC & REGULATORY CHALLENGES AND OPPORTUNITIES Brian DiPaolo 08 June 2017 CASSS Midwest Discussion Group Agenda Introduction Antibody Drug Conjugates
More informationS9 Implementation Working Group ICH S9 Guideline: Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers
S9 Implementation Working Group ICH S9 Guideline: Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers Current version dated 8 June 2016 International Council for Harmonisation of
More informationWhy do LC MS and LBA
Why do LC MS and LBA results differ? A literature evaluation 18 November 2015 Nico van de Merbel An overview In most published BA methods for large molecules, no comparison of platforms (LBA vs LBA, LBA
More informationPredicting Tissue Distribution & Clearance of Antibody Formats to Improve Selectivity of Targeted Therapies
Predicting Tissue Distribution & Clearance of Antibody Formats to Improve Selectivity of Targeted Therapies Ben-Fillippo Krippendorff, Roche Innovation Center Basel ben-fillippo.krippendorff@roche.com
More informationStrategy for Selecting NAb Assay Format
Strategy for Selecting NAb Assay Format European Bioanalysis Forum 27Sept2016 Jim McNally, Ph.D. Associate Director, Global Early Development Head of Clinical Bioanalytics Merck KGaA AAPS Working Group
More informationSite-Specific Protein Conjugation as an ADC Optimization Tool
Site-Specific Protein Conjugation as an ADC ptimization Tool livier Laurent, Ph.D. Vice President, Ambrx AAPS 2014 Conference Ambrx Quick Facts perations San Diego, California-based biopharmaceutical company
More informationICH S9 guideline on nonclinical evaluation for anticancer pharmaceuticals - questions and answers
16 May 2018 EMA/CHMP/ICH/453684/2016 Committee for Human Medicinal Products ICH S9 guideline on nonclinical evaluation for anticancer pharmaceuticals - questions and answers Step 5 Transmission to CHMP
More informationPredicting Clinical Success of ADCs using a Mechanistic Modeling & Simulation Approach
Predicting Clinical Success of ADCs using a Mechanistic Modeling & Simulation Approach Alison Betts Translational Modeling & Simulation Biomedicine Design Department Pfizer Worldwide R&D, Cambridge MA
More informationChallenges in Bioassay Development for ADCs and Their Utility for Measuring In-vitro Activity of Conjugate Variants
Challenges in Bioassay Development for ADCs and Their Utility for Measuring In-vitro Activity of Conjugate Variants Sonia Connaughton, Ph.D. Senior Scientist, Bioanalytical Science Bioassays 214: Scientific
More informationExpert Consensus on Quality Control and Preclinical Evaluation of Antibody-Drug Conjugates
Expert Consensus on Quality Control and Preclinical Evaluation of Antibody-Drug Conjugates National Institutes for Food and Drug Control July 20 th, 2018 Contents 1. Overview... 3 2. Manufacturing... 4
More informationImmunogenicity Assay Strategies for Antibody-Drug Conjugates
Immunogenicity Assay Strategies for Antibody-Drug Conjugates 8th World ADC Conference, San Diego 20 Sep 2017 Seema Kumar, PhD Associate Scientific Director Global Early Development (GED) EMD Serono Research
More informationApplying Affimers. Dr Amanda Nicholl at Avacta Life Sciences. Improving Antibody PK Assay Development
Improving Pharmacokinetic Assays in a Regulatory Bioanalysis Setting Applying Affimers With an increasing number of antibody-based therapeutics entering the clinic, the need for validated anti-idiotypic
More informationS9 Implementation Working Group ICH S9 Guideline: Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers
S9 Implementation Working Group ICH S9 Guideline: Nonclinical Evaluation for Anticancer Pharmaceuticals Questions and Answers Current Step 4 version International Council for Harmonisation of Technical
More informationPreclinical Pharmacokinetic Considerations for the Development of Antibody Drug Conjugates
Pharm Res (2015) 32:3470 3479 DOI 10.1007/s11095-014-1584-z EXPERT REVIEW Preclinical Pharmacokinetic Considerations for the Development of Antibody Drug Conjugates Amrita V. Kamath & Suhasini Iyer Received:
More informationThe Promise of DARPins for Site-Specific Drug Conjugation & Pharmacokinetic Optimization
Department of Biochemistry The Promise of DARPins for Site-Specific Drug Conjugation & Pharmacokinetic Optimization Fabian Brandl, Plückthun Group, University of Zurich / University of Bern World ADC Berlin,
More informationAntibody Targeted Amanitin Conjugates (ATACs) Expanding the ADC Landscape With a New Payload Targeting RNA Polymerase II
Antibody Targeted Amanitin Conjugates (ATACs) Expanding the ADC Landscape With a New Payload Targeting RNA Polymerase II ADC Summit 2016 San Diego Andreas Pahl CS Heidelberg Pharma GmbH Ladenburg, Germany
More information: Case Study: Kadcyla TM (Ado-Trastuzumab Emtansine)
: Case Study: Kadcyla TM (Ado-Trastuzumab Emtansine) European Bioanalysis Forum ADC Training Day Bringing ADC into Practice Antibody-Drug Conjugate Submissions 20 th June, 2017, Lisbon Surinder Kaur, Ph.
More informationCD33-Targeting ADCs in AML
Maturing Clinical Profile of IMGN779, a Next- Generation CD33-Targeting Antibody-Drug Conjugate, in Patients with Relapsed or Refractory Acute Myeloid Leukemia Jorge E. Cortes 1, Daniel J. DeAngelo 2,
More informationAntibody-Drug Conjugate Bioanalytical Assay Development:
Antibody-Drug Conjugate Bioanalytical Assay Development: Immunogenicity Challenges November 16, 2016 Presented by Corinna Fiorotti, Ph.D. Presentation Overview ADC Overview ADC Assays ADC Immunogenicity
More informationHigh affinity target binding: a cause of non-linear Pharmacokinetics of drugs (Target mediated drug disposition: TMDD)
High affinity target binding: a cause of non-linear Pharmacokinetics of drugs (Target mediated drug disposition: TMDD) Devang Shah Senior Principal Investigator Metabolism and Pharmacokinetics, Pharmaceutical
More informationRisk-based testing for anti-drug neutralizing antibodies during development of biological therapeutics
Risk-based testing for anti-drug neutralizing antibodies during development of biological therapeutics April 18 th, 2016 AAPS National Biotechnology Conference, Boston, MA Shalini Gupta, PhD Amgen Inc.
More informationDevelopment and Characterization of Multi-Platform Antibody Drug Conjugates
Development and Characterization of Multi-Platform Antibody Drug Conjugates Jason A. Starkey Senior Principal Scientist - BioTherapeutics Pharmaceutical Sciences Pfizer, Inc. This document provides an
More informationRegulatory Perspectives in Developing Therapeutic Proteins with Novel Scaffolds Translational strategy
Regulatory Perspectives in Developing Therapeutic Proteins with Novel Scaffolds Translational strategy AAPS/ASCPT Joint Symposium: Integrated Translational Strategies for More Efficient Development of
More informationmab quantification in preclinical tissue supports in vitro potency/in vivo efficacy correlations
mab quantification in preclinical tissue supports in vitro potency/in vivo efficacy correlations John T. Mehl, Ph.D. Bioanalytical Research Princeton, NJ AAPS November 4, 2014 San Diego, CA 1 LC-MS/MS
More informationA pre-clinical PKPD framework for biomarker led decision making for prioritising dose and schedules for anti-cancer agents to test in the clinic
A pre-clinical PKPD framework for biomarker led decision making for prioritising dose and schedules for anti-cancer agents to test in the clinic Rhys D Owen Jones, Oncology imed 1st International Workshop
More informationSupplemental Material TARGETING THE HUMAN MUC1-C ONCOPROTEIN WITH AN ANTIBODY-DRUG CONJUGATE. Supplemental Tables S1 S3. and
Supplemental Material TARGETING THE HUMAN MUC1-C ONCOPROTEIN WITH AN ANTIBODY-DRUG CONJUGATE Supplemental Tables S1 S3 and Supplemental Figures S1 S10 Supplemental Table S1. PK Parameters for MAb-3D1-MMAE
More informationDDI Assessment for Therapeutic Proteins and ADCs
DDI Assessment for Therapeutic Proteins and ADCs Elimika Pfuma Fletcher, PharmD, PhD Policy Lead Guidance and Policy Team Office of Clinical Pharmacology CDER/FDA 06/21/2017 DDI- 2017 International Conference
More informationIMPROVE SPEED AND ACCURACY OF MONOCLONAL ANTIBODY BIOANALYSIS USING NANOTECHNOLOGY AND LCMS
IMPROVE SPEED AND ACCURACY OF MONOCLONAL ANTIBODY BIOANALYSIS USING NANOTECHNOLOGY AND LCMS As scientists gain an advanced understanding of diseases at the molecular level, the biopharmaceutical industry
More informationOvercoming drug & target interference in ADA and nabassays
Overcoming drug & target interference in ADA and nabassays Robert Nelson Ph.D. MRQA Head of Bioanalytical Laboratory, Novimmune SA 1 Presentation Outline Case Study 1 Drug & target interference in a clinical
More informationPaving the way for Non-Clinical Bioanalytical Partnerships Louise Angell
Paving the way for Non-Clinical Bioanalytical Partnerships Louise Angell Content Overview of non-clinical immunogenicity testing for biologics Regulatory guidance Bioanalytical considerations Risk based
More informationAntibody-Mediated Effector Function: Learning and Challenges from Early Discovery to Development
Antibody-Mediated Effector Function: Learning and Challenges from Early Discovery to Development Payal Mehta, PhD Research Scientist Eli Lilly & Company CaSSS Bioassay Conference, Silver Spring, MD 9 th
More informationJefferies Healthcare Conference. June 2016
Jefferies Healthcare Conference June 2016 Forward Looking Statements This presentation contains forward-looking statements for purposes of the safe harbor provisions of the Private Securities Litigation
More informationSUPPLEMENTARY INFORMATION
In format provided by Orchard et al. (SEPTEMBER 2011) Supplementary information S1 Sample MIABE file exemplifying data extracted from PMID: 20568778 Responsible Person or Role Contact Person Bryan K. S.
More informationS9 Nonclinical Evaluation for Anticancer Pharmaceuticals
S9 Nonclinical Evaluation for Anticancer Pharmaceuticals This draft guidance, when finalized, will represent the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create
More information参考資料. Joint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products. Draft
参考資料 1 2 3 4 5 Joint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products Draft 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 Table of contents 1.
More informationICH S9 -Nonclinical Evaluation for Anticancer Pharmaceuticals: Questions and Answers
ICH S9 -Nonclinical Evaluation for Anticancer Pharmaceuticals: Questions and Answers May 2018 International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use 1 Legal
More informationJoint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products
Joint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products Table of contents 1.Introduction...2 2.Scope...3 3.Discussion...4 3.1. Chemistry, manufacturing, and controls...4
More informationThe science behind Betalutin : why is it unique? Roy H. Larsen PhD Sciencons AS, Oslo, Norway
The science behind Betalutin : why is it unique? Roy H. Larsen PhD Sciencons AS, Oslo, Norway Speaker credentials Roy H. Larsen, PhD >25 years of experience in research on targeted radionuclide therapy
More informationOverview of the Antibody Drug Conjugate Landscape Godfrey Amphlett WCBP CMC Strategy Forum January 24, 2010
Overview of the Antibody Drug Conjugate Landscape Godfrey Amphlett WCBP CMC Strategy Forum January 24, 2010 Outline of Talk What is an Antibody Drug Conjugate (ADC)? Rationale for developing ADC s What
More informationCloudbreak: Antibody-Drug Conjugates for Treatment of MDR Gram-Negative Bacterial Infections
Cloudbreak: Antibody-Drug Conjugates for Treatment of MDR Gram-Negative Bacterial Infections James C. Levin, Ph.D. Director of Preclinical Development Discovery on Target Conference September 26, 2018
More informationMonitoring Charge Heterogeneity of Antibody-Maytansinoid Conjugates (AMC) with icief
Monitoring Charge Heterogeneity of Antibody-Maytansinoid Conjugates (AMC) with icief Joyce Lin, Rajesh Krishnamurthy, Alexandru Lazar ImmunoGen, Inc., Waltham, MA CE Pharm 2008 utline I. Introduction of
More informationCORPORATE OVERVIEW: REINVENTING THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF CANCER
CORPORATE OVERVIEW: REINVENTING THERAPEUTIC ANTIBODIES FOR THE TREATMENT OF CANCER March 2018 2018 CytomX Therapeutics, Inc. 1 Forward Looking Statements Special Note Regarding Forward-Looking Statements
More informationAntibody-Drug Conjugate Characterization and Quality Assurance
Antibody-Drug Conjugate Characterization and Quality Assurance Sarah Kennett Division of Monoclonal Antibodies Office of Biotechnology Products OPS/CDER/FDA October 12, 2011 1 Disclaimer The views and
More informationJoint MHLW/EMA reflection paper on the development of block copolymer micelle medicinal products
1 2 3 17 January 2013 EMA/CHMP/13099/2013 Committee for Medicinal Products for Human Use (CHMP) 4 5 6 Joint MHLW/EMA reflection paper on the development of block copolymer micelle Agreed by Nanomedicines
More informationPhase 1 Clinical Studies First-In-Human (FIH) <Chapter 31> Pharmacologically-Guided Dose Escalation
Phase 1 Clinical Studies First-In-Human (FIH) Pharmacologically-Guided Dose Escalation Jerry M. Collins, Ph.D. Developmental Therapeutics Program Division of Cancer Treatment and Diagnosis,
More informationCurrent practices on metabolite profiling and quantification in Drug Development at Boehringer-Ingelheim
Current practices on metabolite profiling and quantification in Drug Development at Boehringer-Ingelheim S Blech EBF Focus Workshop: Metabolite Profiling and Quantification Strategies in Drug R&D Sep 25,
More information2D Liquid-Phase Proteomic Profiling in Pre- Clinical and Mechanistic Analysis of Novel Polynuclear Chemotherapeutics for Glioma
2D Liquid-Phase Proteomic Profiling in Pre- Clinical and Mechanistic Analysis of Novel Polynuclear Chemotherapeutics for Glioma Oliver Bogler, PhD Neurosurgery Problem No good treatment for glioma New
More informationUNLEASH THE POWER OF PRECISION MEDICINE
FROM BENCH TO BEDSIDE UNLEASH THE POWER OF PRECISION MEDICINE DCB, pioneer in biotech. Your partner in drug discovery. www.dcb.org.tw The Center for Biotechnology With over 400 dedicated researchers and
More informationAdvanced Therapeutic Antibody Discovery with Multiplexed Screening
Advanced Therapeutic Antibody Discovery with Multiplexed Screening White Paper Scientists need powerful tools that can deliver results to fully understand the ability of candidate antibodies to interrupt
More informationTECHNOLOGIES & SERVICES FOR THERAPEUTIC ANTIBODY DEVELOPMENT
Specialist in tissue analysis by Histology, Immunohistochemistry and In Situ Hybridization TECHNOLOGIES & SERVICES FOR THERAPEUTIC ANTIBODY DEVELOPMENT CONTENTS Histalim: who we are Our areas of expertise
More informationRapidly Characterize Antibody- Drug Conjugates and Derive Drug-to-Antibody Ratios Using LC/MS
Rapidly Characterize Antibody- Drug Conjugates and Derive Drug-to-Antibody Ratios Using LC/MS Ning Tang, Ph.D. Agilent Technologies Santa Clara, California, USA Heterogeneity in ADCs Complexity T-DM1 (Genentech)
More informationUnique PK-PD properties of biotechnology-based therapeutics [mabs] and First In Human dose considerations. [mabs -monoclonal antibodies ] Peter Lloyd
Unique PK-PD properties of biotechnology-based therapeutics [mabs] and First In Human dose considerations [mabs -monoclonal antibodies ] Peter Lloyd Head of Pharmacokinetics-Pharmacodynamics Novartis Biologics
More informationJohn Mehl, Bogdan Sleczka, Eugene Ciccimaro, Christian Caporuscio, Ekaterina Deyanova, Richard Huang, Timothy Olah, Celia D Arienzo
Bioanalytical strategies for the quantitation of in-vivo site specific modifications of therapeutic antibodies in early discovery cyno studies using IP-LC-MS John Mehl, Bogdan Sleczka, Eugene Ciccimaro,
More informationApplication Note. Kwasi Antwi, Amanda Ribar, Urban A. Kiernan, and Eric E. Niederkofler Thermo Fisher Scientific, Tempe, Arizona
Analysis of an Antibody Drug Conjugate using MSIA D.A.R.T. S. Technology, an Integral Part of Ligand Binding Mass Spectrometric Immunoassay (LB-MSIA) Workflow Application Note Kwasi Antwi, Amanda Ribar,
More informationA Hybrid LBA-QPCR Technique (Proseek ) for Improved Assay Sensitivity. Karen Dowers
A Hybrid LBA-QPCR Technique (Proseek ) for Improved Assay Sensitivity Karen Dowers Outline The need for microsampling Microsampling technique Proseek Problems Associated with Sampling Require relatively
More informationAccelerating Therapeutic Development through a look at current Regulatory Applications A Non-Clinical Perspective
Accelerating Therapeutic Development through a look at current Regulatory Applications A Non-Clinical Perspective Imran M. Khan, Ph.D. Division of Psychiatry Center for Drug Evaluation and Research FDA
More informationIn vitro mechanistic studies on Metabolism-Dependent Inactivation of Cytochrome P450 Enzymes
In vitro mechanistic studies on Metabolism-Dependent Inactivation of Cytochrome P450 Enzymes Brooke Rock, 2016 DDI Conference, Seattle, WA Acknowledgements: PKDM, Amgen, San rancisco Chi-Chi Peng, John
More informationCase Studies on ultra-sensitive immunoanalytics based on Imperacer (Immuno-PCR) in clinical settings. Jan Detmers, Ph.D. (Chimera Biotec GmbH)
Case Studies on ultra-sensitive immunoanalytics based on Imperacer (Immuno-PCR) in clinical settings. Jan Detmers, Ph.D. (Chimera Biotec GmbH) Agenda 1.Overview Platforms 2.Immuno-PCR (Imperacer ) Technology
More informationIn Vivo Programs. Contract Research Services. Programs
P r o d u c t N o t e Contract Research Services In Vivo Programs Key Features Evaluation of drug properties Drug efficacy studies Biodistribution studies Complementary tissue analysis services CDAS In
More informationBioanalysis of peptides and proteins in drug research and development: from strategy into practice.
Bioanalysis of peptides and proteins in drug research and development: from strategy into practice. Lieve Dillen Drug Safety Sciences Analytical Sciences, n-regulated Bioanalysis Presentation outline Some
More informationTanja Krainz Current Literature July 9 th, 2016
Discovery and Characterization of BMN673 (Talazoparib), a Novel, Highly Potent, and Orally Efficacious Poly(ADP-ribose) Polymerase-1,2 Inhibitor, as an Anticancer Agent Wang, B.; Chu, D.; Feng, Y.; Shen,
More informationPharmacology. Chatchai Chinpaisal, Ph.D. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Silpakorn University.
Pharmacology Chatchai Chinpaisal, Ph.D. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Silpakorn University. 1 PHARMACODYNAMIC STUDIES A. Primary pharmacodynamics primary action in target
More informationSupporting information. Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo
Supporting information Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo Greg Thurber 1, Katy Yang 1, Thomas Reiner 1, Rainer Kohler 1, Peter Sorger 2, Tim Mitchison
More informationChallenges in Developing a Neutralizing Antibody Assay for a Cyno Toxicology Study
Challenges in Developing a Neutralizing Antibody Assay for a Cyno Toxicology Study Robin Marsden, Sr. Mgr., Bioanalytical Sciences, La Jolla Pharmaceutical Co. Kristine de Dios, M.S., Scientist, Preclinical
More informationWhy Knowledge of Translational PK/PD at Sites of Action Are Important to Optimize Bispecific Antibody Development?
Why Knowledge of Translational PK/PD at Sites of Action Are Important to Optimize Bispecific Antibody Development? Weirong Wang, Ph.D. Biologics Clinical Pharmacology Why Knowledge of Translational PK/PD
More informationSEMI-PHYSIOLOGICAL POPULATION PK/PD MODEL OF ADC NEUTROPENIA
SEMI-PHYSIOLOGICAL POPULATION PK/PD MODEL OF ADC NEUTROPENIA By MANASA TATIPALLI A THESIS PRESENTED TO THE GRADUATE SCHOOL OF THE UNIVERSITY OF FLORIDA IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE
More informationPreclinical pharmacokinetics and pharmacodynamics of AG-519, an allosteric pyruvate kinase activator
S830 Preclinical pharmacokinetics and pharmacodynamics of AG-519, an allosteric pyruvate kinase activator Yue Chen, Raj Nagaraja, Kha Le, Penelope A Kosinski, Gavin Histen, Charles Kung, Hyeryun Kim, Chandra
More informationAntibody drug conjugates
Powered by Antibody drug conjugates TOP ARTICLES SUPPLEMENT CONTENTS RESEARCH ARTICLE: Antibody drug conjugate bioanalysis using LB-LC MS/MS hybrid assays: strategies, methodology and correlation to ligand-binding
More informationCurrent practice and future vision on metabolite profiling and quantification in Drug development
Current practice and future vision on metabolite profiling and quantification in Drug development Geert Mannens EBF Focus workshop Metabolite Profiling and Quantification Strategies in Drug R&D Sept 25,
More informationBuilding a deep immuno-oncology portfolio in less than a year. David Johnson, PhD PEGS Spring 2018
Building a deep immuno-oncology portfolio in less than a year David Johnson, PhD PEGS Spring 2018 Improving early development 15-20 years, >$billion for an innovative new drug Attrition rate Target discovery
More informationBIOSTATISTICAL METHODS
BIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH Phase 0 Trials: EARLY-PHASE CLINICAL TRIALS Steps to New Drug Discovery Get idea for drug target Develop a bioassay Screen chemical compounds
More informationMethods to Determine the Binding of Bevacizumab to Fc receptors
DATASHEET Methods to Determine the Binding of Bevacizumab to Fc receptors BACKGROUND Bevacizumab (Avastin ) is a humanized recombinant monoclonal antibody that inhibits angiogenesis by binding to the vascular
More informationBIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH
BIOSTATISTICAL METHODS FOR TRANSLATIONAL & CLINICAL RESEARCH Phase 0 Trials: EARLY-PHASE CLINICAL TRIALS CLINICAL PHASE Clinical Studies: Class of all scientific approaches to evaluate Disease Prevention,
More informationDISCOVERY AND VALIDATION OF TARGETS AND BIOMARKERS BY MASS SPECTROMETRY-BASED PROTEOMICS. September, 2011
DISCOVERY AND VALIDATION OF TARGETS AND BIOMARKERS BY MASS SPECTROMETRY-BASED PROTEOMICS September, 2011 1 CAPRION PROTEOMICS Leading proteomics-based service provider - Biomarker and target discovery
More informationAntibody Drug Conjugates - Introduction to a new EBE initiative EBE Satellite Session Paris - May 9, 2016
Antibody Drug Conjugates - Introduction to a new EBE initiative EBE Satellite Session Paris - May 9, 2016 Presented by Fred Jacobson (Genentech) on behalf of the ADC task force How it got started... May
More informationControl Strategies for Antibody-based Immuno-oncology Products: It Starts with Product Design!
Control Strategies for Antibody-based Immuno-oncology Products: It Starts with Product Design! Marjorie Shapiro Office of Biotechnology Products/FDA WCBP 2017 January 25, 2017 Disclaimer The views presented
More informationIdentification of Critical Product Quality Attributes: Impact of Product Variants on Safety and Efficacy
Identification of Critical Product Quality Attributes: Impact of Product Variants on Safety and Efficacy Ziping Wei, Ph.D. Analytical Biochemistry MedImmune January 25, 2010 Outline Why do we need to identify
More informationEngage with us on Twitter: #Molecule2Miracle
Engage with us on Twitter: #Molecule2Miracle Kassy Perry President & CEO Perry Communications Group PhRMA Alliance Development Consultant.@kassyperry Emily Burke, Ph.D. Director of Curriculum BioTech
More informationTumor tissues or cells were homogenized and proteins were extracted using
SUPPLEMENTAL MATERIALS AND METHODS Western Blotting Tumor tissues or cells were homogenized and proteins were extracted using T-PER tissue protein extraction buffer. Protein concentrations were determined
More information