Creating Highly Efficacious ADCs for Low-Expression Targets While Improving Therapeutic Index TIM LOWINGER, PHD
|
|
- Abigayle Porter
- 6 years ago
- Views:
Transcription
1 Creating Highly Efficacious ADCs for Low-Expression Targets While Improving Therapeutic Index TIM LOWINGER, PHD CSO
2 Mersana Therapeutics VC-backed Biotech in Cambridge, MA Investors: NEA, Pfizer, Fidelity, Proquest, Rho Proprietary Fleximer Biodegradable Polymer Conjugation Platform for use in creating Antibody Drug Conjugates Strategic collaborations with select partners Independent, wholly owned pipeline programs 2
3 Creating Effective ADCs is Not Trivial Common Obstacles: Payload hydrophobicity Aggregation Limited capacity (3-4) requires very high potency Detrimental effects on PK with higher loading Limited number of payload classes Microenvironmental influences on stability/release Low antigen expression Safety / tolerability 3
4 Fleximer - Tested, Superior Platform New Composition IP Nonimmunogenic Fully Biodegradable Very Safe (~200 Patients) Multiple Conjugation Sites Highly Soluble, Stable 4
5 Facile CMC and Bioconjugation Fleximer polymer Fleximer-drug conjugate payload drug ORGANIC SOLVENT Very High Aqueous Solubility Isolated, characterized and stored long-term Fleximer Antibody-Drug Conjugate WATER Multiple standard and site-specific bioconjugation chemistries available lysine, cysteine, or site-specific / engineered 5
6 Showcasing the Dolaflexin TM ADC Platform Trastuzumab as representative antibody Proprietary Auristatin-derived payload Conjugation via hinge-region cysteines Drug-Antibody ratio of
7 Dolaflexin ADC Structure CYSTEINE-BASED FLEXIMER-DRUG ANTIBODY CONJUGATION PARTIALLY REDUCED ANTIBODY DOLAFLEXIN ADC mab-cys 7
8 Trastuzumab-Dolaflexin ADC Characteristics PARAMETER ANALYSIS ADC size kda ADC Polydispersity PDI < 1.2 Drug/mAb ratio, (DAR) Fleximer/mAb ratio 3-4 Free drug content, % total <0.5% Free mab content, % total <0.5% Free Dolaflexin, % total drug <1% Aggregation, % <2% Free thiol groups Not detected 8
9 Dolaflexin ADC Uniform, No Aggregation DOLAFLEXIN SIZE AND POLYDISPERSITY ANALYSIS: Peak MW ~200 kda PDI ~1.15 ADC SEC, UV 280 nm mau ADC mab Minutes MINUTES 9
10 Dolaflexin ADCs Maintain Target Affinity Trastuzumab-Dolaflexin Affinity Similar to Trastuzumab and T-DM1 by SPR Sample ADC Type DAR k a (M -1 s -1 ) k d (s -1 ) K D (pm) Trastuzumab n/a n/a 9.90(1)e5 2.60(1)e (1) Kadcyla Lys/DM (2)e5 3.17(9)e (3) ADC1 Cys/Dolaflexin TM (2)e5 2.32(2)e (1) ADC2 Cys/Dolaflexin TM (3)e5 2.60(9)e (3) ADC3 Cys/Dolaflexin TM (3)e5 2.43(1)e (3) ADC4 Cys/Dolaflexin TM (5)e5 2.03(1)e (5) Notes: The number in parentheses represents the error in the last digit. For example, 9.9(1)e5 equals (9.9 ± 0.1) x
11 High DAR Fleximer ADCs Retain Excellent PK Half-life of Conjugated Drug in Mice > 5 Days Trastuzumab-Dolaflexin (DAR20) Mouse PK COMPOUND PLASMA CONCENTRATION, ng/ml Free drug 10,000x lower than conjugated drug Total mab (ELISA) Conjugated Drug Free Drug Time, hours 11
12 Excellent PK Across a Range of High DARs Pharmacokinetics Independent of DAR Conjugated Drug Plasma PK 10, CONC. (ng/ml) 1, TIME (HRS) ADC ID ADC1 ADC2 ADC3 DAR Conjugated Drug T 1/2 (hr) AUC (ug*hr/ml)
13 Trastuzumab-Dolaflexin Highly Active in HER2 (3+) Breast Cancer Model 100% Tumor Free Survivors After Single 5 mg/kg Dose 1200 BT-474 HER2 (3+) Breast Cancer Xenograft 500,000 copies of HER2 / cell TUMOR VOLUME (MM 3 ) Single i.v. Injection Day 1 DAYS Vehicle Trastuzumab Dolaflexin 5 mg/kg 10/10 Tumor Free Survivors 13
14 Trastuzumab-Dolaflexin Highly Active in HER2 (3+) Gastric Cancer Model 100% Tumor Free Survivors After Single 3 mg/kg Dose 800 N87 HER2 (3+) Gastric Cancer Xenograft > 500,000 copies of HER2 / cell Vehicle MEAN TUMOR VOLUME (MM 3 ) DAY (DOSING ON DAY 1) Trastuzumab- Dolaflexin 0.67 mg/kg Trastuzumab Dolaflexin 3 mg/kg 10/10 Tumor Free Survivors Single i.v. Injection Day 1 14
15 Fleximer ADCs Increase Delivery Efficiency and Cell Kill for Low Antigen Expression Cells High DAR Fleximer ADCs More Readily Achieve Threshold Concentration HIGH EXPRESSION LOW EXPRESSION 15
16 High DAR Significantly More Active in Low Target Expressing Cells 100-Fold Potency Advantage In Vitro JIMT-1 Cells 79,000 copies of HER2 / cell % VIABILITY Trastuzumab-Dolaflexin IC 50 =0.14nM T-DM1 IC 50 = 18 nm LOG Cpd (nm) 16
17 Trastuzumab-Dolaflexin Shows Dramatic Activity in T-DM1 Resistant Low HER2 Model 100% Tumor Free Survivors After Single 2 mg/kg Dose; T-DM1 inactive at 10x Dose JIMT-1 Breast Cancer Xenograft 79,000 copies of HER2 / cell MEAN TUMOR VOLUME (MM 3 ) Rituximab-Dolaflexin 2 mg/kg Vehicle Single i.v. Injection Day 1 DAY (DOSING ON DAY 1) T-DM1 20 mg/kg 0.67 mg/kg Trastuzumab-Dolaflexin 2 mg/kg 10/10 Tumor Free Survivors 17
18 18 Trastuzumab-Dolaflexin Is Well Tolerated in Mice Therapeutic Index of > 15 vs. Single Dose Leading to 100% Tumor Free Survival Trastuzumab-Dolaflexin Mouse Tolerability 20 mg/kg 30 mg/kg 40 mg/kg 0.67 mg/kg TI > 40 2 mg/kg* 3 mg/kg* Trastuzumab-Dolaflexin mouse efficacy* * Sustained regressions in HER2-high and HER2-low models Non-severely toxic dose Severely toxic dose 20 mg/kg 30 mg/kg 40 mg/kg
19 Single Dose Trastuzumab-Dolaflexin NHP Study 0.67 mg/kg 600 μg/m mg/kg 2.68 mg/kg 1200 μg/m μg/m 2 TRASTUZUMAB- DOLAFLEXIN NHP TOX 3 mg/kg 612 μg/m 2 10 mg/kg 30 mg/kg 2040 μg/m μg/m 2 KADCYLA NHP TOX (POON 2013) 1 mg/kg 232 μg/m 2 3 mg/kg 696 μg/m 2 6 mg/kg 1392 μg/m 2 ADCETRIS NHP TOX (BLA REVIEW) Dose of ADC (mg/kg) Dose of payload (μg/m2) Severely toxic dose 19
20 Summary of Findings in Exploratory Toxicology Trastuzumab-Dolaflexin was well-tolerated at all doses tested All animals survived until scheduled necropsy No test article-related changes on gross pathology Adverse findings on clinical pathology were generally consistent with published observations for Kadcyla Greater AST increases than described for Kadcyla, lesser ALT increases No evidence of myelosuppression Microscopic pathology changes were minimal to mild No microscopic pathology changes in HER2-expressing tissues (heart, lungs, gut) Highest non-severely toxic dose of trastuzumab-dolaflexin exceeds 2.68 mg/kg (2400 μg/m 2 toxin dose)
21 21 Trastuzumab-Dolaflexin NHP Plasma PK Very high stability in NHPs Half life for ADC of ca. 5 Days CYNOMOLGUS MONKEY 2.68 MG/KG SINGLE DOSE Total mab (ELISA) ADC Conjugated Drug Free drug
22 AUC of Highest, Well-Tolerated Dose in Cynos Similar to AUC for 100% Tumor Free Survivors in Mice TRASTUZUMAB-DOLAFLEXIN CONJUGATED DRUG EXPOSURE (MOUSE VS. CYNO MONKEY) Conjugated Drug Plasma Concentration, ng/ml MED in mice (0.67 mg/kg) Single Dose for 100% Tumor Free Survivors In Mice 3 mg/kg 2 mg/kg Highest Tested Dose in Cyno 2.68 mg/kg Time, hrs
23 Favorable Therapeutic Index in NHP 0.67 mg/kg 1.34 mg/kg 2.68 mg/kg 600 μg/m μg/m μg/m 2 Trastuzumab- Dolaflexin NHP tox 0.67 mg/kg 2 mg/kg 3 mg/kg TI > μg/m μg/m μg/m 2 Trastuzumab- Dolaflexin efficacy Trastuzumab-dolaflexin has a favorable therapeutic index in HER2-amplified and HER2-low models TI > 16 by allometrically scaled payload dose TI > 3 by exposure 23
24 Asana 5T4-Targeted Dolaflexin Program
25 Superior Efficacy in Head-to-Head Study Efficacy Comparable to A1mcMMAF at 1/10 th the Dose ASN004 1 mg/kg A1mcMMAF 10 mg/kg
26 Mersana s First ADC Product Highly Active in Multiple Cancer Models Single doses also highly active in other tumor models including NSCLC, breast and ovarian MEAN TUMOR VOLUME (mm3) Western-derived Gastric Cancer High Target Expression 0 Mersana product 1 mg/kg 4 PR / 6 CR / 6 TFS Single i.v. Injection Day 1 Vehicle DAY (DOSING ON DAY 1) MEAN TUMOR VOLUME (mm3) Asian-derived Gastric Cancer Low Target Expression (<25,000 receptors per cell) Vehicle Mersana product 0.67 mg/kg 10 CR / 9 TFS DAY (DOSING ON DAY 1) Single i.v. Injection Day 1 IND Planned for
27 27 Fleximer ADC Platform Enables high drug loading without sacrificing PK Provides excellent physicochemical properties Achieves high efficacy against low expression targets Foundation for Mersana s ADC product portfolio Adds significant value to partners ADC pipelines
28 The Mersana Research Team Pictured from Left to Right: Pat, Alex, Mao, Dmitry, Venu, Xianhua, Alex, Radha, Cheri, Natasha, Laura, Peter, Elena, Roberta, Liu, Dennis, Josh, Mike 28
29 Thank you for your attention!
Antibody 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 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 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 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 informationIntra-tumor Catabolites (fate of ADC) can Predict ADC Efficacy. Donglu Zhang, Ph.D. Genentech Feb 21, 2017 World ADC Berlin-2017
Intra-tumor Catabolites (fate of ADC) can Predict ADC Efficacy Donglu Zhang, Ph.D. Genentech Feb 21, 2017 World ADC Berlin-2017 1 Outline ADC structure and mechanism of action (MOA) Can we use PK or PK-PD
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 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 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 informationphab Amine and Thiol Reactive Dyes for Antibody Internalization Studies Nidhi Nath, Ph.D. Group Leader, Protein Analysis Promega Corporation
phab Amine and Thiol Reactive Dyes for Antibody Internalization Studies Nidhi Nath, Ph.D. Group Leader, Protein Analysis 1 Outline 1. phab Dyes 2. Protocols for conjugating phab Dyes to antibodies 3. Applications:
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 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 information**MATERIAL SAFETY DATA SHEET**
Date Issued: August 19, 2009 Version: 5.0 Supersedes: August 8, 2006 Page 1 of 5 Section 1 Product and Company Identification Product Name: Herceptin Chemical Name: Anti-p185 HER2 Chemical Family: High
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 informationRegulatory Review Considerations of Drug-Linker Quality in ADCs
Regulatory Review Considerations of Drug-Linker Quality in ADCs Xiao Hong Chen, Ph.D. Acting Quality Assessment Lead Division of New Drug Products I, Branch II ONDP/OPQ/CDER/FDA Outlines ADC IND submissions
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 informationCiti s 2017 Global Healthcare Conference 6~7 December 2017, New York
Citi s 2017 Global Healthcare Conference 6~7 December 2017, New York Safe Harbor Statement forward-looking statements. These forward-looking statements may be identified by words sthis presentation contains
More informationDiscovery and Development of Highly Selective and Orally Bioavailable Macrocyclic IDO-1 Inhibitors
Discovery and Development of Highly Selective and Orally Bioavailable Macrocyclic IDO-1 Inhibitors 1 Tim Briggs Senior Director, Medicinal Chemistry Ensemble Therapeutics Corp. Ensemble Therapeutics Corp.
More informationSize Exclusion Chromatography/ Mass Spectrometry Analysis of Antibody Drug Conjugates Using the Agilent 1260 Infinity II Bio-Inert LC
Size Exclusion Chromatography/ Mass Spectrometry Analysis of Antibody Drug Conjugates Using the Agilent 126 Infinity II Bio-Inert LC Application Note Biologics & Biosimilars Author Sonja Schneider Agilent
More informationFirst-in-Class Bispecific Antibodies For Cancer Immunotherapy
First-in-Class Bispecific Antibodies For Cancer Immunotherapy 2015 Company Highlights Vision Team Platform Pipeline Partners To dominate the bispecific antibody space in immunooncology through unique pipeline
More informationATACs fighting Cancer. November 2017
ATACs fighting Cancer November 2017 Safe Harbor Forward looking statements This communication contains certain forward looking statements, relating to the Company s business, which can be identified by
More informationPK and PK/PD Guided Starting Dose Selection for First-In-Human Trials. Sylvia Zhao ( 赵子微 ) Translational Clinical Oncology Novartis
PK and PK/PD Guided Starting Dose Selection for First-In-Human Trials Sylvia Zhao ( 赵子微 ) Translational Clinical Oncology Novartis Disclaimer Contents are the opinion of the author and not that of Novartis
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 informationSafety Assessment of Oligonucleotide Constructs. Scott P. Henry, VP, Preclinical Development, Isis Pharmaceuticals, Inc., USA
Safety Assessment of ligonucleotide Constructs Scott P. Henry, VP, Preclinical Development, Isis Pharmaceuticals, Inc., USA Drug Development of 2 ME AS Platform Technology 2 Platform technologies offer
More informationTIDES 2014 GalNAc-siRNA with Enhanced Stabilization Chemistry: ESC-GalNAc-siRNA. May 14, 2014 Muthiah Manoharan
TIDES 2014 GalNAc-siRNA with Enhanced Stabilization Chemistry: ESC-GalNAc-siRNA May 14, 2014 Muthiah Manoharan Agenda sirna-galnac Conjugates: Background Standard Template Chemistry (STC)» Human POC of
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 informationConsiderations for Control Strategies for mab/mab Combination Therapies An Industry Perspective
Considerations for Control Strategies for mab/mab Combination Therapies An Industry Perspective Dieter Schmalzing, GBQC, South San Francisco Genentech, A Member of the Roche Group CMC Strategy Forum Europe
More informationSafety Pharmacology Strategies to Support Drug Development: Oncology Biotherapeutics
Safety Pharmacology Strategies to Support Drug Development: Oncology Biotherapeutics Hugo M. Vargas, PhD Safety & Exploratory Pharmacology Toxicology Sciences Amgen, Inc Outline Biotherapeutics & Oncology
More informationOPT-302: a VEGF-C/VEGF-D Trap for wet AMD
OPT-302: a VEGF-C/VEGF-D Trap for wet AMD Ophthalmology Innovation Summit, Nov 12 2015 Circadian Technologies (ASX:CIR, OTCQX:CKDXY) Megan Baldwin PhD, CEO & MD megan.baldwin@opthea.com 2 Disclaimer Investment
More informationFile no./drug Name Name of firm/ Institute Recommendations. M/s. AstrazenecaPharma India Limited
Recommendations: I agree the minutes of 51 st SEC-Oncology & Haematology meeting held on 21.03.2017 at CDSCO HQ New Delhi Agenda File /Drug Name Name of firm/ Institute Recommendations New Drugs Division
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 informationAntibody Targeted Amanitin Conjugates (ATACs) Expanding the ADC Landscape With a New Payload Targeting RNA Polymerase II
ntibody Targeted manitin Conjugates (TCs) Expanding the DC Landscape With a New Payload Targeting RN Polymerase II Safe Harbor Forward looking statements This communication contains certain forward-looking
More informationSamatasvir (IDX719), a Potent Pan-Genotypic NS5A Inhibitor, for the Treatment of Hepatitis C Virus (HCV) Infection
Samatasvir (IDX719), a Potent Pan-Genotypic NS5A Inhibitor, for the Treatment of Hepatitis C Virus (HCV) Infection Douglas Mayers, MD December 11, 2013 1 Idenix: Advancing All-Oral, Pan-Genotypic Combination
More informationHow do drugs work? Part 1. PK: Principles & Processes. PK vs. PD. Pharmacokinetics : Basic Principles Overview. What does the body do to a drug?
Pharmacokinetics : Basic Principles verview 1. PK : Basic principles and processes 2. Important PK Parameters 3. Modulating PK Parameters 4. PK : Drugs vs. contrast agents Twan Lammers Dept. of Experimental
More informationNanotechnology: A Brief History and Its Convergence with Medicine. Weston Daniel, PhD Director of Program Management
Nanotechnology: A Brief History and Its Convergence with Medicine Weston Daniel, PhD Director of Program Management Outline Introduction The Nanoscale Applications Realization of a Vision There s Plenty
More informationmabs and ADCs analysis by RP
mabs and ADCs analysis by RP Shanhua Lin, Ph.D. The world leader in serving science Protein and mab Separation by HPLC Size difference? YES Size Exclusion Chromatography (SEC) MAbPac SEC-1 NO NO Charge
More informationModelling and simulation to help define MABEL and Starting dose in FIH studies
Modelling and simulation to help define MABEL and Starting dose in FIH studies B Laurijssens, BEL Pharm Consulting. Steven W Martin, Pharmacometrics Group, Dept Clinical Pharmacology, Pfizer, Sandwich
More informationRecombinant Antibody Production in Therapeutic Antibody Projects. Keshav Vasanthavada Senior Marketing Specialist, GenScript April 7, 2016
Recombinant Antibody Production in Therapeutic Antibody Projects Keshav Vasanthavada Senior Marketing Specialist, GenScript April 7, 2016 Presentation Outline 1 2 3 4 5 Introduction Recombinant Ab Production
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 informationProfibrinolytic diabody targeting PAI-1 and TAFI for treatment of acute thrombotic disorders
ProFiDIΛ Profibrinolytic diabody targeting PAI-1 and TAFI for treatment of acute thrombotic disorders THROMBOLYSIS WITH IMPROVED SAFETY A valorisation project of Unmet Medical Need = Safe Thrombolysis
More informationDrug Tolerance in ADA Analysis
Drug Tolerance in ADA Analysis Matthew Bentley www.eurofins.com DRUG TOLERANCE What is Drug Interference and Why an issue in ADA analysis? Methodologies to overcome Drug Interference Acid Dissociation
More informationDevelopment of best- in- class, homogeneous An9body Drug Conjugates (ADCs) for highly effec9ve and safer cancer therapy
Development of best- in- class, homogeneous An9body Drug Conjugates (ADCs) for highly effec9ve and safer cancer therapy Ulf Grawunder, PhD, CEO NBE- Therapeu9cs AG Technology Park Basel Hochbergerstr.
More informationOptimisation de votre programme de développement
Optimisation de votre programme de développement Cedric Lamy, PhD. Cedric.lamy@crl.com Charles River Overview 65-year history: Founded in 1946, publicly traded (NYSE:CRL) Investment in skilled staff: ~7,500
More informationApplications of HTRF and Tag-lite Assays for HTP Antibody Screening
Applications of HTRF and Tag-lite Assays for HTP Antibody Screening Brigitte Devaux, PhD Bristol Myers Squibb, Redwood City CA HTRF Symposium April 25, 2013 1 Introduction Generate human therapeutic antibodies
More informationPRECLINICAL DRUG DISCOVERY AND DEVELOPMENT BIOBOOT CAMP 2016
PRECLINICAL DRUG DISCOVERY AND DEVELOPMENT BIOBOOT CAMP 2016 1 FROM DISCOVERY TO COMMERCIALIZATION At least 10 years on average Average spend of $1.4B Less than 12% of drugs entering Phase I are approved
More informationA universal chromatography method for aggregate analysis of monoclonal antibodies
APPLICATION NOTE A universal chromatography method for aggregate analysis of monoclonal antibodies No. 2161 Amy Farrell 1, Jonathan Bones 1, and Ken Cook 2 1 NIBRT, Dublin, Ireland; 2 Thermo Fisher Scientific,
More information-Immune phenotype -Cancer xenografts -Immune system humanization -Services
-Immune phenotype -Cancer xenografts -Immune system humanization -Services services@herabiolabs.com 859-414-0648 About Hera BioLabs Precision Toxicology & Efficacy: utilizing precisely gene-edited models
More informationB-cell Epitope Prediction and Cloning monoclonal ADAs
B-cell Epitope Prediction and Cloning monoclonal ADAs Stefan Ryser, CEO, Trellis Bioscience 3 rd International Symposium on Higher Order Structure of Protein Therapeutics Arlington, Virginia, February
More informationBIOPHARMA SOLUTIONS TM Expedite Your Drug Development Program
BIOPHARMA SOLUTIONS TM Expedite Your Drug Program Maximize the Value of Your Asset The journey of drug development can be complex stressful. But it doesn t have to be that way. Join more than 600 biopharmaceutical
More informationCopyright. Jeremiah J. Kelly (2015). All rights reserved. Further dissemination without express written consent strictly prohibited.
Statutory Framework for Biologics Drugs Investigational Use Application IND Pre-Market Approval Applications 505(b)(1) NDA 505(b)(2) NDA 505(j) ANDA Over-the-Counter (OTC) Non- Rx Drugs Monograph Biologics
More informationDrug Development: Why Does it Cost so Much? Lewis J. Smith, MD Professor of Medicine Director, Center for Clinical Research Associate VP for Research
Drug Development: Why Does it Cost so Much? Lewis J. Smith, MD Professor of Medicine Director, Center for Clinical Research Associate VP for Research Drug Development Process by which new chemical entities
More informationOncology Biopharmaceuticals and Preclinical Development: Evolving Regulatory Challenges
The content of this presentation reflects the opinion of the speaker and does not necessarily represent the official position of CDER Oncology Biopharmaceuticals and Preclinical Development: Evolving Regulatory
More informationReal-time 96-well antibody internalization assays using IncuCyte FabFluor Red Antibody Labeling Reagent
Nicola Bevan, Tim Dale, Del Trezise Essen BioScience Welwyn Garden City, Hertfordshire, UK Introduction Monoclonal antibodies are now widely used as anti-cancer, antiinflammatory and anti-viral therapeutic
More informationDevelopment of Multiplex Sensitive Anti-Drug Antibody Assays for CRISPR/Cas9 Gene Therapies
Development of Multiplex Sensitive Anti-Drug Antibody Assays for CRISPR/Cas9 Gene Therapies September 27, 2017 Junxia Wang editasmedicine.com 1 Overview of the presentation Immunogenicity Introduction
More informationBaek, Kyung-min. Recombinant Protein Products Division. Ministry of Food and Drug Safety
Baek, Kyung-min Recombinant Protein Products Division Ministry of Food and Drug Safety About Ministry of Food and Drug Safety Regulation for Biosimilar Principle of Biosimilar Approach Status of Biosimilar
More informationAdopting Virtual R&D in Drug Development
Adopting Virtual R&D in Drug Development 2016 Table of Contents 1. Why virtual R&D? 2. Project management team for drug development 3. Project initiation 4. Clinical study team considerations for virtual
More informationQuality attributes impacting immunogenicity of therapeutic proteins
www.pei.de Quality attributes impacting immunogenicity of therapeutic proteins Workshop on immunogenicity assessment of biotechnology-derived therapeutic proteins 9th March 2016 (EMA, Room 3A) Steffen
More informationmacrofilaricide Robert Don Discovery and Preclinical Director
Development of Flubendazole as a macrofilaricide Robert Don Discovery and Preclinical Director DNDi s Main Objectives Most Neg glected Use and strengthen existing capacity in disease- endemic countries
More informationOptimization of ADC Process Development. Eric LACOSTE PhD, Chemistry and Biotechnology Development Sanofi Aventis R&D, Vitry sur Seine, France 2016
Optimization of ADC Process Development Eric LACOSTE PhD, Chemistry and Biotechnology Development Sanofi Aventis R&D, Vitry sur Seine, France 2016 Strictly confidential do not distribute without prior
More informationMake Your Immunology Research Easy. Kun YIN Associate Director of Marketing Division, GenScript
Make Your Immunology Research Easy Kun YIN Associate Director of Marketing Division, GenScript GenScript Overview Branch Office Amsterdam, Netherlands Branch Office Tokyo, Japan Headquarter, New Jersey,
More informationOutline CLINICALLY RELEVANT SPECIFICATIONS. ISPE Process Validation Conference September 2017 Bethesda, MD
CLINICALLY RELEVANT SPECIFICATIONS Patrick J Marroum Ph.D. Senior Director and ACOS Senior Research Fellow Department of Clinical Pharmacology and Pharmacometrics Abbvie Pharmaceuticals Outline CMC variables
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 informationModel-based Technology Selection for Bioavailability Enhancement CPHI DAVID K. LYON, PH.D. OCTOBER 25, 2017
Model-based Technology Selection for Bioavailability Enhancement CPHI DAVID K. LYON, PH.D. OCTOBER 25, 2017 Biopharmaceutical Classification System Approximately 80% of drugs in the pharmaceutical compounds
More informationADCC Reporter Bioassay: A Novel, Bioluminescent Cell-Based Assay for Quantifying Fc Effector Function of Antibodies
ADCC Reporter Bioassay: A Novel, Bioluminescent Cell-Based Assay for Quantifying Fc Effector Function of Antibodies Richard Somberg, Ph.D. October 2012 Outline Introduction to ADCC Problem with classic
More informationDesign and Validation of a Non Cell-based Receptor Binding Assay for the Detection of Neutralizing Antibodies to a Biological Therapeutic
Design and Validation of a Non Cell-based Receptor Binding Assay for the Detection of Neutralizing Antibodies to a Biological Therapeutic Shalini Gupta Associate Director Amgen, Thousand Oaks, CA shalinig@amgen.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 informationStrategies to Improve Drug Tolerance in Nab Assays
Strategies to Improve Drug Tolerance in Nab Assays Steven J Swanson, PhD Senior Vice President, Research ImmunoCellular Therapeutics Ltd steven.swanson@imuc.com AAPS National Biotech Conference June 2015
More informationBiosimilar regulation in Republic of Korea and Asia-Pacific Economic Cooperation (APEC) developments
Biosimilar regulation in Republic of Korea and Asia-Pacific Economic Cooperation (APEC) developments Ministry of Food and Drug Safety Jeewon Joung Outline I. Korean Regulatory Framework for Biosimilar
More informationGuidelines and criteria for seeking approval to conduct clinical trials in Ayurveda, Siddha and Unani system.
Guidelines and criteria for seeking approval to conduct clinical trials in Ayurveda, Siddha and Unani system. Application for seeking approval of the Central Government for conduct of clinical trial in
More informationPrecise Characterization of Intact Monoclonal Antibodies by the Agilent 6545XT AdvanceBio LC/Q-TOF
Precise Characterization of Intact Monoclonal Antibodies by the Agilent 6545XT AdvanceBio LC/Q-TOF Application Note Author David L. Wong Agilent Technologies, Inc. Santa Clara, CA, USA Introduction Monoclonal
More informationUse of Antisense Oligonucleotides for the Treatment of Inheritable Rare Disorders. C. Frank Bennett Isis Pharmaceuticals
Use of Antisense ligonucleotides for the Treatment of Inheritable Rare Disorders C. Frank Bennett Isis Pharmaceuticals Agenda Review different antisense strategies Delivery of oligonucleotides to the skin,
More informationComparability Assessment of BioTherapeutics: Paving the Way for Late-Stage Projects
Comparability Assessment of BioTherapeutics: Paving the Way for Late-Stage Projects Olga Friese, PhD Associate Research Fellow Pfizer Biotherapeutics PharmSci 28 January 2014 Overview Manufacturing process
More informationKFDA Regulatory Framework on Biopharmaceuticals - Focus on Biosimilar
KFDA Regulatory Framework on Biopharmaceuticals - Focus on Biosimilar Kyung-Min Baek, Ph.D. Recombinant Protein Products Division Korea Food and Drug Administration(KFDA) Biopharmaceuticals A biopharmaceutical
More informationPlatform Advances in RNAi Therapeutics. RNAi Roundtable August 23, 2017
Platform Advances in RNAi Therapeutics RNAi Roundtable August 23, 2017 Agenda Welcome Josh Brodsky, Associate Director, Investor Relations & Corporate Communications Introduction Akshay Vaishnaw, M.D.,
More informationSPEED UP YOUR TIME TO MARKET
SPEED UP YOUR TIME TO MARKET #Pre-clinical #Biologics #Small molecules Welcome to Accelera. As a Contract Research Organization (CRO) serving since more than 30 years pharmaceutical and biotechnology companies
More informationFraction Analysis of Cysteine Linked Antibody-Drug Conjugates Using Hydrophobic Interaction. chromatography. Agilent 1260 Infinity II Bio-Inert System
Application Note Biologics & Biosimilars Fraction Analysis of Cysteine Linked Antibody-Drug Conjugates Using Hydrophobic Interaction Chromatography Agilent 126 Infinity II Bio-Inert System 7 6 5 4 5. 7.5
More informationAntifungal PK/PD Made Simple. David Andes, MD University of Wisconsin
Antifungal PK/PD Made Simple David Andes, MD University of Wisconsin PK/PD Concept Serum Drug Concentration Peak:MIC AUC:MIC Ratio Time Above MIC MIC Time Hypothesis and Concept There is an optimal drug
More informationPharmaceutical Development for ADCs: Not as Simple as ABC
Pharmaceutical Development for ADCs: Not as Simple as ABC Pharmaceutical Development for ADCs Formulation, process, and analytical development for antibody-drug conjugates, or ADCs, is complex. While the
More informationInjectable modified release products
Guideline on the pharmacokinetic and clinical evaluation of modified release dosage forms (EMA/CPMP/EWP/280/96 Corr1) Injectable modified release products Dr Sotiris Michaleas, National Expert for the
More informationRapid Production of Bispecific Antibodies Using Off-the-Shelf IgG
Rapid Production of Bispecific Antibodies Using Off-the-Shelf IgG Andrew Tsourkas, Ph.D. Professor Department of Bioengineering University of Pennsylvania Limitations/Challenges of Nanoparticle Bioconjugations
More informationVecchi anticorpi per nuove terapie biologiche
Vecchi anticorpi per nuove terapie biologiche Rita De Santis PhD Head Biotech Products, R&D rita.desantis@sigma-tau.it Alfasigma headcounts 6% 24% 49% 3500 3033 22% 3000 2500 1177 Sales Force Manufacturing
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 informationDrug Metabolism and Pharmacokinetic (DMPK) Properties of sirna-galnac Conjugates
Drug Metabolism and Pharmacokinetic (DMPK) Properties of sirna-galnac Conjugates Anshul Gupta, Lead Scientist DSM, Alnylam Pharmaceuticals, Cambridge, MA DIA/FDA Oligonucleotide Based Therapeutic Conference,
More informationComparability Studies for Autologous Cell Therapy Products. Chris Shen July, 2017
Comparability Studies for Autologous Cell Therapy Products Chris Shen July, 2017 Forward Looking Statements/Safe Harbor To the extent statements contained in this presentation are not descriptions of historical
More informationDiscovery of Orally Bioavailable Small Molecules for Inhibition of Complement C5
Discovery of Orally Bioavailable Small Molecules for Inhibition of Complement C5 22 nd Congress of the European Hematology Association Madrid, Spain June 24, 2017 Forward Looking Statements This presentation
More informationBeth Hutchins, PhD PhRMA ICH Gene Therapy Discussion Group
ICH Considerations on General Principles to Address the Risk of Inadvertent Germline Integration of Gene Therapy Vectors and Current Topics on Gene Therapy in USA Beth Hutchins, PhD PhRMA ICH Gene Therapy
More informationWhen to Stop Dose Escalation: MTD, MLD or?
When to Stop Dose Escalation: MTD, MLD or? Henri CAPLAIN First Joint Annual Meeting, AGAH Club Phase 1 STRASBOURG, France 1 So called MTD STOP FIM No MTD? 2 WHY WE NEED TO REACH THE MAXIMUM TOLERATED DOSE
More informationDiscovery and Humanization of Novel High Affinity Neutralizing Monoclonal Antibodies to Human IL-17A
Discovery and Humanization of Novel High Affinity Neutralizing Monoclonal Antibodies to Human IL-17A Contacts: Marty Simonetti martysimonetti@gmail.com Kirby Alton kirby.alton@abeomecorp.com Rick Shimkets
More informationIn vivo Efficacy of a Bispecific Molecule Targeting CTLA-4 and EGFR
In vivo Efficacy of a Bispecific Molecule Targeting CTLA-4 and EGFR Miguel Gaspar Senior Scientist F-star Biotechnology Ltd. 6 th World Bispecific Summit September 22-24, 2015 Objectives Demonstrate in
More informationProSEC 300S. Protein Characterization columns
ProSEC 300S Protein Characterization columns Agilent s ProSEC 300S is a silica-based material specifically designed for the analysis of proteins by aqueous size exclusion chromatography. With a proprietary
More informationPharma&Biotech. ADC Process Transfer from a CMO Perspective: How to Make a Collaboration Successful
Pharma&Biotech ADC Process Transfer from a CMO Perspective: How to Make a Collaboration Successful Additional Information and Disclaimer Lonza Group Ltd has its headquarters in Basel, Switzerland, and
More informationTherapeutic RNA delivery
Therapeutic RNA delivery 05/02/2017 TIDES Dr. Adrien Weingärtner Head of Technology Development Forward looking statements THE INFORMATION CONTAINED IN THIS PRESENTATION IS BEING SUPPLIED AND COMMUNICATED
More informationSelection of Well-Tolerated GalNAc-siRNAs by Screening for RNAi-Mediated Off-Target Effects in Rodent Toxicity Studies Maja Janas, PhD, DABT
Selection of Well-Tolerated GalNAc-siRNAs by Screening for RNAi-Mediated Off-Target Effects in Rodent Toxicity Studies Maja Janas, PhD, DABT Senior Scientist, Investigative Toxicology TIDES, May 2 nd 2017
More informationPreclinical Development Discovery to IND
Preclinical Development Discovery to IND Biobootcamp CBSA / Fitzsimons / FBBp / Holland & Hart Lauren C. Costantini, Ph.D. www.lccconsulting.net This Discussion Research and Development Product development
More informationCM-352: a new, potent and safe molecule for the prevention and treatment of haemorrhage
XIV Encuentro de Cooperación Farma-Biotech CM-352: a new, potent and safe molecule for the prevention and treatment of haemorrhage Madrid, 17 de noviembre de 2015 Outline Institution: CIMA Project Partnering
More information8. Clinical Trial Assessment Phase II
8. Clinical Trial Assessment Phase II Junko Sato, PhD Office of New Drug I, PMDA Disclaimer: The information within this presentation is based on the presenter s expertise and experience, and represents
More informationParadigm Shift in Comparability Assessment:
Paradigm Shift in Comparability Assessment: How Quality by Design (QbD) and Process Analytical Technology (PAT) can improve Structure-Activity Relationship (SAR) evaluation and its relevance to comparability
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 informationDevelopment of Analysis Methods for Therapeutic Monoclonal Antibodies Using Innovative Superficially Porous Particle Biocolumns
Development of Analysis Methods for Therapeutic Monoclonal Antibodies Using Innovative Superficially Porous Particle Biocolumns Anne Blackwell Bio Columns Product Support Scientist Suresh Babu Senior Application
More information