4th-6th March 2019
London

 

Day One
Tuesday 5th March 2019

Day Two
Wednesday 6th March 2019

08.50
Chair’s Opening Remarks

  • Alain Beck Senior Director, Biologics CMC and developability, Pierre Fabre Laboratories

Revealing Next Generation ADC Technologies

09.00
Exploring Different Routes to Generate Homogenous ADCs

  • Pedro Cal Post-Doctoral Fellow, University of Lisbon (Instituto de Medicina Molecular)

Synopsis

  • Novel reagents for protein modification
  • Site-selective lysine and cysteine modifications
  • Protein microenvironment importance for bioconjugation.

09.30
Cytotoxic & Steroid ADCs for Cancer & Inflammation

  • William Olson Vice President, Therapeutic Proteins, Regeneron Pharmaceuticals

Synopsis

• Cytotoxic ADCs targeting tubulin
• Non-cytotoxic ADCs targeting the glucocorticoid receptor
• Approaches to discovery and validation of targets for ADC therapy

10.00
Morning Refreshments & Networking

Exploring New Frontiers in ADC Research

11.00 TrypCo® Technology: A versatile enzymatic tool for site-specific generation of ADC’s

  • Introduction into BTI´s novel TrypCo® technology as robust conjugation platform for the enzyme-based generation of site-specific ADC´s
  • POC studies for the N- and C-terminal modification of Trastuzumab will be presented
  • High flexibility of TrypCo® enables orthogonal dual modification of antibodies and their fragments

Marcus Boehme, Head of Research & Development, BTI

11.30 BT5528: A Bicycle Toxin Conjugate Targeting EphA2 for the Treatment of Solid Tumours

  • BT5528 comprises a Bicyclic peptide binder of EphA2 linked to the cleavable linker & toxin vcMMAE
  • The small size and hydrophilicity of Bicycle Toxin Conjugates offers rapid and complete tumour penetration, efficient delivery of toxin and rapid renal elimination of unbound drug
  • BT5528 offers profound efficacy across a range of EphA2- expressing tumour models, including large heterogeneous PDX models, without the profound toxicity seen with previous antibody conjugate approaches

Gavin Bennet, Director, Project Leader, Bicycle Therapeutics

12:00 ThioBridge™ as a tool for the design, optimisation and manufacture of ADCs

  • ThioBridge™ conjugation is a flexible approach for producing stable ADCs with defined location and extent of drug loading
  • The simple design of ThioBridge™ ADCs means they can easily undergo a systematic determination and optimization of their in vitro and in vivo biological properties
  • ThioBridge™ targets natural disulfides with highly reproducible conjugation profiles at milligram to gram scales
  • Abzena’s capabilities for design, optimization and manufacturing of ADCs

Mark Frigerio, Director Chemistry UK, Abzena

Clinical Considerations for Developing Disease Modifying ADCs

11.00 Betalutin® - An Antibodyradionuclide- conjugate (ARC) for the Treatment of Relapsed Non-Hodgkin’s Lymphoma

  • Introduction to Nordic Nanovector ASA
  • Introduction to Betalutin
  • Summary of clinical data and development program of Betalutin

Dr. Reza Safaei, Head, Medical Affairs, Nordic Nanovector

11.30 Challenges & Opportunities in Developing ADCs

  • Main challenge in developing ADCs is the therapeutic index
  • Innovative clinical trials to decrease toxicity and improve efficacy
  • Patient selection strategies that incorporate genomic markers of ADC sensitivity
  • Novel combination approaches that increase the activity of the ADC and reduce toxicities

Steve Coats, Vice President, Research & Development, MedImmune

12.00 MORAb-202 – a Potent Human Folate Receptor Alpha-Targeting ADC that Utilises the Anti-tubulin Agent Eribulin as Payload

  • MORAb-202 is a cleavable cysteine-based conjugate of farletuzumab, a humanised antihuman folate receptor alpha antibody in Phase II clinical trials,
    and eribulin, an anti-tubulin agent approved for the treatment of certain metastatic breast cancers
  • MORAb-202 exhibits clear bystander effects on the tumour microenvironment, in addition to its direct cytotoxic effects on folate receptor-positive tumour cells
  • MORAb-202 is currently in a Phase I clinical trial in Japan

Earl Albone,  Senior Director, Biochemistry and Bioanalytical Development, EPAT, OBG, Eisai Inc

Manufacturing Next Generation ADC Technologies: Optimising Processes & Technical Operations

11.00 Process Understanding and Automated Processing in Development to Ensure First Pass Manufacturing Success of ADCs

  • Studies needed for clinical supplies and for commercial readiness with the goal of providing evidence of process consistency.
  • Use of automated systems for gathering information for early phase process transfers to manufacturing.
  • DOEs that ensure appropriate ranges are evaluated and ensure deep process understanding.

Mary Robinette, Principal Project Engineer, Merck
Lisa McDermott,  Head of Process and Analytical Development, Merck

11.30 Structural & Dynamic Reporters of the Aggregation of ADCs

  • In ADCs, the drug and the distribution of its attachment points to the antibody affect the folding, the stability, and interactions between these macromolecules
  • Advanced characterization techniques applied to study the onset of aggregation
  • Using these could help deciphering whether non-specific interaction is important or whether a subpopulation in the formulation is more prone to aggregation
  • Guiding CMC development for better stability and allow for elaborating a formulation platform for ADCs

Sylvain Huille, Senior Scientist, BioDevelopment, Sanofi

12.00 PROVEO: Fast Track Your End to End Solution for Antibody Drug Conjugates

  • More details to follow

Kasper Møller, General Manager, PROVEO

12:30
Lunch Seminar: Cerbios-Pharma and ADIENNE

Synopsis

Lunch Seminar: Planning Your New ADC. Have You Considered the Payload?

• New payload: it’s really new? Freedom to operate and patentability
• From lab recipe to GMP material. Road map and timing
• Impurities identification, characterization and classification
• Chromatographic purification as control strategy
• New chemical techniques to reduce impurity level

Lunch Seminar: Hematological & Cancer Solid Tumor Treatments in Future Settings

• Introduction of ADIENNE Pharma and Biotech
• Begesand anti-CD26 mAb clinical status of art
• Begesand Antibody Drug Conjugates

Register here

12.30
Lunch & Networking

Optimising Payload-Linker Combinations

14.00 Novel Linker Payload Combination

  • MET is over-expressed in many human tumors
  • MET-ADC is a novel ADC with optimized linker-payload combination and is highly potent in killing a variety of tumor cells in vitro
  • MET-ADC demonstrated profound in vivo efficacy in pre-clinical models therefore is a promising agent to treat many types of cancer

Yiqing Feng, Senior Research Fellow, Eli Lilly

14.30 Pro-PBDs: Novel Warheads for Targeted Therapies of Cancer

  • Conceptual design of next generation PBD-based prodrugs for targeted therapies of cancer
  • Explore Endocyte’s next generation latent warheads – the utility of oxime ethers in pro-PBD formats
  • Learn strategies for efficient synthesis of novel pro-PBDs and their conjugates
  • Review the selection of the clinical candidate EC2629: the first-inclass pro-PBD-based conjugate

Iontcho Vlahov, Vice President, Endocyte

 

15.00 ADCs with Novel Kinesin Spindle Protein Inhibitor Payloads & a Tailor-Made Linker Chemistry

  • Inhibitors of kinesin spindle protein (KSPi) have been developed as a novel payload class in antibody drug conjugates
  • To increase tumour selectivity of ADC metabolism, a tumour associated protease with a unique cleavage sequence is utilised for lysosomal ADC cleavage and release of active metabolites with an appropriate profile matching the KSPi mode of action

Hans-Georg Lerchen, Chief Scientist, Medicinal Chemistry, Bayer

Bullseye: Validating Novel Formats, Engineering Antibodies & Discovering Appropriate Targets

14.00 Dosing Optimisation & Mechanism Assessment of CD33- ADC Antibodies in AML Disease Models: Translating Preclinical Science to the Clinic

  • Exploring the dosing options of CD33-ADC preclinical models
  • Ensuring smooth transition into the clinic
  • Assessing the mechanism of action of CD33-ADC

Cathy Zhang, Senior Principal Scientist, Pfizer

14.30 Exploring a Next Generation ADC: TRPH-CD22

  • TRPH-222 is a CD22-directed ADC, constructed via a novel, site-specific (SMARTagTM) conjugation approach, resulting in highly controlled and reproducible drug loading
  • The molecule was very welltolerated in IND-enabling studies in the non-human primate at repeat doses up to 50 mg/kg administered IV, and demonstrated superior pharmacokinetics relative to ADCs using conventional conjugation approaches
  • TRPH-222 is currently being studied in relapsed and/or refractory B-cell lymphoma patients in a phase 1 clinical trial (NCT03682796)

Nancy Levin, Vice President Development, Triphase

15.00 Challenges of Screening & Characterising ADCs for Low Expression Targets/Rare Diseases

  • Introduction to the cell-based assays for oncology ADC projects at LifeArc
  • The challenges for an ALK-ADC for neuroblastoma will be highlighted
  • Non-internalising ADCs are now being investigated at LifeArc for indications other than oncology

Rachel Forfar, Senior Scientist, LifeArc

Simplifying Process Development to Efficiently Manufacture ADCs

14.00 Scalable Synthesis of of Aza-Cryptophycin, a highly Active Payload for ADCs

  • Evaluated as stand alone agent, but dropped due to tox reason in 2002, Cryptophycin regains attention as highly potent payload for ADCs
  • Synthesis of Cryptophycin and its aza analogues have been hampered by poor overall yield
  • We will describe in this talk a highly efficient synthesis that provided access to multigram of the compound, in order to provide material for tox evaluation
  • In particular, this talk will demonstrate an efficient answer to the 20 + year-old problem of the  epoxide introduction

Antony Bigot, Section Head, Sanofi

14.30 Strategies for Scaling-Up ADC Payload Production

  • An overview of what to consider when scaling-up the synthesis of ADC payloads
  • The importance of route design linker to safety and cost
  • Case study 1: Tubulysin
  • Case study 2: Tesirine

William Goundry, Associate Principal Scientist, AstraZeneca

15.00 Stability Investigations on ADCs Model Compounds with Defined Hydrophobicity Levels

  • Identifying representative model compounds for formulation and process development studies
  • Property alterations upon conjugation
  • Impact of payload hydrophobicity on stability and stress tolerance

Matthias Winzer, Associate Director, Parenteral Development, Merck KGaA

15.30
Afternoon Refreshments & Networking

Driving Synergy: Assessing ADCs as a Combination Therapies

16.00
Review of the ADC Clinical Pipeline

Synopsis

• Update on the key movements in the clinic
• Insight into the rapidly evolving pipeline
• Analysis of novel clinical ADCs

16.30
Single-Cell Pharmacokinetics & Pharmacodynamics of Biologics: Designing Effective Antibody Drug Conjugates & Checkpoint Inhibitors

Synopsis

• Biologics have unique distribution in the body that can impede or enhance efficacy depending on the particular drug and target
• Measuring the single-cell delivery and efficacy of these agents can help design more effective therapeutics and delivery strategies
• The local degradation of these agents in the tumour microenvironment can result in counter-intuitive results, but these can be leveraged to improve therapy as illustrated with several examples

17.00
Chair’s Closing Remarks

  • Alain Beck Senior Director, Biologics CMC and developability, Pierre Fabre Laboratories