Day One

Tuesday, 3rd March, 2020

8:30 am Chair’s Opening Remarks

  • Alain Beck Senior Director, Biologics CMC & developability, Pierre Fabre

8:40 am Is There Method in the Madness? What Have we Learnt from the Last Decade of ADCs

  • Alain Beck Senior Director, Biologics CMC & developability, Pierre Fabre

Synopsis

  • Review the lessons from successes and failures
  • Assess 1st, 2nd, 3rd and next-generation ADCs
  • Discuss ADCs to watch in 2020/2021

9:10 am Impact of Drug Load & DAR of an ADC on Binding & Potency

Synopsis

  • Identification of sites of conjugation on a cysteine-based ADC
  • Impact of drug load and DAR on binding and in vitro and in vivo potency
  • Understanding of the structure-function relationship of drug load and DAR

9:40 am Sacituzumab Govitecan – A Clinical Development Update Across Multiple Indications

Synopsis

  •  A brief introduction on the unique background of SG
  • Clinical update on metastatic TNBC
  • Clinical update on HR+ metastatic Breast Cancer
  •  Clinical update on metastatic Urothelial Cancer

10:10 am Speed Networking

Synopsis

This session is a great opportunity to introduce yourself to the attendees that you would like to have more in depth conversations with. This session is the ideal opportunity to get face-to-face time with many of the brightest minds working in the ADC field and establish meaningful business relationships.

11:00 am Morning Refreshments

Discovery Chemistry Stream

Discovery Biology Stream

Translational Stream

CMC Stream

 

Let’s Focus on the New, Novel Format Payloads & Looking Outside the Payload Box

 

 

 

Developing More Targeted & Stable ADCs with Next Generation Engineered Antibodies

 

 

Focusing on the Relationship of Half Life & Clearance Rates with Efficacy & Safety, to Gain Better Modelling & Improved Prediction

Securing Your Robust ADC Supply Chain & Conjugation Techniques

 

 

 

12.00 NAMPT & Eg5 Inhibitors – Two Novel Payload Classes for Antibody drug Conjugates

  • Exploring insights into discovery of two novel payload classes
  • Evaluating Nicotinamide Phosphoribosyltransferase (NAMPT) Inhibitors as a novel payload class with non-antimitotic mode of action
  • Assessing the discovery of potent and selective ADCs with Eg5 inhibitors through linker and payload optimisation

Alexei Karpov, Senior Investigator I, Novartis

 

 

 

 

 

 

 

 

12.00 Efficacy of the Antibody-Drug Conjugate W0101 in Preclinical Models of IGF-1 Receptor Overexpressing Solid Tumours

  • Evaluating W0101; a unique IGF1Rtargeted ADC, designed to deliver a highly potent cytotoxic auristatin derivative selectively to IGF-1R overexpressing tumour cells
  • The monoclonal antibody (hz208F2-4) used to prepare the ADC was selected for its specific binding properties to IGF-1R compared to the insulin receptor (IR), and for its internalization properties
  • Examining how W0101 induced receptor-dependent cell cytotoxicity in vitro when applied to various cell lines overexpressing IGF-1R but it did not affect normal cells

Barbara AKLA, Senior Scientist, Pierre Fabre

12.00 Targeting CD205-positive Solid Tumors with a Novel Antibody Drug Conjugate to Reverse Immune Tolerance

  • OBT076 is an ADC with an antibody targeting CD205, which is overexpressed in high risk HER2 negative ER/PR positive breast cancer.
  • In addition, the ADC is being developed for CD205 positive gastric-, bladder-, lung- and ovarian cancer.
  • A companion diagnostic is integrated into the development for optimal patient selection.

Christian Rohlff, Chief Executive Officer, Oxford BioTherapeutics

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

12.00  Effective Scale up From ADC Candidate to First Phase I Batch

  • Steps to ensure a successful cGMP batch illustrated by a case study
  • How to adapt the process development activities to the clinical phase
  • Key considerations in analytical development and validation

Bertrand Cottineau, Head of Research and Development,Novasep

 

 

 

 

 

 

 

 

 

 

 

12:30 Novel Immune-Stimmulatory ADCs (iADCs) for Effective Targeting of Solid Tumours

  • Exploring site-specific conjugates with ultra-potent anthracycline toxins
  • Discovering immune-oncology function of NBE’s iADCs
  • Reviewing preclinical validation of a ROR1 targeting iADC

Ulf Grawunder, Chief Executive Officer & Founder, NBE Therapeutics

 

 

 

 

 

 

12.30 Targeting the Receptor for Advanced Glycation Endproducts (RAGE): An ADC Perspective

  • Reviewing the preclinical development of RAGE-ADC versions • Focusing on ovarian cancer
  • Update on Swansea ADC clinical pipeline and development platforms

Deya Gonzalez , Professor, University of Swansea

 

 

 

 

12.30 Full Characterization of ADC, from Native to Subunit Analysis Including DAR Calculation Ratio. Three Industry Case Studies

  • Fast characterization of ADCs trough Native analysis
  • Full characterization of the mAb and payload
  • Easy and fast DAR calculation using LC-MS and CE techniques.

Sibylle Heidelberger, Senior Specialist - Support, SCIEX

12:30 Nanostar Sieving Produces Precise, Unimolecular PEGs for PEGylation

  • Iterative synthesis with liquid phase separations produces unimolecular (completely monodisperse) PEGs 5kDa – 20kDa
  •  Attachment to nanostar hub allows complete control over end-group functionalisation
  • Reactive side chains can be used to deploy controlled derivitisation
  • PEGYlation results in conjugates with order of magnitude less dispersity

Andrew Livingston, Professor of Chemical Engineering, Imperial College London

 

13.00 Site-Specific Antibody Conjugation Leveraging the Native Nucleotide Binding Site

  • What and where is the conserved antibody NBS?
  • How can this naturally occurring antibody location be utilized as a robust site-specific conjugation handle?
  • The current state of the NBS conjugation art including:  benefits/drawbacks of the technique, conditions necessary to perform the crosslinking, and types of linkers and chemistries/functionalities that can be utilized will all be discussed

Nathan Alves, Assistant Professor, Indiana University School of Medicine 

13.00 Accelerating Antibody Development by Monitoring Titer & Glycosylation Together

  • Upstream glycan screening as early as subcloning stage
  • Combined assay for faster decision making
  • Direct measurement in crude samples Move higher quality candidates downstream

Helge Schnerr, Marketing Manager EMEA, FortéBio

13.00 Translational Modelling for a Novel ADC to Support Safe & Efficacious Dosing Regimen in Patients

  •  A PKPD model was developed using PK and tumour growth data collected from mouse xenograft tumour and allow to characterize the tumour-static concentrations (TSC) where the tumour growth and killing rates nullify each other
  • Targeting trough concentrations of W0101 above the in vivo TSC value, a clinical efficacious dosing regimen could be predicted
  • A PK-Toxicodynamic model was developed to characterize ADC induced toxicity in monkey and used to simulate potential patient outcomes

Julie Desrivot-Quénelle, PKPD Project Lead, Pierre Fabre

13.00 Thinking to the Future of ADCs

  • Reviewing the complexity of supply chain for ADCs
  • Securing commercial supply
  • Looking to the future of ADCs

Giorgio Salciarini, Senior Manager - Technical Business Development, BSP

1:30 pm Cerbios Lunch Seminar- Tools for ADC Development & Manufacturing

  • Vítor Sousa Senior Manager, R&D Department, Cerbios-Pharma

Synopsis

. Integrated scaffold solutions

. Novel bioconjugation manufacturing approach

. Uniform analytical solutions across supply chain

. Tools for QbD-based process development

2:00 pm

Refreshing the “Middle-Man”, Looking at & Enhancing Novel Linker Technologies

Delving into the World of Alternative Format Conjugates to Enhance Tumour Penetration

Building your ADC Toolkit; Exploring the Best in Vitro & in Vivo Tools for Preclinical Translation

Reviewing How Drug Product & Formulation Enhances Process Development

15.00 OligoTEA Linkers: A Platform for Multifunctional Antibody Conjugates & Quantification of Intracellular Processes

  • Reviewing site-specific conjugation techniques
  • Understanding how sequence-defined linkers affect in vitro ADC potency
  • Analysing the quantification of intracellular bond degradation rate

Christopher A. Alabi, Associate Professor, Cornell University

15.00 Encoded Self-Assembling Chemical Libraries for the Discovery of New Small Molecules for Tumour-Associated Antigens

  • High-Throughput Screening represented for years the main screening technology for the selection of novel small ligands to target Tumor-Associated Antigens. Nevertheless, most efficient and fastest screening methods are required
  • ESAC (Encoded Self-Assembling Chemical Libraries) technology is a valid alternative to classic screening method to identify different small ligands against TumourAssociated Antigens that can be used for drug delivery and imaging of solid tumours and metastatic lesions

Jacopo Millul, Research Associate Scientist, Philogen

15.00 Reviewing the ADC Clinical Pipeline

  • Update on the key movements in the clinic
  • Gain insight into the rapidly evolving pipeline
  • Analyse of novel clinical ADCs

Jia He, Analyst, Beacon Targeted Therapies

 

15.00 Preformulation & Analytical Characterisation of ADCs

  • Discussing screening methods for the early formulation development of ADCs
  • Extended insights into Dynamic light scattering as powerful screening tool
  • Overview on Polysorbate analytics and stability

Steffen Woell, Principal Scientist, Merck

15:30 Site-selective Antibody Conjugation Enabled by Disulfide Bridging & Cysteine-to-lysine Transfer

  • The development and optimisation of the Next Generation Maleimide and Pyridazinedione reagent classes for the construction of ADCs
  • The rapid formation of robustly stable ADCs from native antibodies by rebridging the native disulfide bonds
  • A new approach to antibody conjugation will be presented, in which cysteine residues are employed as hooks to deliver acylating residues to specific lysines

Jamie Baker, Reader in Chemical Biology, University College London

15.30 ZW49 A Next Generation Bispecific HER2-Targeted ADC Combining Azymetric™ & ZymeLink™ Platforms

  • Discuss ZW49, a biparatopic antibodydrug conjugate armed with our proprietary ZymeLink™ cytotoxic payload
  • In vivo efficacy compared to approved and leading clinical-stage HER2targeted ADCs
  • GLP toxicology studies predict an enhanced therapeutic window enabling extended dosing in the clinic

John Babcook, Senior Vice President of Discovery Research, Zymeworks

15:30 Reductive Desulfuration as an Important Tool in Detection of Small molecule Modifications to Payload of Antibody Drug Conjugates

  • Method development of desulfuration of the thioether linker in ADC. The reaction conditions were optimized for release of the payload to take advantage of the high resolution and high mass accuracy of the Orbitrap to characterize metabolism of the payload.
  • Application of the technique in model ADCs. The resulted information enables characterization of the payload of ADC following its incubation in hepatocytes, liver microsomes and buffers as illustrated by the identification of a hydrolyzed thiosuccinimide ring of SigmaMAb ADC mimic following incubation in buffer.

Jack Wang, Senior Scientist, Johnson & Johnson

15.30 ADC Process Development & Optimization Using Membrane Adsorbers for Conjugate

  • Development of antibody-drug conjugate (ADC) purification processes using single-use membrane adsorbers
  • Fast and scalable removal of excess linker-payload using ion-exchange chromatography, and polishing of conjugates using hydrophobic interaction chromatography
  • Implementation of a tandem purification approach as an efficient ADC processing strategy

Juan Carlos Cordova, Senior Scientist, Process Development, Bioconjugation, Abzena

4:00 pm Afternoon Refreshments & Networking

5:00 pm Combining ADCs & Immunotherapy: Mechanistic Insights & Clinical Observations

  • Nicholas Choong Executive Medical Director and Global Development Lead of the LIV-1 ADC program, Seattle Genetics

Synopsis

  • Discuss preclinical data demonstrating monomethyl auristatin E (MMAE) has the potential to drive immunogenic cell death
  • Review pre-clinical and biomarker data on MMAE that support the induction of inflammatory cytokines and innate inflammatory responses which are consistent with MMAE-induced ICD
  • Share insight from how our data provide the rationale for combining our ADCs with immuno-oncology therapies including PD-L1 checkpoint blockade
  • Share data from combinations of ADCs with PD-1 inhibitors with implications for future development of these combinations

5:30 pm Bioconjugation Process Scale-up: Reactor Mixing

  • Mary Robinette Principal Project Engineer - Engineering Department, Merck

Synopsis

Scale up considerations for bioconjugation reactors include evaluation of reactor mixing criteria.  A case study will be presented outlining scaleup from small scale model to commercial reactor. Engineering mixing simulation and small scale model experiments are used to determine reactor design.  Single use reactor mixing information is presented to meet bioconjugation reactor requirements. Collaboration with client partner is highlighted  for successful  bioconjugation scaleup from lab to clinical and commercial production.

6:00 pm Chair’s Closing Remarks

  • Alain Beck Senior Director, Biologics CMC & developability, Pierre Fabre