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Day Two

Wednesday, 4th March, 2020

8:50 am Chair’s Opening Remarks

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

9:00 am ADC Targets & Payloads: When Friends Become Foes

Synopsis

  • Understand the navigation of targets and payloads for ADCs
  • Wrong pairing of targets and payloads: turning friends into foes
  • Evaluate strategies for selection of targets and payload for improving the therapeutic index
  • Uncover translational medicine strategies to maximise TI

9:30 am Targeted Immunostimulants; A Promising Approach to In Situ Immunisation

Synopsis

  • Assess the role of immunogenic cell death in propogating more robust immune responses in patients on combination therapy with immunotherapeutics such as check-point inhibitors; a promising approach to increase durability of response
  • Review how targeted immunostimulators now look to generate innate immune responses to tumours while increasing systemic tolerability
  • Examine how homogeneous antibody drug conjugates optimised to deliver combinations of mechanistically different payloads demonstrate that targeted “in situ immunisation” is feasible

10:00 am Combining ADCs & Immunotherapy: Mechanistic Insights & Clinical Observations

  • Daejin Abidoye Vice President, Clinical Development , 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

10:30 am Morning Refreshment & Networking

Discovery Chemistry Stream

Discovery Biology Stream

Translational Steam

CMC Stream

How Potent do we Go? Comparing High DAR with High Potency

Tricks of the Trade; Antibody Engineering Techniques to Try to Improve the Off-Target Toxicity Profile

The Balancing Act: Delivering Enough ADC for Meaningful Activity Without Triggering Potency

Sharing Lessons Learned from Scaling Up to Commercial Scale Manufacturing

11.30 The Dark Side of the Moon: The Chemistry Behind Strategies for Building Small Molecule Drug Conjugates – a Legacy

  • Review the conceptual design of a small molecule drug conjugate (SMDC) for targeted therapies of cancer
  • Explore self-immolative linker systems: from theoretical design to practical synthesis • Engineering spacer units: their role in the control of physical properties and to switch toxicity profiles of Folate-Drug Conjugates
  • Selection standards and novel design of payloads: from tradition to innovation

Iontcho Vlahov, Vice President Discovery Chemistry, Endocyte

11.30 Modifying the Antibody to Reduce Non-Specific Uptake in the Tumour

John Harlan, Senior Principal Research Scientist, AbbVie

11.30 Potential Mechanisms of ADC Off-target Toxicities & Strategies/ Opportunities to Improve the Overall TI of ADCs

  • Reviewing mechanisms of action for antibody drug conjugate off target toxicities • Analysing mechanisms of action for antibody drug conjugate off target strategies
  • Delving into opportunities to improve clinical index of ADCs

Prathap Kumar Mahalingaiah, Senior Scientist III, AbbVie

11.30 Panel Discussion: Aligning the Complex ADC Supply Network to Make Drug Products for Patients

  • Evaluate strategies for supply network alignment
  • Identification of risks in the supply chain

Jens Lorhmann, Disease Area Head, OncologyNovartis

12.00 Impact of Linker Chemistry & Metabolite Profile on the Performance of ADCs with KSP-inhibitor Payloads

  •  Evaluate KSP inhibitors; versatile new payload class for the generation of highly potent and selective ADCs
  • Understand how linker composition and metabolite profile can be adapted to the requirements of individual targets

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

12.00 Prodrugs as Drug Delivery System in Oncology

  • What is a prodrug?
  • Reviewing the design of prodrugs targeting the tumour microenvironment
  • Reviewing the design of prodrugs targeting the tumour cell

Charles Skarbek, Bioorganic Chemistry Post-doctoral Researcher, Paris Sud University

12.00 MUC13 mucin, A Novel Candidate for Drug-Antibody Conjugates for GI Cancers

  •  Learn about MUC13 as a novel target for
  • ADC
  • Discussion about novel MUC13 antibodies we have developed
  • Learnings regarding our progress on MUC13 antibody drug conjugate project

Subhash Chauhan, Professor, University of Tennessee

12:00 Synthesis of ADC Payloads – Challenges and Opportunities

  • Payload selection is critical to ensure a suitable therapeutic index is achieved for ADCs
  • Synthetic Chemistry plays a key role in modifying and delivering linker-payloads to meet this objective
  • Significant challenges and opportunities exist within Synthetic Chemistry which need to be addressed to deliver successful ADCs

Jeremy Parker, Senior Principal Scientist – New Modalities & Tissue Targeting, AstraZeneca

12.30 Diels-Alder Bioconjugation for Production of Homogeneous & Stable ADCs

  • Gain insights on how Diels-Alder bioconjugation utilises maleimide payloads for attachment to antibodies
  • Examine how Diene functional groups are incorporated into antibodies via linkers or non-natural amino acids
  • Uncover how ADCs can be produced in a one-step process
  • Assess resulting ADCs that are stable in serum and exhibit potent tumour growth inhibition in vivo

James (Jim) Christie, Senior Scientist, Biologic Therapeutics, AstraZenca

12.30 Development of BT5528 into the Clinic: A Bicycle Toxin Conjugate Targeting EphA2 for the Treatment of Solid Tumours

  • Showcasing the development of BT5528 and the journey into the clinic
  • Case Study: addressing a “toxic” target with a new modality
  • Differentiation: how BT5528 delivers efficacy without toxicity associated with previous ADC approach

Gavin Bennet, Director & Project Leader, Bicycle Therapeutics

12.30 Development of a Probody Drug Conjugate (PDC) Targeting CD71 for the Treatment of Cancer

  • Evaluating the Probody/PDC platform
  • Discussing safety and efficacy in animal models
  • Reviewing diagnostics assay development and validation

Luc Desnoyers, Senior Director of Translational Sciences, CytomX Therapeutics

12.30 CMC Considerations for Targeted Thorium Conjugates – TTCs

Markus Eser, Product Supply, Pharmaceuticals, Bayer

1:00 pm Lunch & Networking

2:30 pm Chimeric Protein Degraders as ADC Payloads

Synopsis

  • Moving beyond pan-cytotoxics for improved tolerability
  • Increasing DAR for lower potency payloads
  • Developing new linkers for alcohols

 

3:00 pm Small Molecule-Drug Conjugates: Getting Small to Enhance Targeting

Synopsis

  • Understanding how ADC products are limited by their slow and inefficient accumulation in solid tumours. Small Molecule-Drug Conjugates have been recently proposed as an alternative approach to deliver potent cytotoxic compounds to the neoplastic site and to solid metastatic lesions
  • Acetazolamide is a small organic compound that exhibits a high binding affinity to the tumour-associated antigen Carbonic Anhydrase IX (CAIX), a marker of Renal Cell Carcinoma and of hypoxic tumours. We compared acetazolamide-based SMDC products to anti-CAIX ADCs for their ability to reach tumours in vivo and for their anti-tumor performance
  • Analysing recent clinical trial data that have confirmed the efficient accumulation of an acetazolamide-based radiotracer (PHC102) to solid tumours and metastatic lesions in Renal Cell Carcinoma patients

3:30 pm Modulating the Potency & Physicochemical Properties of PBD Payloads

Synopsis

  • Analysing next generation PBD payloads
  • Discussing Warhead optimisation
  • Exploring the effect of N10 Capping groups
  • Evaluating DAR1 PBD ADCs

4:00 pm Afternoon Refreshments & Networking

5:00 pm Overview: How an Antibody-drug Conjugate Cures a Stage 1 Model of African Trypanosomiasis (Sleeping Sickness)

Synopsis

  • Understanding the emerging role of ADCs in non-oncological therapeutic areas
  • Gain insight on a generation of an ADC against a Trypanosoma brucei HpHb receptor
  • Examine how a single dose of this ADC cures the first stage of African Trypanosomiasis in a mouse model

5:30 pm A Tissue Factor-Targeting Antibody-drug Conjugate for the Treatment of Advanced Solid Tumours

Synopsis

  • 5 years after FIH, what have we learned?
  • Manageable safety profile
  • Antitumour activity in patients with metastatic cervical cancer

6:00 pm Chair’s Closing Remarks

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