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 Development of a Novel Chemical Site-Specific ADC Conjugation Platform with Enhanced Therapeutic Window

  • Brian Mendelsohn Director, Process Development & Tech Transfer, Ajinomoto Bio-Pharma Services

Synopsis

• Site-specific technologies are being employed in many of the next generation ADCs due to enhanced biological properties in pre-clinical studies.

• We report a new method of affinity peptide mediated regiodivergent antibody functionalization that enables the synthesis of ADCs from native IgGs in a tunable and atom-precise manner.

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

  • In order to minimize ADC heterogeneity in both position and drug load, sitespecific conjugation is rapidly becoming a preferred method for drug attachment
  •  Cys-deletion is one strategy where-by site-specific conjugation can be achieved without adding cysteines to the antibody
  • Here we examine differences in properties of ADCs made with C6 cysdeletion variants:
  • General properties of unconjugated antibodies
  • Impact of conjugation site on ADC stability and toxicity

John Harlan, Senior Principal Research Scientist, AbbVie

11.30 Potential Mechanisms of Target-independent Uptake and Toxicity of ADCs

  • Review of learnings on potential mechanisms ADC off-target toxicities
  • Strategies/opportunities to improve the overall therapeutic index (TI) of ADCs

Prathap Kumar Mahalingaiah, Senior Scientist III, AbbVie

11.30 Process Characterization, Case Study of a Scale-down Model Qualification & Related Proven Acceptable Range Study 

  • Understand the requirement behind the Process Characterization
  • Gain insight on Scale-Down Model (SDM) definition & qualification
  • Share results of the Prove Acceptable Range study for this SDM

Camille Bailly, Process Development Scientist, Sanofi

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 Addressing Development and Technology Transfer Challenges for Early Stage ADC Manufacturing

  • Summary of challenges: tight timelines, no platform process, multiple CMOs
  • Strategies and solutions: parallel development and tech transfer, focused robustness studies, facility-fit, incremental scale-up, detailed tech transfer documents
  • Lessons learned from Ambrx ADC programs

Brian O'Mara, Associate Director - Downstream Process Development, Ambrx

12.30 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
  • Signicant 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 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 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

3:00 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

 

3:30 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 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 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