8:35 am Chair’s Opening Remarks

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

Using ADCs to Overcome & Treat Difficult Cancers & Bring More Life Changing Drugs to Patients

8:40 am Small Molecule-Drug Conjugates: Getting Small to Enhance Targeting

Synopsis

  • While the clinical benefit of ADCs has become evident, the therapeutic window of these biopharmaceuticals is narrower than what had initially been estimated on the basis of preclinical studies
  • The chemical conjugation of a small organic tumour targeting moiety to a cytotoxic drug leads to the generation of a novel class of therapeutic compounds named small molecule-drug conjugates (SMDCs)
  • We present preclinical and clinical results obtained with small ligands targeting two promising tumour-associated antigens overexpressed in solid tumours: CAIX and FAP

9:00 am ADC Therapeutic Window Enhancement Based on the AJICAP Chemical Site-Specific Conjugation Platform

  • Zhala Tawfiq Process Development & TT Associate Scientist, Ajinomoto Bio-Pharma Services

Synopsis

  • Review how site-specific technologies are being employed in many of the next-generation ADCs due to enhancement of clinically-relevant biological properties observed in various preclinical studies
  • We report a novel method of affinity peptide mediated regiodivergent antibody functionalization that enables the synthesis of ADCs from native IgGs in a tunable and atom-precise manner
  • Both thiol-based and azide-based site-specific ADCs produced by “AJICAP” technology demonstrated an expansion of their therapeutic index compared with stochastic technology

9:20 am Antibody Targeted Amanitin Conjugates (ATACs) Overcome Resistance Mechanisms to Establish New Treatment Options for Difficult to Treat Cancers

Synopsis

• ATACs represent a new class of ADCs using the payload Amanitin, introducing a novel mode of action (inhibition of RNA
polymerase II) into oncology therapy.
• The unique MoA facilitates killing of dormant tumor cells (CSCs, TICs) and offers new treatment options for difficult to treat
cancers and high-risk patients.
• HDP-101 is Heidelberg Pharma’s lead ATAC candidate directed against BCMA is entering Phase I clinical trials in relapsed
refractory multiple myeloma patients.

9:40 am Live Discussion & Question Time

10:00 am Morning Refreshments & Virtual Speed Networking

Discovery Stream
Target Discovery; What Targets are Showing the Best Promise & Why?

11:00 am Novel Antibody Engineering Technology to Avoid On-Target Off-Tumour Reaction & Its Possible Application to ADC

Synopsis

  • Addressing on-target off-tumour toxicity; one of the common challenges in the field of therapeutic antibody
  • Demonstrating our unique antibody platform, Switch-Ig®, to avoid on-target off-tumour reaction by exploiting a unique property of tumour microenvironment
  • Switch-Ig® confers antibodies with additional tumour selectivity, which could maximise the therapeutic index of ADC

11:20 am Targeting Potent MSRA Antibiotics to Cells Harboring Bacteria with an ADC

  • Thomas Nittoli Director, R&D Chemistry Therapeutic Proteins, Regeneron

Synopsis

  • Screening a focused library for leads
  • Payload and linker-payload design
  • In vitro screening of payloads and ADCs
  • ADC in vivo efficacy

11:40 am Live Discussion & Question Time

  • Futa Mimoto Research Manager, Chugai Pharmaceuticals
  • Thomas Nittoli Director, R&D Chemistry Therapeutic Proteins, Regeneron

Translational Stream
Improving the Safety Predictions of ADCs from Animals to Humans?

11:00 am ADC Therapies in Lymphoma: Now & the Future?

  • Toby Eyre Haematology Consultant, Oxford University Hospitals NHS Foundation Trust

Synopsis

  • Aim to discuss the key therapeutic advances over the recent years using ADC therapies in lymphoma
  • Discuss some selected new agents moving forward showing promise in clinical trials

11:20 am Overcoming Immunotherapy Resistance: Targeting the Tumour Microenvironment

  • Gareth Thomas Professor - Experimental Pathology, University of Southampton

Synopsis

  • Most solid tumour types contain aggressive subgroups rich in cancer-associated fibroblasts
  • Cancer associated fibroblasts exclude CD8 T-cells from tumours and promote immunotherapy resistance
  • The cancer associated fibroblast phenotype is regulated by the enzyme NOX4, which can be targeted to overcome immunotherapy resistance

11:40 am Live Discussion & Question Time

  • Gareth Thomas Professor - Experimental Pathology, University of Southampton
  • Toby Eyre Haematology Consultant, Oxford University Hospitals NHS Foundation Trust

Manufacturing Stream
Certifying GMP for Your Manufacturing Facility

11:00 am CMC Challenges in the Development of TR1901- ADC, a Bi-specific ADC Targeting CD138 & FGFR3

  • Bob Bayer Director of CMC Drug Development, Tanabe Research Laboratories

Synopsis

  • Mitigation of reversible self-association of bispecific mAb and of reduction of blocked engineered cysteines during cell culture harvest were key to developing a successful mAb process
  • Understanding the process changes required to minimise formation of visible particulates during fill
  • Successful mAb production, conjugation, and fill processes were developed and a clinical manufacturing campaign was successfully executed

11:20 am High Containment Strategies for ADC Toxin Handling and Downstream Processes

Synopsis

  • Validated 1.0 nanogram/m3 Single Use Isolator for handling ADC Toxin
  • Isolation for ADC liquid processing to contain leakage and aerosolization risk
  • Aseptic containment for lyophilization process and final fill / finish

 

11:40 am Live Discussion & Question Time

12:10 pm Visit Demo Area, Virtual Booths & Take Part in Competitions!

Synopsis

Visit the Demo Area to connect with our event partners, take part in raffles and complete our passport competition (Winner will be announced in todays closing remarks!)

12:40 pm Networking Lunch

Synopsis

Grab a quick bite to eat from the comfort of your own kitchen and jump into a group networking session!

Discovery Stream
Looking At Site-Specific ADC Technologies



1:30 pm Site-Specific Conjugation: Impacts of C6 Variant Position on Antibody & ADC Properties

  • John Harlan Senior Principal Research Scientist, AbbVie

Synopsis

  • In order to minimise ADC heterogeneity in both position and drug load, site-specific 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

1:50 pm Designing & Developing Next-Generation Antibody-Drug Conjugates

Synopsis

  • Design and developability assessment is key to select the appropriate combination of antibody, linker and payload for a successful ADC
  • Involvement of a multidisciplinary team of experts in integrated multiple work streams reduces the overall timeline from bench to bedside

2:10 pm A Platform for the Generation of Site-Specific Antibody–Drug Conjugates That Allows for Selective Reduction of Engineered Cysteines

  • Ruud Coumans Project Leader Antibody-Drug Conjugates, Byondis

Synopsis

  • Through use of an in silico screening procedure, optimal sites for conjugating a hydrophobic payload were identified
  • Compared to randomly conjugated ADCs, the site-specific ADCs were less hydrophobic and had better efficacy and exposure in an in vivo xenograft model
  • The site-specific ADCs can be manufactured using a newly discovered selective reducing agent that is able to reduce the engineered cysteines while leaving the interchain disulfides in the oxidized state

2:30 pm Live Discussion & Question Time

  • John Harlan Senior Principal Research Scientist, AbbVie
  • Ruud Coumans Project Leader Antibody-Drug Conjugates, Byondis

Translational Stream
Navigating the Regulatory Framework in Europe, in Particular for Filing BLAs, what do Regulatory Agents Want?

1:30 pm Progress Towards Safe, Curative Treatment of Blood & Immune Diseases: Development of Novel Antibody Conditioning Regimens for Hematopoietic Cell Transplantation

  • Agnieska Czechowicz Assistant Professor of Pediatrics, Stanford University School of Medicine

Synopsis

  • Hematopoietic stem cell transplantation can be used to cure diverse blood and immune diseases
  • Host stem cells compete with donor stem cells for engraftment, but the host stem cells can be selectively depleted with antibodies to enable improved donor stem cell engraftment
  • Understand how antibody-drug-conjugates can be used in this setting as potent conditioning agents for stem cell transplantation

1:50 pm An Introduction to MEDI2228, a PBD-based ADC Directed Against BCMA for the Treatment of Multiple Myeloma

Synopsis

  • Preclinical development of MEDI2228, including the strategy for selection of final mAb and linker-payload
  • How comparative analysis of cleavable and non-cleavable linker-payloads revealed candidate predictive biomarkers for non-cleavable ADCs and guided final payload selection
  • Preclinical exploration of rational combination partners

2:10 pm Tisotumab Vedotin in Previously Treated Recurrent or Metastatic Cervical Cancer: Results from the Phase 2 InnovaTV 204/GOG-3023/ENGOT-cx6 Study

Synopsis

  • Review the high unmet need in cervical cancer and educate on tisotumab vedotin MOA
  • Discuss tisotumab vedotin data in recurrent and/or metastatic cervical cancer (innovaTV 201 + innovaTV 204)
  • Provide an overview of TV clinical development plans

2:30 pm Live Discussion & Question Time

Manufacturing Stream
Sharing Methods to Improve Process Characterisation & Product Heterogeneity


1:30 pm Strategic & Data Driven Controls for Antibody- Drug Conjugates with Multiple Mechanisms of Action

Synopsis

  • Designing a control strategy for an ADC with multiple mechanisms of action requires a strategic and data driven approach
  • The control strategy should directly link critical quality attributes to the process utilizing product and process characterization
  • Proper controls at the appropriate steps throughout the mAb, DS, and DP manufacturing process ensures a holistic and integrated control strategy

1:50 pm Process Development of Chromatographic Purification for ADC Manufacturing

  • Gang Yao Director, Head of Novel Modalities R&D, Merck

Synopsis

  • Reasons to use chromatographic process in the ADC manufacturing
  • Review of typical chromatographic methods in the ADC process
  • Case studies of developing chromatographic processes for ADC purification

 

2:10 pm Considerations for Bolt Biotherapeutics’ Non- Cytotoxic ADCs

  • Nathan Ihle Vice President - Chemistry, Manufacturing, Controls & Quality, Bolt Biotherapeutics

Synopsis

  • Immune-Stimulating Antibody Conjugates (ISACs) seek to extend the utility of ADCs beyond current applications
  • Discussing Bolt’s ISAC technology, and comparing it to cytotoxic ADC technologies
  • Sharing examples of unique CMC challenges and opportunities for ISACs

2:30 pm Live Discussion & Question Time

3:00 pm Visit Demo Area, Virtual Booths: Last Chance to do so!

Synopsis

Last Chance to visit the Demo Area to connect with our event partners!

3:30 pm Afternoon Refreshments & Networking

Synopsis

Grab a quick coffee from the comfort of your own kitchen and jump into this group networking session!

Counting on Combos; Assessing the Critical Attributes of a Combination Clinical Trial

4:00 pm Treatment of Ovarian & Endometrial Cancer with the Novel Folate Receptor-α-targeting Antibody Drug Conjugate, STRO-002

Synopsis

  • Optimising linker-warhead and site-specific conjugation to produce a homogeneous product and improve therapeutic index
  • Preclinical rationale for STRO-002 in cell line, xenograft and PDX studies
  • Dose-escalation study and recommended Phase 2 dose
  • Dose expansion and registration-directed clinical development studies

4:20 pm Update on the Development of DS-1062a, a Trop-2 Targeting DXd ADC

  • Gilles Gallant Senior Vice President, Global Head of Oncology Development, Oncology R&D, Daiichi Sankyo

Synopsis

  • Evaluating the pre-clinical profile and mechanism of action of DS-1062a
  • Sharing the clinical development status of DS-1062a
  • Discussing future developments of DS-1062a

4:40 pm Clinical Pharmacology of Antibody-Drug Conjugates: A Regulatory Perspective

Synopsis

  • Summary of clinical pharmacology studies/information submitted in support of BLA approvals of ADC products
  • Case study of regulatory interest
  • Closing remarks and recommendations

5:20 pm Live Discussion & Question Time

5:40 pm Chair’s Closing Remarks