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

  • Brian Mendelsohn Director, Process Development & Tech Transfer, 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 Road to Clinical Validation of NBE-002, a Novel PNU-anthracycline-based ROR1 Targeting iADC in Solid Tumours

  • Ulf Grawunder Chief Executive Officer & Founder, NBE Therapeutics

Synopsis

  • Understand rationales for targeting ROR1 in solid tumour patients
  • Analyse preliminary data from a phase I/IIa clinical study with NBE-002, a novel ROR1-targeting iADC
  • Gain an overview of clinical study design and biomarker strategy for future efficacy studies, based on NBE-002’s mode of action

9:40 am Live Discussion & Question Time

10:00 am Morning Refreshments & Virtual Speed Networking

Discovery Stream

Translational Stream

Manufacturing Stream

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

Improving the Safety Predictions of ADCs from Animals to Humans?

Certifying GMP for Your Manufacturing Facilityy

11.00 Novel Antibody Engineering Technology to Avoid On-Target Off Tumour Reaction & Its Possible Application to ADC

  • 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

Futa Mimoto, Research Manager, Chugai Pharmaceuticals

 

11.20 Targeting Potent MSRA Antibiotics to Cells Harboring Bacteria with an ADC

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

Thomas Nitolli, Director, R&D Chemistry Therapeutic Proteins, Regeneron

 

11.40 Live Discussion & Question Time

Futa Mimoto, Research Manager, Chugai Pharmaceuticals

Thomas Nitolli, Director, R&D Chemistry Therapeutic Proteins, Regeneron

11.00 ADC Therapies in Lymphoma: Now & the Future?

  • 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

Toby Eyre, Consultant Haematologist, Oxford University Hospitals NHS Foundation Trust

 

11.20 Overcoming Immunotherapy Resistance: Targeting the Tumour Microenvironment

  • 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

Gareth Thomas, Professor - Experimental Pathology, Southampton University

 

11.40 Live Discussion & Question Time

Gareth Thomas, Professor - Experimental Pathology, Southampton University

Toby Eyre, Consultant Haematologist, Oxford University Hospitals NHS Foundation Trust

11.00 CMC Challenges in the Development of TR1901- ADC, a Bi-Specific ADC Targeting CD138 & FGFR3

  • 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

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

 

11.20 Stochastic Lysine Conjugates & Late Stage Process Development Requirement

  • Understand the requirement for late stage project aiming for Quality by Design in the BLA
  • Delve into the Product Understanding: Assess the criticality of charge variant as Quality Attributes; from purification strategy to testing
  • Ensure Process Characterization: From Scale-Down Model (SDM) definition and qualification to Proven Acceptable Range study

Eric Lacoste, Head of Bio-Organic Team & Chemistry Manufacturing & Control Project Manager, Sanofi

 

11.40 Live Discussion & Question

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

Eric Lacoste, Head of Bio-Organic Team & Chemistry Manufacturing & Control Project Manager, Sanof

12:30 pm Lunch & Networking

What Is the Best Conjugation Strategy for your ADC & Showcasing Novel Linker Technologies?

Are we Improving the Therapeutic Index or do we Still have a Narrow TI but just a Lower Dose?

Working Collaboratively with Multiple CMOs VSOne CMO

13.30 Site-Specific Conjugation: Impacts of C6 Variant Position on Antibody & ADC Properties

  • 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

John Harlan, Senior Principal Research Scientist, AbbVie

 

13.50 Target Considerations for the Perfect ADC

  • Searching for bold targets outside of the norm
  • Exploring heavily explored targets and utilising this knowledge

 

14.10 Tumour-Targeted Immune-Stimulating Antibody Conjugates (ISAC): A New Class of Immuno-oncology Therapeutics

  • Introducing Bolt’s ISAC technology platform as the next evolution in immune-oncology and antibody drug conjugates
  • Showcasing key features of ISAC technology and mechanism of action
  • Demonstrating the promise of the ISAC platform and Bolt’s approach to develop this new class

Romas Kudirka, Associate Director, Bolt Biotherapeutics

 

14.30 Live Discussion & Question Time

John Harlan, Senior Principal Research Scientist, AbbVie

Romas Kudirka, Associate Director, Bolt Biotherapeutics

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

  • 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

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

 

13.50 An Introduction to MEDI2228, a PBD-based ADC Directed Against BCMA for the Treatment of Multiple Myeloma

  • 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

Krista Kinneer, Senior Scientist, AstraZeneca

 

14.10 Delving into Probody Conjugates

Luc Desnoyers, Vice President - Translational Sciences, Strategic Development, Biomarker, Diagnostics & Speaker, CytomX

 

14.30 Live Discussion & Question Time

Krista Kinneer, Senior Scientist, AstraZeneca

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

13.30 Strategic & Data Driven Controls for AntibodyDrug Conjugates with Multiple Mechanisms of Action

Jon Van Dyck, Scientist, Seattle Genetics

 

13.50 Panel Discussion: Understanding the Organic Synthesis Processes that Need to be Under GMP

  • Addressing challenges in building and operating a GMP Facility for ADC drug substance and drug product manufacturing
  • Clarifying processes for organic synthesis and the GMP required

 

14.10 Considerations for Bolt Biotherapeutics’ NonCytotoxic ADCs

  • 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

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

 

14.30 Live Discussion & Question Time

Jon Van Dyck, Scientist, Seattle Genetics

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

3:30 pm Afternoon Refreshments & Networking

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 Session Reserved for Seattle Genetics

5:00 pm Clinical Pharmacology of Antibody-Drug Conjugates: A Regulatory Perspective

5:20 pm Live Discussion & Question Time

5:40 pm Chair’s Closing Remarks