Scientific Program - Day 2
Friday October, 11


Breakfast Briefing - Bioconjugation CMC – Successfully Executing a Complex Process

  •  An overview of individual components of a typical Antibody Drug Conjugate and the challenges posed during scale-up of the manufacturing processes for pre-clinical and clinical studies
  •  How to avoid common pitfalls during process knowledge transfer to your chosen CMO
  •  Managing all the moving pieces to bring your ADC to the clinic
  •  What does developing an ADC have in common with developing a small molecule process and what is unique?
  •  Models will be included to illustrate the topics being presented

Scott Miller
Senior Scientific Advisor


Chair’s Opening Remarks

John Lambert


Internalization Rate as a Critical Attribute of ADC Design: A review of HER2 & HER3 ADC's with DXd Linker Technology


Robert Phillips,

Vice President & Global Head of Translational Sciences

Daiichi Sankyo


New Developments with the Pyridinobenzodiazepine (PDD) Payload Platform

• Updates will be presented on ADCs carrying the high-potency PDD G-monoalkylating payload FGX2-62, including toxicity profile in rats.

DNA sequence-selectivity and transcription factor down-regulating activity of FGX2-62 will be presented.

• The development of a new high-potency PDD-based DNA G-A cross-linking payload with an unusually high MTD (> 45 mg/kg) and wide therapeutic window in mice will be described.



David Thurston

Chief Scientific Officer



What Lies Ahead for ADCs?

• What we’ve learned from past studies
• Exciting new developments
• Some challenges for the future

Peter Senter
Vice President Chemistry & Distinguished Research Fellow
Seattle Genetics


Clinical-Stage Technology Enabling ADCs with Best-in-Class Therapeutics Index

Floris van Delft
Chief Scientific Officer


Protoxins: The Next Generation of Toxins for Antibody-Drug Conjugates

• Reversible and non-reversible Protoxins
• Protoxins of PBD dimers, maytansine, and MMAE
• Improved stability of Protoxin-ADCs

Naresh Jain
President & Chief Executive Officer
NJ Biopharmaceuticals, LLC


Morning Refreshments & Networking

Mitigating & Managing Toxicity in Clinical Development

Reviewing Strategies to Ensure Robust ADC Manufacturing Processes

Innovative Frontiers: Showcasing Alternative ADC Formats

Translating Preclinical Lessons to the Clinic to Enhance Understanding of ADC Safety Profiles


Phase 1 Interim Data of MORAb-202 as Eribulin Conjugated Anti FRA-Targeted ADC

• MORAb-202 is the first ADC which is loaded with HALAVEN® as payload
• HALAVEN® is an approved drug which exhibits unique effects on tumor microenvironment
• The interim data of MORAb-202 Phase 1 study in Japan is to be discussed

Keiiji Furuuji, Associate Director & Head of Immunotherapy & Preclinical Development, Eisai


Process Understanding & Automated Processing Development to Ensure First Pass Manufacturing Success of ADCs

• Studies needed for clinical supplies and for commercial readiness with the goal of providing evidence of process consistency
• Use of automated systems for gathering information for early phase process transfers to manufacturing
• Does that ensure appropriate ranges are evaluated and ensure deep process understanding?

Lisa McDermott, Head of Process & Analytical Development, MilliporeSigma


ADCs with Novel Kinesin Spindle Protein Inhibitor Payloads & a TailorMade Linker Chemistry

• Inhibitors of kinesin spindle protein (KSPi) have been developed as a novel payload class in antibody drug conjugates
• To increase tumor selectivity of ADC metabolism, a tumor associated protease with a unique cleavage sequence is utilized for lysosomal ADC cleavage and release of active metabolites with an appropriate profile matching, the KSPi mode of action

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


Development of a 2nd Generation HER2 ADC Comprised of a Novel Antibody Linked to a Reduced Potency PBD Dimer

• The antibody, 7C2, binds domain I and thus does not interfere with trastuzumab, pertuzumab or trastuzuamb emtansine (T-DM1), allowing for combination therapy with these marketed therapeutics
• Reduced potency, mono-alkylating PBD dimers were assessed to allow for higher dose levels and potentially improved TI.
• PBD mono-alkylators were linked to 7C2 using a stable hindered disulfide linker
• Unlike T-DM1, these ADCs exhibit bystander activity • The PBD-mono-alkylator-ADCs show differential potency compared to T-DM1 both in vitro and in vivo

Gail Lewis Phillips, Senior Scientist - Translational Oncology, Genentech


PBPK Modeling to Support DDI Strategy of Polatuzumab Vedotin & Regulatory Implications

• Simcyp is applied for the first time in the prediction of MMAE-DI potential for the two ADCs – brentuximab vedotin and polatuzumab vedotin
• The PBPK model might be sufficient to assess DDI prediction and a dedicated drug interaction study is not required – as a supporting strategy for other vc-MMAE ADCs across the platform
• This model was submitted in the BLA/ MAA for polatuzumab vedotin to provide quantitative DI risk assessment without the need of a dedicated clinical DDI study and FDA has accepted our proposed language

Divya Samineni, Clinical Pharmacologist, Genentech


Key Considerations & Best Practices in Externalization of the ADC Supply Chain

• Strategizing the best outsourcing practices for producing and testing ADCs for use in clinical trials
• Establishing guiding principles for externalization to ensure the selection of the right CMOs for ADC outsourcing and technology transfer
• Sizing appropriately of the ADC supply chain to expedite transition from clinical to commercial manufacturing

Firelli Alonso, Senior Director, External Supply, Pfizer


Creating Next Generation ADCs with Industry Leading DAR Precision & Plasma Stability

• LCB’s novel next-generation site-specific ADC platform technology
• Tumor-specific and ultra-potent DNA damaging crosslinking payload with superior efficacy and reduced toxicity
• Improved solubility compared to other DNA-targeting agents due to addition of hydrophilicity
• Improved manufacturing and CMC properties resulting in homogenous ADC drug product

Jeiwook Chae, Chief Business Development Officer, LegoChem Biosciences


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


Biomarker Measures of Surrogate Endpoints for FDA Qualification of Accelerated ADC Marketing Approvals

• What are the accepted FDA definitions of the contexts of use of biomarkers in clinical trials?
• What is are the regulatory pathways for qualification of biomarker measures for primary surrogate endpoints for accelerated drug marketing approvals by the FDA?
• What are some examples of biomarker measures for primary surrogate endpoints for accelerated drug marketing approvals in oncology that have been approved by the FDA?

Randall Morris, Research Professor of Cardiothoracic Surgery &, by courtesy, Medicine & Surgery (Emeritus), Stanford University School of Medicine


Integrated ADC Development to Production

• What we learnt from the failed ADCs
• What strategy to make a better one
• Does antibody binding affinity influence ADC fate?
• Does conjugation format affect the internalisation?

Xinfang Li, Vice President - Process
Development & Head of Chemistry,
Manufacturing & Controls, Mabplex


Payload Masking in HSP90Targeting Miniature Drug Conjugates to Expand the Therapeutic Window

• HSP90 targeting miniature drug conjugates bind to activated HSP90 thus accumulating in tumor xenograft models followed by a prolonged resident time in the tumor compared to normal tissues and sustained release of therapeutic payload
• Masking the payload in HSP90 targeting conjugates significantly reduces the toxicity of the payload while in the intact conjugate in the circulation. The full potency of the payload is realized when the linker cleaves in the tumor
• Optimizing the linker cleavage kinetics with the differential tumor to normal exposure and the payload masking results in complete and sustained tumor regressions in multiple xenograft models

Mark Bilodeau, Chief Scientific Officer, Tarveda


Complex Population Quantitative Pharmacology Approach to Investigate the Disposition of Antibody-Drug Conjugate

• Complex distribution, catabolism and elimination processes of ADC are not yet well understood
• It is important to quantify the disposition pathway of the conjugate and the release mechanism of unconjugated toxins into the systemic circulation in order to better understand the complex ADC pharmacology that are related to observed efficacy and toxicity
• The objective of this study was to develop complex population quantitative pharmacology model that can simultaneously describe disposition and elimination of multiple analytes, including total antibody, conjugate, and unconjugated toxins of ADC in cynomolgus monkeys

Chee Ng, Associate Professor, University of Kentucky


Lunch & Networking


Cerbios Lunch Seminar: Effective Solutions for ADC Process Development and Manufacturing 

  • Tackling the most common issues during process industrialization
  • Integration of mAb, payload and conjugation manufacturing activities
  • Using the right analytical tools for parameter optimization
  • Merging chemical and biological technologies
  • Multipurpose manufacturing equipment and facilities
  • Adopting the current regulatory frameworks into an ADC process


Vitor Sousa
R&D Biological Senior Manager

Looking at Future & Current Pioneering Scientific Developments


Exploring Biomarker Driven Development Opportunities for Sacituzumab Govitecan

• Discuss Role of TROP-2 in cancer
• Utilizing TROP-2 as a biomarker
• Considerations for development strategies for SG

Trishna Goswami
Vice President, Clinical Development for Non-Breast Indications,


Expanding Kadcyla to Move into Early Breast Cancer (EBC)

• Kadcyla EBC development plan
• Neoadjuvant Kadcyla: KRISTINE results
• Adjuvant Kadcyla for patients with residual disease: KATHERINE results

Chunyan Song
Senior Medical Director


CAB ADCs: Reducing On-target Toxicity & Enabling Potent Combination ADC Therapies

• Reversible ADC activation by the tumor microenvironment for higher therapeutic Index
• Early clinic experiences with CAB-ADCs
• Scrutinize the increasing importance of combination therapies for achieving greater efficacy

Bill Boyle
Chief Science Officer & Vice President - Translational Medicine


The DolaLock-based ADC Platforms: Dolaflexin & Dolasynthen

• Update on the clinical evaluation of XMT-1536, a NaPi2b targeted Dolaflexin ADC
• Overview of Dolasynthen, a fully homogeneous, highly versatile ADC platform which allows for precise DAR ranging from 2-24
• Applications of Dolasynthen to identify optimal ADCs for clinical development

Timothy Lowinger
Chief Scientific Officer


Afternoon Refreshments & Networking

Advancing ADCs That Sit Outside of Oncology 


ADC as a Targeted Therapy for Cancer & Beyond

• Cytotoxic ADCs targeting tubulin
• Non-cytotoxic ADCs targeting glucocorticoid receptor and Liver X receptor
• Approaches to discover site-specific ADCs using novel linkers

Amy Han
Director, Chemistry


Bicycle® Toxin Conjugates – A New Approach to Tumor Targeted Delivery

• Bicycles® are fully synthetic short peptides constrained to form two loops which stabilize their structural geometry. This constraint is designed to confer high affinity and selectivity, and the relatively large surface area presented by the molecule allows targets to be drugged that have historically been intractable to non-biological approaches. Bicycles represent a unique therapeutic class, combining the pharmacological properties normally associated with a biologic with the manufacturing and pharmacokinetic advantages of a small molecule, yet with no signs of immunogenicity
• Bicycle Toxin Conjugates (BTCs) have properties ideal for tumour delivery – they penetrate tumors extensively and rapidly, but are renally eliminated maximizing tumor exposure and minimizing systemic exposure.
• Bicycle has three BTC molecules either in the clinic or undergoing IND enabling studies: BT1718, targeting MT1-MMP expressing tumors is in Phase 1 clinical evaluation with Cancer Research UK, BT5528 targeting EphA2 expressing tumous and BT8009 targeting Nectin-4 expressing tumors. In this presentation we will provide an overview of the properties and data emerging from these programs

Nick Keen
Chief Scientific Officer
Bicycle Therapeutics


The Development of ABBV-155, a First-in-class BCL-XL Inhibitor ADC

• This talk will highlight the preclinical data outlining the development of ABBV-155
• ABBV-155 targets B7H3 expressing cancer cells and delivers a potent and specific BCL-XL inhibitor
• The used of a targeted warhead offers the potential of synergistic mechanism-based combinations with both chemotherapy and other targeted therapeutics

Andrew Phillips
Director, Next Generation AntibodyDrug


Chair’s Closing Remarks

John Lambert