As more Antibody-Drug Conjugates head into the clinic, the next-generation of ADCs looms on the horizon. Next-gen strategies are required to engineer an effective therapeutic combining antibody, payload, linker and conjugation method while ensuring stability,
targeted delivery, and limited off-target effects. The “Next-Generation Antibody-Drug Conjugates” conference explores the engineering finesse required to achieve improved therapeutics while adhering to the underlying biology that continually
emerges, thus highlighting the path to more potent and efficacious molecules. Case Studies and data will be shared that reveal the ongoing efforts to engineer ADCs, move them into the clinic, and fight cancer along with potentially non-oncological
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SC2: The Tumour Microenvironment and Response to Cancer Immunotherapy - LEARN MORE
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MONDAY 18 NOVEMBER
12:00 Conference Registration (Foyer A)
13:30 Organiser’s Welcome
Mary Ruberry, Senior Biomedical Conference Director, Cambridge Healthtech Institute
13:35 Chairperson’s Opening Remarks
James Baker, PhD, Associate Professor, Chemistry, University College London
13:45 FEATURED PRESENTATION: NBE-002, an Anthracycline-Based Immune-Stimulatory Antibody-Drug Conjugate (iADC) Targeting ROR1 for the Treatment of Triple-Negative Breast Cancer
Roger Beerli, PhD, CSO, NBE-Therapeutics AG
Presenting the profound in vivo anti-tumor efficacy of NBE’s lead iADC program, NBE-002, in preclinical, patient-derived triple-negative breast cancer models over a wide range of ROR1 expression levels, as well
as the potent immune-oncology function of NBE’s iADC platform.
14:15 MGC018: A Duocarmycin-Based ADC Targeting B7-H3
Deryk Loo, PhD, Director, Targeted
Therapeutics and Site Operations, MacroGenics, Inc.
MGC018 is an ADC comprised of the cleavable linker-duocarmycin payload, valine-citrulline-seco DUocarmycin hydroxyBenzamide Azaindole (DUBA), conjugated to a humanized anti-B7-H3 antibody through interchain disulfides. MGC018 demonstrated antitumor activity
in vivo toward B7-H3-expressing tumor xenografts at clinically relevant doses. MGC018 was tolerated in cynomolgus monkeys at exposure levels exceeding those required for antitumor activity. Our findings support clinical
development of MGC018 to evaluate its potential as a therapeutic for B7-H3-expressing solid cancers.
14:45 Amanitin-Based Antibody-Drug Conjugates as New Therapeutic Modalities for Cancer Therapy
PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG
Antigen-Targeted Amanitin-Conjugates (ATACs) represent a new class of ADCs using the payload Amanitin. This payload introduces a novel mode of action into oncology therapy, the inhibition of RNA polymerase II. The technology platform includes Amanitin
supply, site-specific conjugation, demonstrated safety profile and biomarker. HDP-101 is the first ATAC directed against BCMA entering Phase I trials in 2020.
15:15 SELECTED POSTER PRESENTATION:
From Site-Selective Bioconjugation of Cysteines or Tryptophans to General Targeting of Aromatic Residues:
Novel Chemistry for Bioconjugation, Structural Proteomics and Interactomics
Václav Matoušek, PhD, CEO, CF Plus Chemicals
15:45 Networking Refreshment Break (Foyer D)
16:15 Moderator’s Opening Remarks
PhD, Professor, Molecular Medicine, University College London Cancer Institute
16:20 Bispecific, Soluble TCR as the Next Therapeutic Platform
Bahija Jallal, PhD, CEO and Director of the
Of the two adaptive immunity recognition motifs, only antibodies have been brought to patients. However, antibody therapeutics only recognize 10% of human proteome (surface-expressed). The other motif, T cell receptor (TCR), has potential to unlock
90% of the human proteome, but requires converting a low-affinity, specificity membrane receptor into a soluble therapeutic. IMCgp100, a soluble, TCR bispecific-targeting melanoma, is the most advanced soluble TCR therapeutic in development.
17:20 Attacking Cancer Cell Surfaceomes with Recombinant Antibodies
James A. Wells, PhD, Professor, Departments of Pharmaceutical Chemistry and Cellular & Molecular Pharmacology, University of California, San Francisco
The cell surface proteome (surfaceome) is the primary hub for cells to communicate with the outside world. Oncogenes are known to cause huge changes in cells and we find this translates to significant remodeling of the surfaceome. We generate
recombinant antibodies to detect and then attack these cells by toxifying the antibodies or recruiting immune cells to kill. I’ll discuss the technologies for surface protein analysis, an industrialized platform for rapid antibody generation
using phage display, and using these tool reagents for target validation.
18:20 Welcome Reception in the Exhibit Hall with Poster Viewing (Rio Pavilion)
19:30 End of Day
TUESDAY 19 NOVEMBER
07:45 Registration (Foyer A) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Pedro MP Gois, PhD, Assistant Professor with Habilitation and Group Leader, Pharmaceutical Chemistry and Therapeutics, Universidade de Lisboa
08:35 KEYNOTE PRESENTATION: How to Build a Diversified Portfolio of Pyrrolobenzodiazepine-Based Antibody-Drug Conjugates
Berkel, PhD, Senior Vice President, R&D, ADC Therapeutics, Ltd.
Pyrrolobenzodiazepine (PBD) dimers represent a promising new class of toxins for the development of antibody-drug conjugates (ADCs) and many PBD-based ADCs are currently in various stages of clinical development. This keynote will highlight
some experiences when developing PBD-based ADCs from bench to clinic, with an emphasis on target, linker and toxin selection.
09:05 Effective Management of ADC Development and Clinical Manufacturing Including Outsourcing – A Big Pharma Perspective
Ulrich Rümenapp, PhD, Head, Launch Preparation and Coordination, Bayer AG
CMC development and manufacturing of ADCs has its special challenges. It is key for companies to establish a comprehensive plan for development including clinical supplies and towards BLA/MAA submission and licensure. This often involves outsourcing
to CDMOs with the need for tech transfers. The presentation will review the benefits and challenges, best practices, and how to avoid pitfalls when developing, manufacturing and outsourcing the production of ADCs.
09:35 Problem-Solving Breakout Discussions
TABLE 3: Is the QbD Toolbox Ready for Cell & Gene Therapies?
Moderator: Jose C. Menezes, PhD, CEO, 4Tune Engineering
- How can Patient Outcomes be Integrated into Manufacturing of C> Bioproducts?
- Can we deliver tailored products to terminally-ill patients and do so effectively right-first-time?
- What will be the right risk-benefit balance that can justify speeding up through development to deliver just in time a-lot-for-a-patient?
- Even if a solution for C> products might be far away, why can’t some streamlining of the current model be done?
TABLE 4: How to Attach Oligonucleotides to Antibodies
Moderator: Philipp Spycher, PhD, PSI Founder Fellow, Center for Radiopharmaceutical Sciences (CRS), Paul Scherrer Institute
- How to best attach them
- Which sizes can be conjugated and their in-vivo effects
- Release in the lysosome, cleavage sequence needed?
10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
11:15 ADCs Targeting CD163: A Platform for Modulating Macrophage Activity in Cancer and Inflammation – Preclinical Proof-of-Concept
Heilskov Graversen, PhD, Associate Professor, Molecular Medicine, University of Southern Denmark
We have utilized the macrophage specific internalization receptor CD163 as an ADC target for modulating macrophage activity in cancer and inflammation. We have obtained PoC data in mice, rats and pigs inflammatory models of sepsis and NASH,
showing a 50-fold reduced effective dose of dexamethasone when targeted to macrophages. In a murine melanoma model, we observe increased tumor infiltration of effector T cells and T cell dependent tumor regression by eradicating CD163+
tumor associated macrophages.
11:45 Drug Conjugates Based on Engineered Affibody Molecules
Torbjörn Gräslund, PhD, Professor, Protein Science, KTH Royal Institute of Technology
Affibody molecules are small and robust alternative scaffold affinity proteins. We have recently investigated drug conjugates consisting of engineered affibody molecules with specific affinity for the HER2 receptor, coupled to the tubulin
polymerization inhibitor DM1. Affibody molecules allow for site-specific drug attachment and easy control over DAR. We found that the drug conjugates were potent agents that prolonged survival of mice with human tumor xenografts.
12:15 SELECTED POSTER PRESENTATION:
Development and Ultrafast Laser Studies of Photoactive Protein Bioconjugates
Roshni Malde, MSc, PhD Student, Chemistry, University College London (UCL)
12:45 Luncheon Presentation I: Next Generation Phage Antibody Libraries for Drug Discovery: Enhanced Affinity & Developability Straight from Selections
André Teixeira, PhD, Scientist, Specifica Inc.
To make good antibodies and antibody drug conjugates (ADC) it is important to start with antibodies with ideal developability profiles. In this work, we present a new antibody display library architecture designed to yield high affinity
(pM or low nM range measured using SPR/Carterra), and highly developable antibodies straight from the initial selection campaign. The combination of natural diversity with clinically proven scaffolds enables the rapid discovery of
good leads for ADC and antibody therapy.
13:15 Luncheon Presentationt II: De-Risking ADC Development through Design and Developability Assessment
Mark Frigerio, PhD, Vice President, Design and Development, Abzena
Key criteria when selecting an antibody for ADC development. Designing ADCs so they can easily undergo systematic evaluation and optimization of their in vitro/in vivo biological properties. Using a flexible approach
for producing stable ADCs with defined location and extent of drug loading. Identify liabilities in ADC candidates early in the developability process, reducing risk and expenditure in later stages of development. Select a lead candidate
for manufacture with a minimized cost and risk profile.
13:45 Dessert Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
14:15 Chairperson’s Remarks
George Badescu, PhD, Vice President, Scientific Affairs, Heidelberg Pharma AG
14:20 Site-Selective, Serum Stable ADCs by Disulfide Bridging and Cysteine Conjugation
PhD, Associate Professor, Chemistry, University College London
This talk will describe the development and optimisation of the Next Generation Maleimide and Pyridazinedione reagent classes for the construction of ADCs. It will include a discussion of their use for the rapid formation of robustly stable
ADCs by either rebridging the native disulfide bonds or conjugating to ThiomabsTM respectively. Insights into the construction of multispecifics using these reagents will also be made, along with recently discovered new conjugation
14:50 Exploring Boron Reagents for the Assembly of Functional Bioconjugates
Pedro MP Gois,
PhD, Assistant Professor with Habilitation and Group Leader, Pharmaceutical Chemistry and Therapeutics, Universidade de Lisboa
Targeting drug conjugates, emerged as a powerful class of chemotherapeutic agents that are capable of sparing healthy tissues by liberating the cytotoxic payload only upon specific antigen recognition. A considerable body of work in this
field highlighted that targeting drug conjugates therapeutic efficacy, correlates well with the conjugate homogeneity and activation of the drug at the diseased site. Therefore, the linker technology used to connect both functions
contributes decisively to the therapeutic usefulness of these constructs. In this communication will be presented the use of boron-based complexes as functional likers in the design of cancer cell targeting conjugates.
15:20 Developing Differentiated Next-Generation ADC Therapeutics
PhD, CSO, Iksuda Therapeutics
Improved ADC stability through novel PermaLink bioconjugation technology paves the way for use of novel payloads. A pipeline of differentiated next-generation ADC candidates is in preclinical development with the lead ADC candidate, IKS01,
showing markedly improved efficacy compared to clinically-validated benchmark ADC in solid tumor models. Initiation of a Phase I clinical trial for IKS01 is expected to initiate in late 2020.
15:50 Clinical-Stage GlycoConnect Technology Enables ADCs with Superior Therapeutic Index
Floris van Delft, PhD, CSO, SynAffix BV, and Special Professor, Bioconjugate Chemistry, Organic Chemistry, Wageningen University
GlycoConnect™ is a site-specific antibody conjugation technology that does not require prior genetic modification, by applying the native glycan as a privileged attachment site for cytotoxic payloads. Combined with the polar HydraSpace™
technology, ADCs are readily generated from any IgG isotype in a straightforward two-stage procedure. GlycoConnect™ and HydraSpace™ technologies may be readily combined with a payload selected from Synaffix’ toxSYN™
platform, covering multiple mode of actions, leading to ADCs with an expanded therapeutic index.
16:20 Refreshment Break in the Exhibit Hall with Poster Viewing (Rio Pavilion)
17:00 Conjugating Payloads to Native Antibodies Without the Need of Any Prior Antibody Engineering in One or Two Steps
Philipp Spycher, PhD, CEO and Co-Founder, Araris Biotech AG, and PSI Founder Fellow, Center for Radiopharmaceutical Sciences (CRS), Paul Scherrer Institute
We will introduce a new linker antibody-conjugation technology that enables site-specific payload attachment to native antibodies ‘off-the-shelf’ without engineering, i.e. neither the antibody nor the glycosylation needs to
be engineered. We will provide a comprehensive set of data demonstrating that the ADCs generated with our new linker technology retain their binding properties, are stable and highly cytotoxic to target over-expressing cell-lines and
show superior in vivo performance versus reference, state-of-the art ADCs.
17:30 DARPin Drug Conjugates (DDC): Combining the Potency of Antibody-Drug Conjugates and the Flexible DARPin Architecture
Christian Reichen, PhD, Senior Scientist Lead Generation, Molecular Partners AG
The use of the robust DARPin® technology enables the exploration of new therapeutic design space and the establishment of drugs acting on multiple disease pathways. We have generated site-specific DARPin drug conjugates (DDCs) using
an anti-EGFR DARPin as a model system to explore the potential of DARPin molecules to deliver potent cytotoxic drugs. We describe here the potency and selectivity of anti-EGFR DDCs and discuss the flexibility of the DARPin platform
to generate DDCs to multiple target classes.
18:00 Tailoring Antibody Fragment Drug Conjugates for Solid Tumours
Mahendra Deonarain, PhD, CEO and CSO, Antikor Biopharma Ltd.
Antikor’s Fragment Drug Conjugate (FDC) platform small-format antibody-drug conjugates with superior penetrating and clearance properties high payload capacity for more potent action PK, tolerability and tumour cure efficacy data
in HER2 and a 2nd undisclosed gastric cancer target.
18:30 End of Next-Generation Antibody-Drug Conjugates