engineering antibody drug conjugates



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 indications.

Final Agenda

Recommended Short Course*

SC2: The Tumour Microenvironment and Response to Cancer Immunotherapy - LEARN MORE

*Separate registration required.

MONDAY 18 NOVEMBER

12:00 Conference Registration

FIGHTING CANCER WITH ADCs

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 AGRoger 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

Loo_DerykDeryk 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

Badescu_GeorgeGeorge Badescu, 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 by the end of 2019.

15:15 Sponsored Presentation (Opportunity Available)

15:45 Networking Refreshment Break


PLENARY KEYNOTE SESSION

16:15 Moderator’s Opening Remarks

Kerry Chester, PhD, Professor, Molecular Medicine, University College London Cancer InstituteKerry Chester, 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 Board, ImmunocoreBahija Jallal, PhD, CEO and Director of the Board, Immunocore

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 FranciscoJames 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

19:30 End of Day

TUESDAY 19 NOVEMBER

07:45 Registration and Morning Coffee

ACHIEVING ADC SUCCESS FROM BENCH TO CLINIC – AND INTO MANUFACTURING

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

Patrick van Berkel, PhD, Senior Vice President, R&D, ADC Therapeutics, Ltd.Patrick van 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

Ruemenapp_UlrichUlrich 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*

*See website for details.

10:30 Coffee Break in the Exhibit Hall with Poster Viewing

ENGINEERING NEXT-GEN ADCs

11:15 ADCs Targeting CD163: A Platform for Modulating Macrophage Activity in Cancer and Inflammation – Preclinical Proof-of-Concept

Graversen_JonasJonas 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

Graslund_TorbjornTorbjörn 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 Sponsored Presentation (Opportunity Available)

Carterra 12:45 Luncheon Presentation: Next Generation Phage Antibody Libraries for Drug Discovery: Enhanced Affinity & Developability Straight from Selections

Teixeira_AndreAndré 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 Presentation II (Opportunity Available)

13:45 Dessert Break in the Exhibit Hall with Poster Viewing

INNOVATING BIOCONJUGATION AND LINKER TECHNOLOGIES

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

Baker_JamesJames Baker, 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 platforms.

14:50 Exploring Boron Reagents for the Assembly of Functional Bioconjugates

Gois_PedroPedro 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

Lutz_RobertRobert Lutz, 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 Sponsored Presentation (Opportunity Available)

16:20 Refreshment Break in the Exhibit Hall with Poster Viewing

NOVEL TECHNOLOGIES

17:00 Overcoming Limitations of Current Antibody-Drug Conjugates (ADCs) by a Novel Linker Technology

Spycher_PhilippPhilipp Spycher, PhD, 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

Reichen_ChristianChristian 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

Deonarain_MahendraMahendra 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

* The program is subject to change without notice, due to unforeseen reason.

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Update History
2019/10/17
Agenda,Sponsor updated
2019/10/03
Event Information updated
2019/09/09
Sponsor updated
2019/08/23
Sponsor updated
2019/08/09
Sponsor updated
2019/08/06
Agenda updated
2019/06/27
Agenda,Sponsor updated