2016 Archived Content
Cambridge Healthtech Institute’s Inaugural
Engineering Next-Generation Antibody-Drug Conjugates
Into the Clinic and Beyond
31 October – 1 November 2016 | EPIC SANA Lisboa Hotel | Lisboa PORTUGAL
ADCs hold great promise as therapeutics, yet pose significant engineering challenges from design to manufacture. How to put all the pieces together for the greatest effect? Multiple payloads and new conjugation techniques are raising the stakes on next-gen
ADCs, as are novel targeting ligands and adjusting the antibody-drug ratio. With all the complexity of ADCs, researchers are forced to tackle how to guarantee safety, while ensuring stability and efficacy. This conference will explore the most promising
engineering strategies, and will take a look at how these complex molecules fare as they move into the clinic particularly for cancer. With all the ongoing developments in the field of Antibody-Drug Conjugates, this conference will also peer into
the future to see where the field is headed.
Final Agenda
Day 1 | Day 2 | Speaker Biographies | Download Brochure
MONDAY 31 OCTOBER
12:00 Registration
13:40 Welcome from PEGS Europe Team
13:45 Chairperson’s Opening Remarks
Ana Barbas, Ph.D., Coordinator, Bayer Satelite Laboratory at iBET, iBET and Bayer Portugal SA
13:50 Biotherapeutic Programs that Re-Direct Cytotoxic Lymphocytes to Cancer Cells
Paul Adam, Ph.D., Executive Director, Immune Modulation and Biotherapeutics Discovery, Boehringer Ingelheim
Cytotoxic lymphocytes such as NK and T cells have the capability to control cancer development and progression. Harnessing this cytotoxic potential with biotherapeutic agents is predicted to become a future pillar of cancer therapy in light of recent
clinical successes. This presentation will describe novel biotherapeutics whose mode of action involves the engagement and re-direction of NK and T cells to hematological tumors.
14:30 Antibody-Based Combination Cancer Immunotherapy at Roche pRED
Christian Klein, Ph.D., Distinguished Scientist, Head, Oncology Programs, Cancer Immunotherapy Discovery,
Roche Pharmaceutical Research and Early Development, Roche Innovation Center Zurich
This presentation will introduce novel antibody cancer immunotherapies developed at Roche pRED including novel IL2 variant immunocytokines and T cell bispecifics as well as preclinical data for their optimal combination and scheduling.
15:10 Safety Concerns Associated with Immunotherapy and Novel Biotherapeutics and Challenges in Investigating Their Immunotoxicity
Sandra S. Diebold, Ph.D., Principal Scientist, Immunotoxicology, Biotherapeutics, National Institute for
Biological Standards and Control (NIBSC)
The pre-clinical assessment of the risks associated with immunotherapy and novel biotherapeutics is challenging since the bioassays have to be individually tailored to the investigated reagent. The immunotoxic activity and adverse responses that may
be observed in patients are depending to a large degree on the mechanism of action of the biotherapeutic. The specific set-up of in vitro assays plus the identification of suitable animal models is critical for obtaining predictive pre-clinical
data.
15:50 Refreshment Break in the Exhibit Hall with Poster Viewing
16:50 Chairperson’s Remarks
Jens Lohrmann, Ph.D., Senior Global Program Manager, Translational Clinical Oncology, Novartis Institutes for BioMedical Research
16:55 Chemical Pharmacology of Protein Conjugates
Gonçalo J.L. Bernardes, Ph.D., Principal Investigator, Chemistry, University of Cambridge
Our work centers on reaction engineering for site-selective chemical protein modification to provide insight into biology and for the development of protein therapeutics. This lecture addresses recent research in: (i) site-selective chemical modification
of proteins and antibodies at cysteine and lysine, and (ii) the development of CO-releasing artificial metalloproteins that are able to deliver CO in a targeted and controlled manner to tumor tissues leading to potent CO-mediated immunomodulation.
17:25 Platform Technologies for Homogeneous and Versatile Full Antibody and Antibody Fragment Modification
Vijay Chudasama, Ph.D., Lecturer, Chemistry, University College London
There is clear demand for the construction of novel antibody-drug conjugate (ADC) platforms that offer greater stability, homogeneity and flexibility. A significant step towards the ideal platform for next generation antibody-based therapeutics
is presented. Our technology provides decorated antibody constructs that are highly stable, with complete retention of antibody binding/structure post-modification. It combines site-specific functionalisation with exceptional versatility
via the functional re-bridging of interchain disulfide bonds native to antibodies.
17:55 POSTER SPOTLIGHT:
Antibody-Drug Conjugates Screening Platform for Selection of Novel Biologics at the National Research Council of Canada
Maria Jaramillo, Ph.D., Senior Research Officer & Project Leader, Primary Assays, Biotechnology Research Institute, National Research Council Canada
18:25 Welcome Reception in the Exhibit Hall with Poster Viewing
19:25 End of Day
Day 1 | Day 2 | Speaker Biographies | Download Brochure
TUESDAY 1 NOVEMBER
07:45 Registration and Morning Coffee
08:30 Chairperson’s Remarks
João Tomé, Ph.D., Associate Professor, Chemical Engineering, Instituto Superior Técnico,
University of Lisbon
08:40 KEYNOTE PRESENTATION:
Advancement in Antibody Drug Conjugates: A Step Closer to Creating Magic Bullets against Deadly Cancers
Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics
Safety Assessment, MedImmune (A member of AstraZeneca Group)
- Discuss 5 Rights (target, antibody, linker, warhead and translationalstrategy) of ADCs
- How to improve and maximize the therapeutic effectiveness of ADCs
- Case studies of a biparatopic ADC for highly resistant low Her2 expressing cancers
- Recent developments in PBD-based ADCs
- Personalized biomarkers-dependent clinical ADC development
09:10 Design, Synthesis and Scale-Up of an ADC Tubulysin Payload
Jeremy S. Parker, D.Phil., Principal Scientist, New Modalities & Tissue Targeting,
AstraZeneca
AstraZeneca has designed, synthesized, and manufactured a novel Tubulysin payload that has been successfully used in the production of MedImmune’s Biparatopic HER2-Targeting Antibody Drug Conjugate which is currently in Phase I clinical
trials.
09:40 Problem-Solving Breakout Discussions
Reducing Off-Target Toxicities of ADCs
Moderator: Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics Safety Assessment, MedImmune (A member of AstraZeneca Group)
- Antibody properties
- Controlling off-target biodistribution of ADCs
- Cytotoxic warhead: potency, metabolism
- Conjugation technologies
- Reducing bystander toxicities
What are the Next Challenges in the Identification, Synthesis and Application of New ADC Payloads?
Moderator: Jeremy Parker, D.Phil., Principal Scientist, New Modalities & Tissue Targeting, AstraZeneca
- Challenges and opportunities for Payloads with new Mechanisms of Action
- Key challenges in the scale-up of ADC Payloads and how can these be overcome
- Opportunities for new linkers and new linker methodology
Next-Generation Drug Conjugates: Non-Antibody Based Scaffolds
Moderator:Joanna Hays, Ph.D., Science Manager, Customer Solution, Albumedix Ltd.
Monoclonal antibodies represent a well-validated and rapidly growing class of human therapeutics. Despite their successes, monoclonal antibodies nevertheless face a range of restrictions that limit their applicability. Consequently, promising
non-antibody based alternative scaffolds are now moving into clinical development and practice.
- Advantages and disadvantages of non-antibody based scaffolds as novel therapeutic approaches
- Overcoming half-life shortcomings of non-antibody based scaffolds
- Clinical and manufacturing challenges of non-antibody based scaffolds
10:40 Coffee Break in the Exhibit Hall with Poster Viewing
11:20 Challenge ADC Therapeutic Index with TG-IPH Site-Specific Technology
Florence Lhospice, Director, Pharmaceutical Operations, Innate Pharma
Here, we describe the in vitro and in vivo characterization of four novel ADCs that are based on the anti-CD30 antibody cAC10, which has the same polypeptide backbone as ADCETRIS®, and compare the results with the latter. Overall,
the results suggest that homogenous ADCs display improved pharmacokinetics and better therapeutic indexes compared to chemically modified ADCs with variable DARs. Of note, equivalent results were confirmed with a panel of drugs and
targets as per our current collaborations and our own programs.
11:50 Tub-Tag Labeling – A Novel Chemoenzymatic Approach for the Generation of Site-Specific ADCs
Jonas Helma, Ph.D., Project Group Leader, Biology II, Ludwig-Maximilians University
A novel chemoenzymatic approach for simple and fast site-specific antibody conjugation is presented. We repurposed tubulin tyrosine ligase (TTL) to attach various unnatural tyrosine derivatives as small bioorthogonal handles to nanobodies
and recombinant antibodies containing a short tubulin-derived recognition sequence (Tub-tag). This novel strategy enables a broad range of chemoselective C-terminal antibody modifications. We foresee a wide field of potential applications
throughout the life sciences, including next-generation Antibody-Drug Conjugates.
12:20 Sponsored Presentation (Opportunity Available)
12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:20 Session Break
14:00 Dessert Break in the Exhibit Hall with Poster Viewing
14:30 Chairperson’s Remarks
Jeremy S. Parker, Ph.D., Principal Scientist, New Modalities & Tissue Targeting, AstraZeneca
14:35 Enhancing the Therapeutic Index of ADCs by Conjugation through Glycans with Improved Linkers
Floris Van Delft, Ph.D., Founder & CSO, SynAffix BV
The globally conserved N-glycan provides a superior, natural anchor point for antibody conjugation. By applying a two-stage process involving enzymatic glycan remodeling, and copper-free click attachment of cytotoxic payload, antibody-drug
conjugates (ADCs) can be readily prepared from any mAb without protein reengineering. Conjugation of highly hydrophobic payloads is facilitated by applying a short and polar spacer technology, leading to ADCs with improved therapeutic
index by increasing in vivo efficacy and tolerability.
15:05 Advances in Bio-Orthogonal and Bio-Specific Bond-Forming Reactions for Improved Antibody-Based Conjugates
Alain Wagner, Ph.D., Research Director, Functional ChemosSystem, Strasbourg University and CNRS
The recent development in the fields of bio therapeutics and chemical biology has shed light on the limitations of current bioconjugation and bio-de-conjugation reactions in terms of bio-stability bio-selectivity and biocompatibility.
The presentation will focus on some methodological approaches we have implemented to discover novel efficient molecular systems to link and release bioactive compounds and biomolecules.
15:35 Photo-Immunoconjugates for Targeted Cancer Photodynamic Therapy
João Tomé, Ph.D., Associate Professor, Chemical Engineering, Instituto Superior
Técnico, University of Lisbon
The recent development of photo-immunoconjugates as photosensitizers (PSs, photoactive drugs) to target cancer cells open new perspectives for cancer photodynamic therapy (PDT). In this talk, some of our recent work on the synthesis
of PSs and PS-antibody conjugates will be shown, as well as highlighting their biological potential against human bladder cancer cell lines.
16:05 POSTER SPOTLIGHT
Abdurin-Drug Conjugates: A New Generation of Targeted Therapeutics
Silvia Peretti, Ph.D., Biochemistry, IRBM Science Park S.p.A.
16:35 Refreshment Break in the Exhibit Hall with Poster Viewing
17:15 Novel Linker Chemistries for Antibody-Drug Conjugates
Thomas Pillow, Ph.D., Senior Scientist, Discovery Chemistry, Genentech, a member of the Roche
Group
This presentation will focus on our development of a novel disulfide linker where we demonstrate for the first time the ability to decouple stability and release. This linker takes advantage of new sites on cysteine-engineered antibodies
that stabilizes both the linker and the payload from metabolism. When applied to PBDs, the disulfide-linked ADC has an improved therapeutic index compared to a peptide-linked ADC.
17:45 Small is Beautiful – Humabodies Drug Conjugates, HDCs a Real Alternative to ADCs
Normann Goodwin, Ph.D., Senior Scientist, Preclinical Development, Crescendo Biologics,
Ltd.
Humabodies enable plug and play engineering allowing simple exploration of limitless format options. HDCs demonstrate exceptionally fast tumor penetration. Half-life can be tailored facilitating low systemic and high tumor exposure.
Different format of HDCs show high-impact on potency both in vitro and in vivo. Therefore the versatility of the Humabody™ format enables creation of optimal HDC format and half-life with improved Therapeutic Index.
18:15 Challenges & Lessons Learned in ADC CMC Development & Outsourcing
Jens Lohrmann, Ph.D., Senior Global Program Manager, Translational Clinical Oncology,
Novartis Institutes for BioMedical Research
A key decision for achieving stable ADCs is whether to “buy or make” these highly active compounds. Leveraging the know-how of CMOs can be powerful; however, to ensure an effective relationship, communication is
key. Technical challenges of site-transfers, especially with concomitant scale-up are to be expected. Case studies will be presented to discuss impact of conjugation process on key product quality attributes, as well as
lessons learned from analytical transfers.
18:45 End of Engineering Next-Generation Antibody-Drug Conjugates
Day 1 | Day 2 | Speaker Biographies | Download Brochure