As more Antibody-Drug Conjugates head to market, the next-generation of ADCs looms on the horizon. Next-gen engineering requires designing an optimal 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 research has uncovered,
showing the way to more potent and efficacious molecules. Case Studies and data will be shared that exemplify the ongoing efforts to engineer ADCs, move them into the clinic, and fight cancer along with potentially non-oncological indications.
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MONDAY 12 NOVEMBER | 09:00 - 12:00 | MORNING
Recommended Short Course*
SC2: Making Antibody Libraries in Phage and Yeast - View Detailed Agenda
Andrew R.M. Bradbury, MB BS, PhD, CSO, Specifica, Inc.
In this short course, students will learn about antibody basics, including structure, genetics and the generation of diversity, as well as the creation of naive antibody libraries in the phage and yeast display formats. This will include a description
of phage and yeast display technologies, the creation of naïve libraries from natural and synthetic sources. The seminar will be fully interactive with students provided ample opportunities to discuss technology with instructors.
*Separate registration required.
MONDAY 12 NOVEMBER
12:00 Conference Registration (Foyer C)
13:30 Organizer’s Welcome
Mary Ruberry, Senior Conference Director, Cambridge Healthtech Institute
13:35 Chairperson’s Opening Remarks
Christian P. R. Hackenberger, PhD, Professor and Department Head, Chemical Biology II, Leibniz-Research Institute for Molecular Pharmacology (FMP) and Humboldt University Berlin
13:45 FEATURED PRESENTATION: Delineating the Role of Normal Tissue Target Expression on PK and Anti-Tumor Activity with a Mouse Cross-Reactive ADC
Jan Pinkas, PhD, Vice President, Translational Research & Development, ImmunoGen,
We have developed a mouse cross-reactive ADC that we have employed to understand the role of normal tissue target expression on PK and anti-tumor activity. Our findings are broadly applicable to the development of ADCs for solid tumor targets. In this
talk, I will share the data that has been generated.
14:15 Clinical and Preclinical Evaluation of Anti-Tumor Antibody-Toxin Fusion Proteins
Jeannick Cizeau, PhD, Associate Director, Research, Sesen Bio,
Anti-tumor antibody fragments genetically fused to protein toxins that block translation can overcome many of the limitations of current generation ADCs. Their ability to drive immunogenic cell death and potentially stimulate host anti-tumor immune responses
also makes them attractive candidates for combination with immuno-oncology agents. Preliminary results from an ongoing mono therapy Phase III clinical trial in patients with high-grade non-muscle invasive bladder cancer will be presented along with
preclinical results of earlier-stage agents.
14:45 Radionuclide Therapy Using Peptide Nucleic Acid (PNA)-Mediated Pretargeting of HER2-Expressing Tumors
Amelie Eriksson Karlström, PhD, Professor, Protein Science,
Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology
In vivo pretargeting is a promising approach to reduce unfavorable biodistribution leading to side effects during treatment with radiolabeled tumor-targeting antibodies or alternative scaffold proteins. We have developed
a concept where the primary, tumor-targeting agent is conjugated to a peptide nucleic acid (PNA) strand, which binds with high affinity to a secondary, radiolabeled, complementary PNA strand. We also applied the same pretargeting system to tumor targeting
with the monoclonal antibody trastuzumab and demonstrated a high contrast between tumor and non-tumor tissue.
15:15 Antibody Fragment Drug Conjugates: Tailored Therapies for Gastric Cancer
Mahendra Deonarain, PhD, Chief Executive and Science Officer, Antikor Biopharma, Ltd.
15:45 Networking Refreshment Break (Foyer D)
16:15 Moderator’s Opening Remarks
Janine Schuurman, PhD, Corporate Vice President, Research & Innovation, Genmab BV
16:20 Bicycles and Bicycle Drug Conjugates
Sir Gregory Winter, PhD, FRS, Master, Trinity College and Co-Founder and Director, Bicycle Therapeutics
Bicycles® are a novel therapeutic class of constrained bicyclic peptides that combine antibody-like affinity and selectivity with small molecule-like tissue penetration, tunable exposure and chemical synthesis. They have potential in many indications,
including oncology, where Bicycles’ unique properties have been used to develop Bicycle Drug Conjugates™ (BDCs), a novel toxin delivery platform which greatly improves toxin loading into tumour tissues. A BDC is expected to enter clinical
trial in Q1 2018.
17:20 Paracrine Delivery: Therapeutic Biomolecules Produced in Situ
Andreas G. Plückthun, PhD, Professor and Director, Department of Biochemistry, University of Zürich
Cancer will have to be fought with cocktails of therapeutics acting locally, which may have to include therapeutic antibodies against receptors, checkpoint inhibitors, as well as cytokines to modify the tumor microenvironment. We have recently developed
a technology of using non-replicative adenovirus carrying no viral genes, engineered to target desired cells and also to be shielded from the immune response, as a vehicle for simultaneous delivery of multiple genes of therapeutic proteins, produced
and secreted by the infected cells.
18:20 Welcome Reception in the Exhibit Hall with Poster Viewing (Pavilion 1)
19:30 End of Day
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TUESDAY 13 NOVEMBER
07:45 Registration (Foyer C) and Morning Coffee (Foyer D)
08:30 Chairperson’s Remarks
Pedro M.S.D. Cal, PhD, Postdoctoral Investigator, Instituto de Medicina Molecular, University of Lisbon
08:35 KEYNOTE PRESENTATION: Strategies & Challenges for the Next Generation of ADCs
Alain Beck, PhD, Senior Director, Analytical Chemistry, NBEs, Centre d’Immunologie
Pierre Fabre; Associate Editor, mAbs
The development of ADCs has benefited from general improvements in the design of therapeutic mAbs and from specific improvements in methods for conjugate synthesis. Diversification of linking strategies and warheads has provided new opportunities to improve
drug delivery to tumors while reducing drug exposure to normal tissues. Protein structural characterization tools such as mass spectrometry are allowing better understanding of ADC structures, stability and biotransformations. This knowledge contributes
to the identification of early-developability criteria for all of the ADC components.
09:05 The Power of Chemoselectivity: Powerful Conjugation Technologies for Next-Generation ADCs
Christian P. R. Hackenberger, PhD, Professor
and Department Head, Chemical Biology II, Leibniz-Research Institute for Molecular Pharmacology (FMP) and Humboldt University Berlin
We develop novel protein functionalization technologies for the generation of site-specific conjugates with high stability and defined activities. With Tub-tag labeling, we recently introduced a novel and versatile chemoenzymatic method for the C-terminal
functionalization of biomolecules. It is based on the microtubule modifying enzyme tubulin tyrosine ligase (TTL) and facilitates one- or two-step functionalization procedures. Moreover, we have developed a new thiol-selective protein conjugation chemistry,
that is characterized by strongly increased conjugate stability compared to previous approaches. Both methods are applied for the generation of defined ADCs with improved stability and potent cytotoxicity.
09:35 Problem-Solving Breakout Discussions (Foyer E)
Grasping the Full Analytical Domain
Moderator: Jose C. Menezes, PhD, CEO & Founder, 4Tune Engineering
- The importance of long-term thinking when building Analytical Protocols
- How risk-based approaches build analytical flexibility and robustness
- How to measure similarity along lifecycle
10:30 Coffee Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
11:15 New Payloads for Antibody-Drug Conjugates
Thomas Pillow, PhD, Senior Scientist, Discovery Chemistry, Genentech,
This presentation will highlight the most recent work on ADCs at Genentech. It will cover our newest effort to deliver targeted protein degraders as a new modality for ADCs as well as new linkers developed to enable this platform.
11:45 Preclinical Validation of Site-Specifically Conjugated ADCs with Potent Anthracycline Payloads in Solid and Hematologic Tumor Models
Rémy Gébleux, PhD, Scientist II,
I will address next-generation ADC technology with an update on preclinical development of our program NBE002, targeting ROR1 in TNBC and lung adenocarcinoma. My talk will cover the validation of a novel ultra-potent anthracycline-toxin in ADCs, including
validation of NBE’s lead ADCs in preclinical tumor models, and the characterization of the immuno-oncology function of NBE’s ADCs. The audience will gain insights into both a novel site-specific conjugation platform as well as a highly
potent payload technology.
Lead-Finding and Optimization of CLIPS Constrained Peptides using High- and Medium-throughput Peptide Libraries
Michael Goldflam, PhD, Head, Peptide Discovery, Pepscan
CLIPS constrained peptides are a compound class that combines the specificity and high-affinity properties of antibodies with the advantageous features of small molecules, such as deep tissue penetration and low manufacturing costs. Pepscan developed
a platform for the discovery and optimization of CLIPS peptides suitable as therapeutics, drug conjugates, diagnostics or affinity reagents.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
13:45 Dessert Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
14:15 Chairperson’s Remarks
Amelie Eriksson Karlström, PhD, Professor, Protein Science, Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology
14:20 Antibody Targeted Amanitin Conjugates (ATACs) - Expanding the ADC Landscape with a New Payload Targeting RNA Polymerase II
Stephanie Voss, PhD, Group Leader,
Bioconjugation & Protein Chemistry, Heidelberg Pharma Research GmbH
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. Improvements of the technology and an update of the development of HDP-101 will be presented. HDP-101 is the first ATAC directed against BCMA entering Phase I trials by
the end of 2018.
14:50 Taming Random Conjugation: A General Approach for Equimolar Linking of Proteins and Payloads
Sergii Kolodych, PhD, CSO, Syndivia SAS
Multiple conjugation sites are usually available on a biomolecule. Upon conjugation, they produce a mixture of species having different degrees of conjugation (DoC). We report a general conjugation approach for achieving a defined DoC, which is virtually
applicable to any biological macromolecule and payload. Applied to native antibodies, the method yields highly homogenous antibody-drug conjugates, antibody-oligonucleotide conjugates as well as bispecific scaffolds.
15:20 Drug Conjugates Based on Engineered Affibody Molecules
Torbjörn Gräslund, PhD, Professor, Department of Protein Science,
KTH Royal Institute of Technology
Affibody molecules are small (58 aa), folded and robust non-Ig based affinity proteins. We have recently developed drug conjugates based on engineered affibody molecules with specific affinity for the HER2 receptor, coupled to the small molecule drug
DM1. Affibody molecules allows for site-specific drug attachment and easy control over DAR. We found that the drug conjugates were potent agents for treatment of xenografted human tumors in mice.
15:50 Treating Tissue Factor-Positive Cancers with Antibody-Drug Conjugates that do not Affect Blood Clotting
PhD, Director, Research, Iconic Therapeutics, Inc.
Antibodies against Tissue Factor (TF) that do not interfere with the coagulation cascade were identified by using a yeast-based selection system and various cell-based assays. A selection of antibodies conjugated to the prototypic cytotoxic agent monomethyl
auristatin E (MMAE) was tested in cell- and patient-derived xenograft models. The coagulation-inert ADCs were as efficacious as tisotumab vedotin, a clinical stage MMAE-based ADC against TF that affected blood clotting.
16:20 Refreshment Break in the Exhibit Hall with Poster Viewing (Pavilion 1)
17:00 Functional Disulfide Re-Bridging Enables Native Full Antibody DAR 2, 4 & 8 Formation, Site-Selective Orthogonal Dual Modification and Homogeneous Fragment Drug Conjugates, as well as Bi- and Tri-Specific Scaffolds
Vijay Chudasama, PhD, Lecturer, Chemistry, University College London
Our latest data on next-generation maleimide (NGM) and pyridazinedione (PD) reagents for the site-selective modification of antibodies will be detailed (including robust serum stability, in vitro selectivity,
in vivo efficacy with options for DAR 2, 4 & 8, dual drug conjugates and fragment drug conjugates). Also presented will be our latest work on using chemical linkers to form bi- and tri-specific scaffolds,
as well as applications to nanoparticle modification.
17:30 Site-Specific Antibody Functionalization at the Antibody NBS
Nathan J. Alves, PhD, Assistant Professor, Emergency Medicine and Biomedical
Engineering, Indiana University School of Medicine
Antibody modification is often necessary to endow antibodies with non-native capabilities from antibody-drug conjugates (ADCs) for targeted therapeutics to fluorescent reporter molecules for use as diagnostic or tracking tools. This session will explore
site-specific antibody modification through conjugation to the conserved antibody nucleotide binding site (NBS) and will demonstrate how various linkers and conjugation strategies can be utilized to leverage the UV-NBS technology for use in next-gen
18:00 Generation of Potent Anti-HER1/2 Immunotoxins by Protein Ligation Using Split Inteins
Harald Kolmar, PhD, Professor and Head, Applied Biochemistry, Technical
University of Darmstadt
We developed a route for the generation of immunotoxins based on full length antibodies using self-splicing split inteins and were able to generate a set of specific and highly potent conjugates. Our robust and generic method for generation of immunotoxins
relies on protein conjugation via split intein ligation. This strategy overcomes notorious problems with immunotoxin production and the resulting conjugates with intrinsic bivalency and longer in vivo half-life
display promising properties for further clinical development.
18:30 End of Next-Generation Antibody-Drug Conjugates
Day 1 | Day 2 | Download Brochure