2017 Archived Content
Antibody-Drug Conjugates have reached a truly exciting level in their ever-evolving development. Nevertheless, many challenges remain especially when translating ADCs from pre-clinical stages into the clinic. Developing new targets and ensuring ADC potency
remain crucial issues, along with how to manufacture such large and complex molecules. This conference examines where ADCs are in their current development, and reveals the emerging strategies and technologies that are leading to new conjugation methods,
warhead design, and cutting-edge research.
Final Agenda
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MONDAY 13 NOVEMBER
12:00 Registration
13:40 Welcome from PEGS Europe Team
Christina C. Lingham, Team Lead, PEGS Europe
13:45 Moderator’s Opening Remarks
Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA
13:50 Safety Considerations for Development of Immune Agonist and Immune Antagonist Biotherapeutics
Rakesh Dixit, Ph.D., DABT, Vice President, Research & Development, and Global Head, Biologics Safety
Assessment, MedImmune (A member of AstraZeneca Group)
In this keynote presentation, the challenges of biotherapeutics impacting on the immune response, and the challenges investigators face managing, dose, scheduling, and satisfying the regulatory requirements will be discussed. The checkpoint pathways modulation
used for cancer immunotherapy has a natural role in controlling autoimmune diseases such as Type 1 Diabetes and Lupus. Immunotherapies in general, and technologies modifying T cell function and those involving cytokines present dangers of cytokine
storm, autoimmune disease, cardiovascular disorders, and additional challenges, especially when used in combination. Strategies to manage and mitigate immune related safety events will be presented.
14:30 Learning What Works from Successful Tumour Infiltrating Lymphocyte Therapy
Andrew Sewell, Ph.D., Professor, Division of Infection and Immunity, Cardiff University School of Medicine
Over 20% of melanoma patients that have been refractory to other treatments undergo complete lasting remission after adoptive cell transfer of tumor-infiltrating lymphocytes (TILs). Dissection of these extraordinary successes by examining the dominant
tumor-reactive T-cell clonotypes in the TIL infusion product and patient blood after ‘cure’ has revealed some surprising, exciting new HLA-restricted and non-HLA restricted targets that are expressed by many other tumour types.
15:10 Widening the Therapeutic Index: The Next Generation of Antibody-Drug Conjugates (ADCs)
John M. Lambert, Ph.D., Executive Vice President Emeritus and Distinguished Research Fellow, ImmunoGen,
Inc.
ADCs with potent tubulin-acting and DNA-acting agents can be effective anti-cancer agents with good TI. However, not all cell-surface targets have proven susceptible to the development of effective ADCs utilizing the first-generation ADC chemistries.
Each element in the ADC design, the antibody, the payload, and the linker (both site of attachment on antibody and payload-release mechanism) are important considerations. Application of the growing “ADC Toolbox” to current
and future ADC developments will be discussed.
15:50 Refreshment Break in the Exhibit Hall with Poster Viewing
16:50 Chairperson’s Remarks
Roger R. Beerli, Ph.D., CSO, NBE-Therapeutics, Ltd.
16:55 High-Throughput Optimization and Mass Spectrometric Analysis of Covalently Labeled Proteins and Antibody-Drug Conjugates
Chawita (Jelly) Netirojjanakul, Ph.D., Scientist, Hybrid Modality Engineering
Group, Therapeutic Discovery Research, Amgen, Inc.
The use of automated high throughput screening in large molecule discovery research still lags behind that of small molecule discovery. Here, we developed an automated platform to complete a bioconjugation optimization workflow in one setting.
Given LC-MS is a widespread analytical bottleneck, we also established an HTS-MS platform to accurately detect and rapidly quantitate mAb and Fc conjugates with acquisition time of 20 sec/sample, 10-50x improvement over traditional LC-MS
methods.
17:25 ADC Manufacturing for Clinical Supply in Multi-Purpose Facilities – Challenges and Solutions
Ulrich Rümenapp, Ph.D., Head, Launch Preparation and Coordination, Bayer AG
The manufacturing of ADCs for clinical supply (or the commercial market after launch) has its special challenges due to the toxicity of the ADC molecule and its payload. This includes, e.g., the need to protect the personnel in the working
area and the environment, measures to avoid cross-contamination, as well as appropriate waste handling. Bayer’s Biologics Development approach for the GMP production of ADCs in its pilot facilities in Wuppertal, Germany up to a 100L-scale
will be presented. With the combination of single-use systems, closed processing and isolator technologies, ADCs can be manufactured in classical multi-purpose pilot-scale facilities without jeopardizing work safety or higher risk of cross-contamination.
This avoids the investment in construction of a dedicated ADC facility.
17:55 POSTER SPOTLIGHT
Biopolymeric Scaffold for High Antibody Drug Ratios Using Site-Specific Conjugation Strategies
Aileen Ebenig, PhD Student, Biochemie, Technische Universitat Darmstadt
18:25 Welcome Reception in the Exhibit Hall with Poster Viewing
19:25 End of Day
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TUESDAY 14 NOVEMBER
07:45 Registration and Morning Coffee
08:30 Chairperson’s Remarks
Philip Howard, Ph.D., Senior Fellow, MedImmune, Inc. and CSO, Spirogen, Ltd.
08:35 Antibody-Drug Conjugates for Treatment of Triple Negative Breast Cancer
Aditya Bardia, M.D., MPH, Attending Physician, Massachusetts General Hospital Cancer Center,
and Assistant Professor, Harvard Medical School
Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that tends to affect young patients and is associated with high risk of recurrence and mortality. Currently, there is no FDA-approved targeted therapy for TNBC.
Consequently, there is considerable interest in identification of potentially actionable molecular alterations in TNBC, including potential targets for antibody drug conjugates (ADCs). In this talk, we will review the current landscape
of ADCs for treatment of triple negative breast cancer, as well as future directions.
09:05 HuMax-AXL-ADC, a Novel Antibody-Drug Conjugate for the Treatment of Solid Cancers
Esther Breij, Ph.D., Associate Director, Antibody Science, Genmab BV
Axl is aberrantly expressed in solid cancers, and expression has been associated with poor prognosis and resistance to therapy. HuMax-AXL-ADC, a novel antibody-drug conjugate that targets Axl-positive cancers, showed promising anti-tumor
activity in a variety of solid cancer xenograft models. Moreover, HuMax-AXL-ADC showed cytotoxic activity in solid cancer models that showed enhanced Axl expression upon acquired resistance to kinase inhibitors.
09:35 Problem-Solving Breakout Discussions (View All Breakout Discussions)
New Bioconjugaion Technologies
Moderator: Chawita (Jelly) Netirojjanakul, Ph.D., Scientist, Hybrid Modality Engineering Group, Therapeutic Discovery Research, Amgen, Inc.
- Site-specific vs non-site-specific conjugation technologies: what’s new?
- Yield improvement and manufacturability
- Therapeutic and other commercial applications of bioconjugates
Effect of Immunogenicity on ADC Efficacy
Moderator: Ronit Mazor, Ph.D., Post-Doctoral Fellow, Lab for Molecular Biology, National Cancer Institute (NCI/NIH)
- Effect of the Payload on immunogenicity
- Effect of the target
- Effect of the combination of ADC with checkpoint inhibitor drug on immunogenicity of the ADC
- What we can do to prevent immunogenicity during early pre-clinical stages
10:35 Coffee Break in the Exhibit Hall with Poster Viewing
11:15 Abdurin-Drug Conjugates: Small Size and Long Half-life to Improve Drug Concentration in the Target Tissue
Silvia Peretti, Ph.D., Senior Research Scientist, Biochemistry, IRBM Science Park SpA
Abdurins are a novel antibody-like scaffold that can be engineered to bind to targets of interest and, due to an FcRn binding motif within the scaffold, Abdurins have a circulating half-life longer than any other protein scaffold of similar
size. We have isolated high-affinity Abdurin binders to a number of cancer targets and engineered various attachment sites for drug conjugation. Abdurin-drug conjugates retained high affinity binding to their targets and FcRn, killed
cells with low nM to pM IC50’s, and had in vivo half-life up to 70 hours for certain conjugates. This presentation will contain data for both Abdurin-drug conjugates and Abdurin-SarcinDI fusions.
11:45 Fragment (Antibody) Drug Conjugates (FDCs): A Unique Drug Class of Just Smaller ADCs?
Mahendra Deonarain, Ph.D., CSO, Antikor Biopharma, Ltd.
- FDCs can carry more payload than ADCs whilst retaining excellent pharmacodynamic and pharmacokinetics properties
- FDCs are better tolerated than ADCs carrying equivalent payloads
- FDCs show promise as a new drug class for oncology therapeutics.
12:15 Utilizing RESPECT™ (REsidue-SPEcific Conjugation Technology) for the Generation of Homogeneous Antibody-Drug Conjugates
Jared Spidel, Ph.D., Principal Scientist Antibody, Core Development, Morphotek, Inc.
Morphotek’s REsidue SPEcific Conjugation Technology (RESPECT™) is a transglutaminase-based conjugation technology that targets specific lysine residues in IgG. Whereas other enzymatic-based conjugation techniques require extensive
antibody modification by either deglycosylation or addition of multiple-amino acid enzyme-recognition tags, RESPECT™ requires just a single amino acid addition or substitution to efficiently produce homogeneous site-specific
antibody conjugates.
12:45 Luncheon Presentation: Abcam’s Custom Services Capabilities – from Development to Commercialization
Joyce L. Young, Ph.D., Vice President, Custom Services Division, Abcam
In this talk, we will discuss Abcam’s three antibody development platforms (recombinant RabMAb®, Next Gen Sequencing, and phage display), which offer a comprehensive approach to developing antibodies against challenging targets.
We partner with biopharma and diagnostic companies to develop antibodies as key reagents in drug discovery, in vitro diagnostics and therapeutics.
13:15 Session Break
13:30 Dessert Break in the Exhibit Hall with Poster Viewing
14:00 Chairperson’s Remarks
Ronit Mazor, Ph.D., Post-Doctoral Fellow, Lab for Molecular Biology, National Cancer Institute (NIH)
14:05 KEYNOTE PRESENTATION:
IMGN632: A CD123-Targeting Antibody-Drug Conjugate (ADC) with a Novel DNA-Alkylating Payload
Jan Pinkas, Ph.D., Executive Director, ImmunoGen, Inc.
• CD123 is an attractive target in hematologic malignancies;
• IMGN632 is an antibody-drug conjugate created by site-specific conjugation to the DNA-alkylating agent, DGN549-C, to the CD123-targeting antibody G4723A;
• CD123-dependent cytotoxicity was demonstrated against a panel of AML cell lines in vitro including cell lines that have poor prognostic markers and against leukemic progenitors from AML patients;
• The concentrations of IMGN632 required to kill leukemic progenitors from healthy donors are at least 100-fold higher than the concentrations needed to kill leukemic progenitors from AML patients; and
• IMGN632 was highly active against a range of sub-cutaneous and disseminated AML tumor xenograft models in mice.
14:35 PBD-ADC Update 2017
Philip Howard, Ph.D., Senior Fellow, MedImmune, Inc. and CSO, Spirogen, Ltd.
Pyrrolobenzodiazepine (PBD) dimers are potent DNA crosslinking agents that have been adapted for use as payloads in antibody drug conjugates (ADCs). A range of PBD payloads has been designed, synthesized and conjugated to antibodies and
currently there are 13 ADCs containing PBD payloads in Phase I, II and III clinical trials. The presentation will provide an update on the development of PBD payloads and their clinical progress.
15:05 HDP-101 – A BCMA-Targeted Amanitin-Based ADC
Christian Breunig, Ph.D., Group Leader, Biomarker & Cell Biology, Heidelberg Pharma 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 around
ATACs includes Amanitin supply, site-specific conjugation, demonstrated safety profile and biomarker. A BCMA-ATAC has been selected based on favorable preclinical data to start the clinical development of the first ATAC.
15:35 Current Status of Clinical Stage Antibody-Drug Conjugates
William R. Strohl, Ph.D., President and Owner, BiStro Biotech Consulting, LLC
Currently there are over 850 different antibody-based drug candidates being tested in clinical trials, approximately 10% of which are antibody drug conjugates (ADCs). ADCs represent the second largest group of non-traditional naked
IgG-based antibody drug candidates, behind the category of antibody-based chimeric antigen receptor (CAR)-T cells, but ahead of bispecific antibodies. ADCs make up about 16% of all anti-cancer antibody-based drug candidates. ADCs
being studied in clinical trials currently target over 50 different cell surface antigens, the most popular of which include HER2 and CD19 (with 4 ADCs targeting each), and CD22, CD33, and mesothelin (3 ADCs targeting each). The
ADC field is rapidly maturing, and with the “rules” for design and use of ADCs currently being elucidated, it is expected that ADCs will play a significant, and perhaps expanded, role in cancer therapy in the future.
16:05 Refreshment Break in the Exhibit Hall with Poster Viewing
16:45 Anthracycline-Based Antibody-Drug Conjugates with Potent Immune-Stimulatory Functions
Roger R. Beerli, Ph.D., CSO, NBE-Therapeutics, Ltd.
We employed enzymatic, site-specific conjugation to generate homogenous ADCs based on a derivative of the highly potent anthracycline toxin PNU-159682 and a non-cleavable peptide linker, using the anti-HER-2 antibody trastuzumab
(part of trastuzumab emtansine) and the anti-CD30 antibody cAC10 (part of brentuximab vedotin). Characterization of the resulting ADCs in vitro and in vivo showed that they were highly stable and exhibited potencies exceeding those of ADCs based on conventional tubulin-targeting payloads.
17:15 Immunotoxins with Low Immunogenicity for Cancer Therapy
Ronit Mazor, Ph.D., Post-Doctoral Fellow, Lab for Molecular Biology, National Cancer Institute
(NIH)
Recombinant Immunotoxins (RITs) are a genetically engineered category of ADC that was developed in our lab to treat cancer. Because they contain a bacterial toxin that kills the cancer cells, RITs are very immunogenic to cancer
patients with a normal immune system. This talk will discuss the clinical results achieved so far, and methods we used to make next-generation immunotoxins by identifying and eliminating of T cell epitopes. Furthermore, we
will describe a novel approach to induce immunological tolerance that allows multiple treatment cycles.
17:45 Novel Calicheamicin Antibody-Drug Conjugates
Julia Gavrilyuk, Ph.D., Principal Scientist, Discovery Chemistry, AbbVie Stemcentrx
Calicheamicin has a long history as an ADC payload, yet only one linker-drug design has been utilized for clinical ADCs. Design of the novel stable linkers for calicheamicin payload may lead to the calicheamicing ADCs with improved
efficacy and safety profile. I will present lessons learned in design and optimization of novel calicheamicin-based ADCs. I will also discuss the influence of the linker stability on ADC cytotoxicity
in vitro, and efficacy and tolerability in vivo.
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