One of the leading areas of antibody research is bispecific antibodies. The Seventh Annual Advancing Bispecific Antibodies and Combination Therapy to the Clinic conference will review recent preclinical and clinical results on a variety
of bispecific and multi-specific constructs. Thought leaders in the community will review progress and discuss the best strategies for improving targeting, safety and efficacy for applications in immuno-oncology, oncology, CNS and infectious disease.
Final Agenda
Scientific Advisory Board
Frank Comer, PhD, Senior Scientist, AstraZeneca
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, AstraZeneca
WEDNESDAY, APRIL 10
7:15 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
7:25 - 8:25 PANEL DISCUSSION: Women in Science – Inspired Professional and Personal Stories (Continental breakfast provided) (Waterfront 1&2)
Moderator:
Jennifer S. Chadwick, PhD, Director of Biologic Development, BioAnalytix, Inc.; Co-Chair, Mentors Advisors and Peers Program, Women In Bio, Boston Chapter
Panelists:
Joanna Brewer, PhD, Vice President, Platform Technologies, AdaptImmune
Charlotte A. Russell, MD, DMSc, CMO, Alligator Bioscience
Susan Richards, PhD, Presidential Scientific Fellow, Translational Medicine Early Development, Sanofi R&D
Kristi Sarno, Senior Director, Business Development, Pfenex
8:30 Chairperson’s Opening Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, AstraZeneca
8:40 Bringing the Tumor-Directed CTLA-4 x OX40 Bispecific Antibody, ATOR-1015, into the Clinic
Charlotte Russell, MD, PhD, CMO, Alligator Bioscience AB
ATOR-1015 is a bispecific antibody targeting CTLA-4 and OX40, designed as a next-generation CTLA-4 antibody with improved benefit-risk profile. The dual targeting directs the effect to the tumor area, allowing ATOR-1015 to induce enhanced anti-tumor
effects with expected lower systemic toxicity compared to CTLA-4 monotherapy. The mode-of-action is a combination of effector T-cell activation and regulatory T cell depletion. ATOR-1015 is planned to enter clinical phase in 2018.
9:10 Design Meets Biology – Engineering a PD-1/CTLA-4 Bispecific Antibody to Improve Both Safety and Efficacy
Yariv Mazor, PhD, Senior Scientist, Antibody Discovery & Protein Engineering, AstraZeneca
MEDI5752 is a monovalent bispecific IgG1 antibody (DuetMab), targeting the two clinically validated receptors, PD-1 and CTLA-4. The bispecific antibody introduces novel MOAs that may provide an improved therapeutic index when compared to the two monotherapies
and mAb combinations. MEDI5752 is currently being clinically evaluated for safety and efficacy.
9:40 A Versatile Modular Bispecific Antibody Platform, BiXAb, for the Development of Innovative Therapeutics
Eugene Zhukovsky, PhD, CSO, Biomunex Pharmaceuticals
BiXAb platform has a tetra-Fab IgG1 antibody structure and enables plug-and-play bispecific antibody formatting from any pair of monospecific mAbs. BiXAb antibodies possess excellent manufacturability in CHO cells and superior drug-like properties
(stability, lack of aggregation, predictable PK). We will illustrate the properties of this bispecific antibody platform by presenting two case studies, in which BiXAbs target either solid tumors or hematological malignancies.
10:10 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
10:15 Women in Science Speed Networking in the Exhibit Hall (Commonwealth Hall)
10:55 KEYNOTE PRESENTATION: The Need for More Effective Combination Therapies
Ronald Herbst, PhD, Vice President and Head, Oncology Research, AstraZeneca
Combination approaches are key to improving clinical response. From preclinical immune-oncology mouse models to patients enrolled in clinical trials, novel high throughput technologies enable us to understand the mechanisms underlying the complex
interactions between the immune system and cancer, identify predictive biomarkers for the patients who will most likely benefit from current immunotherapies, avoid immune-related adverse events, and guide the future combination cancer immunotherapy.
11:25 Bispecific Antibodies for Cancer-Directed Blockade of the PD-1/PD-L1 Immune Checkpoint
Prof. Dr. Wijnand Helfrich, Professor of Translational Surgical Oncology, Department of Surgery, University Medical Center Groningen
On-target/off-tumor activity of current PD-L1-blocking antibodies potentially reduces tumor accretion and promotes autoimmune-related toxicity. Therefore, we constructed human bispecific antibody (bsAb) PD-L1xEGFR which simultaneously binds to
PD-L1 and EGFR resulting in enhanced avidity towards PD-L1+/EGFR+ cancer cells. Importantly, PD-L1xEGFR blocks PD-1/PD-L1 interaction in an EGFR-directed manner, blocks oncogenic EGFR-signaling, and promotes ADCC of EGFR+ tumor cells. BsAb
PD-L1xEGFR may be useful to enhance selectivity, efficacy and safety of PD-1/PD-L1 checkpoint inhibition.
11:55 Development of Novel Fully Human Bispecific Antibodies for Oncology
Eric Smith, PhD, Director, Bispecifics, Regeneron Pharmaceuticals
This presentation will describe Regeneron’s bispecific platform and present pre-clinical data on several new bispecifics being developed for solid and liquid tumor indications. In addition, status updates on Regeneron’s clinical stage
bispecific antibodies (REGN1979, REGN4018, and REGN5458) will be presented.
12:25 WuXiBody™, an Innovative and Versatile Bispecific Antibody Format Opens a New Era for Therapeutic Antibody Development
Jing Li, Senior Vice President, Discovery, WuXi Biologics
Bispecific antibodies are a growing area of biotherapeutics but with many development challenges. Many of the new platforms have limitations in yield, purity, stability, solubility, half-life, and immunogenicity. Thus, a one-size-fit-all
solution is still desired. Aiming to solve those issues, WuXi Biologics has generated WuXiBodyTM, a flexible, proprietary bispecific antibody format that can reduce the development time by 6 -18 months and can decrease cost
of goods by 90%.
12:55 Luncheon Presentation I: CANscript™: A Phenotypic-Based, Tumor Modeling Platform for Drug Discovery and Development
Mark Paris, PhD, Associate Director, Translational Application, Mitra Biotech
Delineation of an intra-tumor microenvironment in a dynamic spatio-temporal setting is required owing to its clinical relevance in many cancer indications. Majority of solid cancers represent a highly complex tumor microenvironment wherein a dysregulated
phenotypic context impacts treatment outcomes at a personalized level. We have developed and validated an ex-vivo platform technology (CANscript™) using patient material (tumor, autologous ligands and immune cells) to predict tumor efficacy
in the clinic across several drug classes.
1:25 Luncheon Presentation II: Design and Development of Innovative Bispecific Antibodies
Timothy Xia, PhD,
Vice President, Biologic Discovery & Development, GenScript, Inc.
Liusong Yin, PhD, Director, Antibody Drug Discovery, GenScript, Inc.
1:55 Session Break
2:10 Chairperson’s Remarks
Rakesh Dixit, PhD, DABT, Vice President, R&D, Global Head, Biologics Safety Assessment, Translational Sciences, AstraZeneca
2:15 Preclinical and Clinical Development of Best-in-Class Anti-HER2 Bispecifics and Bispecific ADCs
Tony Polverino, PhD, Executive Vice President of Early Development and CSO, Zymeworks, Inc.
ZW25 is a bispecific antibody directed against two distinct epitopes (biparatopic) on HER2 that has been successfully engineered using the Azymetric™ IgG1 antibody scaffold. In clinical studies, ZW25 is well tolerated and has demonstrated
promising single-agent anti-tumor activity in heavily pretreated HER2-expressing breast, gastric, and other cancers. Preclinical development of ZW49, a biparatopic antibody-drug conjugate based on the unique design of ZW25 and armed with our
proprietary ZymeLink™ cytotoxic payload, will also be discussed.
2:45 Development of a Novel T-Cell Engager Platform Based on DARPin® Molecules
Sebastian
Grimm, PhD, Senior Scientist, Lead Generation, Molecular Partners AG
T-cell-engaging therapies have shown high therapeutic efficacy in hematological malignancies and promising early clinical data in solid tumors. Favorable biophysical properties and high format flexibility enable T-cell engager formats that may
address limitations of current engagers in the clinic, such as tumor selectivity or antigen coverage. We have developed a flexible T-cell engager platform based on Designed Ankyrin Repeat Proteins binding to human CD3. The characterization
of different multispecific formats with tailored serum half-life will be presented.
3:15 Highlighted Poster Presentation: Efficient in vivo Tumor Clearance and Minimal Cytokine Release with a Novel T-Cell Engaging Bispecific Antibody Platform
Nathan D. Trinklein, PhD, CTO, TeneoBio Inc.
3:45 Refreshment Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
4:45 Problem-Solving Breakout Discussions - Click here for details(Commonwealth Hall)
5:45 Networking Reception in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
7:00 End of Day
THURSDAY, APRIL 11
8:00 am Registration (Commonwealth Hall) and Morning Coffee (Harbor Level)
8:30 Chairperson’s Remarks
Frank Comer, PhD, Senior Scientist, AstraZeneca
8:35 KEYNOTE PRESENTATION: Overview of Bispecific Antibodies
Roland Kontermann, PhD, Professor, Biomedical Engineering, Institute of Cell Biology and Immunology, University of Stuttgart
Bispecific antibodies have experienced a dramatic interest and growth for therapeutic applications, with more than 70 molecules in clinical development, e.g. in oncology, immuno-oncology, but also for non-oncology applications. An overview will
be given on the making of bispecific antibodies and the various therapeutic concepts and applications, e.g. for dual targeting strategies, retargeting of immune effector cells, and substitution therapy by mimicking the function of natural
proteins.
9:05 M7824, a Novel Therapeutic Inhibiting PDL1 and Sequestering TGF-Beta
James L. Gulley, MD, PhD, FACP, Chief, Genitourinary Malignancies Branch, Head, Immunotherapy Group, GMB Director, Medical Oncology Service, Center for Cancer Research, NCI, NIH
M7824 is a first-in-class bifunctional fusion protein composed of a TGFβ trap fused to an anti-PD-L1 antibody. A first-in-human dose escalation study demonstrated safety, saturation of peripheral PD-L1 and sequestration of all released plasma
TGFβ1, -β2, and -β3 throughout the dosing period at doses >1 mg/kg. M7824 1200 mg IV has been tested in multiple cohorts including in HPV-associated cancers (ORR 35%) and NSCLC (ORR 28% with ORR 41% in patients with ≥1%
of tumor cells PDL1+).
9:35 Highlighted Poster Presentation: CB307, a Novel T-Cell Costimulatory Humabody Therapeutic for PSMA-Positive Tumours
Brian McGuinness, PhD, MBA, Senior Director, Business Development, Crescendo Biologics Ltd.
10:05 Coffee Break in the Exhibit Hall with Poster Viewing (Commonwealth Hall)
11:05 A Highly Efficacious Antibody Mixture against MET-Dependent Tumors
Thomas Tuxen Poulsen, PhD, Principal Scientist, Symphogen A/S
Activation of the receptor tyrosine kinase MET is associated with poor clinical outcome in certain cancers. To target MET more effectively, we developed the antagonistic antibody mixture Sym015 consisting of two humanized antibodies directed against
non-overlapping epitopes of MET. Sym015 is well tolerated and strongly inhibits growth of MET-dependent preclinical tumor models. An ongoing clinical trial of Sym015 demonstrates promising signals of clinical activity in a subset of MET-dependent
patients.
11:35 Engineering Bispecific Antibodies for Specific Targeting of Tumor Cells
Rajkumar Ganesan, PhD, Director, Antibody Engineering, Janssen Biotherapeutics
Bispecific antibodies can redirect immune cells such as natural killer cells or cytotoxic T cells to lyse tumor cells by releasing the pro-apoptotic agents. Excessive levels of released cytokines can lead to a series of immune-related adverse
events. To circumvent toxicity issues, we adopted several design strategies such as modulation of binding affinity, geometry and valency to engineer bispecifics antibodies to discriminate healthy versus tumor cells.
12:05 pm Oncolytic Vaccines to Augment BiTE Efficacy against Solid Tumors
Christine E. Engeland, MD, PhD, Head of Laboratory, Virotherapy, National Center for Tumor Diseases
Challenges in treating solid tumors with bispecific antibodies include increasing response rates and decreasing toxicity. We have developed tumor-selective oncolytic vectors for delivery of immunomodulators to avoid systemic exposure and mitigate
toxicity. Furthermore, vector-mediated oncolysis serves as an in situ tumor vaccine, inducing synergistic anti-tumor immune responses. This talk highlights the versatility of our vector system and avenues
for clinical translation.
12:35 End of Advancing Bispecific Antibodies and Combination Therapy to the Clinic