Cambridge Healthtech Institute’s Bispecific Antibody Therapeutics conference explores the challenges of engineering multi-specificity to achieve more effective therapies that bind to at least two molecular targets simultaneously.
These next-generation antibody formats are showing efficacy in the efforts to conquer cancer and other diseases. Case studies will highlight novel engineering approaches that address safety, stability, enhanced targeting, and manufacturability, as
the conference examines current developments, and future directions for these promising molecules.
THURSDAY, JANUARY 11
7:45 am Registration and Morning Coffee
8:15 Chairperson’s Opening Remarks
David E. Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc.
8:20 The Rise of Bispecific Antibodies as Drugs
Paul J. Carter, Ph.D., Staff Scientist and Senior Director, Antibody Engineering, Genentech,
Bispecific antibodies are emerging as drugs with two such molecules approved for human therapy and over 50 more in clinical development. We developed a robust method for production of bispecific IgG in single mammalian host cells to support the clinical
development of these complex hetero-tetrameric molecules. Additionally, we established high-resolution mass spectrometry methods to facilitate the characterization and quantitation of bispecific antibodies and other complex biologics.
9:00 Examples of Development Strategies for Next-Generation Therapeutics
Nicola Beaucamp, Ph.D., Head, Process Research, Pharma Research and Early Development,
Roche Innovation Center Munich, Roche Diagnostics GmbH
A number of novel antibody formats have been advanced into the clinic by Roche pRED. In order to discover and develop differentiated monoclonal antibodies, Roche’s strategy is based on engineering technologies which bear several challenges for
technical development. Examples will be presented on how the development processes were adapted to deliver these new format molecules in the best quality and quantity for clinical studies.
9:30 Engineering IgM CH2 Domain as a Versatile Building Block for the Construction of Various Multi-Specific Antibodies
Jijie Gu, Ph.D., Research Fellow and Function Head, Immunology Discovery, AbbVie Bioresearch Center
Multi-specific antibodies hold great promise as one of the approaches for developing next generation antibody-based therapeutics. We engineered IgM2 CH2 domain from a homodimeric domain to a CH1/CK like heterodimeric domain. Engineered IgM CH2 domain
can be used as a versatile building block for the construction of various multi-specific antibody formats to enable various novel therapeutic concepts.
10:00 Coffee Break in the Exhibit Hall with Poster Viewing
11:00 Tailoring Processing of Amyloid Precursor Protein as a Therapeutic for Alzheimer’s Disease
Michael Sierks, Ph.D., Professor, Chemical Engineering, Arizona State University
Generation of beta-amyloid from the amyloid precursor protein is a key step in the progression of Alzheimer’s disease. We have designed a bispecific antibody that inhibits toxic amyloidogenic processing of the amyloid precursor protein while
simultaneously catalyzing formation of a neuroprotective fragment. We show that the bispecific antibody provides excellent therapeutic benefit in a mouse model of AD.
11:30 Design and Evaluation of Next-Generation Biologics for Cancer Immunotherapy
Christopher Smith, Ph.D., Senior Scientific Consultant, Biologics,
Bi- and multi-specific antibodies, Ab-cytokine fusion proteins, non-Ig scaffolds, chimeric antigen receptors (CARs), engineered TCRs and TCR-based bispecific constructs can provide significant advantages for use in cancer immunotherapy. However,
as highly engineered molecules they pose new design, engineering, cloning, expression, purification, and analytics challenges. Genedata Biologics enables the automated design, screening, production, and testing of large panels of these
candidate therapeutic molecules and includes built-in tools for developability and manufacturability assessments.
12:00 pm Enjoy Lunch on Your Own
1:15 Ice Cream Break in the Exhibit Hall with Poster Viewing
2:00 Chairperson’s Remarks
Eric Smith, Ph.D., Director, Bispecific Antibdies, Regeneron Pharmaceuticals, Inc.
2:05 Non-Engineered Multi-Specific Antibodies
Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA
The κλ body continues to embody an innovative design to incorporate multi-specificity into a human framework devoid of any mutation, foreign sequences or linkers. κλ bodies exploit light chain diversity, conferring
different specificities into >1500 targeting arms directed against >15 targets. The format’s simplicity makes manufacturing from research to clinical easily scalable and ensures high purity and stability. The first κλ
bodies are designed to exploit the innate immune checkpoint, CD47, safely yet effectively, by targeting phagocytosis of cancer cells specifically to B cell malignancies and solid tumors.
2:35 Bispecific Antibodies for Dual Immune Checkpoint Blockade
David E. Szymkowski, Ph.D., Vice President, Cell Biology, Xencor, Inc.
Combinations of checkpoint-blocking antibodies are more efficacious then single inhibitors, but generate greater immune-related toxicities. We reasoned that a bispecific antibody could achieve dual blockade to selectively target tumor-reactive
lymphocytes, improving safety and efficacy. We generated multiple dual-checkpoint inhibitors including XmAb20717 (anti-PD1 x anti-CTLA4) that display compelling in vivo activity relative to combinations
of monospecific antibodies, suggesting that checkpoint bispecifics may have clinical advantages for the treatment of cancer.
View the Interview
3:05 SELECTED POSTER PRESENTATION:
COBRA (Conditional Bispecific Re-Directed Activation) Platform of Protein Therapeutics for Cancer Treatment
Maia Vinogradova, Ph.D., Director, Protein Sciences, Maverick Therapeutics
COBRA platform allows to design bispecific T-cell engaging protein therapeutics with a reduced risk of potential on-target cytotoxicity. COBRAs are multidomain proteins comprising the familiar scaffolds of the antibody repertoire, but not of the immunoglobulin type. We demonstrated the conditional protease dependent activity of our molecules in proof-of-concept T-cell dependent cytotoxicity assays.
3:35 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Development of T Cell Redirecting Fully Human Bispecific Antibodies
Eric Smith, Ph.D., Director, Bispecific Antibodies, Regeneron Pharmaceuticals,
This presentation will describe Regeneron’s bispecific platform and present preclinical data on T cell redirecting bispecifics being developed for solid tumor indications. In addition, a brief update on the status of REGN1979,
Regeneron’s CD20xCD3 bispecific in Phase I clinical trials, will be presented.
4:45 Co-Stimulation of Immune Cells in the Tumor Microenvironment via Bispecific DART and TRIDENT Molecules
Gundo Diedrich, Ph.D., Associate Director, Antibody Engineering,
Targeting costimulatory receptors on immune cells with agonistic antibodies is a promising strategy in cancer therapy. To limit the immune activity to tumors, while sparing effects on normal tissue, we generated bispecific DART and
TRIDENT molecules targeting several tumor antigens together with the costimulatory receptor, CD137. T cell agonistic activity by these molecules was strictly dependent on the expression of the tumor antigens. Preclinical development
of these proteins will be addressed.
5:15 The Benefits of Bispecific mAb2 Antibodies Targeting EGFR and HGF
Kin-Mei Leung, Ph.D., Principal Scientist, Drug Discovery, F-star Biotechnology, Ltd.
F-star’s Modular Antibody TechnologyTM platform was utilized to generate bispecific molecules that bind to Epidermal Growth Factor Receptor (EGFR) and Hepatocyte Growth Factor (HGF). The EGFR/HGF mAb2 inhibit cell proliferation
in vitro and show anti-tumor activity in patient-derived xenograft (PDX) models in vivo. The mAb2 molecules show superior inhibition of tumor growth compared to
combination treatments in tumors with specific molecular profiles suggesting novel biology of the bispecific.
5:45 Close of Day
FRIDAY, JANUARY 12
8:00 am Registration
8:00 BuzZ Sessions with Continental Breakfast
Protein therapeutics is a fast-growing global market. As the science improves, so does the complexity of the R&D organization. Ensuring product quality plus speed to market requires insights from stakeholders working across
the stages of protein science R&D. Join experts representing this PepTalk pipeline, peers, and colleagues for an interactive roundtable discussion. Topics include highlights from the week’s presentations, new technologies
and strategies, challenges, and future trends.
Table Moderator: Nicola Beaucamp, Ph.D., Head, Process Research, Pharma Research and Early Development, Roche Innovation Center Munich, Roche Diagnostics GmbH
9:30 Chairperson’s Remarks
Marie Kosco-Vilbois, Ph.D., CSO, NovImmune SA
9:35 Identification and Quantitation of DuoBody Bispecific IgG1 Using Mass Spectrometry and Automated Data Processing and Analysis Workflow
Ewald Van den Bremer, Ph.D., Senior Scientist,
The characterization of bispecific antibodies (BsAbs) by mass spectrometry (MS) offers several advantages over traditional chromatographic techniques (e.g. HIC, CEX). MS provides unambiguous identification and relevant quantitative
information, and combined with automated data processing and analysis, it can be employed in a high-throughput environment. We present a software solution and the related workflows that enabled us to accelerate BsAb research
batch characterization and release, achieving high quality results and significant time and cost savings.
10:05 From the Bench to the Clinic: Developing Next-Generation ADAPTIR Molecules
David Bienvenue, Ph.D., Senior Director, Protein Sciences,
The presentation will highlight the activity, stability and manufacturability of ADAPTIR bispecifics and will include recent data for a lead preclinical candidate, APVO436, which targets CD123 and CD3. APVO436 has shown potent
biological activity in preclinical studies and is rapidly advancing towards first-in-human clinical trials.
10:35 Coffee Break with a Poster Pavilion
PepTalk is proud to support and recognize the protein scientists of tomorrow during the Poster Pavilion. This time has been set aside to view the Student Fellowship posters and interact with presenters one on one. This opportunity
gives job seekers the chance to share their expertise with future/potential employers or develop contacts to further their research.
11:15 An IgM-Based Bispecific Platform for Enhanced T Cell and Complement Dependent Cytotoxicity on Low Antigen Expressing Cells
Ramesh Baliga, Ph.D., Vice President, Discovery Biology, IGM
IGM Biosciences has built a unique bispecific platform based on a CD3 epsilon binding single chain Fv domain fused to the IgM joining chain. Our CD20 targeted IgM bispecific antibody IGM-2323 binds CD20 antigen greater than
1000X better, and shows functional effects such as CDC greater than 100X better than corresponding IgG’s. Moreover, it shows T cell dependent cytotoxicity even on cells with very low cell surface expression of CD20
11:45 A Novel Trifunctional Antibody Combining PD-1/PD-L1 Blockade and Targeting of a Tumor-Specific Carbohydrate Antigen
Christoph Goletz, Associate Director, Immunomodulation,
We developed a trifunctional antibody combining PD-1/PD-L1 blocking and highly tumor-specific targeting via the novel protein/carbohydrate mixed epitope TA-MUC1 with a functional Fc part in one molecule. By focusing the checkpoint
blockade to the tumor and combining multiple modes of action, that antibody has the potential to increase efficacy and broaden the patient coverage giving additional benefit compared to the respective monospecific antibody.
12:15 pm Conference Wrap-Up
Nicola Beaucamp, Ph.D., Head, Process Research, Pharma Research and Early Development, Roche Innovation Center Munich, Roche Diagnostics GmbH
12:45 Close of Conference