PepTalk 2017
PepTalk 2017
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Cambridge Healthtech Institute’s Fourth Annual
Enhancing Antibody Binding and Specificity
Scientific Strategies for Engineering Biotherapeutic Binding and Specificity
for Next-Generation Antibody Therapeutics

January 10-11, 2017 | Hilton San Diego Bayfront | San Diego, CA


As the industry expands its repertoire of antibody drug products into new therapeutic areas, product formats and protein constructs, the control of antibody/antigen targeting, binding and specificity will take on a new level of importance for researchers in this field. The second meeting in the Peptalk Protein Engineering & Development pipeline, Enhancing Antibody Binding and Specificity, presents innovative approaches to the modulation of binding activity, mechanism of action and difficult target challenges such as transmembrane proteins and intracellular targeting.

TUESDAY, JANUARY 10

1:00 pm Conference Registration

1:30 Refreshment Break in the Exhibit Hall with Poster Viewing

2:00 Chairperson’s Opening Remarks

Javier Chaparro-Riggers, Ph.D., Director, Antibody Technology, Pfizer


Keynote Presentation

2:05 Antibody Generation and Selection: A Very Different Fetal Life

Eric_MeffreEric R.F. Meffre, Ph.D., Associate Professor, Immunobiology, Yale University School of Medicine

By studying the B cell selection in human fetuses, we found that central B cell tolerance is already active in both fetal liver and fetal bone marrow. But peripheral B cell tolerance checkpoint was not yet functional in 3-4 month old fetuses that virtually lacked T cells. Fetal restricted V(D)J recombination may play an important role in restraining autoimmunity in the absence of a peripheral B cell tolerance checkpoint.

ANALYTICAL METHODS

2:45 Toward an Integrated Biosensor Platform to Support Biotherapeutic Discovery

Kerry_KelleherKerry Kelleher, MS, MSCIS, Senior Principal Scientist, Biomedicines Design, Pfizer

We have established an integrated, complementary set of biosensor platforms to enable the efficient selection of lead antibody candidates. This presentation will highlight examples using parallel processing of the OctetRED384 to expedite epitope binning and off-rate ranking; high throughput Biacore 4000 to facilitate screening hundreds of antibody candidates; Biacore T200 to provide flexibility, sensitivity, and accuracy; and KinExA to determine solution equilibrium KDs of ultra-high affinity leads.

3:15 Sponsored Presentation (Opportunity Available)

3:45 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 KinExA vs. SPR and ELISa Binding Characterization

Alexander Ivanov, Ph.D., Senior Scientist, Global Biologics, AbbVie Bioresearch Center

5:00 Epitope Binning and Characterization at the Early Stages of Therapeutic Antibody Discovery

Sam_WuSam Wu, Ph.D., Principal Scientist, Biologics Research, Janssen BioTherapeutics

High-throughput epitope binning can be employed with functional activity screens, enabling the rapid identification of leads that exhibit functional epitopes. To characterize the initial panel of phage-derived antibodies, a label-free, array-based SPR imager was performed. The mapping results, together with relative affinity and functional activities, allowed the selection of lead candidates for testing in vivo. Data suggests that affinity and killing capacity are correlated, but epitope determines killing capacity.

5:30 Close of Day


5:30 - 5:45 Short Course Registration

5:45 - 8:45 Dinner Short Courses*

* Separate registration required

WEDNESDAY, JANUARY 11

8:00 am Conference Registration and Morning Coffee

REGULATING TARGET SELECTIVITY IN BISPECIFIC ANTIBODIES

8:30 Chairperson’s Remarks

David A. Scheinberg, M.D., Ph.D., Vincent Astor Chair and Chairman, Molecular Pharmacology Program, Sloan Kettering Institute

8:35 Optimizing T-Cell Engaging Full Length Bispecific Antibodies

Javier_Chaparro-RiggersJavier Chaparro-Riggers, Ph.D., Director, Antibody Technology, Pfizer

Pfizer developed a T-cell engaging antibody platform, which allows the formation of full length human IgG1 and IgG2 antibodies in vitro or in vivo. The effect of IgG isotype and affinities of the T-cell- and tumor antigen-targeting arm were explored and optimized.

9:05 Enhancing Tumor-Targeting Selectivity by Modulating Bispecific Antibody’s Binding Affinity and Format Valence

Yariv_MazorYariv Mazor, Ph.D., Senior Scientist, Antibody Discovery & Protein Engineering, MedImmune LLC

Dual targeting is believed to enhance biological efficacy, limit escape mechanisms, and increase target selectivity via a strong avidity effect mediated by concurrent binding of the bsAb to both antigens on the surface of the same cell. However, factors that regulate the extent of target selectivity are not well understood and are often overlooked. We show that dual targeting alone is not sufficient to promote efficient target selectivity and report the pivotal role played by the intrinsic affinity of the individual arms, overall avidity and format valence.

9:35 Sponsored Presentation (Opportunity Available)

10:05 Coffee Break in the Exhibit Hall with Poster Viewing

INTRACELLULAR TARGETS

10:50 Targeting Undruggable Proteins with Antibodies

David_ScheinbergDavid A. Scheinberg, M.D., Ph.D., Vincent Astor Chair and Chairman, Molecular Pharmacology Program, Sloan Kettering Institute

Many important mutated or oncogenic proteins are not expressed on the cell surface, nor are these proteins druggable by small molecules. TCR mimic mAb (TCRm) can bind to peptides from intracellular targets in the context of HLA on the cell surface, even at extremely low density. Such TCRm mAb are effective in preclinical models of cancer. Issues related to efficacy, pharmacology, toxicity, and resistance to these approaches will be discussed.

11:20 Intracellular Targets for Cancer Immunotherapy

Bryan Zimdahl, Ph.D., Research Scientist, Preclinical Development, Eureka Therapeutics, Inc.

Chimeric antigen receptor (CAR) T-cell therapies for solid tumors have made little progress. A key challenge facing CAR T therapies for solid tumors is that the majority of specific markers for solid tumors are intracellular/secreted proteins and therefore, inaccessible by conventional antibodies/CARs. We will discuss Eureka’s unique approach to targeting intracellular proteins and demonstrate CAR T-cell therapy can be used to target these proteins for the treatment of solid tumors.

11:50 iTAbs for Therapeutic Regulation of Intracellular Targets

Heehyoung_LeeHeehyoung Lee, Ph.D., Director, Target Discovery and Validatiown, LA Cell, Inc.

Up to now, antibody-based therapies could only reach proteins on the cell surface. However, most disease-causing molecules are located within the cells. To address current unmet clinical needs, LA Cell developed iTAbs, intracellular targeting antibodies which efficiently cross the cell membrane. Using various approaches, the efficacy of iTAbs in binding to the intended targets and in blocking effector pathways was demonstrated, supporting the feasibility of using iTAbs for targeted therapies.

12:20 pm Sponsored Presentation (Opportunity Available)

12:50 Session Break

1:00 Luncheon Presentation I: New Approaches for mAb Discovery against GPCRs, Ion Channels, and Transporters

Joseph Rucker, Ph.D., Vice President, Research & Development, Integral Molecular

To enable the discovery of mAbs against membrane proteins, Integral Molecular has developed the MPS Discovery Engine®. MPS harnesses 15 years of expertise in membrane protein expression and analysis, and proprietary technologies including Lipoparticles for high-concentration membrane protein presentation, Picodroplet technology for microfluidic B-cell screening, and Shotgun Mutagenesis for epitope mapping and mAb optimization. MPS has resulted in mAbs against previously intractable GPCR, ion channel, and transporter targets.

1:30 Luncheon Presentation II (Sponsorship Opportunity Available)

OPTIMIZATION AND CONTROL OF BINDING AND SPECIFICITY

2:00 Chairperson’s Remarks

Tilman Schlothauer, Ph.D., Principal Scientist, Biochemical and Analytical Research, Large Molecule Research, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Penzberg

2:05 In vivo Imaging of Probody™ Activation at the Tumor Site

Olga Vasiljeva, Ph.D., Associate Director, Head, Protease Biology, CytomX Therapeutics

Probody therapeutics are fully recombinant antibody prodrugs that are converted to active antibodies by tumor-associated proteases, thereby minimizing toxicity while maximizing anti-tumor activity. Using NIR optical imaging in combination with antigen or protease activity blocking approaches, activation of Probody therapeutics at the tumor site was demonstrated for multiple programs, supporting the concept of Probody therapeutics for the treatment of cancer.

2:35 Analyzing Specificity and Valency of Antibody Binding by Cell-Free Assays

Tilman_SchlothauerTilman Schlothauer, Ph.D., Principal Scientist, Biochemical and Analytical Research, Large Molecule Research, Roche Pharma Research and Early Development (pRED), Roche Innovation Center Penzberg

Protein-protein interactions can be difficult to evaluate by the classical 1:1 langmuir binding model. Next to the bivalency of wild type IgG scaffolds, the heterogeneity of antibody preparations prevents a meaningful evaluation of surface plasmon resonance data in many cases. An additional difficulty is hidden in the nature of surface-based protein-protein interaction determinations. Here we will show a case study on how to circumvent such problems.

3:05 Highly Efficient Sweeping Antibody Using Novel Engineering Technology

Atsuhiko_MaedaAtsuhiko Maeda, Ph.D., Research Scientist, Pharmaceutical Technology, Chugai Pharmaceutical Co., Ltd.

In this presentation, we will introduce novel sweeping antibody technology that enables highly efficient elimination of soluble antigens from plasma. The novel technology can be applied to various antigens, and these antibodies can efficiently eliminate the antigens from plasma in cynomolgus monkey by >1000-fold compared to conventional antibodies, and allow targeting antigens present in very high concentrations in plasma.

3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

4:30 Achieving Selectivity Using Dual Targeting Bispecific Antibodies

Nicolas_FischerNicolas Fischer, Ph.D., Director, Research, NovImmune SA

Cell surface receptors involved in diseases such as cancer are often also expressed on healthy cells, limiting the therapeutic window of drugs. We have developed a series of bispecific antibodies enabling selective targeting on tumor cells of CD47, a ubiquitously expressed checkpoint molecule. The mode of action relies on co-engagement of two receptors at the cell surface, as well as on different affinities of the two arms of the bispecific antibody.

5:00 Computationally Driven Identification of Antibody Epitopes

Chris_Bailey-KelloggChris Bailey-Kellogg, Ph.D., Professor, Computer Science, Dartmouth College

We have developed an epitope mapping method that, given an antibody sequence, computationally designs and experimentally evaluates targeted mutations to the antigen in order to test predictions of possible antibody binding modes. Retrospective tests, along with prospective application to a tumor cell ligand and binding antibody of unknown binding mode, demonstrate that the method can in general successfully localize an epitope with only a small set of mutagenesis experiments.

Buzz Sessions5:35 BuzZ Session B

Join your peers and colleagues for interactive roundtable discussions.

6:20-7:20 Reception in the Exhibit Hall with Poster Viewing

7:20 Close of Conference