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Key Sessions

Sally Ward, PhD

CLOSING KEYNOTE PRESENTATION: Exploiting the Diverse Functions of FcRn to Generate Therapeutics

University of Southampton and Texas A&M University Health Science Center

Showing of Streams
10:00am - 10:30am

Networking Refreshment Break

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Showing of Streams
12:00pm - 1:25pm

Networking Luncheon

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Showing of Streams
3:30pm - 4:00pm

Networking Refreshment Break

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Showing of Streams
5:15pm - 5:20pm
Close of Conference

Close of Conference

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8:25am - 8:30am 5 mins
Track 1: Antibody Developability
Chairperson's Remarks
  • Karl Dane Wittrup, Ph.D. - C.P. Dubbs Professor, Massachusetts Institute of Technology
8:25am - 8:30am 5 mins
Track 2: Preclinical and Clinical Antibodies in Development
Co-Chairs' Remarks
  • Gregory Adams, PhD - Chief Scientific Officer, Sesen Bio
  • Matthew Robinson, PhD - VP, Research & Development, Immunome, Inc.
8:30am - 9:00am 30 mins
Info
Track 1: Antibody Developability
Establishing Early Developability Screens to Enable Human PK Prediction
  • Laura Lin, PhD - Executive Director, BioMedicine Design, Pfizer Inc.

The presentation will showcase our strategies of applying early stage developability assessment to enable the selection of clinical candidates. In particular, I will focus on efforts to establish in vitro assays that are predictive of human clearance and PK, and will be sharing several examples highlighting the impact of such assessment on lead selection and optimization.

8:30am - 9:00am 30 mins
Info
Track 2: Preclinical and Clinical Antibodies in Development
Preclinical Studies of Targeted Radionuclide Therapy and Radiosensitization Strategies for Cancer Therapy
  • Marika Nestor, PhD - Associate Professor & Head of Research Group, Uppsala University

Targeted radionuclide therapies, including the use of radiolabeled monoclonal antibodies, are gaining importance as anti-cancer treatments. In recent years, new opportunities to utilize molecularly targeted therapies to increase the therapeutic effects of radiotherapy have emerged. Here, we combine the concepts and explore the use of antibodies and peptides for targeted radionuclide therapy and radiosensitization strategies.

9:00am - 9:30am 30 mins
Info
Track 1: Antibody Developability
Physicochemical Determinants of Drug-like Monoclonal Antibodies
  • Peter Tessier, PhD - Albert M. Mattocks Professor of Pharmaceutical Science, University of Michigan

The success of therapeutic drugs is dependent not only on their functional activities but also on their physicochemical properties (e.g., solubility, stability and specificity). We are developing methods for identifying drug-like monoclonal antibodies based on their chemical compositions and biophysical properties. These methods are expected to improve antibody drug development by more reliably identifying antibody candidates with drug-like properties and increased likelihood of success in the clinic.

9:00am - 9:30am 30 mins
Info
Track 2: Preclinical and Clinical Antibodies in Development
IgG Engineering to Mediate the Delivery of Enzymes into the Cytosol of Specific Cells
  • Bradley Pentelute, PhD - Professor, Chemistry, Massachusetts Institute of Technology

Immunoglobulin G (IgG) is currently an important class of therapeutics. Due to its wide application and favorable in vivo properties, there is significant interest in using IgG as a drug carrier. Here we report a bioconjugation method to chemically modify antibodies with the non-toxic 83 kDa protective antigen from anthrax toxin. We found that when protective antigen was conjugated to Trastuzumab or Cetuximab the resulting variant mediated efficient delivery of large enzymes into the cell cytosol in a receptor dependent manner. Further, we showed the antibody-delivered effector protein was able to overcome antibody resistance in multiple cancer cell lines.

9:30am - 10:00am 30 mins
Info
Track 1: Antibody Developability
Biochemical Developability of the Clinical Antibody Landscape
  • Yingda Xu, PhD - Director, Adimab

Isomerization and deamidation of therapeutic leads can often delay development timelines and provide challenge and risks for downstream process.  Sequence based prediction to scan for NG and DG can often lead to false positive results.  Here we report the chemical liability analysis of ~140 clinical stage antibodies, under forced degradation conditions.

9:30am - 10:00am 30 mins
Info
Track 2: Preclinical and Clinical Antibodies in Development
Cancer Therapy Revisited
  • H.Kaspar Binz, Ph.D. - Vice President and Co-Founder, Molecular Partners AG

The DARPin® platform is key in generating novel cancer therapeutics by overcoming classical limitations in oncology. The presentation highlights how we overcome dose-limiting toxicity of immuno-modulating drugs by generating locally restricted immune cell activators, including FAP/4-1BB candidate MP0310. Likewise, we use VEGF/HGF escape pathway blocking in clinical phase II candidate MP0250 to re-sensitize cancer patients to previously failed anti-tumoral therapy.

10:00am - 10:30am 30 mins
Networking Refreshment Break
10:30am - 11:00am 30 mins
Info
Track 1: Antibody Developability
Extensional Flow Induced mAb Aggregation
  • David Brockwell, PhD - Associate Professor, University of Leeds

Protein-based biopharmaceuticals are susceptible to unfolding, mis-folding and aggregation events induced by environmental perturbations that include hydrodynamic flow. Aggregation thus poses an enormous challenge to biopharmaceutical development, production, formulation and storage. To address this problem, we describe the development of a bench-top device to assess candidate manufacturability or process suitability for the manufacture of aggregation-prone biopharmaceuticals.

10:30am - 11:00am 30 mins
Info
Track 2: Preclinical and Clinical Antibodies in Development
Development of a Novel Therapeutic Antibody Drug Conjugate for the Treatment of Autoimmune Disease
  • Michael McPherson, Ph.D. - Principal Research Scientist, In Vitro Technologies and iADCs, Global Biologics

We have developed a plasma stable antibody drug conjugate (ADC) that has steroid molecules linked to an anti-TNF a mAb.  This ADC is targeted to TNF-a expressing inflammatory cells and internalized to cellular lysosomes. We demonstrate that anti-TNF-steroid ADC treatment, after established disease, appears to heal the joints of previously arthritic mice when compared to a group of satellite animals sacrificed 7 days after disease onset.  The tarsal joints from these mice were evaluated using micro computed tomography and by histologic evaluation.  Restoration of normal joint architecture was seen in at least 40% of mice with TNF-steroid ADC treatment that was not seen with either an isotype control ADC or with the anti-TNF mAb alone.  These promising results suggest that a steroid targeted to cells involved in joint destruction via TNF binding has the potential to achieve not only lasting remission but also repair of the arthritic joints in RA patients, while sparing patients from steroid induced side effects.

11:00am - 11:30am 30 mins
Info
Track 1: Antibody Developability
Improving Biotherapeutic Development Through Structured Data Utilization
  • Randal Ketchem, PhD - Vice President of Molecular Design, Just Biotherapeutics

Biotherapeutic development is slow and expensive. Large scale, curated data collection across the therapeutic development pipeline enables predictive modeling and automated decision making, leading to faster development of improved biologics. We explore the challenges of biologics data capture and utilization toward improved biotherapeutic development.

11:00am - 11:30am 30 mins
Info
Track 2: Preclinical and Clinical Antibodies in Development
Design and Preclinical Development of An Anti-CD123 ADC, IMGN632, Which Exhibits Potent and Highly Selective Cytotoxicity to Leukemic Cells
  • Thomas Chittenden, PhD - Executive Director, Pipeline R&D, ImmunoGen


IMGN632 is a novel anti-CD123 ADC incorporating an indolinobenzodiazepine payload that alkylates, but does not cross-link DNA. Of multiple ADC designs evaluated, only IMGN632 demonstrated potent anti-leukemic activity at concentrations 100-fold below those that impact normal cells. The strategy to select an optimal antibody, payload and conjugation method will be discussed for IMGN632, which is currently in a phase I trial for CD123+ heme malignancies.

11:30am - 12:00pm 30 mins
Info
Track 1: Antibody Developability
Proteomics Identifies a CHO Host Cell Protein that May Impact Polysorbate Degradation
  • Kelvin Lee, PhD - Professor of Chemical & Biomolecular Engineering, University of Delaware

There is great interest in a better understanding of difficult to remove host cell proteins. We used proteomics approaches to identify different classes of difficult to remove CHO host cell proteins. One of the proteins that was identified may play a role in polysorbate degradation. We evaluated cell line development strategies to mitigate the expression of this protein and any resulting impact on polysorbate degradation.

11:30am - 12:00pm 30 mins
Info
Track 2: Preclinical and Clinical Antibodies in Development
Preliminary Results of VISTA: A Phase 3 Study of Vicinium in Subjects with High Grade Non-Muscle Invasive Bladder Cancer (NMIBC)
  • Gregory Adams, PhD - Chief Scientific Officer, Sesen Bio

Vicinium, an anti-EpCAM scFv/Pseudomonas Exotoxin A fusion protein, is in development for the local-regional treatment of EpCAM over expressing carcinomas. A registrational phase 3 study of Vicinium for the treatment of NMIBC recently completed enrollment and preliminary 3 month efficacy and safety data will be discussed.

12:00pm - 1:25pm 85 mins
Networking Luncheon
1:25pm - 1:30pm 5 mins
Track 1:Innovating Antibody Therapeutics
Chairman's Remarks
  • Paul Carter, PhD - Senior Director and Staff Scientist , Antibody Engineering, Genentech, Inc.
  • James Larrick, M.D., Ph.D. - Managing Director and Chief Medical Officer , Panorama Research, Inc.
1:25pm - 1:30pm 5 mins
Track 2:Clinical Stories: Antibodies in Development
Chairman's Remarks
  • Gregory Adams, PhD - Chief Scientific Officer, Sesen Bio
  • Matthew Robinson, PhD - VP, Research & Development, Immunome, Inc.
1:30pm - 2:00pm 30 mins
Info
Track 1:Innovating Antibody Therapeutics
The Next Generation of Programmable T cell Engaging Antibody Circuits
  • Werner Meier - Chief Scientific Officer and Acting CEO, Revitope Oncology

Revitope Oncology is developing the next generation of programmable antibody circuits aimed at minimizing toxicity while enabling effective immune-control of solid tumors. T cell Engaging Antibody Circuits (TEAC) are activatable T cell engaging modules that can be combined with any targeting moiety. TEAC consist of two stability-engineered modules with silent T cell engaging half-paratopes that are under the control of target-specific activation sites. The modules are targeted to the tumor through two modality-independent binding moieties. Thus, T cell engagement is subjected to a logic gate in which targeting and activation of TEACs are both required. These novel constructs are designed to expand the antigenic targeting space in immune oncology and constrain immune-activation to the cancer cell surface with the goal to widen the therapeutic index.

2:00pm - 2:30pm 30 mins
Info
Track 1:Innovating Antibody Therapeutics
Orientation-dependent Effector Function of Brain Shuttle Fusion Proteins
  • Jens Niewoehner, PhD - Senior Principal Scientist, Roche Pharmaceutical Research and Early Development

Transferrin receptor (TfR) has shown promise for transport of antibodies (mAbs) across the blood-brain barrier. However, safety liabilities have been reported associated with peripheral TfR binding and Fc effector function. Here, we present the Brain Shuttle-mAb (BS-mAb) technology and investigate the role of Fc effector function in vitro and in a novel FcgR-humanized mouse model. Strong immune reactions were observed for a conventional mAb against TfR with a native IgG1 Fc. Remarkably, no effector cell stimulation was observed for the BS-mAb construct, in spite of a native IgG1 Fc. Using various BS-mAb constructs we show that TfR binding through the C-terminal BS-module attenuates Fc-FcgR interactions, primarily due to steric hindrance. Nevertheless, BS-mAbs maintain effector function activity when bound to their brain target. Taken together, mAbs with full effector function can be transported in a “stealth mode” in the periphery and become activated in the brain when engaged to their target.

2:00pm - 2:30pm 30 mins
Track 2:Clinical Stories: Antibodies in Development
Harnessing the Power of the Immune System: Lessons Learned from the Pembrolizumab Story
  • Jonathan Cheng, M.D - Vice President and Therapeutic Area Head, Late Stage Oncology, Merck Research Laboratories
2:30pm - 3:00pm 30 mins
Info
Track 1:Innovating Antibody Therapeutics
Structure of the 4-1BB/4-1BBL Complex and Distinct Binding and Functional Properties of Therapeutic Antibodies, Utomilumab and Urelumab
  • Christopher Kimberlin, PhD - Senior Scientist, Protein Engineering, Pfizer

4-1BB (CD137, TNFRSF9) is an inducible costimulatory receptor expressed on activated T cells. Clinical trials of two agonist antibodies, utomilumab (PF-05082566) and urelumab (BMS-663513), are ongoing in multiple cancer indications, and both antibodies demonstrate distinct activities in the clinic. To understand these differences, we solved structures of the human 4-1BB/4-1BBL complex, the 4-1BBL trimer alone, and 4-1BB bound to utomilumab or urelumab. The 4-1BB/4-1BBL complex displays a unique interaction between receptor and ligand when compared with other TNF family members. Furthermore, our ligand-only structure differs from previously published data. Utomilumab, a ligand blocking antibody, binds 4-1BB between CRDs 3 and 4. In contrast, urelumab binds 4-1BB CRD-1, away from the ligand binding site. Finally, cell-based assays demonstrate distinct differences in activation by both antibodies. Collectively, our data provide a deeper understanding of the 4-1BB signaling complex, providing a template for future development of next generation 4-1BB targeted biologics.

2:30pm - 3:00pm 30 mins
Track 2:Clinical Stories: Antibodies in Development
Targeting MDSC Derived Resistance to PD1 Based therapies: “In Like A Lion, Out Like a Lamb”
  • Anthony Tolcher, M.D. - CEO and Co-Founder, NEXT OncologyTM
3:00pm - 3:30pm 30 mins
Info
Track 1:Innovating Antibody Therapeutics
Isolation of State-dependent Monoclonal Antibodies against the 12-transmembrane Domain Glucose Transporter 4 Using Virus-like Particles
  • Joseph Rucker, PhD - Vice President Research and Development, Integral Molecular

The insulin-responsive 12 transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational MAbs against complex and highly-conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking,or detect the conformational state of the protein. Here we report the isolation and characterization of novel conformational monoclonal antibodies (MAbs) that recognize the extracellular and intracellular domains of GLUT4, including MAbs that are specific for the inward-open and outward-open states of GLUT4. MAbs against GLUT4 were generated using virus-like particles (VLPs) to present this complex membrane protein in its native conformation, and using a divergent host species (chickens) for immunization to overcome immune tolerance. As a result, the isolated MAbs recognize conformational epitopes on native GLUT4 in cells, with apparent affinities as high as 1 pM and with specificity for GLUT4 across the human membrane proteome. Epitope mapping using shotgun mutagenesis alanine scanning across the 509 amino acids of GLUT4 identified the binding epitopes for MAbs specific for the states of GLUT4, as well as comprehensive identification of the residues that functionally control the GLUT4 inward-open and outward-open states. The MAbs identified here will be valuable molecular tools for monitoring GLUT4 structure, function, and trafficking, for differentiating GLUT4 conformational states, and for the development of novel therapeutics for the treatment of diabetes.

3:00pm - 3:30pm 30 mins
Info
Track 2:Clinical Stories: Antibodies in Development
Short Oral Poster Presentations

Efficient in vivo Tumor Clearance and Minimal Cytokine Release with a Novel T-cell Engaging Bispecific Antibody Platform

Shelley Force Aldred, VP Preclinical Development, TeneoBio

The CAN04 Antibody Targets IL1RAP and Mediates Tumor Growth Inhibition and Increased Cisplatin Sensitivity in a Patient-derived Xenograft Model for Non-small Cell Lung Cancer

David Liberg, VP Cancer Research, Cantargia

Human Antibody Targeting C-type Lectin-like Domain of CLEC14a As a Potential Therapy for Neovascular Age-related Macular Degeneration

Kweon Don Sun, Vice President, BIO Business Division, Woori Technology, Inc., Korea

3:30pm - 4:00pm 30 mins
Networking Refreshment Break
4:00pm - 4:25pm 25 mins
Info
Closing Plenary Session: A Tribute to George P. Smith and Sir Greg Winter, Nobel Prize in Chemistry 2018
Celebrating the Contributions of George P. Smith, Extraordinary Inventor, Mentor and Friend
  • Jamie Scott, MD, PhD - Professor and Canada Research Chair , Simon Fraser University


This presentation will review how Dr. Smith’s ideas for phage display, phage libraries and affinity selection developed, and will draw on some personal observations from my time in his lab.

4:25pm - 4:50pm 25 mins
Info
Closing Plenary Session: A Tribute to George P. Smith and Sir Greg Winter, Nobel Prize in Chemistry 2018
Display Technology: Past, Present and Future
  • John McCafferty, PhD - CEO and Founder, IONTAS and Co-Inventor of Antibody Phage Display

Inspired by the work of Parmley and Smith1 on peptide display I demonstrated for the first time the display of antibodies on the surface of filamentous phage (McCafferty et al 1990)2. This work was closely followed by others and together helped unleash a revolution in antibody discovery leading to 8 approved antibodies to date with another 41 candidates in phase 2 or beyond. The underlying concept of linking genotype and binding phenotype has been extended to other systems including ribosome display, yeast display and mammalian display and has enabled the development of alternative non-antibody scaffolds. This presentation will review this history and reflect on current and future developments.

1. Parmley SF, Smith G (1988) Antibody selectable filamentous fd phage vectors: affinity purification of target genes. Gene 73 p305-318

2. McCafferty J, Griffiths AD, Winter G, Chiswell DJ (1990) Phage antibodies: filamentous phage displaying antibody variable domains. Nature 348 p552-554

4:50pm - 5:15pm 25 mins
Info
Closing Plenary Session: A Tribute to George P. Smith and Sir Greg Winter, Nobel Prize in Chemistry 2018
CLOSING KEYNOTE PRESENTATION: Exploiting the Diverse Functions of FcRn to Generate Therapeutics
  • Sally Ward, PhD - Professor, University of Southampton and Texas A&M University Health Science Center


The presentation will discuss how studies of FcRn, using a combination of antibody engineering, fluorescence microscopy

and mouse disease models, have been used to inform the design of therapeutics to modulate the dynamic behavior of

antibodies. In addition, a novel role for FcRn as a metabolic regulator will be discussed.


5:15pm - 5:20pm 5 mins
Close of Conference