Cambridge Healthtech Institute’s 16th Annual
Recombinant Protein Therapeutics
Fusion Proteins & Beyond
January 20-21, 2020
Part of the Protein Engineering & Development pipeline
Cambridge Healthtech Institute’s Recombinant Protein Therapeutics conference presents the latest developments in non-antibody therapeutics from international leaders. The conference focuses on the varying designs of fusion protein-based therapies
and the latest data from R&D to post-approval, including case studies. By combining modular building blocks that can reach targets not accessible to antibodies, fusion protein therapies possess advantages over antibody-based therapies; their customizable
functionality translates into lower patient dosing, reduced production costs, and improved product homogeneity. This conference will demonstrate how these molecules are being engineered to form more efficacious therapeutics that offer specificity
with enhanced stability and longer half-life.
Final Agenda
Day 1 | Day 2 | Download Brochure
SUNDAY, JANUARY 19
4:00 - 6:00 pm Pre-Conference Registration (Sapphire West Foyer)
MONDAY, JANUARY 20
7:00 am Registration (Sapphire West Foyer) and Morning Coffee (Sapphire West & Aqua West Foyer)
9:00 Organizer’s Welcome Remarks
Mary Ruberry, MA, Senior Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Joachim Feldswich, PhD, Director, Preclinical Development, Affibody AB
KEYNOTE PRESENTATION
9:10 From Cytokine Traps to Antibodies to Antibody-Protein Fusions
Aris N. Economides, PhD, Vice President, Research, Regeneron Pharmaceuticals, Inc.
Antibodies, endowed by nature with desirable properties, have provided an excellent starting point for engineering protein-based therapeutics. Even preceding the ability to generate human (or humanized) mAbs, the constant region of antibodies was
used to generate Immunoadhesins and Cytokines Traps, a good number of which became approved drugs. The ability to generate human mAbs has enabled the exploration of many novel formats. A select set of these will be discussed in the context of
relevant therapeutic applications.
9:50 Strategic and Technical Considerations on Designing, Manufacturing and Using Complex Protein Therapeutics
Stefan Schmidt, PhD, MBA, COO/Head, Operations, BioAtrium AG
Triggered by the tremendous success of antibodies, complex and multifunctional proteins represent a current trend in therapeutic modalities. Here several elements are combined in a single molecule to optimize on-target activities, simplify the manufacturing
process and improve administration schemes. This presentation connects these different approaches and gives recommendations supported by examples from case studies and a review of the current fusion protein pipeline.
10:20 Networking Coffee Break (Sapphire West & Aqua West Foyer)
10:45 Targeting the Brain with IgG-Bifunctional Fusion Proteins: Preclinical and Clinical Update
Ruben J. Boado, PhD,
Co-Founder, ArmaGen, Inc.
Protein therapeutics can be re-engineered as brain-penetrating IgG-bifunctional fusion proteins for the treatment of CNS disorders. The IgG domain targets a specific endogenous receptor-mediated transporter system within the blood-brain barrier (BBB),
i.e., insulin or transferrin receptor, respectively. The therapeutic domain of the fusion protein exerts the pharmacological effect in brain once across the BBB. Preclinical and first in human clinical trials will be discussed.
11:15 A Brain-Penetrating Erythropoietin-Transferrin Receptor Antibody Fusion Protein for Alzheimer’s Disease
Rachita Sumbria, PhD, Associate Professor, Biopharmaceutical Sciences, Keck Graduate Institute
Erythropoietin (EPO) is a promising neurotherapeutic for Alzheimer’s disease (AD). However, blood-brain barrier (BBB) penetration and negative hematopoietic effects are the challenges for the therapeutic development of EPO for AD. A BBB-penetrating
EPO is engineered by fusing EPO to a monoclonal antibody targeting the BBB transferrin receptor (TfRMAb) to ferry EPO into the brain. The talk will focus on the therapeutic effects of this BBB-penetrating EPO in AD mice.
11:45 ALPN-202, a Novel Tri-Functional Immuno-Oncology Biologic
Mark Rixon, PhD, Senior
Director, Protein Therapeutics, Alpine Immune Sciences
ALPN-202 is an Fc-fusion protein of a human CD80 variant immunoglobulin domain (vIgD™) designed to block PD-L1 and CTLA-4, and to provide PD-L1-dependent T cell activation via the CD28 costimulatory receptor. ALPN-202 has potent single agent
immunomodulatory activity in mouse tumor models that is superior to single PD-L1 blockade and elicits a unique proinflammatory gene signature in the tumor microenvironment.
12:15 pm Sponsored Presentation (Opportunity Available)
12:45 Session Break
12:55 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
2:00 Chairperson’s Remarks
Stefan Schmidt, PhD, MBA, COO/Head, Operations, BioAtrium AG
FEATURED PRESENTATION
2:05 Engineered Fc-Fusion Proteins as Next-Generation Cancer Therapeutics
Jennifer Cochran, PhD, Professor, Bioengineering and Chemical Engineering, and Shriram Chair, Bioengineering, Stanford University
We create novel engineered ligands and receptors as therapeutic candidates to address limitations of their antibody counterparts, such as the need to achieve ultra-high target binding affinity or the ability to modulate multiple receptors. Within
these constructs, we utilize antibody Fc domain fusions to increase circulation half-life, achieve avidity effects, or recruit immune cell effector function. My talk will describe several examples of clinical and pre-clinical stage Fc-fusion proteins
against emerging targets in oncology.
2:35 HERA-CD40L: A Unique Hexavalent CD40 Agonist for Cancer Immunotherapy
Katharina Billian-Frey, PhD, Senior Scientist, Protein Engineering, Drug Discovery, Apogenix AG
HERA-CD40L is a member of a novel class of TNFR superfamily agonists for immuno-oncology therapies. The engineering is based on a trivalent, but single-chain mimic of the natural CD40L fused to a dimerization scaffold, leading to a potent crosslinking-independent
hexavalent agonist. HERA-CD40L is superior to other agonistic formats regarding activation and maturation of distinct immune cells, and demonstrates anti-tumor activity as single agent in tumor mouse models.
3:05 Find Your Table and Meet Your BuzZ Session Moderator
3:15 BuzZ Sessions with Refreshments
Join your peers and colleagues for interactive roundtable discussions.
Click here for more details
4:30 Preconditioning the Tumor Microenvironment to Enable Effective Immunotherapy Using Antibody Fusion Proteins
Alan Epstein, MD,
PhD, Professor, Pathology, Keck School of Medicine, University of Southern California (USC)
As surrogates for patient investigations, syngeneic murine tumor models are being treated with antibody and Fc-fusion proteins to precondition the tumor microenvironment and rearm the immune system. When used in combination with suppressor cell inhibition,
tumor eradication can be achieved even in the face of high tumor burden. For solid tumors, where tumor heterogeneity is the norm, the induction of innate immunity, antigen spreading, and immunologic memory are especially important to prevent the
reoccurrence of tumor growth and treatment failure.
5:00 T Cells Engineered with Immunomodulatory Fusion Proteins Enhance Adoptive Cell Therapy of Liquid and Solid Tumors
Shannon K. Oda, PhD,
Research Associate, Philip D. Greenberg Laboratory, Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center
To improve the efficacy of adoptive cell therapy (ACT), we have developed immunomodulatory fusion proteins (IFPs) that combine an inhibitory ectodomain with a costimulatory signal to “replace a brake with an accelerator.” IFP-engineered
T cells exhibit enhanced function, metabolic reprogramming, and in vivo persistence, significantly improving survival in murine models of leukemia and pancreatic cancer. Human primary IFP-T cells also exhibit increased
antitumor function, supporting clinical translation of this strategy.
5:30 Antibody-Cytokine Fusion Proteins to Promote Proliferation of Tumor-Reactive T Cell Subsets
Elissa Leonard,
PhD, Postdoctoral Research Fellow, Biomedical Engineering, Johns Hopkins University
Many solid tumors are allowed to proliferate due to suppression of T effector cells (Teffs) by T regulatory cells (Tregs). We have engineered and optimized an antibody-cytokine fusion in which the antibody blocks key interactions with the high affinity
domain of the Tregs’ IL-2 receptor, while still permitting signaling through the moderate affinity IL-2 receptor expressed on Teffs. This promotes a more proinflammatory T cell response that reduces tumor growth.
6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
7:15 Close of Day
Day 1 | Day 2 | Download Brochure
TUESDAY, JANUARY 21
8:15 am Registration (Sapphire West Foyer) and Morning Coffee (Sapphire West & Aqua West Foyer)
8:45 Chairperson’s Remarks
Shannon K. Oda, PhD, Research Associate, Philip D. Greenberg Laboratory, Program in Immunology, Clinical Research Division, Fred Hutchinson Cancer Research Center
8:50 NEW: Speaker Replacement -- Novel Fc Platform Development and Applications for Fc-Fusion Proteins
Qing Li, PhD, Scientist, Antibody Discovery & Protein Engineering, AstraZenecaplc
Monovalent fusion proteins are often a necessary drug format for optimal structure and activity profiles. We present our novel monovalent fusion platform in target validation and lead discovery.
9:20 NEW: SPEAKER CANCELLED -- Molecular Landscape of Anti-Drug Antibodies Reveals the Mechanism of the Immune Response following Treatment with TNFa Antagonists
Yariv Wine, PhD, Assistant Professor, Molecular Cell Biology and Biotechnology, Tel Aviv University
While therapeutic mAbs hold significant promise for improving human health, repeated administration of mAbs often leads to the induction of undesirable Anti-Drug Antibodies (ADA) that reduces drug efficacy. The mechanisms that lead to the generation
of ADA and their molecular composition are unknown. ADA repertoire analysis reveals the possible mechanism involved in generation of ADA following infusion with TNFa antagonists. The data suggests that mAb administration elicits a vaccine-like
response in the marginal zone that is a T cell independent (TI) response.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 In vitro Evolution of a Vaccine-Elicited Antibody Identifies New Capabilities for Effective Fusion Peptide-Based HIV Neutralization
Bharat Madan, PhD,
Postdoctoral Researcher, Pharmaceutical Chemistry, University of Kansas
We present a new platform for interrogating the functional landscape of somatic hypermutation pathways for antibody improvement. We leveraged precision antibody library generation with yeast surface display and NGS to identify a comprehensive
set of beneficial mutations across the entire antibody variable region. This work has identified multiple independent pathways for antibody therapeutic improvement and provided new insights on the developmental dynamics of antibody immune
responses.
11:30 Affibody Molecules in Psoriasis, Autoimmune Disease, and Cancer: From Lab Bench to Patient Outcomes
Joachim Feldswich, PhD, Director, Preclinical Development, Affibody AB
Affibody molecules are engineered affinity proteins based on a compact three-helical bundle scaffold. The molecules are ideally suited to create novel biologic therapeutics and diagnostics. Two different therapeutic clinical programs and one diagnostic
(HER2) will be presented to exemplify how Affibody molecules can be used as modular building blocks to create novel innovative mono- and bifunctional therapeutics. ABY-035 is a best in class IL-17A blocking ligand trap with femtomolar binding
affinity that translates to high therapeutic efficacy in patients with psoriasis.
12:00 pm Sponsored Presentation (Opportunity Available)
12:30 Session Break
12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:10 Close of Recombinant Protein Therapeutics Conference
5:45 - 8:45 Recommended Dinner Short Course*
SC2: The Safety of Immunotherapy and ADCs: How to Mitigate Risk and Adverse Effects - Detailed Agenda
Instructors:
Rakesh Dixit, PhD, DABT, President & CEO, Bionavigen, LLC
Stephanie Voss, PhD, Group Leader, Bioconjugation & Protein Chemistry, Heidelberg Pharma Research GmbH
*Separate registration required
Day 1 | Day 2 | Download Brochure