Cambridge Healthtech Institute’s 15th Annual
Recombinant Protein Therapeutics
Fusion Proteins and Beyond
January 14-15, 2019
Cambridge Healthtech Institute’s 15th Annual 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
therapeutics 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
SUNDAY, JANUARY 13
4:00 - 6:00 pm Pre-Conference Registration (Sapphire West Foyer)
MONDAY, JANUARY 14
7:00 am Registration and Morning Coffee (Sapphire West Foyer)
9:00 Welcome by Conference Organizer
Mary Ruberry, Senior Conference Director, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Uli Binder, MSc, CTO, XL-protein GmbH
KEYNOTE PRESENTATION
9:10 The Evolving Science and Long-Term Outcomes of Fc Fusion Factors
Jennifer Dumont, PhD, Executive Director, Medical Affairs, Bioverativ, Inc.
9:50 Selection of the Recommended Phase II Dose for M7824, a Bifunctional Fusion Protein Targeting TGF-β and PD-L1
Yulia Vugmeyster, PhD, Associate Director, Clinical
Pharmacology, EMD Serono R&D Institute, Inc.
M7824 (MSB0011359C) is an innovative, first-in-class, bifunctional fusion protein composed of a human IgG1 mAb against PDL1 fused with two extracellular domains of TGF-β receptor II to function as a TGF-β “trap.” The selection of
the recommended Phase II dose (RP2D) for M7824 will be presented. The current RP2D dose selection is informed by preclinical and clinical data, such as tolerability/safety, efficacy, pharmacokinetic and pharmacodynamic profiles, and is supported by
the population PK and exposure-response modeling.
10:20 Networking Coffee Break (Sapphire & Aqua West Foyer)
10:45 Proinsulin-Transferrin Fusion Protein to Overcome Insulin Resistance
Wei-Chiang Shen, PhD, John A. Biles Professor, Pharmacology
and Pharmaceutical Sciences, University of Southern California School of Pharmacy
We have previously shown that proinsulin-transferrin fusion protein (ProINS-Tf) is a highly liver-targeted and long-lasting insulin analog for the treatment of diabetes in mouse models. Recently, we have found that the liver-activated ProINS-Tf, due to
simultaneous binding to both transferrin and insulin receptor, can overcome insulin-resistance in cell cultures and in NOD mice. ProINS-Tf can serve as a model of insulin analogs for treating insulin-resistance in diabetes and other diseases.
11:15 IL-DR2 Fc Is a Novel Regulator of Immune Homeostasis and Inducer of Antigen-Specific Tolerance
Stephen D. Miller, PhD, Judy Gugenheim Research Professor,
Director, Interdepartmental Immunobiology Center, Microbiology-Immunology, Northwestern University Medical School
ILDR2 is a member of the Ig superfamily and has a putative role in pancreatic islet health and survival. We recently found a novel role for ILDR2 in delivering inhibitory signals to T cells. ILDR2-Fc displays a unique mode of action, combining immunomodulation,
regulation of immune homeostasis, and re-establishment of Ag-specific immune tolerance via induction of regulatory T cells. These findings support the potential of ILDR-Fc as a promising therapeutic approach for the treatment of autoimmune diseases.
11:45 xB3 Platform Delivers a Protein-Based Interleukin 1 Receptor Antagonist across the BBB and Ameliorates Neuropathic Pain in a Preclinical Model
Mei Mei Tian, PhD, Vice President and Head, External Research,
Bioasis Technologies, Inc.
Utilizing a 12 amino-acid peptide, xB3, we have shown improved brain delivery of antibody payload. xB3-antibody fusion demonstrated similar plasma kinetics to control antibody, however, with significantly increased brain exposure for the duration
of the study. In a neuropathic pain model, fusion to interleukin-1receptor antagonist is able to induce significant and durable analgesia following peripheral administration. These data demonstrate the utility of xB3 in delivering therapeutic
levels of drug to the brain.
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
Vladimir Muzykantov, MD, PhD, Professor,
Pharmacology, The Center for Translational Targeted Therapeutics and Nanomedicine (CT3N) and Systems Pharmacology, Perelman School of Medicine, University of Pennsylvania
2:05 Antibody-Cytokine Fusion Proteins Targeting Tumor Associated Antigens for the Treatment of Malignancy
Sherie Morrison, PhD, Distinguished Research Professor,
Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles
Many cytokines have anti-tumor efficacy, however, their utility for treating malignancy is often limited by toxicities that are dose limiting. To address this problem, we have genetically fused cytokines to antibodies that recognize tumor-associated-antigens.
Among other things, we have used this strategy to target interferons to tumor cells using anti-CD20 and anti-CD138 specific antibodies. We have found these antibody fusion proteins effective in the treatment of both lymphoma and myeloma.
2:35 Optimization of a Bispecific Anti-CD3 Antibody-Folate Conjugate for the Treatment of Ovarian Cancer
Harun Rashid, PhD, Senior Principal Scientist, Molecular Technology, Ambrx, Inc.
Here, we report the optimization of an anti-CD3 Fab-folate conjugate that targets cytotoxic T cells to folate receptor positive (FR+) tumor cells for optimal efficacy, reduced toxicity and optimal pharmacokinetic (PK). The optimized conjugates
showed potent and selective in vitro activity, good serum half-life, and potent in vivo activity in xenograft mouse models. This semi-synthetic approach shows promise for the generation
of additional anti-CD3 bispecific agents using small molecule ligands selective for other TAAs.
3:05 Find Your Table and Meet Your BuzZ Session Moderator
3:15 BuzZ Sessions with Refreshments (Sapphire & Aqua Foyer)
Join your peers and colleagues for interactive roundtable discussions.
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4:30 Advancing Targeted Protein Therapeutics (TPTs) in Clinical Drug Development
Jeannick Cizeau, PhD, Director, Research, Sesen
Bio, Inc.
The design and differential mechanism of action of Sesen’s TPTs comprising an antibody fragment genetically fused to a protein toxin versus traditional small molecule drugs used for ADCs will be discussed. Data from an ongoing pivotal Phase
III trial in non-muscle invasive bladder cancer will be presented to illustrate the rationale design approach of TPTs for use in clinical oncology.
5:00 Hexavalent Agonists Targeting Co-Stimulatory Receptors of the TNFR-Superfamily for Cancer Immunotherapy
Christian Gieffers, PhD, Vice President, Analytics/Protein Chemistry, Apogenix AG
Apogenix’s novel hexavalent TNFR-SF agonists (HERA) are developed for the immunologic treatment of cancer. The construction principle is based on trivalent molecular mimics of the TNF-SF Receptor binding domains fused to a dimerization scaffold.
The resulting hexavalent fusion proteins are potent TNFR-SF agonists that activate distinct immune cell populations. HERA compounds show single-agent anti-tumor activity and provide exciting opportunities for combinatorial treatment.
5:30 Prospects of PASylation for the Design of Protein Therapeutics and Tumor Imaging Reagents
Uli Binder, MSc, CTO, XL-protein GmbH
PASylation®, the genetic fusion or chemical coupling of proteins or peptides with conformationally disordered polypeptides comprising the L-amino acids Pro, Ala, and/or
Ser (PAS), is a superior way to enlarge the hydrodynamic volume and to extend plasma half-life. Further to illustrating the fundamental concepts of PASylation technology, this presentation will highlight a first proof-of-concept tumor imaging
study in a human patient.
6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
7:15 Close of Day
TUESDAY, JANUARY 15
8:00 am Registration and Morning Coffee (Sapphire West Foyer)
8:45 Chairperson’s Remarks
Stefan Ståhl, PhD, Professor and Head, Protein Science, KTH Royal Institute of Technology
8:50 Engineered FcRn Binding Fusion Peptides for Half-Life Extension
Jeffrey Boyles, MSc, Research Scientist, Protein Optimization, Eli Lilly and Company
The therapeutic potential of small proteins, peptides, and mAb derived domains can be significantly limited by their rapid peripheral clearance in vivo. We show that small FcRn binding peptides (FcRnBPs) fused to
the N- and/or C-termini of a Fab can significantly improve the pharmacokinetics of the protein in cynomolgus monkeys. The extent of this benefit can be modulated by number, structure, and post-translational modifications of the FcRnBP.
9:20 Developing a Conjugation-Based Multivalent Ab Format
Diego Ellerman, PhD, Principal Scientific Researcher,
Protein Chemistry, Genentech, Inc.
A multivalent Ab format based on protein conjugation was developed (TRAC) to enable a plug and play system for the rapid screening of new multispecific/multivalent Abs. The building blocks used are mAbs and Fabs with good expression yields
and stability. A conjugation site was identified that supports high conjugation rates, an efficient process and a stable molecule. We provide examples of different TRACS that require concurrent binding of all Fabs for their biological
activity.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 Therapeutic Fusion Proteins Targeted to Blood and Vascular Cells
Vladimir Muzykantov, MD, PhD, Professor,
Pharmacology, The Center for Translational Targeted Therapeutics and Nanomedicine (CT3N) and Systems Pharmacology, Perelman School of Medicine, University of Pennsylvania
Conjugating biotherapeutics including thrombomodulin with scFv to blood cells boosts bioavailability, while conjugating with scFv binding to endothelial determinants provides endothelial targeting. Selecting determinants that permit fusion
cooperation with cofactors boosts the effect. Further, dual targeting of two fusions delivering collaborative cargoes to adjacent epitopes maximizes binding and effect. Vascular targeting of anti-thrombotic and anti-inflammatory fusions
affords beneficial effects unrivaled by untargeted counterparts in animal models of acute lung injury, ischemia-reperfusion and sepsis.
11:30 Affibody-Based Next-Generation Therapeutics
Stefan Ståhl, PhD, Professor and Head, Protein Science, KTH Royal Institute of Technology
Affibody molecules [Ståhl et al, Trends Biotechnol. 8, 691-712, 2017] have been investigated extensively for medical imaging applications and been found safe and efficacious in humans (currently in late-stage clinical evaluations for imaging of HER2-positive breast cancer). This has paved the way for development of affibody-based therapeutics. A couple of projects are now in clinical testing, e.g., for plaques psoriasis, and several are in preclinical evaluation, e.g., targeting cancer and neurodegenerative disorders.
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 Courses*
SC1: Introduction to CAR-T Engineering for Protein Scientists - Detailed Agenda
SC4: Immunogenicity for Biologics
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*Separate registration required