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Cambridge Healthtech Institute’s 11th Annual
Recombinant Protein Therapeutics
Fusion Proteins and Beyond
January 19-20, 2015

The customizable functionality of fusion protein therapeutics creates advantages over antibody-based therapies by combining modular building blocks that can reach targets not accessible to antibodies. Additional advantages include lower patient dosing, reduced production costs and improved product homogeneity. The Recombinant Protein Therapeutics conference explores the varying constructs and “designs” of fusion protein molecules, and discloses how they are being engineered to form more efficacious therapeutics that offer specificity with enhanced stability and longer half life. Experts present case studies from R&D through clinical data and share the results they have achieved.

Day 1 | Day 2 | Download Brochure | Speaker Biographies 

Final Agenda 


4:00-5:00 pm Short Course Registration

5:00-8:00 Pre-Conference Dinner Short Courses (More Details >>)

4:00-8:00 Main Conference Registration


7:30 am Conference Registration and Morning Coffee

Next-Generation Biologics

9:00 Chairperson’s Opening Remarks

Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology

Keynote Presentation

9:10 Roche’s Strategies to Discover, Design, Develop, and Deliver New Innovative Therapeutic Biologics

Ralf SchumacherRalf Schumacher, Ph.D., Site Head, Large Molecule Research Penzberg, and pRED Center Manager, Roche Diagnostics GmbH

Biologics have become a key component in the treatment of various life-threatening diseases. The majority of these drugs are classical monoclonal antibodies. In order to discover and develop differentiated monoclonal antibodies, Roche’s strategy is based on engineering technologies. ADCC-enhancement, multi-pathway-inhibition, specific tumor-targeting of pharmacophores and blood-brain-barrier crossing are examples for successfully engineered mAbs and fusion proteins. In this presentation, I will describe Roche’s strategies to design such molecules, give examples but will also address challenges for technical development.

Featured Presentation

9:50 Monomeric Fc Fusion Clotting Factors for the Treatment of Hemophilia

Jennifer DumontJennifer Dumont, Ph.D., Director, Medical Affairs, Biogen Idec, Inc.

Prophylactic clotting factor replacement in patients with hemophilia improves outcomes, but requires frequent injections with traditional therapies. Recombinant fusion of the Fc domain of human IgG with clotting factors VIII and IX was performed to extend the half-life of these factors and provide the potential to reduce the frequency of injections needed to control bleeding in hemophilia A and B patients, respectively. The Fc fusion factors are configured with monomeric factor VIII or IX covalently linked to dimeric Fc. These protein fusion products have recently been approved for the treatment of hemophilia and the development programs will be discussed.

10:20 Coffee Break

Engineering Breakthroughs

10:45 A Small Biologic Alternative to PCSK9 Antibodies: Pharmacologic Profile and Demonstration of Robust LDL Lowering with an Anti-PCSK9 Adnectin

Tracy MitchellTracy Mitchell, Ph.D., Principal Scientist and Group Leader, Biomolecular Characterization, Bristol Myers-Squibb Co.

PCSK9 is perhaps the most promising drug target for treating cardiovascular disease since the discovery of statins. Compared with therapeutic IgG antibodies currently in clinical trials, targeting circulating PCSK9 with a smaller molecular scaffold could offer reduced dose burdens and different pharmacologic profiles. We present the pharmacological profile of BMS-962476, a potent Adnectin inhibitor of PCSK9 that has demonstrated robust target engagement and LDL lowering in mice, cynos and humans.

11:15 Development of an Intein-Based Conjugation Platform for the Synthesis of Fc-Fusion Proteins

Oliver ThielOliver Thiel, Ph.D., Principal Scientist, Chemical Process Research & Development, Amgen, Inc.

Identification of an ideal platform technology for conjugation of small molecules and peptides to biomolecules for improved pharmacokinetics has been a recent focus within academic and industrial laboratories. This contribution will focus on the development of an intein-based platform for conjugation of peptides at the C-terminus of the Fc domain of immunoglobulins. In the course of platform development, selection of intein, cleavage residue, and linker between Fc and intein were examined.

11:45 A Bi-Functional Antibody-Receptor Domain Fusion Protein Simultaneously Targeting IGF-IR and VEGF for Degradation

Yang ShenYang Shen, Ph.D., Research Advisor, Antibody Engineering, Eli Lilly & Company

A fully human Bi-functional Antibody-receptor domain (VEGFR1 domain 2) fusion molecule with ligand Capture (BiAbCap) targeting IGF-IR and VEGF was designed and developed, that displays excellent thermal and physical stability. Taking advantage of natural receptor-ligand interaction, bi-AbCap represents a novel and developable format of bi-functional antibodies with potent neutralizing activities against both targets. The unique “capture-for-degradation” mechanism translates to potent anti-tumor activity superior to the combination in vivo.

ProteinSimple Large12:15 pm Reinventing Immunoassays: Introducing the Simple ELISA

Pande_RajivRajiv Pande, Ph.D., ProteinSimple

Although ELISA is routinely used for measuring individual protein analytes it has limitations in translational research applications where precise and accurate analysis of multiple analytes from small sample volumes is required. ProteinSimple has developed the Simple Plex, a fully automated, hands-free immunoassay platform that retains the specificity of single-analyte ELISAs, but provides rapid multi-analyte analysis. The Simple Plex integrates a desktop analyzer with a disposable microfluidic cartridge to deliver superior performance and unprecedented ease of use in research and diagnostic applications.

12:45 Session Break

Applications of Acoustic Membrane Micro Particle in Large Molecule Bioanalysis

Mora_JohannaJohanna Mora, Ph.D., Senior Research Investigator II, Bristol-Myers Squibb

In cases where established technologies cannot deliver on the assay sensitivity requirements set by a specific drug development program, alternative platforms may need to be evaluated. This presentation will share a case study on the application of the Acoustic Membrane Micro Particle (AMMP) technology for PK determination of a domain antibody and cover results on accuracy and precision and selectivity assessments. The second case study will cover the development of an immunogenicity assay on the AMMP where none of the established platforms were able to achieve adequate sensitivity.

Enhancing Properties

2:00 Chairperson’s Remarks

Manfred Schuster, Ph.D., COO, Apeiron Biologics AG

2:05 Unravelling the Molecular Basis of Host Cell-Specific Glycosylation and Species-Specific Pharmacokinetics

Catherine HuntingtonCatherine Huntington, Ph.D., Research Scientist II, Antibody Discovery and Protein Engineering (ADPE), MedImmune, LLC

Glycosylation plays a significant role in the half-life of recombinant proteins in vivo, with the production cell lines affecting PK. Here, we expand on observations that HEK-293 expressed proteins are rapidly cleared in mouse models and our efforts to characterise the glycan forms responsible. Additionally, we will present our work to develop methods to profile glycan forms on recombinant proteins with the aim to predict impact on half-life of different species.

2:35 Enhancing Stability of the Therapeutic Enzyme L-Asparaginase by Biocompatible Nanoparticles

Manfred KonradManfred Konrad, Ph.D., Research Director, Enzyme Biochemistry, Max Planck Institute for Biophysical Chemistry

The enzyme L-asparaginase is a protein drug of high value in antileukemic therapy. Clinically approved L-asparaginases are of bacterial origin, though they elicit severe side effects, in particular immunogenicity. We present a novel approach for encapsulation of the enzyme using calcium carbonate particles surrounded by layers of biocompatible polymers, thus forming nanocontainers as carriers to enhance serum stability and suppress recognition by the immune system.

3:05 Manufacturing of Half-Life Extended Fusion Proteins: Current Trends and Challenges

Stefan SchmidtStefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology

Second and third generation therapeutic proteins often contain a half-life extension moiety. These additional modules of fusion proteins often complicate the manufacturing process as they require specific adaptations of both up- and downstream processes. First, we give a comprehensive overview on the current state-of-the-art regarding half-life extension technologies, and second, we illustrate manufacturing challenges and solutions presented through selected case studies, additionally giving practical advice on optimization potential.

3:35 Sponsored Presentation (Opportunity Available)

3:50 Refreshment Break

Conquering Disease

4:15 A Neuroprotective Brain-Penetrating Endopeptidase Fusion Protein Ameliorates Alzheimer Disease Pathology and Restores Neurogenesis

Eliezer Masliah, M.D., Professor, Neuroscience and Pathology, University of California at San Diego 

Alzheimer’s (AD) and Parkinson’s Disease (PD) are the most common neurodegenerative disorders. We developed recombinant endopeptidases and antibodies with a unique brain targeting sequence derived from ApoB and have shown in animal models of AD and PD that these hybrid proteins ameliorate the pathology and recover the functional deficits. These results suggest that the recombinant brain-targeted proteins might be of use in the treatment of AD and PD.

4:45 Novel Human Resistant Mutant that Acts as Antagonist Reduced Body Weight Gain and Restored Insulin Responsiveness in Mice Fed High Fat Diet

Arieh GertlerArieh Gertler, Ph.D., CEO, Protein Laboratories Rehovot; Professor-Emeritus and Head of Research Team, Biochemistry, The Hebrew University of Jerusalem

Resistin promotes both inflammation and insulin resistance associated with energy homeostasis impairment. To block resistin action, we developed a recombinant human resistin mutant (C6A) that acts as a resistin antagonist (RA). We clearly show that RA leads to a significant decrease in body weight of HFD mice. Importantly, RA treatment completely restored glucose tolerance as evidenced by glucose tolerance test and also restored insulin-responsiveness as estimated by insulin tolerance test.

5:15 Local Inhibition of Cytokine Signaling to Treat Anterior and Posterior Ocular Disorders

Eric FurfineEric Furfine, Ph.D., CSO, Eleven Biotherapeutics

Cytokines, chemokines, and growth factors mediate anterior and posterior eye diseases. Our lead product, the IL-1 receptor inhibitor EBI-005, was designed and engineered for the topical treatment of dry eye disease and was biologically active in subjects with dry eye disease. In addition, we engineered an IL-6 inhibitor with potential for local treatment diabetic macular edema. Finally, a novel soluble receptor inhibitor of cytokines IL-17A and IL-17F was engineered for the local treatment of uveitis. Both IL-6- and IL-17-targeted drugs were designed and engineered for intravitreal administration.

ProteinSimple Large5:45-7:00 Welcome Reception in the Exhibit Hall with Poster Viewing

Day 1 | Day 2 | Download Brochure | Speaker Biographies