Combining ingenuity and biology, recombinant protein therapeutics are forming new and different ‘designs’ to enhance the safety and efficacy of biotherapeutics. Moving through the exciting world of biopharmaceuticals beyond antibodies, this meeting will survey the different classes of therapeutic fusion proteins, including those that have reached approval as well as products that are currently in clinical development. Thought leaders will reveal the significant advances that have been made while addressing persistent challenges, such as specific construction and immunogenicity.
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MONDAY, JANUARY 9
7:30 am Conference Registration and Morning Coffee
8:55 Chairperson's Opening Remarks
Dimiter Dimitrov, Ph.D., Head, Protein Interaction Group, and Senior Investigator, Center for Cancer Research, NCI-Frederick, NIH
» 9:10 OPENING KEYNOTE PRESENTATION
Building a Biologics Pipeline: From Traps to VelocImmune
George Yancopoulos, M.D., Ph.D., Executive Vice President, CSO & President, Regeneron Pharmaceuticals, Inc. - Speaker Biography
Regeneron has long been committed to developing technology platforms in biologics that would enable us to repeatedly go from discovery to the clinic. These approaches led to development of a novel class of soluble decoy receptor fusion proteins, known as the Traps (Economides et al., Nat Med 2003, 9:47; Holash et al. 2002, PNAS 99:11393), as well as to our novel mouse platform for generating fully human monoclonal antibodies, known as VelocImmune. Our Interleukin-1 Trap (IL1 Trap) is now an approved therapeutic for a rare genetic autoinflammatory disease, and we have reported on positive Phase 3 data for our Vascular Endothelial Growth Factor Trap (VEGF Trap) in cancer as well as in two types of blinding eye diseases. Our belief in mouse genetics, together with our frustration with the technological limitations of early approaches in this area, led us to develop a series of integrated technologies termed VelociGene (Valenzuela et al., Nature Biotechnology 2003, 21:652) and VelociMouse (Poueymirou et al., Nature Biotechnology 2007, 25:91) that together allow for an unprecedented rate of generation of specifically designed mouse mutants – easily scaled to thousands per year - which we used to generate an entirely different type of genetically humanized immune system in a mouse, termed VelocImmune (Murphy et al., MacDonald et al.). I will end by describing how we have integrated VelociGene in our efforts to identify new therapeutic targets, and how we subsequently exploited VelocImmune to efficiently produce fully human antibodies against such targets, allowing for rapid transition from the lab to the clinic.
» 9:50 FEATURED PRESENTATION
Therapeutic Fusion Proteins and their Modular Components: From Albumin to XL-Protein
Stefan Schmidt, Ph.D., M.B.A., CEO/CSO, XL-Biologics GmbH - Speaker Biography
Enbrel, the archetype of fusion proteins, is very successful, but in tight competition with monoclonal antibodies. However, fusion proteins in comparison to monoclonal antibodies have the advantage of a customizable functionality by combining modular building blocks. These fusion partners range from Albumin to XL-Protein and can be selected to improve activity, extend stability and half life, target specific cells and tissue, or exert toxicity. This presentation will cover basic concepts and novel developments of fusion proteins and their molecular components.
10:20 Networking Coffee Break
10:45 XTENylation Enables Monthly Dosing of Biopharmaceuticals
Volker Schellenberger, Ph.D., Vice President, Drug Discovery, Amunix - Speaker Biography
XTENs are extremely hydrophilic proteins that can be readily fused to most biopharmaceuticals. XTENylated proteins meet or exceed the in vivo half-lives of similar PEGylated proteins. XTENylation eliminates the need for chemical conjugation resulting in improved product homogeneity and drastically reduced production costs. XTEN is biodegradable, which eliminates the risk of tissue accumulation observed for PEG conjugates. Recently, two XTENylated biopharmaceuticals have entered clinical trials and additional products are in advanced pre-clinical development.
11:15 From Clinical Imaging to Serum Half-Life Extension of Affibody Molecules and Biopharmaceuticals
Joachim Feldwisch, Ph.D., Director, Pre-Clinical Development, Affibody AB - Speaker Biography
Pre-clinical data as well as recent clinical results for a HER2-targeting Affibody imaging agent will be presented. Affibody molecules are proven scaffold proteins with rapid in vivo kinetics. This makes them suitable for clinical imaging studies and thus target characterization in man. The half-life and distribution profile of the imaging molecule was enhanced using a novel albumin binding technology, allowing for successful targeted radionuclide therapy in xenografted mice using a bispecific construct
11:45 Bi-functional Recombinant Protein Therapeutics Engineered to Penetrate the Blood-Brain Barrier
Ruben J. Boado, Ph.D., Vice President, Molecular Biology, ArmaGen Technologies, Inc. - Speaker Biography
A platform technology has been developed to enable re-engineering of recombinant protein therapeutics for penetration of the blood-brain barrier (BBB), and future clinical development for the treatment of neurological diseases. Treatment of neurological disorders with large molecule biotherapeutics requires that the drug be BBB-penetrating. However, recombinant biotherapeutics, such as neurotrophins, enzymes, decoy receptors, and monoclonal antibodies, do not cross the BBB. These biotherapeutics can be re-engineered as bi-functional IgG-fusion proteins, wherein the IgG transport domain targets a specific endogenous receptor-mediated transporter within the BBB, such as the insulin or transferring receptors. The engineering of these brain-penetrating novel IgG fusion proteins and preclinical work will be discussed.
12:15 pm Sponsored Presentation (Opportunity Available)
12:45 pm Close of Morning Session
1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
2:00 Chairperson's Remarks
Jennifer Cochran, Ph.D., Assistant Professor, Bioengineering, Stanford University
2:05 Engineering Chimeric Cytokines
Thomas Barnes, Ph.D., VP Discovery, Eleven Biotherapeutics - Speaker Biography
Eukaryotyic proteins are often organized as a series of domains joined together, such that the properties of individual domains are both relatively separable and context-independent. This has been widely exploited in protein engineering and in biotherapeutics by making chimeric proteins, with Fc domain fusions being a classic example. There are fewer examples of subdomains or especially domain fragments functioning in this way. In order to create superior treatments for dry eye disease, we have shown that the IL-1 protein family does have domain fragments that function in this way, and this can be exploited to make proteins with properties superior to and/or different from the parental proteins. We will present data in support of this and describe progress in bringing a novel therapeutic of this type to the clinic.
2:35 Interleukin-15 Receptor Alpha Scaffold for Creation of Multi-Specific and Multi-Valent Targeted Immune Molecules
Hing C. Wong, Ph.D., President & CEO, Altor Bioscience - Speaker Biography
We have demonstrated that the interleukin-15 complex (IL-15:IL-15 receptor alpha) can be utilized to create multi-specific and multi-valent targeted immune molecules. In this presentation, we will present evidence that targeted immunotherapeutics created using the IL-15:IL-15 receptor scaffold are highly potent immunomodulators with great potential as a new class of anti-cancer and anti-viral drugs.
3:05 The Advantages of the Alphabody Scaffold for Designing and Formatting New Protein Therapeutics
Ignace Lasters, Ph.D., CSO, Complix - Speaker Biography
The main competitive advantages of the Alphabody platform include: (a) an unprecedented formatting flexibility, (b) the ability to design both agonistic and antagonistic Alphabodies, and (c) the potential to generate Alphabodies against selected epitopes on targets that are not accessible to antibodies. In addition, Alphabodies have a tunable plasma half-life and can be manufactured in a cost effective way.
3:35 POSTER SPOTLIGHT:
NExpedite™: A Next Generation Technology for Modulation of Pharmacokinetic Properties and Therapeutic Efficacy of Biopharmaceuticals, Poster A301
Hilde Revets, Ph.D., Senior Research Fellow, Technology, Ablynx nv
3:50 Networking Refreshment Break
4:15 Multifunctional Fusion Proteins Based on Engineered Antibody Domains
Dimiter Dimitrov, Ph.D., Head, Protein Interaction Group, and Senior Investigator, Center for Cancer Research, NCI-Frederick, NIH - Speaker Biography
Multifunctional fusion proteins can access several targets on different proteins or on the same protein. We have constructed a multifunctional multivalent protein based on our newly engineered one-domain soluble CD4 (Chen et al, J Virology, in press) and an engineered VH domain targeting synergistically two different epitopes on the HIV-1 envelope glycoprotein gp120 and simultaneously the FcRn as well as another multi-specific fusion protein targeting components of the IGF system. These proteins exhibited exceptional binding and neutralizing potency and are being evaluated as candidate therapeutics. Other candidate therapeutics based on engineered CH2 domains will be also discussed.
4:45 Multifunctional Nanolipoprotein Particles using Telodendrimer Chemistry for Immunomodulation
Matthew Coleman, Ph.D., Associate Adjunct Professor, Radiation Oncology, University of California, Davis; Senior Scientist, Biology and Biotechnology, Lawrence Livermore National Laboratory - Speaker Biography
We have developed multifunctional nanoparticles for supporting ex vivo and in vivo delivery of therapeutic molecules that modulate immune function. Our process uses a unique combination of apolipoprotein (APOA1), lipids and telodendrimers to create highly homogeneous nanoparticles not achieved by other means. The 4T1 breast carcinoma mouse model is being used for these studies using the T cell cytokine, IL2, which can be assembled in a single day to demonstrate activation of anti-tumor responses. Current data from in vivo tumor models and analysis of tumor-specific immune responses will be presented.
5:15 Long-Lasting Clotting Factors for the Treatment of Hemophilia using Monomeric Fc Fusion Technology
Jennifer A. Dumont, Ph.D., Director, Pharmacology, Biogen Idec Hemophilia
Fusion of the Fc domain of immunoglobulin G to various effector molecules has been successfully used to extend their biological half-life by leveraging a natural pathway. Traditional Fc fusion proteins are dimeric with respect to both the effector molecule and Fc. However, it was discovered that monomeric Fc fusion proteins comprised of a single effector molecule attached to the Fc domain of IgG1 had improved biologic properties. This technology has been applied to clotting factors such as factor IX, factor VIII and factor VII. Two of these fusion proteins are in late-stage clinical studies. Characterization and development of these clotting factor-Fc fusion proteins shall be discussed.
5:45 – 7:00 Welcoming Reception in Exhibit Hall, Poster Viewing
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Links to Companion Meetings
Antibodies for the 21st Century
Bispecific Antibody Therapeutics