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As we examine the exciting world of next-generation biopharmaceuticals beyond antibodies, we will take a special look at the different classes of therapeutic fusion proteins, including those that have reached approval as well as fusion protein products that are currently in clinical development. We will explore the significant advances that have been made and also address some of the challenges such as specific construction and immunogenicity.
This meeting will feature talks from experts who will address:
- How to best construct a fusion protein?
- What are the most successful techniques for enhancing stability and prolonging half life?
- How do the different classes of fusion proteins function?
- What are the benefits and challenges associated with fusion proteins?
- How patentable are fusion proteins?
Please join leaders from around the world for this indepth discussion of the innovations being developed for the next-generation protein therapeutics.
Tuesday, January 12
Arrive early and join BuzZ Session Roundtable Discussions, Poster Awards and Short Courses!
2:45 Networking Refreshment Break in the Exhibit Hall
3:15 Poster Awards in the Exhibit Hall
4:15 Close of Optimizing Biologics Formulation Development
4:15 Registration for Short Courses
4:30 – 7:30 Concurrent Short Courses* (SC 5 – SC 8)
Wednesday, January 13
7:00 am Registration for Recombinant Proteins
7:30 Breakfast Presentation or Morning Coffee
8:15 Chairperson’s Remarks
Rose Lance, Business Development Manager, Novozymes
8:20 OPENING KEYNOTE PRESENTATION
Multi-Specific Adnectins: Realizing the Promise of a Novel of Targeted Biologics
Eric Furfine, Ph.D., Senior Vice President, Research & Preclinical Development, Adnexus–a Bristol Myers Squibb R&D Company
Adnectins offer several potential advantages compared to traditional targeted biologics, including speed of discovery, efficient manufacturing, and the ability to create multi-functional targeted products. We are currently advancing products combining two Adnectins to enable modulation of two distinct targets. We will present methods to engineer and optimize multi-specific Adnectins, and preclinical data on a bispecific Adnectin to EGFR and IGF1R.
9:00 Engineering TPR Repeat Proteins for in vivo and in vitro Applications
Lynne Regan, Ph.D., Professor, Molecular Biophysics & Biochemistry and Chemistry, Yale University
9:30 Computational Redesign of Receptor-Specific Ligands
John Karanicolas, Ph.D., Assistant Professor, Department of Molecular Biosciences, and Center for Bioinformatics, University of Kansas
The encoding of multiple functions in a single cytokine has confounded attempts to understand - and manipulate - cell-cell signaling. We are developing computational protein design methods, and applying these to build novel receptor-specific ligands. These protein variants will in turn allow detailed dissection of cytokine-receptor interactions.
10:00 Networking Coffee Break in the Exhibit Hall
10:45 Protein Therapeutics with Long in vivo Half-Life and Low Immunogenicity by XTEN Fusion
Nathan Geething, Ph.D., Scientist, Process Development, Amunix, Inc.
rPEGs are protein sequences that mimic the polymer properties of polyethylene glycol. Fusion proteins between protein therapeutics and rPEG can be efficiently expressed in E. coli, which eliminates the need for chemical PEGylation. rPEGs are stable in blood but rapidly degraded by intracellular proteases. This provides a significant safety advantage over PEG. rPEG fusion confers long in vivo half-life, enabling week to monthly dosing depending on the payload.
11:15 Albuminfusion—An Excellent Method to Extend the Half-Life of Coagulation Factors
Stefan Schulte, Ph.D., Head, R&D, CSL Behring Marburg GmbH
Patients with hemophilia are suffering from a genetic deficiency of coagulation factors that impose a high risk of bleeding to them. Currently these patients are successfully treated with concentrates that contain the missing coagulation factor. However, the short in vivo half-life of these coagulation factors makes multiple injections necessary, which is inconvenient for both physicians and patients. In order to extend the half-life coagulation factors were fused to albumin. The resulting album infusion proteins displayed comparable biological activity and extended the in vivo half-life significantly.
11:45 Affibody Albumin Binding Technology: A Tool for Half-Life Extension of Biopharmaceuticals
Joachim Feldwisch, Ph.D., Project Manager, Affibody AB
Second generation Affibody molecules are 6.5 kDa affinity proteins based on a non immunoglobulin re-designed scaffold with very rapid in vivo kinetics. A HER2-binding Affibody molecule has proven to be highly suitable for tumor imaging in patients. Rapid blood clearance is however not always optimal for therapeutic applications. Fusing Affibody molecules to an improved femtomolar affinity albumin binding domain (ABD), shifts the plasma half-life from minutes to days. Thus fusion to an engineered ABD convert a short-lived imaging tracer to therapeutic tracer with a half-life long enough to yield efficient cancer treatment. Higher dose to the tumor, longer residence time in blood and drastically decreased dose to the kidneys are some of the new properties of the Affibody molecule when fused to ABD, allowing for complete eradication of xenografts in a murine model.
12:15 pm Close of Morning Session
12:30 Luncheon Presentation or Lunch on Your Own
2:00 Chairperson’s Remarks
Lynne Regan, Ph.D., Professor, Molecular Biophysics & Biochemistry and Chemistry, Yale University
2:05 Recombinant Crystallins for Treatment of Multiple Sclerosis, Atherosclerosis, and Neurodegeneration
Lawrence Steinman, M.D., Professor, Neurology, Stanford University
Small heat shock proteins with a crystallin domain have been effective at treating animal models of multiple sclerosis, atherosclerosis, and show promise in neurodegeneration. sHSP’s including alpha B crystallin inhibit the p38 Map kinase pathway and reduce cleavage of Caspase 3 thus, inhibiting apoptosis. When delivered as therapeutic proteins these sHSP’s are effective and structure activity relationships reveal the active site on these proteins that provides their therapeutic effect.
2:35 Erythrocyte-Targeted scFv-Fibrinolytic Fusions: Preclinical Studies of Prophylactic Thrombolysis
Vladimir Muzykantov, Ph.D., Associate Professor, Pharmacology, University of Pennsylvania
We have devised and tested in animals a paradigm-shifting concept of prophylactic thrombolysis, based on loading fibrinolytic plasminogen activators to erythrocytes. To enable translation of this approach into the clinical domain, we now designed and produced a series of recombinant mutant plasminogent activators fused with anti-erythrocyte scFv. Animal studies show that these fusions safely load on circulating erythrocytes, which prolong drug circulation, restrict side effects and afford effective thromoblysis of clots formed after administration of the drug. This opens the path for swift industrial development of this new of biotherapeutics, for testing a wide spectrum of opportunities for improved management of pro-thrombotic states.
3:05 Latest Advances in Dual-Affinity Retargeting for Oncology and Autoimmunity
Syd Johnson, Ph.D., Vice President, Antibody Engineering, MacroGenics, Inc.
3:35 Poster Presentation: Investigating the Intracellular Fate of Gelonin Immunotoxins (#705)
Christopher Pirie, Biological Engineering, Massachusetts Institute of Technology
3:50 Networking Refreshment Break
4:30 Altering the Tumor Microenvironment with Antibody Fusion Proteins for the Immunotherapy of Cancer
Alan L. Epstein, M.D., Ph.D., Professor, Pathology, Keck School of Medicine, University of Southern California
Fusion proteins provide an ideal tool for targeting molecules to the tumor microenvironment and can provide required signals to reverse immune tolerance and suppression responsible for immune evasion. Using chTNT-3, an antibody that binds preferentially to necrosis present in all tumors, our laboratory has generated a series of fusion proteins consisting of cytokine, chemokine, co-stimulatory molecules, and innate immune activators to treat several syngeneic murine solid tumor models in order to identify those reagents or combinations that may be translatable to man. Special emphasis on the detection, mechanism of action, and therapy of suppressor cell populations in the tumor microenvironment has been made in these investigations. To date, therapeutic protocols have been devised which can reverse tolerance in both early and advanced tumor models demonstrating the potential of this approach for the treatment of solid tumors.
5:00 Recombinant Immunotoxins for the Treatment of Hematologic Malignancies
Robert J. Kreitman, M.D., Principal Investigator, Clinical Immunotherapy Section, National Cancer Institute (NCI), National Institutes of Health (NIH)
Recombinant immunotoxins are fusions proteins containing a protein toxin connected to a variable fragment (Fv) of a monoclonal antibody so that the targeting molecule can be produced from bacteria without chemical conjugation. LMB-2 is a single-chain anti-CD25 recombinant immunotoxin with reported activity in hematologic malignancies undergoing phase II testing in patients with cutaneous T-cell lymphoma (CTCL), chronic lymphocytic leukemia (CLL), adult T-cell leukemia (ATL), and hairy cell leukemia (HCL). BL22 is a disulfide stabilized anti-CD22 recombinant immunotoxin reported to have a high complete remission (CR) rate in patients with HCL despite failure of standard chemotherapy. HA22 (CAT-801), a high affinity mutant of BL22, is much more cytotoxic than BL22 toward cells with limited CD22 expression, particularly CLL, and is currently undergoing phase I testing in HCL, CLL and non-Hodgkin’s lymphoma.
5:30 Reception in the Exhibit Hall
6:30 Close of Day
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