2014 Archived Content
Cambridge Healthtech Institute’s Tenth Annual
Recombinant Protein Therapeutics
Fusion Proteins and Beyond
January 13-14, 2014
By combining modular building blocks, fusion protein therapeutics have an advantage over antibody-based therapies resulting in a customizable functionality. Fusion protein therapeutics can also access several targets on different proteins or on the same protein with the potential to reach targets that are not accessible to antibodies. Additional advantages include lower patient dosing, reduced production costs and improved product homogeneity. This meeting will explore the varying constructs and "designs" of fusion protein therapeutics, and will discuss how they are being engineered to form more efficacious therapeutics that offer specificity with enhanced stability and longer half life. Experts will present case studies from R&D through clinical data, and will share the results they’ve achieved.
Please join leaders from around the world for this in-depth discussion of the innovations being developed for the next-generation protein-based therapeutics.
Day 1 | Day 2 | Download Engineering Brochure | Speaker Biographies
SUNDAY, JANUARY 12
4:00-5:00 pm Short Course Registration
5:00-8:00 Dinner Short Courses (SC1-SC7) More Details >>
4:00-8:00 Main Conference Registration
MONDAY, JANUARY 13
7:30 am Conference Registration and Morning Coffee
9:00 Chairperson’s Opening Remarks
Stefan Schmidt, Ph.D., Vice President, DSP, Rentschler Biotechnology
9:10 Recombinant Immunotoxins as New Approaches to Cancer Treatment
Ira H. Pastan, M.D., Head, Molecular Biology, NCI, NIH
Recombinant immunotoxins (RITs) are chimeric proteins composed of an Fv that binds to an antigen on cancer cells attached to a portion of Pseudomonas exotoxin A. We have made a RIT targeting CD22 on B cell malignancies named Moxetumomab pasudotox and mesothelin on mesothelioma and other solid tumors (pancreas, lung, stomach and breast) named SS1P. In clinical trials Moxe has shown anti-tumor activity in Hairy Cell Leukemia and acute lymphoblastic leukemia and SS1P in mesothelioma. The results of these trials and efforts to improve the activity of these agents will be discussed.
9:50 Antibody-Interferon Fusion Protein for the Treatment of Malignancy
Sherie Morrison, Ph.D., Professor, Microbiology Immunology & Molecular Genetics, University of California, Los Angeles
Type I interferons (IFNa/IFNb) are potent regulators of cell growth with inhibitory effects against many cancers. However, their clinical use has been limited by the inability to achieve effective IFN concentrations at the tumor without systemic toxicity. We addressed this limitation by using antibodies recognizing tumor-associated antigens to carry IFNs to cancer sites. Genetically fusing IFN to anti-CD20 or anti-CD138 results in molecules effective in treating CD20 expressing tumors such as lymphoma and CD138 expressing tumors such as multiple myeloma.
10:20 Coffee Break
10:45 Featured Presentation:
Cytokine Traps: From Engineering Concept to Clinical Development
Aris N. Economides, Ph.D., Senior Director, Genome Engineering Technologies Group & Skeletal Diseases TFA Group, Regeneron Pharmaceuticals, Inc.
Cytokine Traps are heteromeric receptor ectodomain-Fc fusion proteins that act as high-affinity blockers for their cognate ligands. The design principle underlying Cytokine Traps is to mimic the ligand-receptor signaling complexes of cytokines that utilize multicomponent receptors. The particular combination of receptor subunits determines specificity, whereas configuration into preformed “complexes” imparts high affinity. Cytokine Traps have been engineered for many cytokines, and two have reached clinical approval: IL1 Trap and VEGF Trap. Their engineering and development will be presented.
11:15 Ultra-High Affinity Engineered Protein Therapeutics for Treating Metastatic Disease
Jennifer Cochran, Ph.D., Associate Professor, Bioengineering & Chemical Engineering, Stanford University
A soluble receptor was used as a therapeutic strategy to inhibit the biological activity of a ligand involved in cancer metastasis. Combinatorial and rational methods were used to engineer variants that bound ligand with affinities in the femtomolar range. The engineered receptors exhibited a remarkable ability to inhibit cancer metastasis in several aggressive tumor models in contrast to the wild-type receptor which was only marginally effective.
11:45 Re-Engineering Recombinant Protein Therapeutics for Penetration of the Blood-Brain Barrier Via Transport on the Human Insulin Receptor
Ruben Boado, Ph.D., President, ArmaGen Technologies, Inc.
AmaGen’s platform technology enables re-engineering of recombinant protein therapeutics for penetration of the blood-brain barrier (BBB). 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 human insulin receptor (HIR). The therapeutic domain of the IgG fusion protein exerts the pharmacological effect in brain once across the BBB. Several bi-functional IgG-fusion proteins have been engineered using a genetically engineered monoclonal antibody directed to the BBB HIR as the transport domain. First in human clinical trials are planned for 2014.
12:15pm Extending Serum Half-life of Albumin by Engineering FcRn Binding
Jason Cameron, Science Manager, Pharma R&D, Novozymes Biopharma UK Ltd
Through modification of the Human albumin molecule, we have altered the affinity to the FcRn receptor and have been able to demonstrate extended serum half-life of a range of albumin variants in in vivo models. This innovative technology provides an attractive approach for optimizing the serum half-life of biopharmaceuticals.
12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own
2:00 Chairperson’s Remarks
Xiaotian Zhong, Ph.D., Principal Scientist & Lab Head, GBT, Pfizer Global BioTherapeutic R&D
2:05 ImmTACs – Novel Bi-Functional Monoclonal T Cell Receptor Fusions
Annelise Vuidepot, Ph.D., Head, Protein Engineering & Biochemistry, Immunocore, Ltd.
ImmTACs (Immune mobilising mTCR Against Cancer) are bispecific biologics comprising a soluble, high-affinity T cell receptor fused to an anti-CD3 scFv-based effector function. The TCR moiety targets disease-specific HLA-peptides with extremely high affinity (typically <50pM), simultaneously decorating the target cell with lower affinity (nM) CD3-specific scFv fragments. Any T cell that comes into direct physical contact with an ImmTAC-decorated cell is automatically redirected to kill the cancer cell, regardless of the T cell’s native antigen specificity.
2:35 Targeting Intracellular Protein-Protein Interactions with Engineered Cyclotides
Julio A. Camarero, Ph.D., Associate Professor, Pharmacology and Pharmaceutical Sciences, University of Southern California
Here, we report the engineering of the cyclotide MCoTI-I to efficiently antagonize intracellular p53 degradation. The resulting cyclotide MCo-PMI was able to bind with low nanomolar affinity to both Hdm2 and HdmX, showed high stability in human serum and was cytotoxic to wild-type p53 cancer cell lines by activating the p53 tumor suppressor pathway both in vitro and in vivo. These features make the cyclotide MCoTI-I an optimal scaffold for targeting intracellular protein-protein interactions.
3:05 i-Bodies: Single Domain Human Scaffolds as Novel Therapeutics
Mick Foley, Ph.D., CSO, Biochemistry, AdAlta
The i-body scaffold is a new human scaffold that is able to target molecules such as GPCRs that have been difficult to target using traditional MAb approaches. Combining high affinity, exquisite specificity, and extraordinary stability, i-bodies have been identified to a number of molecular targets and are proceeding through preclinical studies. i-bodies are small and extremely stable, yet can exhibit high affinity and specificity they occupy a niche between antibodies and small molecules.
3:35 Extended Q&A
3:50 Refreshment Break
4:15 Albumin Fusion Technology: A Highly Efficient Method to Extend the Half-Life of Complex Proteins
Thomas Weimer, Ph.D., Director, Recombinant Technology, CSL Behring GmbH
Haemophilia and von Willebrand disease are disorders characterized by deficiency of a single coagulation factor. Current treatment is based on replacement therapy applying the missing coagulation factor. To improve these therapies it is desirable to reduce the dosing frequency by improving the pharmacokinetic properties of these factors. Albuminfusion technology has been successfully applied to extend the half-life of coagulation factors resulting in fully active molecules with a significantly, therapeutically relevant half-life extension.
4:45 XTEN: A Protein-Based Polymer for Targeted Drug Delivery
Volker Schellenberger, Ph.D., CEO and President, Amunix
Amunix has developed XTEN, a protein-based polymer that mimics the biophysical properties of PEG but without its limitations. XTEN can be produced in high-titer microbial fermentation yielding a polymer that with chemically defined structure and a precisely defined number and location of conjugation sites. XTEN-drug conjugates have very low systemic toxicity as XTEN prevents non-specific tissue uptake of drug moities. Targeting domains can be recombinantly fused or chemically conjugated to confer tumor-selective uptake of XTEN-drug molecules.
5:15 Engineered Affibody Molecules in Multiple Formats for Targeted Therapy and Diagnosis
Joachim Feldwisch, Ph.D., Director, Preclinical Development, Affibody AB
Affibody molecules are small scaffold proteins with high specificity, tunable kinetics and biodistribution making them highly suited for targeted therapy. The ease of production as well as high stability allows the design of mono and multi-specific drugs for use as antagonists, vehicles for payload delivery and molecular imaging. Functionalizing antibodies with different Affibody molecules for better efficacy by creating fusion proteins opens novel ways for drug design.
5:45-7:00 Welcome Reception in the Exhibit Hall
Day 1 | Day 2 | Download Engineering Brochure | Speaker Biographies