PepTalk 2017
PepTalk 2017
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Cambridge Healthtech Institute’s Thirteenth Annual
Recombinant Protein Therapeutics
Fusion Proteins and Beyond
January 9-10, 2017 | Hilton San Diego Bayfront | San Diego, CA


By combining modular building blocks that can reach targets not accessible to antibodies, Fusion Protein Therapeutics possess advantages over antibody-based therapies. Fusion Proteins’ customizable functionality translates into 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 will disclose how these proteins 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.

SUNDAY, JANUARY 8

4:00 - 5:30 pm Registration

5:00 - 8:00 Dinner Short Courses

MONDAY, JANUARY 9

7:30 am Conference Registration and Morning Coffee

INNOVATING PROTEIN THERAPEUTICS

9:00 Welcome by Conference Organizer

Mary Ruberry, Senior Conference Director, Cambridge Healthtech Institute

9:05 Chairperson’s Opening Remarks

Jennifer R. Cochran, Ph.D., Associate Professor, Bioengineering, Stanford University


Keynote Presentation

9:10 Fusion Protein Strategies for Generation of Biobetters

William_StrohlWilliam R. Strohl, Ph.D., Vice President and Head, BioTherapeutics, Janssen R&D, Pharmaceutical Companies of Johnson & Johnson

The concept of making a “biobetter” biologic is to improve on the salient characteristics of a known biologic having clinical proof-of-concept or marketed product data. There already are several examples of biobetter biologics such as Neulasta®, a PEGylated, longer half-life version of Neupogen®, and Aranesp®, a longer half-life version of Epogen®. This presentation describes the use of protein fusion technologies to make biobetter drugs with more desirable pharmacokinetic profiles.

9:50 Therapeutic Strategies Combining Specificities on the Outside and Inside of Cells

Stefan_DübelStefan Dübel, Ph.D., Professor and Head, Biotechnology, Technische Universität Braunschweig

We designed novel fusion proteins providing a cell-specific delivery of an intracellular regulator of immune activation. The E-selectin–specific “Sneaking Ligand” fusion protein inhibited NF- κB by interfering with endothelial IκB kinase 2 activity inside the cells in vitro and in vivo. The treatment drastically reduced the extravasation of inflammatory cells murine experimental peritonitis and significantly ameliorated the disease course in murine models of rheumatoid arthritis.

10:20 Coffee Break

RECOMBINANT PROTEINS TO HEAL AND FIGHT DISEASE

10:45 IgG Fusion Protein Therapeutics for CNS Treatment of Rare Disorders: Rett Syndrome and Lysosomal Storage Disorders

Ruben_BoadoRuben J. Boado, Ph.D., Vice President and Co-Founder, ArmaGen, Inc.

Protein therapeutics can be re-engineered as brain-penetrating IgG-fusion proteins for the CNS treatment of rare disorders, like Rett Syndrome and Lysosomal Storage Disorders (LSD). The protein therapeutic domain of the fusion protein exerts the pharmacological effect in the brain once across the BBB. Several brain penetrating enzyme fusion proteins have been engineered for LSD, and potentially for the treatment of Rett Syndrome. First-in-human clinical LSD trials are in progress.

11:15 Blocking IL-17A with Unparalleled Affinity Using an Engineered Affibody-Based Ligand Trap

Joachim_FeldwischJoachim Feldwisch, Ph.D., Director, Preclincal Development, Research, Affibody AB

Psoriasis is an IL-17-driven disease. An Affibody®-based ligand trap engineered to block IL-17A with femtomolar affinity will be described. The ligand trap has dual binding specificities and consists of two small Affibody® domains for IL-17A inhibition and an albumin binding domain for half-life extension. Clinical data confirm the expected half-life extension effect of the albumin binding domain and data from the ongoing first-in-human clinical trial will be provided.

11:45 Development of the Pharmacologically Highly Active Endogenous Protein Stathmin-1 to Treat Chronic Wounds

Manfred_SchusterManfred Schuster, Ph.D., CEO, RMB-Research GmbH

Stathmin-1 is a small, highly conserved protein, which was identified as an intra-cellular modulator of the eukaryotic cytoskeleton. We overtook development of this pharmacologically potent biologic and have started to investigate its therapeutic potential in a topical formulation to eventually treat chronic, not healing wounds. This presentation highlights our troubleshooting program, which identified and overcame several mistakes from previous development activities, and describes how we will address further clinical issues.

12:15 pm Extending Drug Half-Life to Achieve Monthly Dosing? The Potential of Veltis® Engineered Albumins for Optimized Dosing

Karen_BuntingKaren Bunting, Ph.D., Science Director, Molecular Biology & Fermentation, Albumedix Ltd.

Short circulatory half-life represents a major obstacle for many protein and peptide-based therapeutics. This can be significantly improved by conjugation or fusion to albumin, due to increased size and recycling via the neonatal Fc receptor (FcRn). The increased FcRn affinity of the Veltis® engineered albumins translates to more than doubling of the already long half-life of native albumin. We will describe rationally engineered albumins and their application to improve the pharmacokinetic properties of therapeutic candidates.

12:45 Session Break

1:00 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

FIGHTING CANCER

2:00 Chairperson’s Remarks

Yanzhang Wei, Ph.D., Professor, Biological Sciences, Clemson University

2:05 Targeted Thorium Conjugates: Novel First in Class Alpha Pharmaceuticals

Jenny Karlsson, Ph.D., Head, TCR Biochemistry, Thorium Conjugate Research, Bayer AS

Targeted Thorium Conjugates (TTCs) have the potential to deliver localised cell-killing power of alpha-particle emission directly to tumour cells by combining the highly potent alpha-particle emitter, thorium-227. Advantages of TTCs are the lack of cellular resistance mechanisms to alpha-particle emission and their ability to kill non-dividing cells. A specific chelator technology has been developed to ensure stable binding of thorium-227 to targeting molecules such as monoclonal antibodies. Preclinical in vitro and in vivo data will be presented.

2:35 Bispecific TNFR-Superfamily Agonists for Tumor Localized Immune Modulation

Shane_OlwillShane Olwill, Ph.D., Vice President, Development and Head, Immuno-Oncology, Pieris Pharmaceuticals, Inc.

While multiple lines of evidence show that TNFR superfamily members are highly promising therapeutic targets in cancer, mAb-based approaches are not designed to achieve a tumor-target-driven activation of these pathways and may display a limited therapeutic window due to peripheral T cell and / or NK cell activation. To overcome this limitation, Pieris has generated bispecific TNFR-Superfamily Agonists that are only activated when they bind to a specific receptor on a tumor cell.

3:05 Sponsored Presentation (Opportunity Available)

3:20 Refreshment Break in the Exhibit Hall with Poster Viewing

4:00 Engineered Ligand and Receptor Based Fusion Proteins as Next-Generation Cancer Therapeutics

Jennifer_CochranJennifer R. Cochran, Ph.D., Associate Professor, Bioengineering, Stanford University

We use natural ligands and receptors as scaffolds for protein engineering to leverage their inherent biophysical and biochemical properties. I will present our recent data on therapeutic candidates engineered to possess high affinity and unique specificities for applications in oncology.

4:30 Strategies for Improving Current Enzyme-Based Therapy of Acute Lymphoblastic Leukemia: Molecular Engineering and Directed Evolution of Human L-Asparaginases

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

The therapeutic effect of the enzyme drug L-asparaginase (L-ASNase) relies on the fact that in cancerous cells of acute lymphoblastic leukemia (ALL) the metabolic enzyme asparagine synthetase is downregulated. We designed in vitro evolved human enzymes displaying ASNase activity to identify catalytically improved variants. Furthermore, to increase the serum half-life of the proteins, we loaded L-ASNases into biocompatible microcapsules, thus enhancing serum stability and preventing exposure of the enzyme to the immune system.

5:00 Reshaping the Immunosuppressive Tumor Microenvironment: The Fusion Protein Strategy

Yanzhang Wei, Ph.D., Professor, Biological Sciences, Clemson University

Advanced tumor cells often create immunosuppressive microenvironment. The conversion of the environment from immunosuppressive to immunoactive holds hopes for effective cancer immunotherapy. Fusion proteins coupled with appropriate delivery approaches represent a promising strategy for this conversion. In the last decade, we created various fusion cytokine proteins (GPI-anchored IL-2/IL-12, MULT1E/FasTI, MULT1E/IL-12, IL-12/FasTI) and demonstrated their anticancer activities. We are in the process of developing effective methods to deliver the fusion proteins specifically into tumors.

Buzz Sessions5:35 BuzZ Session A

Join your peers and colleagues for interactive roundtable discussions.

6:20-7:30 Welcome Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

TUESDAY, JANUARY 10

8:00 am Conference Registration and Morning Coffee

ALBUMIN FUSION PROTEINS

8:30 Chairperson’s Remarks

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

8:35 FcRn Mediated Intracellular Trafficking and Recycling of Albumin Fusion Protein Therapeutics

Anne Verhagen, Ph.D., Group Leader, Cellular Biochemistry, CSL Limited

Albumin and IgG are abundant plasma proteins with long half-lives owing to an efficient recycling system mediated by the neonatal Fc receptor (FcRn). Fusion to Fc or albumin provides a mechanism for otherwise short-lived proteins to engage with the FcRn recycling system and avoid lysosomal degradation. We have developed novel cellular assays to track the movement of FcRn therapeutic ligands through the early, lysosomal and recycling endosomes.

9:05 Human Serum Albumin Fusion Proteins Function as Therapeutics as Well as Drug Carriers for Synergistic Cancer Treatment

Zhiyu_LiZhiyu Li, Ph.D., Associate Professor, Pharmaceutical Sciences, Philadelphia College of Pharmacy

HSA and p53-derived peptide fusion protein (rHSA-p53i) induces cytotoxicity irrespective of p53 status in cancer cells. Fatty acid-modified 5-flurouracil and paclitaxel form stable non-covalent complexes with rHSA-p53i. This new formulation co-delivers two or more therapeutics together to one target. Chemotherapeutics cause DNA damage and induce apoptosis, while rHSA-p53i enhances apoptotic responses of cancer cells. The synergistic therapeutic efficacies of this approach have been well demonstrated in SJSA-1 and MDA-MB-231 xenograft mouse models.

9:35 Sponsored Presentation (Opportunity Available)

9:50 Coffee Break in the Exhibit Hall with Poster Viewing

EFFICACIOUS ENGINEERING

11:00 Effects of Protein Aggregates on Fc Receptor Binding of Fusion Protein and Antibody Therapeutics

Marina Feschenko, Ph.D., Senior Scientist, Analytical Development, Biogen

11:30 Antibody Glycosylation and Its Impact on the Pharmacokinetics and Pharmacodynamics of Monoclonal Antibodies and Fc-Fusion Proteins

Liming Liu, D.Phil., Principal Scientist, Pharmacokinetics, Pharmacodynamics and Drug Metabolism (PPDM), Merck Research Laboratory

Understanding the impact of glycosylation and keeping a close control on glycosylation of product candidates are required for both novel and biosimilar monoclonal antibodies (mAbs) and Fc-fusion protein development to ensure proper safety and efficacy profiles. This presentation will review and discuss the impacts of major glycans on the pharmacokinetics (PK) and pharmacodynamics (PD) of mAb and Fc-fusion proteins.

12:00 pm Sponsored Presentation (Opportunity Available)

12:30 Session Break

12:45 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Close of Conference