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. This meeting explores the varying constructs and ‘designs’ of fusion protein molecules, and will disclose 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.


7:00 am Registration and Morning Coffee

The Promise of Fusion Proteins

8:30 Chairperson’s Remarks

Eric Furfine, Ph.D., Chief Scientific Officer and Acting Chief Executive Officer, ImmuneXcite, Inc.


Fusion Proteins: Introduction to the Field and Case Studies from Roche’s Research & Early Development Pipeline

Stefan_WeigandStefan Weigand, Ph.D., Head, Large Molecule Research, Roche Pharma Research and Early Development (pRED), F.
 Hoffmann-La Roche, Ltd.

This talk will introduce the concept of fusion proteins and provide examples from Roche’s pipeline how to discover, design, develop and deliver differentiated, multi-functional therapeutics that allow for tailored solutions for the biological
 problem at hand. In this presentation, I will describe Roche’s strategies to discover and design such molecules, give examples but will also address challenges for technical development.

9:10 Fc Fusion Coagulation Factors for Improved Hemophilia Therapies: Clinical Development of rFVIIIFc and rFIXFc

Baisong_MeiBaisong Mei, M.D., Ph.D., Senior Director, Global Clinical Development, Biogen

Longer-acting coagulation factors FVIII and FIX would represent a key advancement in the management of hemophilia A and B. Biogen has developed a novel monomeric recombinant Fc fusion technology to extend the half-life of coagulation factors. The safety,
 efficacy, and prolonged half-life of rFVIIIFc and rFIXFc were demonstrated in clinical studies. rFVIIIFc and rFIXFc have been approved in US and other countries.

9:40 Fusion Protein Design: Consequences for Manufacturability

Stefan_SchmidtStefan Schmidt, Ph.D., MBA, Vice President, Process Science and Production, Rentschler Biotechnologie GmbH

Fusion proteins are generated by artificially combining unrelated domains not connected in nature, resulting in novel properties and promise for therapeutic success. The specific design of these engineered proteins requires highly specific process development
 strategies and adaptations during manufacturing that differ from traditional platform approaches. Here I demonstrate in a number of examples what general principles to follow to meet critical manufacturing parameters.


10:10 Coffee Break

Engineering Improved Properties

10:50 Overcoming AAT Deficiency with Recombinant AAT-Fc: An Optimized Therapeutic for Improved Efficacy

John_TimmerJohn Timmer, Ph.D., Research Director, InhibRx LLC

AAT deficient patients are treated with serum derived AAT at high doses weekly. However, sdAAT is rapidly cleared leaving patients susceptible to lung degradation by neutrophil elastase. Inhibrx has developed a recombinant AAT-Fc with improved properties
 (extended half-life, and oxidation resistance) that is highly protective in a model of acute lung injury. Bi-weekly or monthly dosing with Inhibrx’s AAT-Fc is expected to be more efficacious than sdAAT.

11:20 Epsi-gam: A Novel Fusion Protein for the Treatment of Asthma and Other Allergic Diseases

Nolan_SigalNolan Sigal, M.D., Ph.D., President and CEO, Tunitas Therapeutics, Inc.

Epsi-gam is a genetically engineered and expressed bifunctional human fusion protein that is comprised of the Fc portions of human IgE and IgG1. This platform was designed to link the receptors for IgE on basophils, mast cells and B cells with the
 inhibitory FcγRIIb receptor on these cells and thereby inhibit their function. This intervention is designed as a therapeutic agent for the treatment of asthma and other serious allergic diseases.

11:50 MabXcite: A Novel Technology that Elicits the Innate and Adaptive Immune Responses to Kill Tumor Cells

Eric_FurfineEric Furfine, Ph.D., Chief Scientific Officer and Acting Chief Executive Officer, ImmuneXcite, Inc.

While the field of immuno-oncology has historically focused on the adaptive immune system, ImmuneXcite is executing a targeted approach that leverages the power of the body’s innate and adaptive immune systems in pursuit of effective treatments for cancer. ImmuneXcite’s product platform, mAbXcite, is based on discoveries which identified a unique fungal carbohydrate responsible for stimulating the innate immune system—the immune system’s first response against fungal infections. These carbohydrates are covalently attached to tumor-targeting monoclonal antibodies, which specifically attract complement that then recruits other immune cells, such as neutrophils, to kill tumor cells. This innate immune response subsequently primes the natural adaptive immune response to further limit tumor growth and metastasis.


 pm Optimized Serum Half-Life Extension with Veltis® Engineered Albumins

Blunting_KarenKaren 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.

12:50 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on your Own

1:50 Session Break

2:20 Problem-Solving Breakout Discussions

1. Immunotoxins/Fusion Toxins
Moderator: Zhirui Wang, Ph.D., Assistant Professor, Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School

  • Immunogenicity of the immunotoxin
  • In vivo half-life of the recombinant immunotoxin
  • Expression of the recombinant immunotoxin
  • Chemical conjugated immunotoxin vs. recombinant immunotoxin
  • Immunotoxin vs. mAb

2. Immunotherapy
Moderator: Dario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich

  • Immunomodulatory strategies: stimulation vs. inhibition of the immune system
  • Intact antibodies vs. antibody derivatives (e.g., immunocytokines, bispecific antibodies)
  • Balance between therapeutic activity and safety aspects
  • Understanding the mechanism of action (dissecting the contribution of T cells, NK cells, macrophages and other leukocytes)
  • Profiling T cell specificities (e.g., TCR sequencing, multiplex tetramer technology, peptide-based stimulation assays)
  • Therapeutic vaccines

3. Clinical Challenges of Fusion Proteins Compared to Monoclonal Antibodies and How to Address Them
Moderator: Matthieu Chodorge, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering, MedImmune, Ltd.

  • Pharmacokinetics, exposure and dosing regimen
  • Manufacturing and characterization of clinical batches drug substance
  • Regulatory and interactions with governmental agencies
  • Safety and immunogenicity
  • Efficacy and mode of action notably for agonist and multispecific compounds

  • 4. Transition of Projects from Discovery to Development: What are Important Points to Consider or Lessons Learned?
    Moderator: Stefan Schmidt, Ph.D., MBA, Vice President, Process Science and Production, Rentschler Biotechnologie GmbH

    • Manufacturability
    • Developability
    • What are the key parameters?

    • 5. Next-Generation Drug Conjugates: Non-Antibody Based Scaffolds
      Moderator: Darrell Sleep, Ph.D., CSO, Albumedix Ltd.

      • Advantages and disadvantages of non-antibody based scaffolds as novel therapeutic approaches
      • Overcoming half-life shortcomings of non-antibody based scaffolds
      • Clinical and manufacturing challenges of non-antibody based scaffolds

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


      4:00 Chairperson’s Remarks

      4:10 The Promise of Cancer Immunotherapy: An Overview of Recent Advances and Jounce’s Approach to Delivering the Right Therapy to the Right Patient

      Deborah_LawDeborah Law, D. Phil. CSO Jounce Therapeutics, Inc.

      As immunotherapies become an increasingly important component of cancer treatment the challenge will be to identify ways to provide the best therapy(s) to the individual. This presentation will provide an overview of current cancer
 immunotherapies as well as highlight some of the challenges ahead including selection of optimal combinations, moving outside of T cell-directed approaches, and will highlight how Jounce Therapeutics is using its Translational
 Science Platform as an approach to develop and deliver the right therapy to the right patient.

      4:50 Antibody as Drugs: Then, Now and Tomorrow

      Paul_CarterPaul J. Carter, Ph.D., Senior Director and Staff Scientist, Antibody Engineering, Genentech

      Antibodies have grown into a clinically and commercially important drug class with more than >45 antibodies marketed for imaging or therapy in the USA and/or Europe and with ~$63 billion in worldwide sales in 2013.  This presentation
 will highlight progress in developing antibody drugs and consider opportunities for future innovation.  



      5:30 Welcome Reception in the Exhibit Hall with Poster Viewing

      6:45 End of Day


      8:00 am Morning Coffee


      8:25 Chairperson’s Remarks

      Stefan Schmidt, Ph.D., MBA, Vice President, Process Science and Production, Rentschler Biotechnologie GmbH

      8:30 Immunocytokines for the Therapy of Cancer and of Chronic Inflammation: From the Bench to Phase II Clinical Trials

      Dario_NeriDario Neri, Ph.D., Professor, Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, ETH Zürich

      Certain monoclonal antibodies can be used as vehicles for the selective pharmacodelivery of potent immunomodulatory payloads, including cytokines. In this lecture, I will review our work in the field and present the most recent clinical
 data, originating from on-going Phase II clinical trials.

      9:00 Combination Immunotherapy Enabled by a Tumor-Targeting Peptide-Fc Fusion

      Jennifer_ChochranJennifer R. Cochran, Ph.D., Associate Professor, Bioengineering and Chemical Engineering,
 Stanford University

      I will discuss an engineered peptide-Fc fusion protein that we have adapted for targeted delivery of chemotherapeutic agents, as well as recruitment of immune cell effector functions to tumors. The co-administration of peptide-Fc fusion
 and an immune stimulating cytokine results in significant control of tumor growth in melanoma and colon carcinoma models, which is further enhanced by combination with checkpoint blockade inhibitors.

      9:30 Diphtheria-Toxin Based Anti-Human CCR4 Immunotoxin for Targeting Human CCR4+ Tumors and Tregs

      Zhirui_WangZhirui Wang, Ph.D., Assistant Professor, Center for Transplantation Sciences, Massachusetts General Hospital
 and Harvard Medical School

      We have successfully developed an anti-human CCR4 immunotoxin using yeast Pichia Pastoris expression system. In vivo efficacy for targeting CCR4+ tumors was assessed using human CCR4+ tumor-bearing NSG mouse model. In vivo efficacy for depleting CCR4+ Tregs was characterized in two naïve cyno monkeys. This immunotoxin is a promising drug candidate for targeting human CCR4+ tumors and Tregs.

      10:00 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Awards

      Peptide Fusions

      10:50 Engineering of a GLP-1 Analogue Peptide in Fusion with a PCSK9 Antibody for Type 2 Diabetes Patients at High Cardiovascular Risk

      Matthieu_ChodorgeMatthieu Chodorge, Ph.D., Senior Scientist, Antibody Discovery and Protein Engineering,
 MedImmune, Ltd.

      In addition to high blood glycose, Type 2 diabetic patients often have an impaired cholesterol balance and are at greater risk of cardiovascular disease. We have developed a GLP-1 receptor agonist peptide in fusion with a PCSK9 antibody
 to provide glucose control and LDL cholesterol reduction in one molecule. Here we will present how the fusion has been exquisitely engineered to deliver optimum pharmacology on both axis and adequate manufacturability.

      11:20 Apolipoprotein A-I as a Novel Scaffold for Protein Delivery

      Pedro_BerraondoPedro Berraondo, Ph.D., Researcher, Program of Immunology & Immunotherapy, University of Navarra

      Clinical use of therapeutic proteins and peptides is limited by the short half-life in circulation and the absence of a specific targeting. Fusion to apolipoprotein A-I is a strategy to improve the pharmacokinetic and pharmacodynamics
 properties: the half-life in circulation is improved, the fusion proteins are targeted to the liver and tumors, the blood brain passage is modified and the activity of the fused protein is modulated by the interaction with the scavenger
 receptor class B type I.


      11:50 Human Serum Albumin and p53-Derived Peptide Fusion Protein Promotes Cytotoxicity Irrespective of p53 Status in Cancer Cells

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

      Human serum albumin (HSA) fusion protein is a feasible and effective approach to target and inhibit essential intracellular pathways. HSA and p53-derived peptide fusion protein (rHSA-p53i) binds to 4 intracellular proteins, including
 MDM2, MDMX, BCL-XL, and Mcl-1. Therefore, rHSA-p53i is capable of promoting cytotoxicity irrespective of p53 status (wild type, mutation, and deficiency). Moreover, rHSA-p53i can carry fatty acid-modified chemotherapeutics for
 synergistic therapeutic efficacy.

      12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on your Own

      1:20 Ice Cream Break in the Exhibit Hall with Poster Viewing


      2:00  Chairperson’s Remarks

      Zhirui Wang, Ph.D., Assistant Professor, Center for Transplantation Sciences, Massachusetts General Hospital and Harvard Medical School

      Increasing the Proteolytic Stability of Affibody Molecules by Intramolecular Cross-Linking
      Anders Nilsson, Ph.D. Student, Biotechnology, Royal Institute of Technology (KTH)

      2:35  A Novel Protease-Based Fusion Protein Platform with Utility across a Range of Disease Areas

      Nathanial_GordonNathaniel Gordon, Ph.D., Senior Scientist, MedImmune, Ltd.

      Proteases have a unique mechanism of action and could offer a number of therapeutic advantages relative to neutralizing monoclonal antibodies, however their practical realization is impeded by the difficulty in engineering protease
 specificity. We have bypassed limitations in protease engineering by designing protease-fusion proteins with a modular, multi-domain architecture, in which specificity and hydrolytic activity are conferred by complementary domains.
 Further engineering principles and therapeutic implications of our platform will be discussed.

      3:05  Multiple Domain Challenges of Fc Fusions and Fab Fusion Bispecific Antibodies

      Tu_HuaHua Tu, Ph.D., Chairman and CEO, LakePharma, Inc.

      We will describe several fusion platform technologies, addressing challenges arising from the multiple domain nature of fusion protein therapeutics. Case studies showing successful engineering of Fc fusions and bispecific antibodies
 will be presented, including applying integrated solutions to protein design and engineering, activity testing, bioanalytical characterization, and manufacturability assessment.

      3:35 Refreshment Break in the Exhibit Hall with Poster Viewing

      Innovating Technologies

      4:25 Target-Engaged Complementation: Replacing ELISA and Resurrecting ADEPT

      Shawn_OwenShawn Owen, Ph.D., Assistant Professor, Pharmaceutics and Pharmaceutical Chemistry, University of Utah

      We are developing a technology, termed Target Engaged Complementation (TEC), which utilizes enzymes split into inactive components. Each fragment is fused to an individual antibody Fab; the binding of the Fabs forces the split enzyme
 fragments into proximity where they refold to the active form. The activity of the split enzyme is used to activate luminescence for diagnostic applications or activate prodrug for therapeutic applications.


      4:55 Therapeutic Strategies Combining Specificities on the Outside and Inside: Ligands Sneaking into Cells

      Stefan_DübelStefan Dübel, Ph.D., Director, Biotechnology, Technical University of Braunschweig

      Our “Sneaking Ligand” fusion proteins provided 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.

      5:25 End of Fusion Protein Therapeutics

      5:30 Registration for Dinner Short Courses*

      *Separate registration required