March 26-28, 2019

Boston, USA

Day One
WEDNESDAY, MARCH 27, 2019

Day Two
THURSDAY, MARCH 28, 2019

08.00
Breakfast & Networking

08.25
Chair’s Opening Remarks

  • Jack Ragheb Senior Medical Fellow for Immunology- Global Patient Safety , Eli Lilly

Optimization of Tolerance Delivery Systems & Translation of Antigen-Specific Tolerance Strategies into Clinic

08.30
Mechanisms Underlying Tolerance Induction with Antigen- Encapsulating PLG Nanoparticles

  • Stephen Miller Co-founder of Cour Pharmaceutical; Professor of Microbiology-Immunology , Northwestern University Medical School

Synopsis

  • Tolerance induction using antigen-encapsulating PLG nanoparticles (Ag-PLG) recapitulates how self-tolerance is maintained in the hematopoietic system
  • Ag-PLG uptake by splenic and liver APCs confers a tolerogenic phenotype
  • Ag-PLG induces the induction of CD4+Foxp3+ and CD8+CD122+ regulatory T cells

09.00
Antigen-Specific Targeting of B cells in Type 1 Diabetes

  • David Alleva Executive Director- Immunotherapeutics , Akston Biosciences

Synopsis

  • Insulin-specific B cells promote T1D pathogenesis by acting as antigen-presenting cells (APCs) that activate pathogenic effector T cells
  • Antigen-specific deletion of such B cells has not yet been successful, mainlybecause of the requirement of a fully-conformational antigen that contains a deletional mechanism. Akston has created such a therapeutic, AKS-107
  • The presence of autoantibodies produced by autoreactive B cells allows for feasible clinical biomarker assays for both entry criteria (patient stratification) and therapeutic response monitoring

09.30
Soluble Antigen Arrays’ Mimic Peripheral Tolerance to Intercept Autoimmune Disease and Restore Health

Synopsis

  • The importance of restoring tolerance mechanisms after an autoimmune break
  • The role of physiochemical as well as molecular properties in therapeutic design
  • The value of leveraging safety in early stage or adolescent autoimmune disease patients

10.00
Morning Refreshments & Networking

10.30
Preparation of Liver-Targeting Nanoparticles for Clinical Trials

Synopsis

  • The liver as tolerance mediator
  • Nanoparticles as therapeutic agents
  • Regulatory aspects of nanomedicine

11.00
Obstacles for Bringing Antigenic Tolerance Induction to the Clinic

  • Matthias von Herrath Professor at the La Jolla Institute for Allergy & Immunology; VP of T1D R&D Center Seattle , Novo Nordisk

Synopsis

  • Front runners can be chosen with smart in vivo and in vitro comparative assays
  • A key obstacle for clinical development of antigenic tolerance induction is the lack of human biomarkers as surrogate endpoint in safety/dosing trials
  • We do not understand how tolerance is optimally achieved in humans (regulation versus exhaustion versus anergy versus deletion)?

11.30
Networking Lunch

Fulfilling the Future of Tolerance Clinical Development with Insights from Patient Data

12.30
Preclinical & Clinical Development of Tolerogenic Nanoparticles to Mitigate Immunogenicity of Biotherapeutics

Synopsis

  • Immunogenicity is a major cause of treatment failure for many biologic therapies
  • Selecta Biosceinces has developed rapamycin-carrying nanoparticles to mitigate immunogenicity to a wide variety of biologics
  • An update on preclinical applications, including gene therapy, and early clinical data from a Phase 2 trial with an enzyme therapy for the treatment of severe gout

13.00
Immunotherapy for Celiac Disease Using Immuno-Dominant Gluten Epitopes (Nexvax2®) – Discovery to Phase 2

Synopsis

  • Celiac disease, as both a food hypersensitivity and autoimmune disease, facilitates antigen challenge in patients that is enabling for epitope identification, biomarker discovery, and efficacy assessment
  • The first dose effect observed when immuno-dominant gluten epitopes are administered systemically recapitulates cytokine release and symptoms caused by gluten ingestion in celiac disease
  • Stepwise updosing allows immuno-dominant gluten epitopes to be administered in a standardized regimen that uniformly achieves immune non-responsiveness to dose levels that are well above the MTD for single dose exposure

13.30
Lessons Learned from Multi-Center Trials of Antigen Therapy in T1D

Synopsis

  • What are the specific clinical trial design considerations for multi-center trials of antigen therapy in T1D?
  • How to get around the practical problems of running a multi-center GCP clinical trial?
  • TrialNet observations as a solution led case study

14.00
Long-Term Consequences of Tolerance Induction Strategies Using AntiB-Cell (Rituximab), Especially to the Growing Child: Lessons Learned from Oncology & Pompe Disease

  • Yoav Messinger Medical Director- Cancer and Blood Disorders , Children’s Hospitals and Clinics of Minnesota

Synopsis

  • If immune modulation includes anti-B-cell agents, a proportion of patients exposed to Rituximab develop long-term B-cell dysfunction
  • Successful tolerance induction to enzyme replacement (ERT) for infantile Pompe disease includes rituximab. However, some patients are left with ongoing IVIG requirement and long-term B-cell dysfunction
  • Monitoring guidelines are suggested

14.30
Long-Term Consequences of Tolerance Induction Strategies Using Anti- B-Cell (Rituximab), Especially to the Growing Child: Lessons Learned from Oncology & Pompe Disease

  • Yoav Messinger Medical Director- Cancer and Blood Disorders , Children’s Hospitals and Clinics of Minnesota

Synopsis

  • If immune modulation includes anti-B-cell agents, a proportion of patients exposed to Rituximab develop long-term B-cell dysfunction
  • Successful tolerance induction to enzyme replacement (ERT) for infantile Pompe disease includes rituximab. However, some patients are left with ongoing IVIrequirement and long-term B-cell dysfunction
  • Monitoring guidelines are suggested

14.30
Afternoon Refreshments & Networking

The Future landscape of Antigen-Specific Immune Tolerance Therapies: The Promise of Combination Strategies

15.00
Combining Induction with Consolidation Therapy in ITN Clinical Trials for Autoimmunity

Synopsis

  • Induction therapy targets persistent effector cells that are a barrier to durable response
  • Consolidation therapy allows homeostatic and regulatory mechanisms to mature
  • Sequential combinations of induction and consolidation offer prospects for tolerogenic outcomes

15.30
Tregitopes Induce Active Tolerance in Autoimmune Diabetes & Allergy

Synopsis

  • Tregitopes (natural T cell epitopes derived from IgG) that (a) bind to multiple MHC class II molecules, (b) suppress effector T cell responses to co-delivered antigen, and (c) up-regulate Treg-associated cytokines and chemokines
  • Tregitopes promote tolerance by activating Regulatory T cell (Treg) activity and expanding Tregs in vitro and in vivo
  • Tregitopes provide an explanation for the mechanism of action IVIg on DC and T-cells and may ultimately provide a safe alternative to plasma-based immune regulation therapies
  • Case study on combination of Tregitope-albumin fusions and PPI peptides (T1D ASATI): Antigen-specific adaptive tolerance induction (ASATI) is induced when antigens are administered in combination with Tregitopes

16.00
Immune Modulation + Antigen Specificity: Exploring Combination Approaches for Tolerance Induction & Maintenance in Autoimmunity & Immunogenicity

Synopsis

  • The combination of immune-modulatory agents and antigen-specific approaches may yield superior efficacy in the induction and maintenance of immune tolerance
  • A review of the unmet need in autoimmunity and in the immunogenicity of therapeutic agents, as well as current attempts to address the issue
  • The combination of a T cell modulator (teplizumab) and a B cell inhibitor (PRV- 3279) with antigen-specific approaches will be presented as examples

16.30
Panel Discussion: Evaluation of Combination Therapies to Address Unmet Clinical Needs

Synopsis

  • What are the translational challenges of combination therapies in the context of disease complexity and mechanism of action?
  • What are the regulatory guidelines and considerations for combining two unapproved drugs as a combination strategy?
  • What is the expected value-split between the stakeholders?

17.00
Chair’s Closing Remarks & Close of 2nd Antigen-Specific Immune Tolerance Drug Development Summit 2019