Immuno-Oncology: Emerging Targets and Therapeutics

 

The paradigm of immuno-oncology: figuring out and then circumventing how cancer cells evade the immune system has been validated by a few high-impact therapeutic successes in the past few years and has thus spurred a flurry of more drug discovery and development in the field. However much of the current pharmaceutical activity is focused on a few cell surface drug targets and their inhibition by biologics-based therapies. CHI’s Inaugural Immuno-Oncology: Emerging Targets and Therapeutics conference will cover newer cell surface targets in the IO field that are being investigated for modulation by biologics as well as by other modalities, especially small molecules that have the potential to be oral-based medicines. We will also cover drug targets that are intracellular, thus only accessible to small molecules or newer, non-biologic modalities. Please join us to stay abreast of this rapidly progressing field.

RECOMMENDED PREMIUM PACKAGE:
Choose 2 Short Courses and 2 Conferences/Training Seminars
September 16 Pre-Conference Short Course: SC1: Immunology Basics: Focusing on Autoimmunity and Cancer
September 17-18 Conference: Immuno-Oncology: Emerging Targets and Therapeutics
September 18 Dinner Short Course: SC8: GPCR Structure-Based Drug Discovery
September 18-19 Conference: Targeting Fibrosis

Final Agenda

Monday, September 16

1:00 pm Pre-Conference Short Course Registration
Click here for details on short courses offered.

Tuesday, September 17

7:00 am Registration Open and Morning Coffee

Re-Activating The Innate Immune System Against Cancer

8:00 Organizer's Welcome Remarks

8:05 Chairperson’s Opening Remarks

Daniela Cipolletta, PhD, Investigator III, Exploratory ImmunoOncology, Novartis

8:10 Discovery of STING Agonist with Systemic Anti-Tumor Response

Pesiridis_ScottScott Pesiridis, PhD, Associate Fellow, Scientific Leader - Discovery Biology, GSK

Medicines targeting STING are intensely pursued as innate immune modulators with potential to complement other immuno-oncology agents. While the first wave of STING agonists are derived from cyclic dinucleotides limited to intra-tumoral delivery, we discovered a small molecule dimeric ligand known as the ABZI series that is selective STING agonists with remarkable single agent efficacy upon intravenous delivery.

8:40 Characterization of Novel STING Ligands

Schroeder_GottfriedGottfried Schroeder, PhD, Senior Scientist, Department of Pharmacology, Merck Research Labs Boston

Modulation of the innate immune receptor STING is of pharmacological interest for both oncology and autoimmune indications. Binding of cyclic dinucleotide 2’3’-cGAMP to dimeric STING stabilizes a ‘lid-closed’ protein conformation, ultimately inducing interferon production. Biophysical characterization of different classes of STING ligands using surface plasmon resonance (SPR) has revealed significant differences in binding kinetics, stoichiometry and mode of action. The results of complimentary techniques further support these observed mechanistic differences.

9:10 Potent STING and RIG-1 Agonists for Immuno-Therapy of Cancer

Iyer_RadhakrishnanRadhakrishnan P. Iyer, PhD, CSO, Spring Bank Pharmaceuticals

The induction of innate and adaptive immunity via activation of Stimulator of Interferon Genes (STING) signaling and the retinoic acid-inducible gene 1 receptor (RIG-1)-like receptor pathway, which responds to viral RNA, are potentially transformative immuno-therapeutic strategies in cancer. Using structure-based drug design and focused library synthesis, we have discovered novel cyclic dinucleotides (CDNs) as STING ligands and nucleotide compounds as dsRNA mimics of RIG-I agonism. The CDNs self-assemble into cell-permeable nanostructures for uptake by immune cells. The lead CDNs administered by i.v., i.p., and i.t. routes in subcutaneous and orthotopic syngeneic tumor models show potent STING-mediated induction of Type I IFNs and cytokines resulting in profound and durable anti-tumor activity, abscopal effects and induction of immune memory. The lead CDNs have been formulated into nanospheres for controlled and sustained delivery and have also been conjugated with antibodies to enable targeted delivery to the tumor site. Nucleotide compounds are first-in-class RIG-1 agonists and recent results will be presented.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

10:25 Using Synthetic Biology to Target Innate Immunity in the Tumor Microenvironment

Leventhal_DanielDaniel Leventhal, PhD, Lead Biologist, Immuno-Oncology, Synlogic, Inc.

STING plays an essential role in initiating anti-tumor immunity through activation of antigen presenting cells (APCs), production of type I interferon and T cell priming. Bacteria provide an ideal mechanism for STING activation as they can be deployed within the tumor microenvironment, are engulfed by APCs and activate parallel pathways of innate immunity. We have generated an engineered bacterial strain, SYNB1891, that is capable of efficient activation of innate immunity through engagement of TLRs and activation of STING.

10:55 Using the Gut Microbiome to Re-Direct Innate Immunity for Enhancing Responses to Engineered T-Cell Therapy

Abid_MuhammadMuhammad Bilal Abid, MD, Clinician-Scientist, Division of Hematology/Oncology & Infectious Diseases, Medical College of Wisconsin

Despite impressive outcomes in select patients, there remains significant heterogeneity in clinical responses to both immunotherapy and CAR T-cells. The diversity and composition of the gut microbiome influences response to immunotherapy, according to recent evidence. The role of the gut microbiome in ACT or CAR T-cell setting have not been explored. We hypothesize that the gut microbiome modulation carries the potential for enhancing CAR T-cell responses.

11:25 Presentation to be Announced

11:55 Talk Title to be Announced

Speaker to be Announced, CRELUX, a WuXi AppTec Company

12:25 pm Session Break

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:15 Refreshment Break in the Exhibit Hall with Poster Viewing

Immuno-Metabolism And Remodeling The Tumor Microenvironment (TME)

1:50 Chairperson’s Remarks

Scott Pesiridis, PhD, Associate Fellow, Scientific Leader - Discovery Biology, GSK

1:55 Antagonists of the Adenosine 2a Receptor (A2AR) to Reverse Tumor Suppression in the TME

Schuller_AlwinAlwin Schuller, PhD, Senior Principal Scientist/Team Lead, Oncology, IMED Biotech Unit, Astra Zeneca

Adenosine, signaling through the high affinity A2AR receptor, contributes to an immune suppressed tumor micro environment by inhibiting multiple cell types involved in both innate and adaptive immunity. AZD4635 (HTL-1071) is a potent oral A2AR antagonist in clinical development in combination with durvalumab (anti-PDL1). This presentation will highlight our current pre-clinical understanding of the mechanism of action of AZD4635, including activation of various immune cell types, and anti-tumor activity in different syngeneic tumor models.

2:25 Targeting the Adenosine Immunosuppressive Pathway

Daniela Cipolletta, PhD, Investigator III, Exploratory ImmunoOncology, Novartis

2:55 Sponsored Presentation (Opportunity Available)

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

4:05 A Dual CD73-A2AR Antagonist to Reduce Adenosine in the TME

Ramachandra_MuraliMurali Ramachandra, PhD, CEO, Aurigene Discovery Technologies Limited

Adenosine generated within the tumor by CD73 thwarts the anti-tumor immune response by signaling through receptors such as A2AR on immune cells. Interestingly, the co-blockade of CD73 and A2AR results in a more pronounced anti-tumor activity than blockade of either, likely due to production of adenosine by alternate routes, increased CD73 expression upon A2AR inhibition and compensatory activity of other adenosine receptors. We will discuss our success in discovering inhibitors that dually target CD73 and A2AR.

4:35 Discovery of Small Molecule Aryl Hydrocarbon Receptor (AhR) Antagonists for Cancer Immunotherapy

Hoffman_ThomasThomas Hoffman, PhD, CFO, Phenex Pharmaceuticals

Activation and accumulation of the nuclear aryl hydrocarbon receptor (AhR) protein is frequently seen in different tumor types and has been linked to immunosuppression, resulting in a diminished anti-tumor immune response. Targeting of AhR with an antagonist may therefore provide a novel immunotherapeutic approach for enhancing anti-tumoral immune responses. We identified small molecule AhR antagonists to block activated downstream signaling of AhR. The lead molecules show high potency, selectivity, favorable ADME/PK and in vivo efficacy in different preclinical models.

5:05 Interactive Breakout Discussion Groups - View All Breakouts

Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic.

STING: an IntereSTING IO Target

Moderators: Gottfried Schroeder, PhD, Senior Scientist, Department of Pharmacology, Merck Research Labs Boston
Charles A. Lesburg, PhD, Senior Principal Scientist, Computational and Structural Chemistry, Merck & Co., Inc.

  • Distinct structural features of STING to design modulators against
  • Biologics vs. small molecule approaches for modulating STING
  • MOA and physiological considerations, possible side effects, etc.

Targeting the IDO/TDO-Kynurenine-Arylhydrocarbon Receptor Pathway and Beyond

Moderator: Claus Kremoser, PhD, CEO, Phenex Pharmaceuticals

  • Pros and cons of IDO / TDO single / dual inhibitors vs. AHR antagonists?
  • Which tumor autonomous effects and which effects on the immune system can you expect?
  • For which cancers might such IDO / TDO / AHR inhibitors be applicable?

Targeting the Adenosine Pathway

Moderator: Alwin Schuller, PhD, Senior Principal Scientist/Team Lead, Oncology, IMED, Biotech Unit, AstraZeneca

  • Targeting A2AR vs. CD73 vs. Dual Inhibitors
  • Other ways to modulate adenosine levels
  • Promising ‘synergistic’ combinations

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing (Sponsorship Opportunity Available)

7:10 Close of Day

Wednesday, September 18

7:30 am Registration Open and Morning Coffee

New Inhibitors Of Checkpoint Blockade

8:00 Chairperson’s Remarks

Alwin Schuller, PhD, Senior Principal Scientist/Team Lead, Oncology, IMED, Biotech Unit, Astra Zeneca

8:05 Beyond PD-1: TIM-3 Combinations to Enhance Therapeutic Activity

Ghosh_SrimoyeeSrimoyee Ghosh, PhD, Senior Principal Scientist, Translational Research & Strategy, Research and Early Development, Tesaro

T cell immunoglobulin and mucin-domain containing-3 (TIM-3) is a key immune checkpoint protein that is often co-expressed with PD-1 and has been implicated in both effector T cell exhaustion and immune suppression mediated by myeloid cells.  On effector T cells, TIM-3 expression is associated with reduced cell proliferation and cytokine production while on dendritic and other myeloid cells, TIM-3 expression may prevent recruitment and priming of T cells.  In combination with PD-1 blockade, anti-TIM-3 enhances the activation of T cells and demonstrates greater anti-tumor activity to aPD-1 alone in preclinical models.  TSR-022 is a potent, selective anti-TIM-3 antibody that is being developed in combination with PD-1 blockade.

8:35 MBG453: a FIH anti-TIM-3 antibody

Longmire_TylerTyler Longmire, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis
TIM-3 is a type I trans-membrane protein that is widely expressed on cells of the immune system.  When given in combination, TIM-3 blockade has been shown to enhance the anti-tumor activity of PD-1/L1 checkpoint inhibitors in multiple in vivo models.   MBG453 is a fully humanized, phosphatidylserine blocking anti-TIM3 IgG4 monoclonal antibody currently under investigation in advanced malignancies.

Eurofins Discovery 9:05 Robust and Reproducible Target Biology-Based Bioassays for Characterization and Potency Measurement of Biologics Targeting Checkpoint Modulators

Alpana Prasad, PhD, Product Manager, Marketing, Eurofins Discovery

A quantitative and robust bioassay that is reflective of the MOA of the drug is a critical component of any development program.  PathHunter® cell-based assay platform offers ready to use bioassays for potency determination & stability testing of biological drugs. These quantitative and robust assays rely on the native biology of the relevant receptor, allowing developers to choose a readout reflective of the MOA of their drug. Importantly, since these are homogeneous assays that employ thaw-and-use cryopreserved cells, they not only provide convenience while minimizing assay variability, they are also highly scalable and suitable for automation. We will share case studies from our expanding portfolio of qualified bioassays for several immune-oncology targets.

9:20 Sponsored Presentation (Opportunity Available)

9:35 Coffee Break in the Exhibit Hall with Poster Viewing

10:20 CA-170, a First-in-Class, Orally Available, Small Molecule Immune Checkpoint Inhibitor Dually Targeting VISTA and PDL1

Raul Soikes, PhD, Senior Director & Global Program Leader, Curis

10:50 Presentation to be Announced

11:20 Enjoy Lunch on Your Own

11:20 Conference Registration for Programs 1B-7B


PLENARY KEYNOTE PROGRAM
Click here for full abstracts.

12:20 pm Event Chairperson’s Opening Remarks

An-Dinh Nguyen, Team Lead, Discovery on Target 2019, Cambridge Healthtech Institute

 

12:30 Plenary Keynote Introduction

Anjan Chakrabarti, Vice President, Discovery Chemistry, Syngene International Ltd

12:40 Base Editing: Chemistry on a Target Nucleotide in the Genome of Living Cells

David R. Liu, PhD, Howard Hughes Medical Institute Investigator, Professor of Chemistry & Chemical Biology, Harvard University

 

 

1:20 PROTACs: Past, Present, and Future

Craig M. Crews, PhD, Professor, Chemistry; Pharmacology; Molecular, Cellular & Developmental Biology; Yale University

 

 

2:00 Close of Plenary Keynote Program

2:00 Dessert Break in the Exhibit Hall with Poster Viewing

2:45 Close of Immuno-Oncology: Emerging Targets and Therapeutics Conference