8:00 am Registration & Coffee

CLINICAL PROGRESS WITH INNATE IMMUNE-TARGETING COMPOUNDS

9:20 am Chair’s Opening Remarks

  • Joanne Lim Immunology Scientist, Codiak BioSciences

9:30 am Breakfast Panel Discussion: How Far Have We Come & Where Do We Want to Go?

  • Arthur Krieg Chief Scientific Officer , Checkmate Pharmaceuticals
  • Robert Andtbacka Chief Medical Officer , Seven and Eight Biopharmaceuticals
  • Jim Appleman Chief Scientific Officer, Co- Founder, Director & Senior Vice President - Research & Development , Primmune Therapeutics
  • Thomas W. Dubensky President, Tempest Therapeutics

Synopsis

  • Dissecting the recent advances in PRR-targeting drugs
  • Sharing insights into the directions for more successful immune system manipulation
  • Thoughts on modes of action being investigated, conclusions drawn from setbacks and ways to improve the clinical outcomes
  • Pathway understanding, indications, toxicity outlooks, combinations, drug formats and delivery mechanisms
  • Biological understanding update: pathway, biomarker and translational updates plus validation from the lab
  • Update on exciting learnings on the mechanisms, pathways, interactions and key changes in the landscape
  • Discussions on gaps in knowledge and how we can fill these: mechanisms, modelling, translation

10:00 am Challenges in Harnessing Innate Immunity for Cancer Immunotherapy

  • Arthur Krieg Chief Scientific Officer , Checkmate Pharmaceuticals

Synopsis

  • A broad overview of all of the PRRs, their similarities and differences, and the various modalities by which they are being targeted

10:30 am Translatable Preclinical Models for Profiling STING & TLR-Targeted Therapies

Synopsis

• hSTING syngeneic mouse models for assessment of STING-targeted therapies
• Immunodeficient mouse model reconstituted with human immune system for assessment of immunomodulators in mono and combination therapy

11:00 am Speed Networking

RATIONALE & PROGRESS IN NOVEL METHODS OF TARGETING STING & TLR

12:00 pm Systemic Small Molecule TREX1 Inhibitors to Selectively Activate STING in the TME of Metastatic Disease

Synopsis

  • Although STING is a critical innate immune receptor, the clinical activity of STING agonists given by intratumoral administration has not compared well to preclinical studies
  • TREX1 is a cytosolic dsDNA exonuclease that modulates the cGAS/STING pathway activation, is a DNA repair enzyme, is upregulated in tumors, and is a target to preferentially activate the STING pathway in the TME
  • Systemic small molecule inhibitors TREX1 confer significant anti-tumor activity in mice given in combination with subtherapeutic doses of doxorubicin and are cytotoxic in DNA repair deficient human tumor cell lines

12:30 pm Considerations & Progress in Developing a Dual TLR Agonist

Synopsis

  • Exploring the drug discovery process: target identification & validation, antitumor effect, pathway understanding, biomarkers
  • Discussing potential indications?
  • Latest data & future directions

1:00 pm TLR9 Activation & STAT3 Inhibition: a Bifunctional Approach to Immuno-Oncology

  • Alan Horsager President & Chief Executive Officer, Duet Therapeutics

Synopsis

  • While TLR9 continues to be a high-value target in immuno-oncology, single agent agonists of this receptor have shown limited efficacy in clinical studies.
  • This is likely due, in part, to the immunosuppression created by the tumor microenvironment, which acts as a shield protecting the tumor from the activated immune system.
  • Duet has developed a suite of bifunctional oligonucleotides that activate antigen-presenting cells (APCs) within the tumor microenvironment, while releasing the immunosuppressive brakes to jump-start T cell-mediated immune responses.
  • The unique mechanism-of-action of these synthetic oligonucleotides comes from simultaneously targeting two intracellular immune pathways – signal transducer and activator of transcription 3 (STAT3) and toll-like receptor 9 (TLR9).
  • The targeted inhibition of STAT3, a master immune checkpoint inhibitor, reawakens immune cells and allows for the full potential of TLR9-driven innate and adaptive immune responses.

1:30 pm Targeted Immune Activation by Systemic Delivery of Toll-Like Receptor 9 Agonist Antibody Conjugates

  • Pavel Strop Vice President, Biologics Discovery, Tallac Therapeutics

Synopsis

  • Toll-like Receptor Agonist Antibody Conjugate (TRAAC) platform delivers potent TLR-9 (T-CpG) for targeted immune activation via systemic administration
  • TRAAC platform is amenable for immune-targeting, tumor/immune-targeting and tumor-targeting to promote adaptive and innate responses
  • TAC-001, CD22 TRAAAC, targets B-cells to drive potent anti-tumor activity in preclinical solid tumor models

2:00 pm Lunch Break

3:00 pm Bridging Innate & Adaptive Immune Systems with TLR7/8 Activation

  • Edith Perez Chief Medical Officer, Bolt Biotherapeutics

3:30 pm Discovery of Innate Immune Agonists Using Deep Learning on High- Dimensional Phenomics

Synopsis

  • We apply computational methods to high content imaging of PBMCs to construct highly accurate models that discriminate between many distinct innate immune signalling pathways
  • These imaging models are paired with proteomics to build a deep understanding of the relationship between high level cell behaviours and molecular signalling
  • This understanding is applied to high throughput screening to identify new compounds that induce inflammation with potential applications as vaccine adjuvants and immunotherapies

OPTIMIZING THE USE OF PRE-CLINICAL MODELS IN YOUR PRR DRUG DEVELOPMENT TO ACHIEVE HUMAN-SPECIFIC TRANSLATION

4:00 pm Lymph-Node Targeted TLR9 Agonists Enable Potent Cellular Immune Responses Against Cancer & Infectious Disease

  • Peter DeMuth Vice President - Research , Elicio Therapeutics

Synopsis

  • Dissecting what exactly is lacking in the current models and bridging the translation gap
  • Exploring how we can design/strategize/use the right models to really represent what we want
  • Exploring what constitutes sensitivity
  • Using models to predict the severe side effects seen in humans
  • Understanding what the best setting is to do efficacy/new target discovery for optimizing compounds and biomarker discovery
  • Toxicity models – what preclinical models are out there that could help us to identify toxicity of these therapies?

4:30 pm Oral Administration of Tissue-Targeted TLR7 Agonists for Immune Oncology

  • Andrew Miller Co-founder & Vice President - Immunology & Operations , Apros Therapeutics

Synopsis

  • Unpicking the mechanistic studies of our tissue-targeted approaches,
  • Exploring the preclinical models
  • Assessing cytokine responses as it pertains to tissue distribution and residence time

5:00 pm Chair’s Closing Remarks & End of Conference Day 1