8:00 am Registration & Coffee

CLINICAL PROGRESS WITH INNATE IMMUNE-TARGETING COMPOUNDS

9:00 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
  • John Flygare Senior Principal Scientist , Merck & Co
  • Jim Appleman Chief Scientific Officer, Co- Founder, Director & Senior Vice President - Research & Development , Primmune 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

9:30 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

10:00 am Networking Break

RATIONALE & PROGRESS IN NOVEL METHODS OF TARGETING STING & TLR

11:00 am 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

11:30 am 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

12:00 pm Targeted Immune Activation by Systemic Delivery of Toll-Like Receptor 9 Agonist Antibody Conjugates

  • Paval 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

12:30 pm Panel Discussion: What is the Best TLR to Target & Why?

  • Diwakar Davar Assistant Professor - Phase, Therapeutics & Melanoma , University of Pittsburgh
  • Paval Strop Vice President, Biologics Discovery, Tallac Therapeutics
  • Robert Andtbacka Chief Medical Officer , Seven and Eight Biopharmaceuticals
  • Bettina Werle Chief Scientific Officer , Tollys

Synopsis

  • Triggering effective and durable response via the innate–adaptive immune axis
  • Dissecting the rationale behind targeting each TLR from different perspectives
  • Preclinical analysis, clinical analysis, combination discussion, delivery mechanisms, dosing discussions

1:00 pm Lunch Break

DEVELOPING PREDICTIVE PRE-CLINICAL MODELS IN PRR RESEARCH TO ACHIEVE HUMAN-SPECIFIC TRANSLATION

2:00 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?

2:30 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

3:00 pm Panel Discussion: Towards Bridging the Gap with the Clinic

  • Adi Diab Associate Professor - Melanoma Medical Oncology , MD Anderson Cancer Center
  • Lei Jin Assistant Professor - Medicine , University of Florida
  • Brian Horsburgh Chief Executive Officer, Activate Therapeutics
  • Diwakar Davar Assistant Professor - Phase, Therapeutics & Melanoma , University of Pittsburgh

Synopsis

  • How have clinical results traced back to what was shown preclinically?
  • Exploring optimal validation in clinics
  • Standardizing the approach in the clinic so we can go back preclinically – which models?
  • Gathering early clinical information – robust translational medicine program
  • How can you best parallel with translational – ctDNA metabolmics
  • Discussing mathematical modelling use potentials for dose adjustement and tolerability
  • Why do the colony formation assays take so long and what are the alternatives? Reliability and taking cell proliferation rate into account
  • Transition from preclinical to clinical trials
  • Collecting preclinical data to demonstrate how initiation of innate immune responses can lead to subsequent adaptive long-term cancer immunity
  • Identifying successful localized intratumoral innate immune activation coupled with concurrent systemic adaptive tumor antigen specific cytotoxic T-cells
  • Predicting the successful integration of innate immune activation strategies into combination therapies for cancer treatment which lead to more effective and long-term clinical benefit

3:30 pm Afternoon Refreshments & Networking Break

EXPLORING THE EMERGING TARGETS IN PRR TARGETING: STRATEGY, EXECUTION, DEVELOPMENT & PROMISE

4:00 pm Mitochondria as a Central Rheostat of NLRP3 Inflammasome Activation

  • Elsa Sanchez-Lopez Assistant Professor , Department of Orthopaedic Surgery School of Medicine University of California San Diego

Synopsis

  • Mitochondria Can Both Activate and Inhibit NLRP3 Inflammasome Activation
  • Mitochondria Fitness is Essential for Mounting a Proper NLRP3 Inflammasome Response
  • Targeting Mitochondria can Regulate NLRP3 Inflammasome Activity

4:30 pm Chair’s Closing Remarks & End of Conference Day 1