8.00 - 16.10 EST | 5.00 - 13.10 PST

8:00 am Virtual Coffee & Networking

Innate Immune Stimulating Antibody Conjugates

8:35 am Chair’s Opening Remarks

8:45 am Boltbody Immune Stimulating Antibodies: From Preclinical to Clinical Path

  • Edith Perez Chief Medical Officer, Bolt Biotherapeutics

Synopsis

  • Exploring the biology of toll like receptor activation in cancer
  • Activation of the innate and then adaptive immune systems
  • Update from the global phase I/II first-in-human trial using BDC-1001 in advanced HER2-expressing solid tumors

9:10 am STING-Agonist Antibody-Drug Conjugates Induce an Anti- Tumor Immune Response by Activating STING in Tumor Cells and Tumor-Resident Immune Cells

Synopsis

  • Tumor cell-targeted STING-agonist Antibody-Drug Conjugates (ADCs) activate the STING pathway in immune cells via Fcγ receptor-mediated internalization
  • Tumor cell-intrinsic STING pathway can be activated in the presence of cues from immune cells and contributes to the tumor-targeted STING agonist ADC activity
  • The ability of Immunosynthen-based ADCs to activate STING in tumor cells as well as in immune cells may represent a significant therapeutic advantage of targeting the STING pathway

9:35 am Speaker Q&A

Demonstrating Tumor Specific Immunity and Anti-Viral Immunity In Vivo

9:45 am Chair’s opening remarks

9:50 am Leveraging STING Agonism for Antiviral Immunity

Synopsis

  • This talk will cover mechanisms of STING driven anti-viral immunity
  • Small molecule STING agonists in anti-viral defense
  • STING agonists as immune modulating therapies in COVID19 and other viral infections

10:15 am TL-532, the First Rationally Designed TLR3 Agonist Creates Long-Lasting Tumor Specific Immunity In Vivo

Synopsis

  • TL-532, a double stranded RNA of 70 base pairs has been designed to obtain optimal dual action of immune cell stimulation and cancer cell apoptosis
  • In vitro TLR3 specificity and TLR3 specific cell death by apoptosis has been demonstrated in multiple cancer cell lines. Comparing its activity on normal versus cancer cells, TL-532 demonstrates an optimal profile and potential best-in-class TLR3 agonist
  • In vivo activity of TL532 has been demonstrated in the syngeneic MBT2 mice model with substantial tumor growth delay and survival benefits. Long lasting tumor specific immunity has been demonstrated by rechallenging complete responders to TL-532 treatment one year later: More than 70% showed long term autovaccination by totally preventing tumor development after two consecutive rechallenges with tumor cells

10:40 am Speaker Q&A

11:05 am cGAMP-VLP: cGAMP-containing Virus-Like Particles, a biological platform to activate STING for cancer immunotherapy

  • Nicolas Manel Co-Founder and Scientific Consultant, Stimunity; Director of Research at INSERM, Group Leader, Institut Curie

Synopsis

  • Viruses with a lipid envelope transfer the natural STING agonist cGAMP between cells
  • cGAMP-loaded Virus-Like Particles (cGAMP-VLP) efficiently deliver cGAMP to cells leading to STING activation
  • cGAMP-VLP induce anti-tumor immunity

11:30 am A unique holistic oncology drug development platform using fresh human tumor tissue which retains the tumor microenvironment including ECM, immune and tumor cells.

  • Bonnie Philips Associate Director of Translational Applications, Nilogen Oncosystems

Synopsis

  •  Study the impact of singlet and combination therapies on STING and TLRs in the same patient tumor tissue – published data to be presented.
  • Study Penetration, Phagocytosis, Tumor Cell Killing using Confocal Microscopy, and Cytokine release whilst quantifying the immune profile and cellular proliferation using Flow Cytometry, and proteogenomics using Nanostring , scRNAseq and CITE-seq.
  • One living tissue platform for use with all therapeutics – chemotherapies, monoclonal antibodies, bi and tri-specifics, ADCs, ADCCs, ACTs and Oncolytic Viruses.

12:00 pm Speaker Q&A

  • Nicolas Manel Co-Founder and Scientific Consultant, Stimunity; Director of Research at INSERM, Group Leader, Institut Curie
  • Bonnie Philips Associate Director of Translational Applications, Nilogen Oncosystems

12:10 pm Reprogramming the Tumor Microenvironment via engineered bacterial delivery of immune effectors: SYNB1891, a STING agonist

  • David Hava Chief Scientific Officer, Synlogic Therapeutics

Synopsis

  • SYNB1891: Phase 1, Dose Escalation Study as a mono and combo treatment (atezolizumab) in multi-solid tumors and lymphoma
  • Synthetic Biology Effector Delivery
  • Dual Action: Ability to stimulate the innate and adaptive immune system

12:35 pm Title to be Announced

  • Kader Thiam Senior Vice President Discovery - Preclinical Models & Services, Genoway

1:05 pm Speaker Q&A

  • David Hava Chief Scientific Officer, Synlogic Therapeutics
  • Kader Thiam Senior Vice President Discovery - Preclinical Models & Services, Genoway

1:15 pm Networking Break & Round Table Discussions

Synopsis

 

Challenges in the Discovery of Novel STING Agonists

  • Developing agonists which are potent, specific,
    and active against all human isoforms of STING and
    rapidly induce downstream signaling and type I IFN.
  • Progressing drug candidates which simulate a
    crosspresentation, antigen-specific T cell response, and a
    rapid multi-lineage anti-tumor immunity.
  • Development of systemically administered STING
    agonists to overcome pharmacokinetic limitations
    and improve drug delivery.

Woody Sherman
Chief Scientific Officer
Silicon Therapeutics

 

 

 

 

 

Looking for Synergy in the Front-line
Optimizing Combination Approaches

  • Evaluating the synergistic potential of combinations
    with other frontline treatments to distinguish the best
    combination approach
  • Combining TLR/STING agonists with other
    immunotherapies to promote sustained antitumoral
    immune responses
  • Identifying and overcoming mechanisms of resistance
    to current checkpoint inhibitors through combination
    strategies

James Wooldridge
Chief Medical Officer
Checkmate Pharmaceuticals

 

 

 

 

 

 

Improving the therapeutic index and efficacy of TLR and STING-targeted therapies

1:45 pm Opening Remarks from Chairperson

  • David Hava Chief Scientific Officer, Synlogic Therapeutics

1:50 pm Cross talk between STING, RIG-I and purinergic signaling.

Synopsis

  • A successful resolution of an encounter with a pathogen depends on a response finetuned in strength and duration. As pathogens often activate several pattern recognition receptors during invasion and intracellular steps of their life cycle the cross talk between signaling pathways is essential for that tuning and termination of the response.
  • In addition, paracrine signals alert local cells which have not yet had any contact with the pathogen. These signals carry general danger signals as well as specific information about the nature of the alarm via a combination of secreted factors such as interferon type I or ISG15 as well as purinergic signals.
  • ATP is a general pro-inflammatory signal whereas cGAMP is specifically released in response to cytoplasmic detection of double stranded DNA by cGAS. Both signals are terminated by the same hydrolase at the cell surface, ENPP1.
  • Acknowledging the cross talk and feedback between the receptors and signals provides a framework which enables the understanding of unexpected responses to direct and full agonists of the pattern recognition pathways and points at signal modulation and enhancement as a promising alternative for pharmacological intervention.

2:15 pm exo-STING: An Engineered Exosome Therapeutic that Selectively Delivers STING Agonists to Antigen Presenting Cells & Enhances Tumor Antigen Specific Adaptive Immune Responses

Synopsis

  • In preclinical syngeneic tumor models, exoSTING, an exosome based therapeutic comprised of a human cell line derived exosome that is loaded with a synthetic cyclic dinucleotide, shows increased potency and anti-tumor activity over free cyclic dinucleotide STING agonists
  • Enhancing local IFN-γ induction while limiting systemic inflammation
  • Preserving immune cell viability and enhancing DC activation and T cell recruitment
  • Generating a tumor antigen specific CD8 T cell-dependent systemic immunity

2:40 pm Improving the therapeutic index of TLR and STING agonist therapies with dual-responsive polymer-drug conjugates (PDCs)

  • Geoffrey Lynn Chief Executive Officer and Co-Founder, Avidea Therapeutics

Synopsis

  • Agonists of TLRs and STING suffer from dose-limiting toxicity when used systemically.
  • Conventional nanocarriers (e.g., liposomes) can reduce toxicity but are designed to evade APCs required for TLR and STING agonist activity.
  • Avidea has developed dual-responsive PDCs to evade APCs in the bloodstream but promote APC uptake in the tumor.
  • Avidea’s lead dual-responsive PDC improves the safety and efficacy of an intravenously administered TLR-7 agonist

3:05 pm Speaker Q&A

Lifting the Innate Immune Barriers to Prime Anti-Tumor Immunity in Difficult-to-Treat Cancers

3:45 pm Opening Remarks from Chairperson

  • David Hava Chief Scientific Officer, Synlogic Therapeutics

3:55 pm Title To Be Confirmed

  • Adi Diab Associate Professor, Melanoma Medical Oncology, MD Anderson

4:30 pm Investigating STING in Glioblastoma

  • Sean Lawler Associate Professor of Neurosurger, Brigham and Women’s Hospital Harvard Medical School

Synopsis

  • Glioblastoma is a highly immunosuppressive brain tumor, that has low intrinsic T cell infiltrates. To improve immunotherapies, local activation of immune sensing pathways such as STING may be useful, by overcoming the immunosuppressive tumor microenvironment
  • STING is present in human GBM and mouse models, although its activity in tumor cells is very low
  • STING is present in the tumor microenvironment and STING agonists administered intratumorally in murine GBM models cause profound activation of tumor infiltrating immune cells, and improve animal survival. These results suggest STING it may be possible to target STING in glioblastoma

4:55 pm A clinical view on the innate immunity landscape in Non-small cell lung cancer

  • Lena Horvath Resident Physician, Department of Hematology and Oncology, Medical University Innsbruck

Synopsis

  • NSCLC is a highly heterogenous disease with distinct histological and molecular signatures.
  • The immunogenic characteristics of NSCLC are becoming more evident but innate immunity has not yet entered the clinical spotlight.
  • TLR and STING expression have been related to lung cancer progression and prognosis. Their true clinical relevance is still not clear.
  • We will discuss the relevance of boosting innate immune sensing in NSCLC.

5:20 pm Speaker Q&A

  • Adi Diab Associate Professor, Melanoma Medical Oncology, MD Anderson
  • Sean Lawler Associate Professor of Neurosurger, Brigham and Women’s Hospital Harvard Medical School
  • Lena Horvath Resident Physician, Department of Hematology and Oncology, Medical University Innsbruck

5:35 pm Closing remarks

5:45 pm End of conference