8:30 am Login & Networking
Maximising Translation into Clinical Trials Through Innovative Pre-Clinical Models
8:50 am Chair’s Opening Remarks
9:00 am Understanding how Innate Immune Stimulation in Immuno-Oncology Enhances Anti-Tumour Immunity
•The Type I IFN/IL-15 pathway is a critical pathway bridging the innate and adaptive immune responses, promoting anti-tumor responses
• Understanding how the differential ability to express innate immune factors between tumor subtypes in rodents and humans impacts the ability to mediate anti-tumor responses
9:20 am Intravesical Delivery of a Pan-Genotypically Active STING Agonist to Treat Non-Muscle Invasive Bladder Cancer (NMIBC)
• Discovery of a pan-genotypic active STING agonist
• Demonstrate potent anti-tumor activity in orthotopic NMIBC models via intravesical administration
• First clinical study of STING agonist in NMIBC patients
9:40 am A Spoonful of Sugar Helps STING Agonists Go Down!
• Acetalated dextran nano/microparticles are used to deliver cGAMP intracellularly, significantly more efficient than soluble agonist
• Our particle formulation has better IFN production in comparison to other polymeric formulations and liposomes
• We have illustrated greater efficacy as an influenza vaccine and in triple negative breast cancer and melanoma
10:00 am TBC
10:20 am Live Q&A
Combination Therapy & How to Develop Combination Approaches
10:50 am Morning Refreshments & Speed Networking
11:20 am Neoadjuvant Evaluation of TLR9 Agonist CMP-001 in Melanoma
• Neoadjuvant TLR9 agonist CMP-001 in combination with PD-1 inhibitor Nivolumab produces high pathologic response rates in PD-1 naive high-risk respectable melanoma
• Neoadjuvant treatment response is associated with other biomarkers of response including circulating Ki67 high CD8+ T cells and CD8 TIL
• Response to neoadjuvant therapy is associated with durable RFS
11:40 am Perspective on STING activators as critical components of combinatorial therapeutic strategies with checkpoint inhibition
• Rationale for STING activation to induce anti-tumor immunity
• Highlight examples and define mechanisms by which STING enhances the therapeutic effect of checkpoint inhibition
• Overview of clinical approaches utilizing STING agonists in combination with checkpoint inhibition
12:00 pm Imprime PGG- a novel, systemically-delivered, Dectin Receptor Agonist- activates innate immunity, reprogramming the myeloid cells of the tumor microenvironment and driving antigen presentation to enhance the anti-cancer efficacy of the immune checkpoint inhibitor, pembrolizumab
• Phase 2 clinical data have now shown that Imprime + pembrolizumab provides substantial clinical benefit for patients with metastatic Triple Negative Breast Cancer (mTNBC)
• Paired tumor biopsies taken before and on – therapy show robust infiltration of tumor tissue by activated myeloid and T cells
• Peripheral blood analyses show monocyte activation as well as T cell activation in patients with greatest clinical benefit
12:20 pm Live Q&A
12:50 pm Networking Lunch
Enhancing Administration & Delivery of Innate Immune Stimulating Therapies for Safe & Effective Clinical Outcomes
1:50 pm Development of a Potent, Tumor Localized TLR8 Agonist
• Tumors refractory to immunotherapies, such as T cell checkpoint blockade, as known to be replete with myeloid cells.
• Clinical development of systemically administered myeloid cell agonists has been hindered by acute toxicities due to peripheral activation of these cell types
• Development of a novel therapeutic comprised of a potent toll-like receptor (TLR) 8 agonist conjugated to a HER2-directed monoclonal antibody, is designed for systemic delivery with tumor-localized activation of human myeloid cells
2:10 pm Tumor Targeting of a STING Agonist by Means of an Antibody-Drug Conjugate Induces Potent Anti-Tumor Immune Responses
• Mersana has developed the Immunosynthen platform to enable tumor-targeted delivery of a STING agonist by means of antibody-drug conjugates (ADC)
• Targeted STING-agonist ADCs induce potent anti-tumor immune responses and outperform systemically administered STING agonist.
• Targeted STING-agonist ADCs induce significantly lower levels of systemic cytokines than free STING agonist
2:30 pm Induction of Durable Tumor Regression in Advanced PD-1 refractory Melanoma with Intratumoral injection of CMP-001, a CpG-A oligodeoxynucleotide in a Virus-like Particle
• Tumor-associated plasmacytoid dendritic cells (pDC) mediate tumor tolerance vs. Immunity
• CMP-001 activates pDC into the most powerful IFN-secreting cells known
• Intratumoral injection of CMP-001 can induce a systemic T cell response that eradicates visceral metastases
2:50 pm Purine nucleoside phosphorylase inhibitors as TLR agonist
• Purine Nucleoside Phosphorylase (PNP) deficiency in humans causes lymphopenia and that led to development of PNP inhibitors as immunosuppressive agents.
• Careful evaluation of clinical history of PNP deficient patients and clinical
experience with PNP inhibitors together with new experimental data we have
discovered that inhibition of PNP activates immune system through elevation of guanosine and activation of toll like receptors (TLRs).
• PNP inhibitors represents novel first-in-class, orally bioavailable TLR agonist with demonstrated safety in the clinic
3:10 pm Live Q&A
Optimizing TLR Treatment Without Reducing Efficacy
3:40 pm Afternoon Break & Networking
4:00 pm Dose Regimen Considerations to Optimize TLR Agonist Therapy for Cancer: How, How much, How often, How long?
•These are central questions for the optimization of TLR (and STING) agonists for the treatment of cancer. What can we learn from emerging clinical data and applications of these agents in other contexts outside of cancer?
• Can a therapeutic index be achieved with IV administration of a TLR agonist?
• How can PK-PD and the efficacy-toxicity frameworks be effectively employed to support these aims?
4:20 pm Combination Systemic Therapy with a Multiple TLR agonist Safely Eradicates Established Tumors with Induction of Innate and Adaptive Immunological Memory
• Decoy Biosystems is developing a new and improved systemically administered version of Coley’s Toxins (killed, non-pathogenic, Gram-negative bacteria) that exhibits single agent activity and also synergizes with approved agents to safely eradicate established, solid tumors with induction of innate and adaptive immunological memory
• Decoy bacteria are also active in pre-clinical models of chronic human HBV and HIV infection
4:40 pm Deconstructing the Antigen-Presenting Cell Compartment in Cancer
• Use the polyoma middle T (PyMT) model of spontaneous breast cancer to explore the identity and function of various APCs both in the tumor and in secondary lymphoid organs
• Clarify a role for both dendritic cells and tumor-associated macrophages in influencing anti-tumor T cell responses, as well as a shared reliance on the transcription factor IRF8 for proper function
• Lead to a better understanding of the tumor APC compartment to allow for a more complete picture of how anti-tumor immunity is regulated and thus how it may be modulated by novel therapies