Immuno-Oncology Europe 2019 Agenda

Conference Registration, Conference Materials Pick-Up, Coffee and Pastries

Determinants of Antibody Immunotherapy
Mark Cragg, Professor and Chair in Experimental Cancer Biology, Centre for Cancer Immunology, University of Southampton, Southampton General Hospital, United Kingdom

There is growing appreciation of the depth of interaction between tumour cells and their surrounding microenvironment. These interactions augment tumour growth, proliferation and mediate immune suppression. Of critical importance is how these interactions affect antibody immunotherapy and how they might be targeted to improve treatment efficacy. This presentation will discuss several key determinants of antibody immunotherapy.

Morning Coffee Break and Networking

Using Immuno-Oncological Biomarker-Directed Strategies as a Blueprint For Developing Effective Treatments for Alzheimer’s Disease
CJ Barnum, Director of Neuroscience, INmune Bio, Inc., United States of America

INmune Bio approaches Alzheimer’s disease (AD) as an immunological disease, not a neurological disease. This changes the clinical strategy in many ways but perhaps none more important than we now have biomarkers. We have developed a suite of biomarkers that extend beyond classical blood inflammatory measures that will inform go/no decisions.

Networking Lunch

Recruiting Neutrophils with IgA and CD47 Modification to Treat Cancer
Jeanette H W Leusen, Associate Professor & Head of Immunotherapy Group, University Medical Center Utrecht, Netherlands

IgA is a strong activator of neutrophils to kill cancer cells. CD47 is a 'don't eat me' signal for cancer cells and healthy cells, that binds to SIRPalpha on neutrophils as an inhibitory receptor or an innate checkpoint molecule. CD47 can be manipulated to not bind to SIRPalpha anymore, and this strongly enhances the IgA anti-tumor effect in vitro and in vivo (Nature Medicine, in press).

Spherical Nucleic Acids - Activating the Immune System
David Giljohann, CEO, Exicure, United States of America

Exicure develops spherical nucleic acid (SNA) constructs, which are 3-dimensional arrangements of oligonucleotides where the nucleic acids are densely packed and radially oriented around a nanoparticle. AST-008 is an SNA configuration of a toll-like receptor 9 (TLR9) agonist oligonucleotide, designed to trigger anti-tumor immune responses in patients with cancer. AST-008 is intended to be administered intratumorally in combination with checkpoint inhibitors for the treatment of solid tumors. AST-008 has potent antitumor activity as a monotherapy and synergizes with anti-PD-1 antibody therapy in several preclinical tumor models. Clinical progress with our Phase Ib trial will be discussed.

Afternoon Coffee and Snack Break

CB307: A Novel CD137/4-1BB Agonist Humabody Therapeutic for PSMA-Positive Tumours
James Legg, Senior Vice President of Research, Crescendo Biologics, United Kingdom

• Crescendo Biologics has initiated pre-clinical development of CB307, a novel trispecific Humabody VH targeting CD137 (4-1BB), prostate specific membrane antigen (PSMA) and human serum albumin (HSA)
• The talk will describe the identification, mechanism of action and preclinical characterisation of CB307
• The benefits of using the modular Humabody VH platform, rather than an IgG format to develop this molecule will be discussed, including optimal (monovalent) engagement of both targets with small VH domains and the avoidance of Fc receptor interactions
• The unique design of CB307 enables highly potent and tumour selective T-cell co-stimulation

3D-Bioprinting Applications For the Study of Tissues and Disease
Saviz Ehyai, Product Specialist, CELLINK

3D bioprinting has become an attractive method of studying various tissues and diseases, owing to its ability to better recreate in vivo conditions while culturing. Allowing cells to grow, migrate, and proliferate in a 3D environment results in enhanced secretion of proteins and ECM, with the possibility of printing complex structures housing different cell types, thereby creating superior model systems for study. We present an overview of the 3D bioprinting process, bioink development, and selected applications that have been performed using this technology.

Single-Cell Secretion Cytokine Signatures – Enhanced Tools For Therapeutic Design and Prediction of Clinical Response
Miles Rackliff, Senior Sales Manager – Northern Europe, IsoPlexis

We will present data showing how polyfunctionality measured by IsoPlexis, correlates with patient objective response, can be used to enhance pre-clinical development across CAR-T and combination therapies.

Networking Reception with Beer and Wine at the Pillars Bar, Marriott Rotterdam -- Network and Engage with Colleagues in a Relaxed Atmosphere

Close of Day 1 of the Conference

Morning Coffee, Pastries and Networking

Emergence of ICOS hi CD4 T Cells is Associated with Tumor Reduction, Progression-Free Survival, and Overall Survival in Advanced Cancer Patients Treated with Vopratelimab, an ICOS Agonist
Johan Baeck, VP, Clinical Development & Medical Affairs, Jounce Therapeutics, United States of America

Vopratelimab is an ICOS agonist antibody intended to stimulate primed CD4 T effector cells. In the ICONIC trial, peripheral T cell phenotyping demonstrated emergence of an ICOS^hi subset of activated CD4 T effector cells associated with tumor reductions and improved PFS and OS, with expansion of peripheral T cell receptor clones found in the original matched archival tumor.  Future development focuses on settings in which ICOS^hi CD 4 T effector cells are primed to respond to vopratelimab.

ONCR-177, A miR-Attenuated Oncolytic HSV-1 for Potent Activation of Anti-Tumor Immunity
Lorena Lerner, Vice President, Molecular Biology & Virology, Oncorus, United States of America

Oncolytic viruses (OVs) represent a new class of therapeutic agents for the treatment of cancers that poorly respond to immune checkpoint inhibitors. OV promote anti-tumor responses by a dual mechanism of action: the selective oncolysis of tumor cells, followed by the development of systemic anti-tumor immune responses.

Oncorus has developed a robust OV platform, including a novel approach to maintain safety while enhancing oncolytic potency by leveraging the differential expression of micro-RNA (miR) technology to deliver multiple warheads in a single injection. ONCR-177, a highly engineered recombinant oncolytic Herpes Simplex Virus (oHSV), expresses transgenes which can potently activates local and systemic anti-tumor immune response. ONCR-177, or its mouse surrogate virus mONCR-171, was tested in a series of experiments designed to characterize its biodistribution, anti-tumor activity, and mechanisms of action. ONCR-177/mONCR-171 potently activates local and systemic anti-tumor immune responses that result in durable responses, extended survival, and the elicitation of protective immunity.  These encouraging preclinical data warrant the clinical investigation of ONCR-177 in patients with metastatic cancer.

A Selective and Safe Bispecific Antibody Approach to Targeting CD47 Blockade on Tumor Cells
Walter Ferlin, CSO, Light Chain Bioscience, Switzerland

The CD47-signal regulatory protein alpha (SIRP-alpha) axis, originally discovered as a mechanism of self-recognition, has emerged as a novel innate immune check-point employed by cancer cells to escape immune surveillance. Over-expression of CD47 on a plethora of hematologic and solid cancers has been shown to be associated with poor prognosis. CD47 blockade is thus considered as an attractive strategy to redirect the host immune system toward eliminating cancer cells. A combination of the anti-CD20 monoclonal antibody (mAb), rituximab, and the anti-CD47 mAb, Hu5F9-G4 has shown clinical efficacy in patients with Non-Hodgkin lymphoma (NHL) treated. However, in parallel, due to the ubiquitous expression of CD47 on healthy cells, toxicity is observed limiting exposure which impairs clinical development of anti-CD47 mAbs. To harness the tumoricidal potential and avoid the liabilities of CD47 blockade, we have developed bispecific antibodies, co-targeting CD47 and a tumor associated antigen, for selective and safe blockade of CD47 on malignant cells.

Discovery and Development of Monoclonal Antibodies Targeting Tumor Neo-Epitopes
Philip Arlen, President and CEO, Precision Biologics, Inc, United States of America

An allogeneic cancer vaccine developed from human tumors surgically resected had demonstrated anti-tumor responses in a clinical trial. These responses correlated with the ability of patients to mount and sustain antibody responses against the vaccine. This vaccine was utilized as a platform to identify monoclonal antibodies with tumor sensitivity, specificity and anti-tumor killing.

Morning Coffee Break and Networking

Immuno-STATs™: A Novel Biologics Platform for Antigen-Specific Immunotherapy
Saso Cemerski, Senior Director, CUE Biopharma, United States of America

Immuno-STATs are proprietary biologics that incorporate, in a single molecular framework, key signals needed to selectively modulate antigen-specific T cells: namely, the pMHC-complex and relevant co-stimulatory/co-inhibitory signals, dependent upon the disease indication. The modularity and versatility of the platform allows for incorporation of diverse HLA alleles, different T cell epitopes along with various biologically relevant activating or regulatory signals. This ability to generate polyspecific therapeutic molecules enables targeting diverse geographical patient populations encompassing numerous disease indications. Harnessing selective immune-targeting while avoiding broad non-specific modulation of the immune system should provide a superior safety and therapeutic profile. Mechanistic data to this end will be discussed. The lead clinical candidate CUE-101 is comprised of HLA-A*0201, genetically bound to a HPV16 epitope (E7 protein, peptide 11-20), along with affinity-attenuated human interleukin-2 to selectively activate and expand HPV16 E711-20-specific CD8+ T cells for HPV-driven malignancies.

SB 11285, A Novel STING Agonist that Self-Assembles into Nanostructures, is a Highly Potent Immuno-Therapeutic Agent for Cancer
Radhakrishnan Iyer, Co-Founder & Chief Scientific Officer, Spring Bank Pharmaceuticals, Inc., United States of America

Immunotherapy has emerged as a transformative approach for the treatment of cancer.  Recent work has highlighted a significant role for Stimulator of Interferon Genes (STING) agonists in immunotherapy. Conceptually, the activation of STING pathway in immune cells in the tumor microenvironment and/or tumor cells could result in the induction of innate and adaptive immunity for anti-tumor activity.

SB 11285, a synthetic cyclic dinucleotide, is a first-in-class STING agonist engineered for self-assembly into nanostructures and enhanced uptake by immune cells. SB 11285 has demonstrated highly potent, and durable antitumor activity when administered by intravenous, intraperitoneal and intratumoral routes in subcutaneous and orthotopic tumor models including A20 lymphoma, 4T1 breast cancer, B16F10 melanoma, NBT-II bladder cancer, as well as, CT26, and MC38 colon cancer models. The enhanced anti-tumor activity of SB 11285 in combination with other anti-cancer agents such as cyclophosphamide, anti-CTLA and anti-PD-1 antibody has also been demonstrated in MC38 colon carcinoma, A20 lymphoma, and CT26 colon carcinoma syngeneic mouse tumor models. The STING-mediated anti-tumor activity of SB 11285 is characterized by the induction of immune memory and abscopal effects and is consistent with the activation of innate and adaptive immunity by SB 11285. Thus, pharmacodynamic studies in syngeneic mouse tumor models revealed that administration of SB 11285 resulted in the induction of cytokines such as IFN, IL-10, and IL-12p70 at the site of the tumor, and periphery, as well as, the induction of increased numbers of several effector immune cell types including CD8+ T-cells. Furthermore, a reduction in the number of suppressive immune cell types, including granulocytic myeloid-derived suppressor cells, as well as, reduction of Treg cells at the site of the tumor were observed. Ex-vivo analysis using ELISPOT assays of spleen samples from SB 11285-treated mice in the CT26, B16F10 syngeneic mouse models, demonstrated that there was a tumor-specific IFN? T cell response following IT or IV dosing. In the CT26 colon carcinoma syngeneic mouse model, depletion of CD+T cell function by administration of anti-CD8 antibody, significantly diminished the antitumor activity of SB 11285. Overall, these data are all consistent with the anti-tumor activity of SB 11285 being mediated by the activation of STING and the priming and amplification of cytotoxic CD8+ T cells, as well as, the activation of NK cells and Th-1 macrophages, which is consistent with the induction of innate and adaptive immune system. These preclinical studies have enabled the advancement of SB 11285 towards clinical trials.

Networking Lunch

Neutralizing Soluble TNF to Overcome Resistance to Immunotherapy
RJ Tesi, CEO/CMO, Inmune Bio Inc, United States of America

The complexity of TNF biology is not understood by scientists, biopharma or clinicians.  In cancer, soluble TNF promotes tumor growth, EMT and metastasis.  In the TME, sTNF directly or indirectly recruits MDSC, TAM and Tregs while decreasing the TIL infiltration.  The result is a tumor that grows, is resistant to therapy and prone to metastasis.  Neutralizing sTNF reverses these immunologic resistance factors to allow the patient’s immune system and immunotherapy to better control the tumor.  The therapy must be targeted, selective inhibitor of only sTNF.  Currently approved non-selective TNF inhibitors should not be used because they inhibit trans-membrane TNF to promote immunosuppression.  Pre-clinical and clinical data will be presented.

Afternoon Round Table Discussions on IO with Coffee

Close of Day 2 of the Conference