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SELECTBIO Conferences Immuno-Oncology Europe 2019

Immuno-Oncology Europe 2019 Agenda


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Monday, 28 October 2019

00:00

Graham PockleyKeynote Presentation

The Theranostic Potential of Membrane Hsp70 in Cancer: An Autologous Natural Killer (NK) Cell-based Therapeutic and Companion Diagnostic for Treating Tumours Expressing Membrane Hsp70
Graham Pockley, Director and Professor, John van Geest Cancer Research Centre, Nottingham Trent University, CEO, multimmune GmbH, United Kingdom

A cell surface bound form of the 70 kDa heat shock (stress) protein Hsp70 is selectively, and widely expressed on the plasma membranes of many tumour entities. This presentation will summarise the current status of an NK cell-based therapeutic for the treatment of such tumours, the impact of checkpoint inhibition thereupon and the development of a Companion Diagnostic to identify patients bearing membrane Hsp70-expressing tumours.

00:00

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.

00:00

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.

00:00

Christophe Le TourneauKeynote Presentation

Novel Patterns of Response to Immunotherapy
Christophe Le Tourneau, Head, Department of Drug Development & Innovation (D3i), Institut Curie, France

Novel patterns of response and progression to immunotherapy have been reported that are not observed with conventional cytotoxic or targeted anti-cancer treatments. A major breakthrough with immunotherapy is potential to achieve durable responses in a subset of patients with advanced cancer that can be maintained several years even after stopping treatment. No standardized definition of durable response exists in the literature, and the optimal duration of treatment in case of durable response is not clearly established. However, the majority of patients do not respond to immunotherapy. Initially reported in advanced melanoma patients, pseudoprogression occurs when tumor index lesions regress after initial progression, supporting the concept of treating some patients beyond progression. Overall, reported rates of pseudoprogression never exceed 10%, meaning that the large majority of patients who have a disease progression will not eventually respond to treatment. The decision to pursue treatment beyond progression must therefore only be taken in carefully selected patients with clinical benefit, who did not experience severe toxicities with immunotherapy. Conversely, rapid progressions, called hyperprogressions, were reported by several teams with rates ranging from 4% to 29%. These observations need to be confirmed from randomized trials. It is essential to interrupt treatment in patients with hyperprogression, in order to switch to another potentially active treatment. Finally, some patients experience dissociated responses, with some lesions shrinking and others growing. Local treatment with surgery or radiotherapy for growing lesions may be considered. Several immune specific related response criteria were developed to better capture benefits of immunotherapy. These criteria only address the pseudoprogression pattern of response, and do not capture the other patterns of response such as hyperprogression and dissociated response. The classic RECIST remains a reasonable and meaningful method to assess response to immunotherapy in the clinic.

00:00

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.

00:00

Stephen BeersKeynote Presentation

Optimizing Anti-Cancer Therapy with Immune Stimulatory Antibodies: Big Doors Swing on Little Hinges
Stephen Beers, Professor of Immunology and Immunotherapy, University of Southampton, United Kingdom

Clinical successes with immunomodulatory monoclonal antibodies (mAb) have confirmed that the adaptive immune system can produce long-term cures for cancer patients. These remarkable findings with immunomodulatory mAb have, to date, been restricted to checkpoint blockers with their co-stimulatory counterparts failing to translate. Here, data will be presented that illustrates the mechanistic complexity of co-stimulatory mAb targeting 4-1BB (CD137). We will show that these mAb are able to perform multiple functions with opposing Fc?R requirements. Further, we will demonstrate that inappropriate Fc selection can lead to blunted responses that limit efficacy. Finally, once the mechanistic requirements for therapeutic efficacy are established we show that these can be used to design optimal combination therapies and to engineer single agent combination mAb. These data provide a framework for engineering co-stimulatory mAb for clinical translation.

00:00

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).

00:00

Ed SchuuringKeynote Presentation

Circulating Tumor DNA as a Molecular Blood-borne Biomarker to Predict Tumor Response In Lung Cancer Patients Treated with Immunotherapy
Ed Schuuring, Professor in Molecular Oncological Pathology, University Medical Center Groningen, Netherlands

A significant minority of patients treated with immune checkpoint inhibitors shows durable responses but no adequate biomarkers are available for predicting which patients will benefit.  Immunotherapy is expensive and potentially toxic. Tumor response is monitored by tumor volume using CT scanning. The aim of our study is to assess plasma levels of non-targetable tumor-specific mutations as molecular biomarkers and monitoring tool for durable responses to immunotherapy in advanced NSCLC.

00:00

Immuno-STATs™: A Novel Biologics Platform for Antigen-Specific Immunotherapy
Anish Suri, Senior vice President and Chief Scientific Officer, Cue Biopharma, Inc., 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.

00:00

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

00:00

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.

00:00

Sara ColombettiKeynote Presentation

Sharpening the Preclinical Insight: Improve Clinical Relevance and Predictive Value
Sara Colombetti, Global Head Oncology Discovery Pharmacology, pharma Research and Early Development (pRED), Roche Innovation Center Zürich, Switzerland

We will present how the Pharmacology Group at the Roche Innovation Center Zurich has been developing over the past years a cutting edge mouse models platform for in vivo profiling of cancer immunotherapy combination. First internal Ph1 data will be also presented, which support the relevance of the pre-clinical model platform.

00:00

Using Immunooncological 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.

00:00

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

00:00

Development of Synthetic Self-Replicating RNA Platforms For Oncology Vaccines and Therapeutics
Nathaniel Wang, Head of R&D, Synthetic Genomics, United States of America

RNA as a vaccine and therapeutic modality has become a focus of significant interest.  SGI has engineered a novel, self-replicating RNA that overcomes existing limitations and has shown improved immunogenicity and versatility for use in immuno-oncology therapeutics. Vaccination with an engineered self-replicating RNA encoding a neoantigen leads to polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that inhibited tumor growth, with additional synergy observed with the administration of anti-PD-1 antibody. Self-replicating RNAs are also capable of generating T cell responses of sufficient magnitudes and quality to provide survival advantages when administered as a monotherapy. Combined with the capability of self-replicating RNAs to express biologics, this technology represents a future avenue for multidimensional therapies.

00:00

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 ICOShi 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 ICOShi CD 4 T effector cells are primed to respond to vopratelimab.

00:00

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.


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Add to Calendar ▼2019-10-28 00:00:002019-10-29 00:00:00Europe/LondonImmuno-Oncology Europe 2019Immuno-Oncology Europe 2019 in Rotterdam, The NetherlandsRotterdam, The NetherlandsSELECTBIOenquiries@selectbiosciences.com