Cambridge Healthtech Institute’s 2nd Annual

Preclinical and Translational Immuno-Oncology

Advanced Immuno-Oncology Models and How They Translate to the Clinic

10-11 March 2020

 

Modeling the immune system and its response to cancer sets a particularly difficult challenge. The different cell types required, heterogeneity of tumours and the signaling pathways involved mean that multiple advanced models are required to justify clinical trials. But which ones do you choose and how do they relate to the clinic? At the Preclinical and Translational Immuno-Oncology conference, we will delve deeper into the advantages and disadvantages of each model and the strategies employed to help translate positive results to clinical trials. Models to be discussed include humanized mice models, syngeneic and xenograph models, 3D models and organoids, plus many more.

Final Agenda

MONDAY 9 MARCH

Recommended Short Course*

SC1: Oncolytic Virus Therapy – Current Field, Challenges and Future Directions - LEARN MORE

Ulrich M. Lauer, MD, Professor, Vice Chairman, Internal Medicine VIII, Medicine, University Hospital Tübingen

Alan Melcher, MD, PhD, Professor, Team Leader, Translational Immunology, The Institute of Cancer Research

*Separate registration required.

TUESDAY 10 MARCH

7:30 Registration and Morning Coffee

TRANSLATIONAL STRATEGIES

8:30 Organizer’s Welcome Remarks

Joel Hornby, BSc Hons, Conference Director, Cambridge Healthtech Institute

8:35 Chairperson’s Remarks

Stefan Ries, PhD, Global Head of External Innovation, Oncology, pRED Oncology, Roche Pharma, Roche Innovation Center Munich

8:40 Partnering for Success: External Innovation as Essential Component for a Successful Cancer Immunotherapy Portfolio

Ries_StefanStefan Ries, PhD, Global Head of External Innovation, Oncology, pRED Oncology, Roche Pharma, Roche Innovation Center Munich

Cancer immunotherapy is a promising field in oncology. However, competition is fierce with currently hundreds of compounds in development. Diversity of thought, understanding biology and access to novel modalities is essential to progress cancer research. By joining forces between academia, biotech and pharma we can truly make a difference for cancer patients. This talk will cover our approach to leverage external innovation including case studies of recent collaborations.

9:10 Multidisciplinary Approaches to Enhancing Cancer Biotherapeutics within the CRUK City of London Centre

Ng_TonyTony Ng, FMEDSCI, MB, ChB, MRCP, FRCPath, PhD, Head of School of Cancer and Pharmaceutical Sciences, King’s College London; CRUK City of London Centre Executive Member; Richard Dimbleby Chair of Cancer Research; Group Leader, KCL Breast Cancer Now Research Unit; Director, KCL and UCL Comprehensive Cancer Imaging Centre; Chair of Molecular Oncology, UCL Cancer Institute

Within the cross-disciplinary approaches enhancing biotherapeutics theme of the CRUK City of London Centre, we use our cross-disciplinary strengths (engineering, physics, chemistry, mathematics) to maximise the impact of biological therapies. We are exploring responses to biological therapies in a manner analogous to pharmacokinetic/pharmacodynamic studies of small molecule-based therapies, using advanced imaging to track (pharmacokinetics) and quantify the impact (pharmacodynamics) of biological therapies thereby increasing our understanding of the immune-tumour interaction and effect on tumour microenvironment.

ImmuNeed 9:40 Presentation to be Announced

9:55 Sponsored Presentation (Opportunity Available)

10:10 Coffee Break in the Exhibit Hall with Poster Viewing

10:50 Combinatorial Approaches to Enhance Bispecific Anti-Tumor Efficacy

Smith_EricEric Smith, PhD, Senior Director, Bispecific Antibodies, Regeneron Pharmaceuticals

This presentation will describe Regeneron’s bispecific platform and present preclinical data on REGN4018, a clinical stage T cell engaging bispecific targeting Muc16 for solid tumor indications. In addition, status updates on Regeneron’s other clinical stage bispecific antibodies (REGN1979, REGN5458, REGN5678) will be presented as well as a discussion of new combinatorial approaches being taken to enhance bispecific anti-tumor efficacy.

11:20 Regulatory Strategies for Early Clinical Development

Elena_SpanjaardElena Spanjaard, PhD, Global Head of Regulatory Affairs, Celyad

Regulatory guidelines provide a framework for preclinical development, and key regulatory concepts will be highlighted. Preclinical studies must be tailored to support individual product and development program features. Considerations for different immuno-oncology modalities will be presented, including a discussion on challenges and suggested approaches for successful development.

11:50 Translational Aspects of Tissue/Site Agnostic Indications

Andrew ExleyAndrew Exley, PhD, Medical Assessor, Biologicals and Biotechnology Unit, MHRA

Tissue or Site agnostic therapies in oncology are the epitome of precision therapies targeted to molecularly defined tumors. The first tissue agnostic approvals granted by the FDA in 2017, pembrolizumab for unresectable or metastatic, MSI-H or dMMR solid tumors and the orphan-drug designated larotrectinib and entrectinib for solid tumours with NTRK-fusion proteins, provide useful exemplars. We review the specific opportunities and challenges of this molecular approach.

12:20 Luncheon Presentation (Sponsorship Opportunity Available)

12:50 Session Break

ADDRESSING NOVEL IO TARGETS

13:20 Chairperson’s Remarks

Jane Willoughby, Senior Post-Doc, Antibody and Vaccine Group, Centre for Cancer Immunology, University of Southampton

13:25 Tissue Distribution, Elimination and Target Engagement of Biologics – Going from Mice to Men and from in vivo to in Silico

Sepp_ArminArmin Sepp, PhD, Scientific Leader and GSK Fellow, IVIVT DMPK Modelling, GlaxoSmithKline

We describe a two-pore physiologically-based pharmacokinetic model to describe and predict the tissue distribution, elimination and turnover of soluble proteins, dosed or endogenous, from mice to men. The model includes all major organs and neonatal Fc receptor mediated recycling in the endosomal compartments. We evaluate the model by comparing the ab initio predictions for the tissue distribution and elimination properties of albumin-binding domain antibody with the experimental observations in humans.

13:55 DNA-Based Nanobody Delivery

Boutton_CarloCarlo Boutton, PhD, Head Nanobody Explorative Technologies, Discovery, Ablynx - Sanofi

Small Nanobodies® with their modular design show a different pharmacokinetic profile compared to conventional antibodies and this can be exploited by alternative delivery methods. DNA-based gene transfer of Nanobodies and biopharmaceuticals in general is an appealing alternative to conventional protein therapy. We demonstrate that multivalent Nanobodies encoded as DNA results in a stronger, longer-term and more localized exposure compared to conventional protein therapy.

14:25 FEATURED PRESENTATION: Stress Induced Post-Translational Modifications (siPTMs) as Targets for Cancer Vaccines

Lindy Durrant, PhD, Professor of Cancer Immunotherapy, University of Nottingham; CSO, Scancell Ltd.

Citrullination is a widely expressed, novel, stress induced post-translational modification that is a potent target for cancer vaccines. There is a repertoire of cytotoxic CD4 T cells in mice and humans that recognises citrullinated epitopes. Tumors over-express PAD enzymes. Inflammation and stress induce high levels of autophagy and MHC-II presentation of citrullinated epitopes on tumors. Citrullinated peptides demonstrate potent anti-tumor immunity with no associated toxicity and will shortly enter the clinic.

Biocytogen 14:55 Presentation to be Announced

15:25 Refreshment Break in the Exhibit Hall with Poster Viewing

16:05 TNFR2 Antagonism: Specificity for the TME and the TNFR2 Oncogenes

Faustman_DeniseDenise Faustman, MD, PhD, Director of Immunobiology, Medicine, Harvard Medical School/Massachusetts General Hospital

Over the past 2 years, disappointing data has appeared on agonistic approaches to cancer with antibodies. The TNFR2 receptor is overexpressed in Tregs and MDSC and cancer cells thus antagonistic antibodies are desired. We now will show the novel pathway and binding specificity of this new class of antibodies.

16:35 Immunotherapy by Design – Induction of Systemic Anti-Tumour Immunity by Targeting Recruitment of Natural Antibodies

Glossop_MelanieMelanie Glossop, BSc, CChem, FRSC, Head of Chemistry, Centauri Therapeutics

Centauri Therapeutics is designing highly disruptive treatments for life-threatening bacterial infections and cancer using the power of natural antibodies. The technology has the potential to induce broad and universal anti-tumour immunity using proprietary Alphamers. Alphamers selectively bind their target and simultaneously recruit natural antibodies for engagement of both the innate and adaptive immune system.

17:05 Problem Solving Roundtable Discussions

In Silico Modelling in IO, How Useful and Predictive?

Sepp_ArminModerator: Armin Sepp, PhD, Scientific Leader and GSK Fellow, IVIVT DMPK Modelling, GlaxoSmithKline


  • Target engagement in combination and bispecific therapies, when can one or the other be preferred?
  • Tumour penetration of biotherapeutics
  • Drug interactions with innate and adaptive immune system cells

How Can We Leverage Cutting Edge In Vivo Pre-Clinical Models for Cancer Immunotherapy Profiling?

Colombetti_SaraModerator: Sara Colombetti, PhD, Global Head of Oncology Discovery Pharmacology, Pharma Research and Early Development (pRED), Roche Innovation Center Zurich


  • Current limitations of pre-clinical mouse models for cancer immuno-therapy
  • How can CPI resistant patient population can be modeled pre-clinically
  • New frontiers of tumor immuno-profiling

18:05 Welcome Reception in the Exhibit Hall with Poster Viewing

19:05 Close of Day

WEDNESDAY 11 MARCH

7:45 Registration and Morning Coffee

ADVANCED IO MODELS

8:30 Chairperson’s Remarks

Catarina Brito, PhD, Lab Head, Advanced Cell Models Lab, Animal Cell Technology Unit, iBET

8:35 In vitro/ex vivo 3D Models to Address the Immune Tumor Microenvironment

Brito_CatarinaCatarina Brito, PhD, Lab Head, Advanced Cell Models Lab, Animal Cell Technology Unit, iBET

We have been developing in vitro and ex vivo 3D cell models to depict features of the tumor microenvironment, such as the crosstalk between different cell players and the ECM remodeling, drivers of the immunosuppressive and invasive microenvironment typical of advanced stage carcinomas. Case studies in ovarian and breast cancer will be discussed, including the interrogation of chemotherapeutics and targeted drugs, including immunomodulatory ones.

9:05 How Can Cutting-Edge Preclinical Models Help Rational Cancer Immuno-Therapy Design?

Colombetti_SaraSara Colombetti, PhD, Global Head of Oncology Discovery Pharmacology, Pharma Research and Early Development (pRED), Roche Innovation Center Zurich

Preclinical mouse models are key tools to evaluate the activity of cancer immuno-therapy. Here we will present our cutting edge mouse models platform which allows the identification of relevant pharmacodynamic biomarkers, and helps design rational immunotherapy combinations. The translational relevance of the preclinical data obtained will be shown.

9:35 Ex vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids

Jenkins_RussellRussell W. Jenkins, MD, PhD, Assistant Professor, MGH Cancer Center, Massachusetts General Hospital, Harvard Medical School

Ex vivo systems that incorporate features of the tumor microenvironment and model the dynamic response to PD-1 blockade may facilitate efforts in precision immuno-oncology. We have developed a system for ex vivo profiling of PD-1 blockade using 3D microfluidic culture of murine- and patient-derived organotypic tumor spheroids (MDOTS/PDOTS) using established murine models as well as clinically relevant patient specimens.

Reaction_Bio_2019 10:05 Presentation to be Announced 

10:20 Sponsored Presentation (Opportunity Available)

10:35 Coffee Break in the Exhibit Hall with Poster Viewing

10:45 Solutions-Focused Speed Networking in the Exhibit Hall


PLENARY KEYNOTE SESSION

11:15 Organizer’s Remarks

Ngoc ‘Emily’ Le, PhD, Conference Producer, Cambridge Healthtech Institute

11:20 Chairperson’s Remarks

Andrew Sewell, PhD, Distinguished Research Professor and Wellcome Trust Senior Investigator, Infection & Immunity, Cardiff University School of Medicine

11:30 Strategies to Improve Antitumor Efficacy of Genetically Engineered T Cells

Stanley Riddell, MD, Scientific Director, Clinical Research, Fred Hutchinson Cancer Research Center; Professor, University of Washington School of Medicine

Immune cells can be readily genetically modified to express natural tumor targeting antigen receptors or synthetic chimeric antigen receptors (CARs) that activate immune cell signaling pathways to result in destruction of tumor cells expressing the relevant target molecule. The presentation will discuss advances in our understanding of receptor signaling and the development of strategies that combine therapeutic agents to improve efficacy and safely extend the spectrum of cancers that can be treated with cell therapies.

12:00 PD-1 Antibodies Are Transforming Cancer Treatment

Roy D. Baynes, MD, PhD, Senior Vice President and Head, Global Clinical Development, CMO, Merck Sharpe & Dohme

PD-1 antibodies have shown significant activity as monotherapy across multiple cancer types and lines of therapy. Precision medicine tools have been used to identify subjects most likely to respond to PD-1 antibody monotherapy, to provide insight to potential resistance mechanisms, and to inform combination therapies. A number of these combinations have demonstrated significant activity in additional tumor types and lines of therapy.

12:30 Close of Preclinical and Translational Immuno-Oncology

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