Preclinical and Translational Immuno-Oncology

The rise of cancer immunotherapy such as immune checkpoint modulators, bispecific antibodies, T cell therapy and personalized cancer vaccines, instigated a wide range of unique preclinical and translational challenges. The demand for predictive and robust preclinical models and approaches to minimize translational failures in immuno-oncology is at an all-time high. The need for leveraging phenotypic features of models, for early identification of predictive biomarkers, for rational design of combination therapies, and for researching the cancer-immune cell interactions add to the complexity of translational research in immune-oncology. Cambridge Healthtech Institute’s Sixth Annual Preclinical and Translational Immuno-Oncology conference is designed as a forum for ideas and opinions exchange to decrease the rate of clinical failures in immuno-oncology.

Monday, February 12

10:30 am Conference Program Registration Open

TRANSLATIONAL STRATEGIES FOR COMBINATION THERAPY

11:50 Chairperson’s Opening Remarks

James Smothers, Ph.D., Vice President, DPU Head, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

12:00 pm Non-Clinical Approaches to Predict Single Agent vs. Combination Value and Clinical Development Strategies for Emerging Cancer Immunotherapies

James Smothers, Ph.D., Vice President, DPU Head, Immuno-Oncology & Combinations DPU, Oncology R&D, GlaxoSmithKline

Non-clinical research studies historically support preclinical development and regulatory submission satisfaction and provide critical support of early clinical development hypotheses and clinical trial design including managing expectations of single agent efficacy or setting strategic vision for combination value through biology synergies. Moreover, following early clinical development milestones, an experimental medicine requires ongoing translational review of the clinical readouts beyond efficacy which in turn requires additional non-clinical analyses and experimental execution to drive results-based decision making and data-informed design of late stage clinical trials in anticipation and hope of drug approvals. Examples of non-clinical studies to support all of these activities will be reviewed including choice of experimental models and design.

12:30 Drivers, Passengers, and Checkpoints: Biomarker Development for Novel Oncology Immuno-Therapies

Nicholas C. Dracopoli, Ph.D.,Senior Vice President, Translational Science, Personal Genome Diagnostics

The majority of novel oncology drugs are still approved without a companion diagnostic even though the probability of regulatory approval is much higher for drugs developed with a diagnostic biomarker. This presentation will review the development of companion diagnostics for novel immuno-oncology drugs and describe strategies to release a prior, but suppressed, immune response to a tumor, or to prime a new response in patients with no prior immune response.

1:00 Session Break

1:10 Luncheon Presentation I: The Current and Future Landscape of Combinational immuno-Oncology Targets

Matthew E. Wampole, Ph.D., Manager, Solution Scientists, Clarivate Analytics

Ongoing challenges for cancer immunotherapies are resistance and lack of efficacy with current treatments. The tumor microenvironment and infiltrating immune cells play an important role in the response to treatment. Combinational therapies are being rigorously tested to overcome these challenges, but additional targets are needed. This presentation will review the current landscape of combinational immuno-oncology therapies and discuss strategies for identifying new combinations.

1:40 Luncheon Presentation II: Overcoming Technology Limitations in Molecular and Cellular Workflows. Case: Standardizing Cell Therapy Workflows

Winny Tan, Ph.D., Strategic Partnerships Manager, imec

A major hurdle to scale up the market of cell therapies is the cost and complexity of the workflow. We propose a novel approach based on a standardised workflow which will be easy to use, reliable and reproducible. Using Silicon chip technology, fully integrated solutions can be built, combining microfluidics, photonics based biosensors, PCR, and single cell manipulation. We will present a portfolio of technologies which will be the building blocks for bioprocessing and delivery of future personalised therapies.

2:10 Session Break

APPROACHES AND TECHNOLOGIES TO ADVANCE DISCOVERY AND TRANSLATION

2:30 Chairperson’s Remarks

Norman Greenberg, Ph.D., CSO and Senior Vice President, Therapeutics, Atreca

2:40 Defining the Difference: Accelerating Both Small Molecule and Large Molecule Drug Discovery through Technology Solutions and Translational Screening Models

Litao Zhang, Ph.D., Vice President, Leads Discovery and Optimization, Bristol-Myers Squibb

Cancer immunity in nature requires the coordination of both immune stimulatory and inhibitory signaling mechanisms that occur in the tumor microenvironment. In this talk, we will share how to select right translational models to quantitative monitor and characterize IO therapeutic agents. 3D bioprinting technology, co-culture systems and CRISPR will be used to model and mimic tumor microenvironment. Through these advanced technology platforms, biomarker profiling strategy will be discussed. The challenges and solutions to close the gaps in the IO drug discovery will be shared.

3:10 CO-PRESENTATION: Leveraging Artificial Intelligence for Drug Discovery to Help Identify and Rank Potential Promising Immuno-Oncology Targets

John Gregory, Director, R&D Project & Portfolio Management Business Technology, Pfizer

Jadwiga Bienkowska, Sr. Director, Computational Biology, Oncology R&D, Pfizer

Pfizer’s private cloud-based implementation of IBM Watson for Drug Discovery is intelligently helping our Oncology R&D researchers to analyze millions of scientific documents, and supporting Pfizer data, to help identify and rank potential promising Immuno-Oncology targets, and identify potential adverse events.

3:40 Discovery and Characterization of Functional Anti-Tumor Antibodies from Non-Progressing Cancer Patients Undergoing Immunotherapy

Norman Greenberg, Ph.D., CSO and Senior Vice President, Therapeutics, Atreca

We used a cell-barcoding technology to sequence the plasmablast antibody repertoires from patients with metastatic non-progressing cancers that received check point inhibitor immunotherapy. We identified recombinant antibodies that bound non-autologous human tumor tissues and cell lines, some of which caused regression of, and durable immunity toward, heterologous syngeneic tumors in mice. This research demonstrates that functional anti-tumor antibody responses target public antigens in cancer patients and provides an approach to identify antibodies with diagnostic and / or therapeutic utility.

4:10 The Use of Genetics in Early Signals of Efficacy Trials

Jean-Claude Marshall, MSc., PhD., Head of Clinical Genetics and Biospecimens, Pfizer

The recent rapid technological advancements in the field of genomics has made the ability to use genetic enrollment and on going analysis criteria possible during early phase clinical trials. These early sign of efficacy trials now form an important cornerstone of Pfizer clinical trial protocols. This presentation will focus on those on going efforts to accelerate early phase clinical trials within the Pfizer portfolio

4:40 Refreshment Break and Transition to Plenary Session

5:00 Plenary Keynote Session (click here for more details)

 

Precision for Medicine

6:00 Grand Opening Reception in the Exhibit Hall with Poster Viewing

7:30 Close of Day

Tuesday, February 13

7:30 am Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

9:00 Refreshment Break in the Exhibit Hall with Poster Viewing

MODELING RESPONSE AND RESISTANCE

10:05 Chairperson’s Remarks

Shailaja Kasibhatla, Ph.D., Director, Translational Development, Celgene

10:15 Translation Challenges of Novel Immuno-Oncology Therapies

Shailaja Kasibhatla, Ph.D., Director, Translational Development, Celgene

Therapeutic strategies harnessing the immune system have led to breakthroughs in cancer management offering the hope for “cures”. Drug development in oncology has advanced significantly over the past decade with successful approved drugs in both tumor targeted and immunotherapies across indications. There is great potential to leverage the combinations of these along with targeted delivery to bring clinical benefit to non-responders and long-term benefits in the responding patients. In this presentation, I will discuss integrated biomarker approaches from early preclinical discovery to guide translational research and potential clinical proof-of-concept.

10:45 Pre-Clinical Modeling of Immune Responses to Cancer: From Bench-Side to Clinical Outcomes

Mithun Khattar, Ph.D., Immuno-Oncology Lead, Cancer Pharmacology, Takeda Pharmaceuticals

Murine models for pre-clinical studies in immuno-oncology and cancer pharmacology have greatly evolved. However, not all pre-clinical breakthrough therapies translate into clinical successes. Fundamental differences in the immune composition, tumor microenvironments, progression of disease, etc. between mice and humans may contribute to translational failures. A deeper exploration of the relevant immunological MoAs and biomarker strategies can minimize such failures by facilitating patient selection as well as designing potential combination therapies.

11:15 Response and Resistance to PD1 Checkpoint Inhibitor

Siwen Hu-Lieskovan, M.D., Ph.D., Assistant Clinical Professor, Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine UCLA

Inhibiting adaptive immune resistance is the mechanistic basis of the antitumor activity of PD-1 immune checkpoints blockade therapies, by unleashing the anti-tumor response that already exists in the patient but was being blocked by the PD-1/L1 checkpoint. Genetic (and likely epigenetic) alterations leading to crippled IFN-receptor signaling and loss of function mutations in antigen presenting machinery mediate primary and/or acquired resistance to PD-1 blockade therapy, providing rationale for combination therapies to increase the benefit to more tumor types and patients.

11:45 Selected Poster Presentation: A Personalized Cancer Vaccine Approach to Treat Lynch Syndrome

Papia Chakraborty, Senior Scientist, Head of Immuno-Oncology, MedGenome Inc.

12:00 pm Selected Poster Presentation: Targeted RNA Replacement for Personalized Cancer Therapeutics

Seong-Wook Lee, Ph.D. , Professor, Graduate School of Integrated Life Sciences, Research Institute of Advanced Omics, Dankook University

12:15 pm Session Break

12:25 Luncheon Presentation I: Clinically Validated ex vivo Tumor Culture to Explore MOA and Predict Efficacy

Mark Paris, Associate Director, Translational Applications, Biopharma Services, Mitra Biotech

12:55 Luncheon Presentation II (Sponsorship Opportunity Available)  

1:25 Refreshment Break in the Exhibit Hall with Poster Viewing

ADVANCED TUMOR MODELING

2:00 Chairperson’s Remarks

Siwen Hu-Lieskovan, M.D., Ph.D., Assistant Clinical Professor, Department of Medicine, Division of Hematology-Oncology, David Geffen School of Medicine UCLA

2:10 Pre-Clinical Models of Small Cell Lung Cancer and the Validation of Therapeutic Targets

Julien Sage, Ph.D., Professor of Pediatrics, Hematology/Oncology, Genetics, Stanford University

Small cell lung cancer (SCLC) is the most lethal form of lung cancer. We will discuss the functional validation of novel therapeutic targets in SCLC based on human cancer genomic data and pre-clinical mouse models, including recent work on the Notch signaling pathway.

2:40 Enhancing T-cell-Mediated Tumor Killing

Shane R. Horman, Ph.D., Research Investigator III, Functional Genomics, GNF-Novartis

Deconvoluting and enhancing T-cell-mediated tumor killing is a central focus of immuno-oncology initiatives. We have developed a novel microphysiological 3D assay platform that quantitates T-cell-mediated killing of colorectal cancer tumor spheroids and enables parallel assessment of spheroid size and viability as well as T-cell penetration into the microtumor structure. Employing this assay platform in industrialized drug discovery, we profiled 1,800 annotated compounds and found a variety of targets that can be modulated to improve tumor-specific T-cell cytotoxicity.

3:10 Human Tissue Based Models in Immune-Oncology

Svetlana Sadekova, Ph.D., Senior Principal Scientist, Head of Translational Pathology Group, Merck

Rapid advancement of immuno-oncology is creating the need for translational strategies to guide indication selection, understand mechanisms of resistance and identify biomarkers of response. This talk will highlight the importance of understanding human tumor microenvironment and focus on strategies based on utilizing human tissues for pre-clinical and clinical translational research

3:40 The NANT Cancer Vaccine

David Pyrce, Ph.D., Senior Vice President, Innovation & Chief Commercial Officer, NantKwest, Inc.

The NANT Cancer Vaccine is an integrated, molecularly informed, multi-agent immunotherapy combining off-the-shelf natural killer cell therapy with adenoviral and yeast-based cancer vaccines designed to induce innate and adaptive immune responses in patients with cancer.

4:10 Valentine’s Day Celebration in the Exhibit Hall with Poster Viewing

5:00 Breakout Discussions in the Exhibit Hall

These interactive discussion groups are open to all attendees, speakers, sponsors, & exhibitors. Participants choose a specific breakout discussion group to join. Each group has a moderator to ensure focused discussions around key issues within the topic. This format allows participants to meet potential collaborators, share examples from their work, vet ideas with peers, and be part of a group problem-solving endeavor. The discussions provide an informal exchange of ideas and are not meant to be a corporate or specific product discussion.

Preclinical Strategies for Combination Therapies

Mithun Khattar, Ph.D., Immuno-Oncology Lead, Cancer Pharmacology, Takeda Pharmaceuticals

  • Key factors to consider when selecting combination strategy
  • Immunomodulatory effects of small molecules
  • Translating preclinical models to the clinic-the expected and unexpected

How to Integrate Right Technology, Translational Model And Data Science To Accelerate Drug Discovery In Immuno-Oncology

Litao Zhang, Ph.D., Vice President, Leads Discovery and Optimization, Bristol-Myers Squibb

  • 3D bioprinting technology, co-culture systems, CRISPR and appropriate translational models
  • Challenges and solutions to close the gaps in the IO drug discovery

6:00 Close of Day

Wednesday, February 14

7:00 am Breakfast Presentation (Sponsorship Opportunity Available)  

7:30 Registration Open and Morning Coffee

8:00 Plenary Keynote Session (click here for more details)

10:00 Refreshment Break and Poster Competition Winner Announced in the Exhibit Hall

BIOMARKER STRATEGIES FOR COMBINATION THERAPIES

10:50 Chairperson’s Remarks

Scott D. Patterson, Ph.D., Vice President, Biomarker Sciences, Gilead Sciences, Inc

11:00 High-Content Molecular Profiling in Development of Combination Immunotherapies: Making Rational from Non-Rational

Ruslan Novosiadly, Ph.D., Senior Research Advisor, Cancer Immunobiology, Biomarkers, Eli Lilly

Biomarker discovery paradigm in immuno-oncology has been shifting from hypothesis-testing to hypothesis-generating mode. High-throughput, high-content molecular and immune profiling enables comprehensive biomarker evaluation. Interrogation of mechanistic biomarkers in preclinical mouse tumor models helps identify and guide rational combinations in immune-oncology.

11:30 Next Generation Biomarkers for the Era of Combination Cancer Immunotherapies

Sarah Javaid, Ph.D., Senior Scientist, Discovery Pharmacogenomics, Genetics, Pharmacogenomics, Merck

Immune checkpoint blockade therapies are revolutionizing the standard cancer treatment. Despite the current success of these therapies, not all patients respond to immunotherapy and even those that do often experience toxicities. Combination approaches are the keys to improving clinical response. Novel high throughput technologies enable us to understand the mechanisms underlying the complex interactions between the immune system and cancer and identify predictive biomarkers for patients.

12:00 pm PANEL DISCUSSION: Biomarkers for Combination Cancer Immunotherapy

Moderator: Scott D. Patterson, Ph.D., Vice President, Biomarker Sciences, Gilead Sciences, Inc.

Panelists: Paul Robbins, Senior Director, Early Development and Translational Oncology, Pfizer

Mark Gardner, CEO, OmniSeq Inc.

  • Current and emerging biomarkers for patient selection for immuno-oncology therapies – will current assays be completely superseded?
  • Beyond the biopsy - what future blood-based biomarkers?
  • NGS panels have arrived – are we ready for complex transcript panels?
  • Harmonization of multiple assays for the same biomarker(s) – can this be achieved during development?

12:30 Session Break

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:10 Dessert Break in the Exhibit Hall and Last Chance for Poster Viewing

PRECLINICAL STRATEGIES FOR T CELL THERAPY

1:50 Chairperson’s Remarks

Ian McNiece, Consultant, CellMED Consulting (CMC)

2:00 Establishing an Optimized in vitro Human T Cell Activation Method that Mimics Activated Phenotype of Circulating T Cells

Sadiye Rieder, Ph.D., Scientist, Respiratory Inflammation and Autoimmune, MedImmune

In vitro activation of T cells can be artificial, and testing drug candidates within that setting may not harbor accurate results. We set out to compare different in vitro activation methods for human T cells in order to mimic the phenotype and functionality of T cells in the circulation of healthy donors and autoimmune patients. This presentation will highlight some of the data, and provide insights into proper activation of T cells.

2:30 Exploiting Drug Resistant Allogeneic CAR-T Cells for Cancer Immunotherapy

Ming-Wei Chen, Ph.D., Investigator, Immuno-Oncology, Novartis Institute for BioMedical Research

CAR-T cell therapy makes a meaningful difference in the lives of patients. By using CRISPR to knock-out FKBP1A and TRAC gene, we can create another kind of universal CAR-T resistant to Rapamycin which can be used to suppress host rejection and GVHD. We are able to achieve the double editing more than 90%, and gene-edited T cell was resistant to the immunosuppressive effects over a range of concentrations in vitro.

3:00 Use of Pharmacodynamic Biomarkers to Assess Mechanisms of Bispecific Redirected T cell Therapies in Preclinical Tumor Models

Andrea T. Hooper, Ph.D., Associate Director, Pfizer Oncology Research

Strong evidence exists supporting the important role T-cells play in the immune response against tumors. Still, the ability to initiate tumor-specific immune responses remains a challenge. We have developed a bispecific protein engineered with enhanced pharmacokinetic properties to extend in vivo half-life, and designed to engage and activate endogenous polyclonal T-cell populations via the CD3 complex in the presence of solid tumors expressing target antigens.

3:30 Session Break

TRANSLATIONAL IMAGING IN IO

3:40 Chairperson’s Remarks

Charles Glaus, Ph.D., Head of Research Imaging Sciences, Amgen

3:45 Incorporation of Preclinical And Translational Imaging Methods In The Development Of A Broad Array Immuno-Oncology Therapeutics

Charles Glaus, Ph.D., Head of Research Imaging Sciences, Amgen

The central therapeutic concept of immunotherapy is to use an administered medicine to prompt an immune response in the host. Noninvasive imaging methods that allow monitoring of drug distribution, initial PD response, and subsequent lymphocyte infiltrative response are key to understanding the development of new immune-oncology medicines. In this talk we will review three case studies of Amgen efforts using translational imaging to monitor immune response.

4:15 Translational Imaging Biomarkers in Development of Cancer Immunotherapeutics

Tapan K. Nayak, Director, Translational Imaging Biomarkers, Merck Research Laboratories

The success rate of cancer immunotherapy is difficult to predict, as its efficacy often depends not only upon characteristics of the tumor lesions, but also of the tumor microenvironment involving immune cells and soluble mediators. Molecular imaging with Positron Emission Tomography (PET) allows repeated non-invasive in vivo measurement of many critical molecular features of tumor lesions and microenvironment, such as metabolism, hypoxia and immune cell infiltrate, which can assist the knowledge of how cancer immunotherapy works and also facilitates decision making in development of novel cancer immunotherapeutics. The presentation will cover the use of translational imaging biomarkers in development of cancer immunotherapeutics with examples from preclinical and early clinical studies.

4:45 Dissecting the Components of Combined Immunotherapy, Models Systems and Microscopy

Alexander "Sandy" D. Borowsky, M.D., Associate Professor, University of California, Davis


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