(Shared Conference with World Preclinical Congress and IO Pharma Congress)
Cambridge Healthtech Institute’s 8th Annual
Preclinical Strategies, Models & Tools in Oncology
Advancing Translation in Oncology and Immuno-Oncology
June 18-19, 2019
The rise of cancer immunotherapy 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 immuno-oncology. Cambridge Healthtech Institute’s Eighth Annual Preclinical Strategies, Models & Tools in Oncology conference is designed as a forum for ideas and opinions exchange on how to decrease the rate of clinical failures
in oncology and immuno-oncology.
Tuesday, June 18
7:00 am Registration Open and Morning Coffee
8:00 Chairperson’s Remarks
Elaine Pinheiro, PhD, Senior Principal Scientist, Oncology, Merck
8:10 Mastering Translational Immuno-Oncology
Emma Lees, PhD, Vice President and Oncology Site Head, Bristol-Myers Squibb
This talk will address translational strategies, reverse translation and multidisciplinary approaches to new immuno-oncology agents discovery and development. The new BMS site located in Cambridge, MA will be introduced to the IO community.
8:40 Reverse Translational Studies to Guide Cancer Combination Strategies in the Clinic
PhD, Senior Principal Scientist, Oncology, Merck
Immunotherapeutic strategies, such as checkpoint blockade, have changed the way cancers are being treated, providing significant benefit to patients. Despite success, a large fraction of patients do not respond to single agent therapy. Combination approaches
may be the key to improving response rates in these patients. Preclinical immuno-oncology mouse models provide tremendous value to shaping clinical strategies given that countless potential combinations exist with other immunotherapies, radiation,
and/or standard of care.
9:10 BCMA-Targeting BiTE® Antibody Constructs for the Treatment of Multiple Myeloma – From Bench to Bedside
Friedrich, PhD, Scientific Director, Comparative Biology and Safety Sciences, Amgen
B-cell maturation antigen (BCMA) is a highly plasma cell-selective protein that is expressed on malignant plasma cells of multiple myeloma patients and therefore is an ideal target for T cell redirecting therapies. We developed Bispecific T cell engager
(BiTE®) targeting BCMA and CD3ε and studied their therapeutic impact on Multiple Myeloma.
9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing
10:25 Chairperson’s Remarks
Viviana Cremasco, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)
10:30 Strategies for Generating Novel and Biologically Relevant TcRs for Cancer Cell Therapy
Andy Hurwitz, PhD,
Vice President, Head of Preclinical Research, AgenTus Therapeutics
This presentation will share a mammalian display-based platform for T Cell Receptor (TCR) discovery and identification of novel TCRs targeting NY-ESO-1. Overall translational approaches for TCR-based agents will be discussed.
10:55 Stromal-Imposed Immunosuppression in the Era of Checkpoint Blockade
Cremasco, PhD, Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)
Despite the increasing interest in targeting stromal elements of the tumor microenvironment, we still face tremendous challenges in developing adequate therapeutics to modify the tumor stromal landscape. The biggest obstacle is represented by our poor
understanding of the phenotypic and functional heterogeneity of stromal cells in tumors. Our work aims at addressing some of this ambiguity, focusing on the immunoregulatory roles exerted by specific subsets of mesenchymal cells in the tumor microenvironment.
11:25 Translational Immuno-Oncology: Use of Humanized Mice and Human Tumor Tissue Based Models in Preclinical Research
Yuan Zhang, PhD, Vice President, BD/Marketing & Logistics, Pharmalegacy
There is a major obstacle to the evaluation of new human immunotherapies due to a lack of experimental models with a fully functional human immune system. We have developed both humanized mouse and human tissue based models which harness the human
immune system against human tumors for pre-clinical research.
11:40 The Power of Single Molecule Imaging in IO Biomarker Discovery and Target Engagement Studies
Valerio Pereno, PhD, Business Development, ONI
Quantitative imaging techniques are powerful tools enhancing the predictability and reliability of pre-clinical models for drug discovery and target validation. ONI crafts desktop-compatible instruments with single-molecule sensitivity allowing
for direct observation and measurement of molecular interactions, cellular dynamics and complex tissue phenotypes.
11:55 Transition to Lunch
12:00 pm Luncheon Presentation: Reference Biospecimen Cohort Development Strategies Supporting Cancer Therapeutic Discovery Studies
Adel Mikhail, PhD, CSO, Discovery Life Sciences
One of the primary issues in biomarker research is the lack of a reference set of highly characterized biospecimens that can be used collaboratively by multiple groups within or between organizations. This session will provide case studies
in custom cohort development designed to expedite preclinical and translational research through the integration of high-quality biospecimens with clinical data, phenotypic, and genotypic characterizations.
12:30 Session Break
1:05 Chairperson’s Remarks
N. Michael Greenberg, PhD, CSO and Senior Vice President, Atreca Inc.
1:10 Preclinically Developed Next Generation Selective Estrogen Receptor Degrader (SERD) SAR439859 for ER+ Metastatic Breast Cancer Patients
Sun, MD, PhD, Lead Research Investigator, Pharmacology, Sanofi
Nearly 70% newly diagnosed cases of breast cancer (BC) are estrogen receptor positive (ER+) and approximately 40% of those patients undergone endocrine therapy developed resistance. We developed SAR439859, an orally bioavailable SERD with
potent antagonist and degradation activity against ER both in vitro and in vivo. SAR439859 treatment inhibits ER signaling activity in multiple ER+ breast cancer cell lines and patients in clinic. Across a panel of ER+
cells, SAR439859 demonstrated superior ER degradation activity compared with other SERDs that resulted in better growth inhibition. Our results indicated SAR439859 is a novel, oral, nonsteroidal, selective estrogen receptor antagonist
and degrader that could provide therapeutic benefit to ER+ breast cancer patients.
1:40 Selected Poster Presentation: Targeting IL-1b Pathway for Cancer Immunotherapy
Pushpa Jayaraman, PhD, Senior Investigator I, Novartis Institutes for BioMedical Research (NIBR)
Despite advances with T cell checkpoint blockade, the ability of tumors to foster an immunosuppressive tumor microenvironment may hinder the successful translation of checkpoint inhibitors into effective immunotherapy. IL-1b plays a key role
in carcinogenesis by accelerating tumor invasiveness, growth, and metastatic spread by promoting an immunosuppressive tumor microenvironment. Our work highlights the pathophysiological role of IL-1b in tumor immunomodulation and that IL-1b
might have important consequences on T cell function and checkpoint blockade in cancer.
2:10 Q&A with Speakers
2:25 Refreshment Break in the Exhibit Hall with Poster Viewing
2:30-2:45 Speed Networking: Young Professionals
3:10 PANEL DISCUSSION: Partnering, Preclinical Strategies and Tools, IO Clinical Trials; Capital Invested in IO Relative to Other Oncology Areas
Moderator: Leigh Zawel, PhD, CSO, Cullinan Oncology; Executive Partner, MPM Capital
Michael Woo, PhD, Head, Search & Evaluation, Immuno-Oncology, Business Development & Licensing, Novartis Institutes for BioMedical Research, Inc.
Sybil Williams, PhD, Director, Biology Oncology Discovery, Merck
Paul Young, PhD, Executive Director, Business Development & Licensing, Merck
Stacey J. Adam, PhD, Director, Cancer Research Partnerships, Foundation for the National Institutes of Health
- Has the IO bubble popped? Why have no other IO drugs emerged with PD1/PDL1-like efficacy?
- What combination strategies are being explored to convert poorly PD1 responsive tumors to more responsive ones?
- Are there new IO monotherapies or combos that appear promising?
- Is patient stratification practical with IO therapies?
- What partnering strategies are most effective?
- What is a recent deal your firm signed that you’re excited about?
4:10 Transition to Keynote
4:20 5:20 Taste of New England Welcome Reception in the Exhibit Hall with Poster Viewing
5:25 Meet the Plenary Keynotes
6:25 Find Your Table, Meet Your Moderator
6:30 Breakout Discussion Groups
7:30 Close of Day
Wednesday, June 19
7:00 am Registration Open and Morning Coffee
8:00 Chairperson’s Remarks
Charles Glaus, PhD, Director, Translational Research & Early Clinical, Takeda
8:05 Preclinical and Translational Imaging Methods in the Development of Immuno-Oncology Therapeutics
Glaus, PhD, Director, Translational Research & Early Clinical, Takeda
The primary method to measure biomarkers of IO therapeutic activity in solid tumors is biopsy, yet it is widely understood that biopsies spatially and temporally under-sample the tissues in question. Imaging technologies can provide whole-body,
longitudinal, noninvasive monitoring of IO drug distribution, PD, and lymphocyte infiltration. In this talk, we will review examples of advanced imaging biomarkers that will play a key role in the development of new immune-oncology
8:35 CO-PRESENTATION: Determining Markers of Sensitivity to p70S6K/AKT1/3 Inhibition of SCLC PDX Mouse Models: Correlating in vivo Sensitivity with Profiles of Surface Protein Markers and Gene Expression
from Individually Dissociated Tumor Cells
Anderson Clark, PhD, Director, Translational in vivo Pharmacology, Translational Innovation Platform, Oncology, EMD Serono
Rainer Blaesius, PhD, Technology Manager, BD Technologies and Innovation
Small Cell Lung Cancer (SCLC) is characterized by rapid tumor growth and currently, there are few therapeutic options or predictive biomarkers. In a Phase I clinical trial of the p70S6K/AKT1/3 inhibitor M2698 one SCLC patient had prolonged
stable disease while on treatment. A follow-up screen in 45 preclinical in vivo patient-derived xenograft (PDX) models resulted in a tumor control rate of roughly 27%. Failure of “traditional” genomic analyses
of the models to identify biomarkers predicting sensitivity in patient tumors, prompted us to pursue a novel approach. Tumors from the 7 most and 7 least sensitive models were re-implanted into mice and the tumors later dissociated
for FACS, single cell surface marker profiling and genomic analysis. We will review the data from this study and discuss options to apply the methodology to translational preclinical work and also clinical samples.
9:05 Transcriptome Profiling and Functional Screening to Identify Genes Driving Biological Responses and Disease Progression
Paul Diehl, PhD, COO, Cellecta
Pooled libraries of heterogenous lentiviral constructs have proven to be an effective approach to individually label cells in a target population with cell-specific barcodes and/or other genetic effectors. NGS analysis of targeted multiplex
RT-PCR from cell samples enables parallel analysis of differences in gene activation as a result of perturbation. These approaches can be used to gain a more comprehensive understanding of genetic pathways in disease.
9:35 Coffee Break in the Exhibit Hall with Poster Viewing
10:05 Poster Winner Announced
10:20 Utilizing Preclinical in vivo Models to Elucidate Mechanisms of Drug Resistance
Juliet Williams, PhD, Executive Director, Oncology Drug Discovery, Novartis
Drug resistance plagues the efficacy of cancer therapies, by showing ineffectiveness to primary treatment and from secondary resistance that often arises. In vivo models are important tools to attempt to predict which cancers
will be sensitive and resistant to certain therapies, and to determine what targets maybe crucial in primary and secondary resistance mechanisms. Importantly, it has been shown there are very often disconnects between in vitro and in vivo findings, emphasizing the necessity to use in vivo models for patient stratification translatability and to identify novel targets which may overcome resistance mechanisms.
10:50 COBRA: A Novel Conditionally Active Bispecific Antibody that Regresses Established Solid Tumors in Mice
Chad May, PhD,
Senior Vice President, Research and Development, Maverick Therapeutics
T-cell redirecting bispecific antibodies are so potent that even very low levels of target expression on normal tissues may quickly become a safety liability and prevent the administration of efficacious doses. To overcome this challenge,
we have developed a novel recombinant platform that is engineered to pursue more broadly expressed cell surface targets, by limiting T cell engagement to within the tumor microenvironment.
11:20 The Impact on Tumor Microenvironment by Tissue Type, Genotype, Clonal Diversity and in vitro Culture Artifacts During Tumor Initiation
Zhao Chen, PhD,
Investigator III, Exploratory Immuno-Oncology, Novartis Institutes for BioMedical Research (NIBR)
Cancer immunologists like to farm in the complex tumor microenvironment (TME). Most of us are trying to find the common denominators and make sense out of this mess in order to pin down the key components that we can intervene and tip
balance of anti-tumor immunity. We have seen reports claiming many of the biological features possibly having major influences on the TME. However, the truth is most of these factors probably contribute to part of the story, but the
importance of each factor maybe highly context dependent or even totally random in some cases. We have done some of the analysis using an engineered organoid tumor system to answer some these basic questions.
11:50 Transition to Lunch
12:00 pm Bridging Luncheon: New Insourcing and Outsourcing Options PDX Tumors for Oncology Drug Discovery
Rick Huntress, Director, Commercial Business Development, JAX Mice and Clinical Research Services, The Jackson Laboratory
The Jackson Laboratory maintains a repository of over 400+ Patient Derived Tumors for PDX studies.Our open source interface allows researchers to review tumors by indication, genetic signature (NGS) , gene expression (RNASeq) and other
parameters. We'll review the common features of early passage tumors on study and provide helpful strategies for researchers interested in working with PDX tumors. We'll also present options for organizations to insource these
tumors for their own discovery efforts
12:30 Transition to Plenary
12:50 PLENARY KEYNOTE SESSION
2:20 Booth Crawl and Dessert Break in the Exhibit Hall with Poster Viewing
2:25 Meet the Plenary Keynotes
3:05 Close of Conference