Finding novel, druggable targets for therapeutic intervention remains a top priority for the pharma/biotech industry, especially when it comes to building a robust drug discovery pipeline. It also remains a formidable challenge and companies continue to invest a lot of time and resources in identifying and validating good drug targets to pursue. What are the challenges in target discovery? What tools and strategies are being used and how well are they working? What’s being done to ensure that validated targets lead to better and safer therapies? Cambridge Healthtech Institute’s conference on Target Identification and Validation will bring together leading experts to discuss some of these critical questions. The conference will help attendees meet and interact with experts and peers from around the world to share ideas and hear about new strategies and technologies helping target discovery.

Part 1: Focus on Functional Genomics & Computational Screening

This part of the Target Identification & Validation conference will highlight some of the existing and emerging functional genomics, artificial intelligence and machine learning tools that are being used for generating novel drug targets. The use of such tools and screens for validating existing targets or associating them with new disease indications will also be discussed.

Final Agenda

Choose 2 Short Courses
or 1 Symposium and 2 Conferences/Training Seminars

Wednesday, September 26

7:00 am Registration Open and Morning Coffee


8:00 Welcome Remarks

Tanuja Koppal, PhD, Conference Director, Cambridge Healthtech Institute

8:05 Chairperson’s Opening Remarks

Roderick Beijersbergen, PhD, Group Leader, Division of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute

8:10 Exploring New Biology and Targets Identified through Big CRISPR Data

Martin_ScottScott Martin, PhD, Group Lead, Functional Genomics, Genentech

CRISPR screening has rapidly transformed our approaches towards new target discovery. A major hope for these efforts is to identify new dependencies in cancer that remain undiscovered by analogous RNAi-based screens. I will discuss efforts to leverage large-scale CRISPR screening data for this purpose, including both computational and bench-level approaches.

8:40 Leveraging Functional Genomics to Identify and Characterize Novel Targets

Lauren Drowley, PhD, Functional Genomics Lead, Translational Medicine, UCB Pharma

Functional genomics provides tools that enable identification and interrogation of complex disease mechanisms in patient samples and relevant cellular models, improving disease understanding. Using a suite of functional genomic capabilities including CRISPR, investigation/modulation of regulatory elements and examining chromatin structure, UCB is improving understanding of the role of genome structure and function in health and disease allowing for more directed and improved therapies in the future.

9:10 Building CRISPR/Cas9-Based Platforms for Therapeutic Target Identification and Validation

Wang_RuiRui Wang, PhD, Senior Scientist, Department of Immunology, AbbVie Bioresearch Center

To better understand the immune system and discover novel therapeutics for autoimmune diseases, we have built CRISPR/Cas9-based platforms for new target identification, target exploration and validation, and evaluation of the efficacy and toxicity for early targets. With those platforms, we aim to build a mechanism to continuously screen new targets from various data sources and to explore novel biology involved in the immunological diseases.

9:40 Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing

10:25 Target Deconvolution Using CRISPR Mutagenesis Scanning

Daelemans_DirkDirk Daelemans, PhD, Associate Professor, Rega Institute - Laboratory of Virology and Chemotherapy, KU Leuven

Deconvoluting and validating the molecular target of small-molecule hits from a screen is still a major challenge but is a must for further drug development. The discovery of mutations that confer resistance is recognized as the gold standard proof for a drug’s target. We will present a high-density tiling CRISPR genetic screening approach to rapidly deconvolute the target protein and binding site of small-molecule inhibitors based on drug resistance mutations.

10:55 Investigating Cancer Drug Specificity with CRISPR/Cas9 Mutagenesis

Sheltzer_JasonJason Sheltzer, PhD, Principal Investigator, Cold Spring Harbor Laboratory

CRISPR/Cas9 gene editing can be applied to characterize potential genetic dependencies in cancer. We show that cancer cells can tolerate CRISPR/Cas9 mutagenesis of many reported cancer drug targets with no loss in cell fitness. In contrast, RNAi hairpins and small-molecules designed against those targets continue to kill cancer cells, even when their putative target is knocked out using CRISPR. We suggest that many RNAi constructs and clinical compounds exhibit greater target-independent killing than previously realized.

11:25 TECHNOLOGY PANEL DISCUSSION: Do We Have the Right Tools to Find Drug Targets That Are Difficult to Identify and Validate?

This panel will bring together speakers and 3-5 technical experts from leading technology and service companies to discuss improvements and limitations in assays, platforms, and data analysis tools available for target discovery and validation.

Roderick Beijersbergen, PhD, Group Leader, Division of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute (Moderator)

11:55 Efficient Tools to Enable Drug Target and Biomarker Discovery

Diehl_Paul_TVD1Paul Diehl, PhD, COO, Cellecta, Inc.

Cellecta’s technologies allow for precise and convenient analysis of the genes responsible for driving biological responses. Using NGS with multiplex RT-PCR in our DriverMap Genome-wide Expression Profiling Assay enables rapid association of gene expression changes in large numbers of cell, tissue, and blood samples. Examples of this approach will be discussed.

eurofins 12:10 pm Development of High- Throughput Cellular Thermal Shift Assays: Cellular Mechanistic Assays in Early Drug Discovery

Marc Holbert, PhD, Scientific Leader Protein, Cellular and Structural Sciences, GSK

A problem in early drug discovery is lack of rank-order correlation between biochemical potencies from initial screens and diminished potency and efficacy in cellular phenotypic assays. Cellular thermal shift assays bridge this gap, enabling assessment of drug target engagement in live cells based on ligand-induced changes in protein thermal stability.

12:25 Session Break

Synthego 12:35 Luncheon Presentation: Enabling Arrayed CRISPR Screens in Primary T Cells, iPSCs & Immortalized Cell Lines

Abhi Saharia, PhD Director of Product Management, Synthego

Loss-of-function screens in primary & stem cells can be incredibly valuable in identifying novel drug targets or uncovering functional complexity within the human genome.  To date, loss-of-function CRISPR-Cas9 screens have largely been conducted using pooled lentiviral libraries and/or in immortalized cell lines. Although valuable, these limit the type of assay, model system or phenotype that one can screen. We have developed ready-to-transfect chemically modified single guide CRISPR libraries, that simplify  high-fidelity arrayed screening in a wide variety of cell types, including Primary T cells & induced Pluripotent Stem Cells (iPSCs). Here, we discuss various screens in T cells, iPSCs & immortalized cell lines where we monitor a variety of assays. High efficiency protein knockouts were confirmed by genotypic, protein and functional analyses, indicating that these screens are capable of producing high confidence hits with low false negatives. These results highlight the ease & power of arrayed screening in immortalized cell lines, or biologically relevant primary & stem cells using chemically modified single guide RNAs.


1:15 Refreshment Break in the Exhibit Hall with Poster Viewing


1:50 Chairperson’s Remarks

Scott Martin, PhD, Group Lead, Functional Genomics, Genentech

1:55 FEATURED PRESENTATION: Dissecting Functional Genomics

Michael T. McManus, PhD, Professor, University of California, San Francisco

The field of human genetics and epigenetics has been rife with scientific debate as scientists struggle to understand the complex nature of population and familial incidence patterns and their relationships to molecular mechanism of gene expression. A cornerstone in the debate is the unresolved genetic architecture of complex disease and the functional relationship between genes. We have developed powerful tools and methodologies to dissect polygenic architecture and dissect functional genomics as related to genetic epistasis, in both cells and in vivo models.

2:25 Up, Down, and Out: Complementary CRISPR Technologies for Genetic Screens

Doench_JohnJohn Doench, PhD, Associate Director, Genetic Perturbation Platform, Broad Institute of Harvard and MIT

The ease of programming Cas9 with an sgRNA presents an abundance of potential target sites, but the on-target activity and off-target effects of individual sgRNAs can vary. We will discuss the design and use of libraries for conventional CRISPR-based knockout screens, as well as activation (CRISPRa) and interference (CRISPRi) approaches.

2:55 CRISPR Technology Mimicking the Fibrosis Process

Lieke Geerts, PhD, Senior Scientist, Biology, Charles River

CRISPR technology is an asset for target validation in the drug discovery process with its ability to generate full gene knockouts. Using an adenovirus delivery system, efficient CRISPR-mediated gene knockout was obtained in a complex cellular assay mimicking the fibrosis process.

3:25 Refreshment Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

4:05 The Screen Drives the Targets: Development of Clinically Relevant Screening Models

Beijersbergen_RodericknewRoderick Beijersbergen, PhD, Group Leader, Division of Molecular Carcinogenesis and NKI Robotics and Screening Center, The Netherlands Cancer Institute

A major challenge is the large genomic and epigenomic diversity of human cancers. The development of appropriate cell line models for large scale in vitro screens with strong predictive powers to clinical utility remains crucial. This will be crucial for the discovery of novel targets, elucidation of potential resistance mechanisms and novel combinations. The development and implementation of such models will be presented and discussed.

4:35 3’-Digital Gene Expression Transcriptional Screening

Boswell_SarahSarah Boswell, PhD, Director of Sequencing Technologies, Laboratory of Systems Pharmacology and Director, Single-Cell Sequencing Core, Harvard Medical School

3’ Digital Gene Expression (3’-DGE) was developed by the Broad Institute as a single-cell sequencing method. Here, we implement 3’-DGE as a low-read density transcriptome (mRNA) profiling method. A few thousand cells are plated and treated in 384-well format. 3’-DGE libraries sequenced at 1-2 million reads per sample yield 4,000-6,000 transcripts per well all for roughly $4000. Using 3’-DGE we obtain information about drug targets, polypharmacology, and toxicity in one assay.

5:05 Interactive Breakout Discussion Groups - View Details

Join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic.

Exploiting CRISPR, RNAi and Single-Cell Analysis: What You Need to Know Before and After

Moderators: Sarah Boswell, PhD, Director of Sequencing Technologies, Laboratory of Systems Pharmacology and Director, Single-Cell Sequencing Core, Harvard Medical School

Roderick Beijersbergen, PhD, Group Leader, Netherlands Cancer Institute and Head, NKI Robotics and Screening Center

  • Understanding inherent limitations and need for using complementary techniques
  • Examples of how multiple techniques have been put to good use for addressing biological questions
  • Evaluating and testing the reagents and tools
  • Insights on inherent challenges and ways to overcome it
  • Tackling data analysis

Exploring Artificial Intelligence for Improving Drug Discovery and Healthcare

Moderators: Arvind Rao, PhD, Associate Professor, Department of Computational Medicine and Bioinformatics, University of Michigan

Nicholas P. Tatonetti, PhD, Herbert Irving Assistant Professor of Biomedical Informatics and Director of Clinical Informatics, Herbert Irving Comprehensive Cancer Center, Columbia University

  • In silico modeling of complex cellular phenotypes and disease models: paradigms to bridge the computational-experimental gap
  • Deconvolution of preclinical data and translating into clinical space: integrative modeling, generalizability, transportability and data harmonization
  • Why ML/AI in healthcare data will never work; bias, missingness, and confounding in secondary data use
  • Why ML/AI is our only hope to solve healthcare’s biggest problems; the power of scale, the complexity of medicine, and where the opportunities lie

Growing Use of 3D Spheroids and PDX Models in Drug Discovery

Moderators: Madhu Lal-Nag, PhD, Group Leader, Trans-NIH RNAi Facility, National Center for Advancing Translational Sciences, National Institutes of Health

Geoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

  • Developing multi-cellular 3D cell culture models for high-throughput screening
  • Specific 3D models for target identification and validation screens
  • Challenges with high-throughput screens utilizing 3D spheroid models
  • Patient-derived xenograft ex vivo (PDXEx) models as a screening platform

6:05 Welcome Reception in the Exhibit Hall with Poster Viewing

7:10 Close of Day

Thursday, September 27

7:30 am Registration Open and Morning Coffee

New Screening Platforms And Computational Tools For Finding Novel Targets

8:00 Chairperson’s Remarks

Deepak K. Rajpal, PhD, Senior Scientific Director, Computational Biology, GlaxoSmithKline R&D

8:05 Target Identification & Validation for Immune-Mediated Indications

Deepak K. Rajpal, PhD, Senior Scientific Director, Computational Biology, GlaxoSmithKline R&D

We share an overview of our computational approaches to identify targets. Additionally, we share application of disease signatures in our drug discovery approaches, along with some thoughts on creating a validation approach for generating further evidence on targets. We conclude by sharing a conceptual approach that may be broadly applied for target identification and validation.

8:35 A High-Throughput Imaging-Genetic Screen Identifies MEK-PI3K Modulation for TNBC

Rao_ArvindArvind Rao, PhD, Associate Professor, Department of Computational Medicine and Bioinformatics, The University of Michigan, Ann Arbor

As combination therapies enter mainstream clinical oncology, there is now a need for infrastructure to integrate multiple modalities of data to prioritize drug combinations rationally. In this vein, we examine a scenario using machine learning methods to prioritize drug combinations selected based on phenotypic screening via RNAi, coupled with known genetic vulnerabilities in Triple Negative Breast Cancer cells. Such a strategy leverages imaging and genetic information to prioritize the MEKi+PI3Ki combination as a possible regimen.

9:05 Applications of AI in Drug Target Discovery

Yu_Jane_TVD_CNSJane Yu, Technical Pre-Sales, Life Sciences, IBM Watson Health

With millions of scientific research articles published each year, innovation in the life sciences suffers from knowledge waste and lack of knowledge integration. IBM Watson for Drug Discovery addresses this issue by extensively mining literature and data to help scientists accelerate biomedical research. Using advanced analytics and machine learning, the platform can also predict novel relationships, as demonstrated through our recent work with Barrow Neurological in ALS disease, and Pfizer in immuno-oncology, among many projects.

9:35 Coffee Break in the Exhibit Hall with Poster Viewing

10:20 Patient-Derived Xenograft-Derived ex vivo (PDXEx) Model for Evaluation of Tumor-Specific Therapies

Bartholomeusz_GeoffreyGeoffrey Bartholomeusz, PhD, Associate Professor and Director, Target Identification and Validation Program, Department of Experimental Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center

We have developed a PDXEx model that closely replicates the tissue architecture of the original tumor and has a gene expression profile showing a high degree of correlation to that of the original tumor. Our model has great application as a screening platform exhibiting a high predictive value in identifying effective tumor-specific therapies in a resource-, time-, and cost-efficient manner.

10:50 Development of a Biologically Intelligent High-Throughput Assay Platform for Phenotypic Screening - Redefining the Screening Toolbox

Lal_MadhuMadhu Lal-Nag, PhD, Team Leader, RNAi Screening, National Center for Advancing Translational Sciences, National Institutes of Health

Developing physiologically relevant assays with predictive, measurable phenotypic end points has been the pain point for high-throughput screening in drug discovery. Here we describe the development of a platform of physiologically relevant screenable phenotypes and biologically intuitive analysis algorithms that capture and define these phenotypes in a physiologically relevant context. This also encompasses the development of a biologist’s toolbox designed to target a majority of diverse biological phenotypes.

Idiopathic Pulmonary Fibrosis is a lethal disease driven by pathological fibroblast accumulation and differentiation. Recent evidence indicates that transcription co-activators YAP and TAZ integrate the chemical and mechanical signals that activate fibroblasts. We designed a small molecule and siRNA screen to identify YAP inhibitors and new pathways controlling YAP activation in human fibroblasts. The resulting hits may lead to the development of novel anti-fibrotic therapies.

11:20 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

11:50 Conference Registration Open

12:20 pm Plenary Keynote Program

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing

2:45 Close of Conference

Stay back to attend -

Part 2: Focus on Chemical Biology and Phenotypic Screening

This part of the Target Identification and Validation conference will describe how phenotypic screening and chemical biology can be used to find new drug targets, validate existing targets for new indications, and better understand how inhibiting or activating these targets could impact other cellular pathways.



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