Cambridge Healthtech Institute’s 17th Annual

Target Identification and Validation - Part 2

Genomics-Based Target Discovery

September 17 - 18, 2020 ALL TIMES EDT

Finding novel, druggable targets for therapeutic intervention remains a top priority for the pharma/biotech industry. It also remains a formidable challenge and companies continue to invest a lot of time and resources in identifying and validating targets that will yield viable drugs. The second part of the Target Identification and Validation conference focuses on Genomics-Based Target Discovery. It includes applications of RNAi, CRISPR, chemical genetics, single-cell sequencing, and other genomics-based tools to identify and validate new cellular pathways and drug targets. Complementary use of these technologies integrated with emerging data analysis and AI/ML approaches will also be discussed.

Thursday, September 17

PLENARY KEYNOTE PROGRAM

12:20 pm

PLENARY KEYNOTE: Tackling Undruggable Oncoproteins: Lessons from the VHL Tumor Suppressor Protein

William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics

VHL tumor suppressor protein (pVHL) inactivation is common in kidney cancer and upregulates the HIF2 transcription factor. PT2977/MK-6482 is an allosteric HIF2 inhibitor now in Phase 3 testing. Thalidomide-like drugs (IMiDs) bind to cereblon which, like pVHL, is the substrate-binding unit of a ubiquitin ligase. IMiDs redirect cereblon to destroy the myeloma oncoproteins, IKZF1 and IKZF3. We have developed new assays for identifying drugs that can destabilize oncoproteins of interest.

12:45 pm LIVE Q&A:

Plenary Keynote Discussion

Panel Moderator:
Stewart Fisher, PhD, CSO, C4 Therapeutics, Inc.
Panelist:
William G. Kaelin, Jr., MD, 2019 Nobel Laureate; Professor, Medical Oncology, Dana-Farber Cancer Institute; Investigator, Howard Hughes Medical Institute; Co-Founder, Cedilla and Tango Therapeutics
12:55 pm LIVE PANEL AND Q&A:

Plenary Keynote Discussion: De-Risking Early Drug Discovery

Panel Moderator:
Nadeem Sarwar, PhD, Founder & President, Eisai Center for Genetics Guided Dementia Discovery, Eisai, Inc.
  • Data Sciences
  • ​Novel Chemical Modalities
  • Investment and Partnering Models
  • COVID-19 Progress as Examples of Successful Partnerships
Panelists:
Anthony A. Philippakis, PhD, Chief Data Officer, Data Sciences & Data Engineering, Broad Institute; Venture Partner, GV
Stephen A. Hitchcock, PhD, Head, Research, Takeda Pharmaceuticals, Inc.
1:35 pm Lunch Break - View Our Virtual Exhibit Hall

FUNCTIONAL GENOMICS FOR TARGET SCREENING

2:05 pm

Where Are We with Human Genetics-Based Drug Discovery?

Narender Gavva, PhD, Director, Early Target Discovery, Takeda California, Inc.

Human genetics supported targets are sought after for higher success in the clinic during the last decade. While population genetics studies are revealing disease associated locations in the genome, biobank genotyping, whole exome, and whole genome sequencing efforts are in full swing to find rare causal and protective variants that would become drug discovery targets. This presentation willcover the status of current efforts and future directions.

2:25 pm

Translating the Genetic Vulnerabilities of Cancer into Therapeutics: Lessons from the Cancer Dependency Map Project

Brenton Paolella, PhD, Research Scientist, Cancer Dependency Map, Broad Institute of Harvard and MIT and Dana-Farber Cancer Institute

Recent technological advances have enabled the systematic identification of genes that cancer cells rely on for their survival. However, translating these biological insights into new cancer therapeutic targets remains challenging. To facilitate cancer target discovery and advancement, we have developed computational pipelines to prioritize targets from the Cancer Dependency Map datasets and also cell-based assays to validate the most promising gene dependencies towards drug discovery to accelerate precision cancer medicine.

2:45 pm

Small Molecule Target Identification Using CRISPR-Cas9 Functional Screens

Susanne E. Swalley, PhD, Principal Scientist, Chemical Biology & Proteomics, Biogen

While phenotypic approaches allow for the discovery of new targets and mechanisms, target deconvolution represents a key challenge due to the intrinsic difficulty, time, and expense. Compound-sensitized genome-wide screens using CRISPR/Cas9 are a powerful tool to aid in target identification. We will describe the development of an arrayed screening platform, and its application to generation of target hypotheses for a small molecule that enhances antisense oligonucleotide (ASO) uptake.

Nicole Abreu, PhD, Science & Technology Advisor, 10X Genomics

Single-cell CRISPR screens produce rich gene expression phenotype information by directly linking to each CRISPR perturbation at single-cell resolution. In this presentation, we explore how recent advances in single cell methodology provide scalable approaches for deeper insights into cellular response and pathways as compared to output from traditional screening methods.

3:25 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
Narender Gavva, PhD, Director, Early Target Discovery, Takeda California, Inc.
Panelists:
Brenton Paolella, PhD, Research Scientist, Cancer Dependency Map, Broad Institute of Harvard and MIT and Dana-Farber Cancer Institute
Susanne E. Swalley, PhD, Principal Scientist, Chemical Biology & Proteomics, Biogen
Nicole Abreu, PhD, Science & Technology Advisor, 10X Genomics
3:45 pm Happy Hour - View Our Virtual Exhibit Hall
4:15 pm Close of Day

Friday, September 18

INNOVATIVE APPROACHES FOR TARGET DISCOVERY

10:00 am

End-to-End Target Discovery Capabilities in AstraZeneca

Davide Gianni, PhD, Associate Director, Functional Genomics, AstraZeneca

Identification and validation of the “right” target is critical to reduce clinical attrition and to make drug discovery more sustainable. We have invested in the establishment of “end to end” target discovery capability to enable the identification of novel drug targets with better attrition rates, building on advancements in genome editing, translatable models and computational power. I will describe a couple of case studies that epitomise this capability.  

10:40 am

Multi-Scale Network Biology Approach to Identify Novel Targets for Parkinson's Disease (PD)

Bin Zhang, PhD, Professor, Genetics & Genomic Sciences, Icahn School of Medicine at Mount Sinai

Molecular mechanisms underlying idiopathic PD, which account for 80% of the PD cases, remain elusive. We performed multi-scale gene network analysis of a large gene expression dataset in the substantia nigra from 83 PD cases and 70 controls, and systematically identified and prioritized co-expressed gene modules and key regulators in PD. This study lays down a foundation for developing a comprehensive signaling map and novel therapeutics for PD.

11:00 am Session Break
11:40 am Coffee Break - View Our Virtual Exhibit Hall

ON AND OFF-TARGET SCREENING USING CRISPR

11:55 am

Deeper, Finer and Wider with CRISPR Screens for Gene Function

John Doench, PhD, Director R&D, Genetic Perturbation Platform, Broad Institute of Harvard and MIT

Genome-wide CRISPR screens have revitalized functional genomics. Large-scale data sets enable rapid hypothesis generation, and focused screening efforts can provide detailed mechanistic insights into the function of any gene of interest. Here I will discuss how CRISPR screens are being employed in gene function discovery projects, with an emphasis on the latest technological advances.

12:15 pm

Biases and Blind Spots for CRISPR Screens in Target Finding

Traver Hart, PhD, Assistant Professor, Department of Bioinformatics and Computational Biology; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center

CRISPR knockout screening can identify essential genes in cancer cell lines, and when these genetic vulnerabilities are strongly associated with a specific oncogene or tissue, they present ideal candidate therapeutic targets. However, functional buffering by related genes masks these vulnerabilities. We discuss how this blind spot in CRISPR screens can mislead drug targeting efforts, and discuss new CRISPR multiplex perturbation technologies to fill in the gap.

12:35 pm

In vivo T Cell CRISPR Screen for Immunotherapy Target Discovery

Sidi Chen, PhD, Assistant Professor, Department of Genetics and Systems Biology Institute, Yale University; Member, Yale Cancer Center and the Yale Stem Cell Center

In vivo CRISPR screen is a powerful means for discovering therapeutic targets in physiologically relevant settings. Here, we describe recent advancements in in vivo T cell CRISPR screen for immunotherapy target discovery and characterization of example targets.

12:55 pm LIVE Q&A:

Session Wrap-Up Panel Discussion

Panel Moderator:
John Doench, PhD, Director R&D, Genetic Perturbation Platform, Broad Institute of Harvard and MIT
Panelists:
Traver Hart, PhD, Assistant Professor, Department of Bioinformatics and Computational Biology; Department of Cancer Biology, The University of Texas MD Anderson Cancer Center
Sidi Chen, PhD, Assistant Professor, Department of Genetics and Systems Biology Institute, Yale University; Member, Yale Cancer Center and the Yale Stem Cell Center
1:15 pm Refresh Break - View Our Virtual Exhibit Hall
1:25 pm Brown Bag Lunch and Interactive Breakout Discussions - View Our Virtual Exhibit Hall

Grab your own lunch and 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. Discussion topics and moderators will be listed on the website.


LEVERAGING THE RIGHT ASSAYS & MODELS

2:20 pm

Developing Standards for Potential Prognostic Complex Multicellular Models

Madhu Lal-Nag, PhD, Program Lead, Research Governance Council, Office of Translational Sciences, Center for Drug Evaluation & Research, U.S. Food and Drug Administration
Marc Ferrer, PhD, Leader, Biomolecular Screening and Probe Development, Division of Pre-Clinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health (NIH)

There has been much progress towards the experimental development of robust, scalable, and reproducible 3D cellular models, including spheroids, organoids, biofabricated tissues and microphysiological on chip systems, as assay platforms for preclinical drug testing.  However, there is a need for systematic physiological and pharmacological validation and benchmarking of the different 3D cellular models to establish their true clinical predictability and use for decision making in the drug discovery and development pipeline.

3:00 pm Close of Conference





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