eProceedings – Day 1: Charles River Laboratories – 3rd World Congress, Delivering Therapies to the Clinic Faster, September 23 – 24, 2019, Cambridge, MA | Leaders in Pharmaceutical Business Intelligence (LPBI) Group

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eProceedings – Day 1: Charles River Laboratories – 3rd World Congress, Delivering Therapies to the Clinic Faster, September 23 – 24, 2019, Cambridge, MA

July 19, 2019 by 2012pharmaceutical

eProceedings – Day 1: Charles River Laboratories – 3rd World Congress, Delivering Therapies to the Clinic Faster, September 23 – 24, 2019, 25 Edwin H. Land Boulevard, Cambridge, MA

https://events.criver.com/event/9eab0ee1-982e-42c6-a4cd-fb43f9f2f1d0/confirmation:7c68cf9b-c599-469e-b602-42178c77e4f9

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Join us this year as we explore novel approaches to drug development that effectively reduce program timelines and accelerate delivery to the clinic. Using a variety of case studies, our speakers will illustrate methods that successfully cut time to market and highlight how artificial intelligence and genomics are expediting target discovery and drug development. In an agenda that includes presentations, panel discussions, and short technology demonstrations, you will learn how the latest science and regulatory strategies are helping us get drugs to patients faster than ever.

AGENDA

Day One, September 23, 2019

Novel approaches to silence disease drivers
The role of AI in expediting drug discovery

Monday, September 23

8:30 – 9:00 a.m.	Introduction and Welcome Remarks James C. Foster, Chairman of the Board, President, and Chief Executive Officer, Charles River
9:00 – 9:30 a.m.	2019 Award Winner: A Silicon Valley Approach to Understanding and Treating Disease Matt Wilsey, Chairman, President, and Co-Founder, Grace Science Foundation
9:30 – 10:15 a.m.	Keynote Session Brian Hubbard, PhD, Chief Executive Officer, Dogma Therapeutics
10:15 – 10:30 a.m.	Break
10:30 – 11:15 a.m.	Novel Approaches to Silence Disease Drivers Systemic Delivery of Investigational RNAi Therapeutics: Safety Considerations and Clinical Outcomes Peter Smith, PhD, Senior Vice President, Early Development, Alnylam Pharmaceuticals
11:15 a.m. – 12:00 p.m.	Novel Approaches to Silence Disease Drivers: Considerations for Viral Vector Manufacturing to Support Product Commercialization Richard Snyder, PhD, Chief Scientific Officer and Founder, Brammer Bio
12:00 – 1:00 p.m.	Lunch
1:00 – 1:45 p.m.	Accelerating Drug Discovery Through the Power of Microscopy Images Anne E. Carpenter, Ph.D., Institute Scientist, Sr. Director, Imaging Platform, Merkin Institute Fellow, Broad Institute of Harvard and MIT
1:45 – 2:30 p.m.	The Role of AI in Expediting Drug Discovery Target Identification for Nonalcoholic Steatohepatitis Using Machine Learning: The Case for nference Tyler Wagner PhD, Head of Cardiovascular Research, nference
2:30 – 2:45 p.m.	Break
2:45 – 3:30 p.m.	Technobite Sessions with Emulate Bio and University of Pittsburgh Drug Discovery Institute Kyung Jin H Jang, VP of Bio Product development, Emulate, Inc. Albert Gough, PhD, U Pittsburg School of Medicine
3:30 – 4:15 p.m.	Artificial Intelligence Panel Discussion: Real World Applications from Discovery to Clinic Moderated by Carey Goldberg, WBUR
4:15 – 4:45 p.m.	Jack’s Journey Jake and Elizabeth Burke, Cure NF with Jack
4:45 – 5:00 p.m.	Closing Remarks
5:00 – 6:00 p.m.	Networking Reception

Day Two – September 24, 2019

How genomics is expediting drug discovery
Accelerating therapies through the regulatory process

Tuesday, September 24

8:45 – 9:00 a.m.	Opening Remarks and Recap James C. Foster, Chairman of the Board, President, and Chief Executive Officer, Charles River
9:00 – 9:30 a.m.	2018 Award Winner Update David Hysong, Patient Founder and Chief Executive Officer, Shepherd Therapeutics William Siders, CDO, Shepherd Therapeutics
9:30 – 10:15 a.m.	Advances in Human Genetics and Therapeutic Modalities Enable Novel Therapies Eric Green, Vice President of Research and Development, Maze Therapeutics
10:15 – 11:00 a.m.	How Genomics is Expediting Drug Discovery Manuel Rivas, Assistant Professor, Department of Biomedical Data Science, Stanford University
11:00 – 11:15 a.m.	Break
11:15 a.m. – 12:00 p.m.	Genomics Panel Discussion: Signposting Targets That Will Speed the Path to Market Moderated by Martin Mackay, Co-Founder, RallyBio
12:00 – 1:00 p.m.	Lunch
1:00 – 1:45 p.m	Truly Personalized Medicines for Ultra-rare Diseases: New Opportunities in Genomic Medicine Timothy Yu, Attending Physician, Division of Genetics and Genomics and Assistant Professor in Pediatrics, Boston Children’s Hospital
1:45 – 2:30 p.m.	Application of Machine Learning Technology for the Assessment of Bulbar Symptoms in ALS Fernando Vieira, Chief Scientific Officer, ALS Therapy Development Institute
2:30 – 2:45 p.m.	Break
2:45 – 3:30 p.m.	Accelerating Rare Disease Therapies Through the Regulatory Process Martine Zimmermann, Senior Vice President and Head of Global Regulatory Affairs, Alexion Pharmaceuticals, Inc.
3:30 – 4:00 p.m.	Wearing ALL the Hats: From Impossible to Possible Allyson Berent, Chief Operating Officer, GeneTx Biotherapeutics
4:00 – 4:15 p.m.	Closing Remarks

Introduction and Welcome Remarks

8:30 AM-9:00 AM

A Silicon Valley Approach to Understanding and Treating Disease

9:00 AM-9:30 AM

Accelerating Therapies Through the Regulatory Process

Keynote Session

9:30 AM-10:15 AM

Keynote Session Brian Hubbard, PhD, Chief Executive Officer, Dogma Therapeutics

Find a cause and work with passion
CVD increased 53% from 2005 to 2016
Cholesterol, LDL receptor and CV disease
Genetics evolution and discovery of PCSK9

A PCSK9 Variant lowers CV risk
complete lack of PCSK9 is safe – protects from CVD

LDL receptor
Statins do not work on LDL receptor if the mutation exists
Antibody and antisense for the PCSK9 mutation – Inexpensive Oral Medications can change Global Diseases
Dogma of Drug DIscovery: Approach a Patent vs Approach a Disease
Ligands bind within a cryptic binding pocket adjacent to a novel PCSK9 polymorphism

12 years of drug discovery

2003: PCSK9 mutation discovered
2005:
2006:
2012;
2012: Dogma Scientists begin
compound found binds to primates
2015:
2018: Efficiency DGM-4403 lowers LDL-c by 55% 0ver 14 days

Break

10:15 AM-10:30 AM

Systemic Delivery of Investigational RNAi Therapeutics: Safety Considerations and Clinical Outcomes

10:30 AM-11:15 AM

Novel Approaches to Silence Disease Drivers

2014 – @Moderna, mRNA
2017 – Alnylam

RNAi – delivery is the most difficult

gene silencing changes medicine and diseases
Small Interfeering RNA (siRNA) Therapeutics
Delivery challenges – stability and targeting
RNA Interference (RNAi) – Onpattro (patisiran)
GalNAc-siRNA Conjugates – delivery to the hepatocytes
N-Acetyl Galactosamine (GalNACc-siRNA conjugates
Hepatocyte specific : Liver across species: ASGPR expression
Metabolic Stability: Chemistry to Improve siRNA
Platform for genetic diseases
Evolution of COnjugate Design: GalNAc-siRNA – enhanced stabilization chemistry
ALN-TTRSC02 compared to Revusiran
ALN-TTRsc02 (advanced) – – tetrameric protein binds transports serum retinol binding
AL Amyloidosis
ApoA1 Amyloidosis
ATTR Amyloidosis – manufacture in the Liver: Hereditery vs non-hereditary – Wild-Type
Patisiran Therapeutic Hypothesis – siRNA targeting TTR formulated
Pharmacology of TTR siRNA in Animal Model
V30M TTR Transgenic Mouse Model: Patisiran Phase 1 Study to Phase 3 APOLLA Study Design for any TTR mutation – Prior tetramer stabilizer used permitted
hATTR Amyloidosis and APOLLO Assessment: Phase 3 is Global – Cardiomyopathy – potential,
Patisiran met all secondary Endpoints: Canadian, Japanese approval – US approved indication, European approved
Alnylam Investigational RNAi Therapeutics:
Pipeline: Genetic medicines
Hepatic Infectious diseases
CNS & Ocular
Cardiovascular

11:15 AM-12:00 PM

Considerations for Viral Vector Manufacturing to Support Product Commercialization

Viral-Vector-mediated in vivo Gene Therapy
VVS Viral Vector Platforms:

Adenovirus immunogenicity
Lentivirus
Retrovirus
Herpes
Recombinant Adeno-Associated Viral Vectors: Glybera, Luxturna
Zolgenzma

Establish the product specifications based on data (CQAs)
Is the vector product: parenteral or anciliary material

Considerations:

Large scall vs small
lot demand vs platform choice
Proof of concept
Own/License the manufacturing reagents (portability) vs reliance on providers
Process and Analytical Design & Development: Cell line: Mamalian, others
Raw materials: Viral clearance steps – cell banks generation
impurity profiles
Cell Substrates
Cell clone screening
Preclinical/Clinical, Alachua, FL; Phase III/Commercial: Cambridge & Lexington
Biologics Upstream Process Flow: Master cell banks
Transient Transfection Process (Lenti and AAV)
rAAV Proviral cell line
Production Vector-based Process (Baculo or HSV)
Product purification: Filtration methods, Chromatography, centrifugal separation: Concentration/filtration
Formulation
Compatibility wiht vial: Glass, CZ, COP: absorption vs Inactivation
Single use
Frozen storage
Storage, Packing and Distribution
Technology Transfer: Research vs Mature Process (Qualified cell bank)
Plasmids: E.coli MCB backbone
Analytics Design & Development: Testing: Nucleic-acid based, protein-based

AAV Vector Lot Release Assays
Lentivirus

QA: QA Management System –
Analytical Assays
FDA Issues SIX New Draft Guidance Documents in 7/2018
Process Validation: Life cycle approach: Process caracterizationProcess performance qualification

Lunch

12:00 PM-1:00 PM

Accelerating Drug Discovery Through the Power of Microscopy Images

1:00 PM-1:45 PM

The Role of AI in Drug Discovery

assayGene clusterbased on morphological similarity: Express each gene, gene painting Image analysis, cluster morphological profiles
identification of allelle that are not constitutively activating mutants.
weakly supervised deep learning to extract features
identify similarities and differences among treatments at the same population level
Predict many distinct expensive assays on a huge compound library using a single cell painting

Test 5,000 compounds in the assay of interest as well as cell painting
Find combination of iamge-based features that predict in the assay of interest
Predict “hit” from existing 1Million compound cell paining data set

The Role of AI in Expediting Drug Discovery Target Identification for Nonalcoholic Steatohepatitis Using Machine Learning: The Case for nference

Tyler Wagner PhD, Head of Cardiovascular Research, nference

1:45 PM-2:30 PM

The Role of AI in Drug Discovery

In Kendall Square
Partnership with Janssen
all employees: MD/PhD and Data Scientists

NASH

Gene FXR

Literature Synthesis
Molecular Analytics
Competitive Intelligence

Diseases – GI, digestive, Signs & Symptoms, cellular Profileration, Carcinoma, GI
Biomolecules – Cholesterol,
Drugs: Inhibitors, agonists, Antagonists
Cells and Tissues – Cell ontology

Epigenetics – effects on systems:

Endocrine
Liver
Enrichment Set & related Phenotypes
Genes: signal expression strong vs weak

PROCESS –

Increase research efficiency,
assess the validity of associations
evaluate the clinical and regulatory landscapes
large-scale workflows

Literature Signals
molecular data sets
protein expression
epigenetics
SNP Phenotypes
Druggability Clinical novelty

Break

2:30 PM-2:45 PM

Technobite Sessions : Towards organ-on-a-chip

Kyung Jin Jang, VP of Bio Product development, Emulate, Inc.

2:45 PM-3:30 PM

Lung-Chip Applications
Pulmonary inflammation
Intestine-chip Applications
Liver-Chip: Building Tissue Complexity: Co-culture, tri-culture, quatro-culture, Transcriptomic Analysis
Liver-Chip: Kupffer cells Characterization
Stellate Cells
parenchymal channel, non-parenchymal channel
Liver Chip: Predicting species differences in liver toxicity: Effects of Bosentan on Albumin secretion
Acetaminophen Toxicity in Liver-Chip: APAP Metabolism: detected changes in morphology, ATP, GSH – Dosepdependent increase of ROS
Steatosis and Stellate Cell Activation: and Species difference in Toxicity Liver chip data correlates with in vivo data
Predict Human safety risks with liver chip

Albert Gough, PhD, U Pittsburg School of Medicine

Approaches for repurposing drugs:

Integrated, fluidic organ MPD,
cells, 3D structures,
O2 Modulation & Sensing
Biosensors
secretome

Higher Biomimetic content Higher throughput
regulatory liver-pancreas axis in Type 2 Diabetes model
Estradiol-Induced proliferation of mutants in Breast Cancer varies from 2D monoculture to 3D LAMP
MPS Models: