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Craig M. Crews, Ph.D.Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology Chemistry, PharmacologyCenter for Molecular DiscoveryYale University
Dennis Wright, Ph.D.Professor of Medicinal ChemistryNPDD InitiativeUCONN School of PharmacyUniversity of Connecticut
PITCH: What?
An Collaboration between Yale and UCONN to Help Academic Projects Cross the Valley of Death
PITCH: What?
PITCH: What?
• Provide a streamlined translational pathway for researchers to convert their discoveries to new therapeutics
PITCH: What?
• Provide a streamlined translational pathway for researchers to convert their discoveries to new therapeutics
• Increase the number of biotech companies in the State by encouraging faculty entrepreneurism
PITCH: What?
• Provide a streamlined translational pathway for researchers to convert their discoveries to new therapeutics
• Increase the number of biotech companies in the State by encouraging faculty entrepreneurism
• Employ the latent pool of pharmaceutical talent statewide
PITCH: What?
• Provide a streamlined translational pathway for researchers to convert their discoveries to new therapeutics
• Increase the number of biotech companies in the State by encouraging faculty entrepreneurism
• Employ the latent pool of pharmaceutical talent statewide
• Establish a new paradigm for robust, synergistic research programs between Yale and UCONN, and ultimately to other institutions in the state
PITCH: What?
• Provide a streamlined translational pathway for researchers to convert their discoveries to new therapeutics
• Increase the number of biotech companies in the State by encouraging faculty entrepreneurism
• Employ the latent pool of pharmaceutical talent statewide
• Establish a new paradigm for robust, synergistic research programs between Yale and UCONN, and ultimately to other institutions in the state
• Recruit additional venture investment to the state
PITCH: What?
• Provide a streamlined translational pathway for researchers to convert their discoveries to new therapeutics
• Increase the number of biotech companies in the State by encouraging faculty entrepreneurism
• Employ the latent pool of pharmaceutical talent statewide
• Establish a new paradigm for robust, synergistic research programs between Yale and UCONN, and ultimately to other institutions in the state
• Recruit additional venture investment to the state
• Put Connecticut on the map for a new paradigm in drug discovery
PITCH: Who?
Craig M. Crews, Ph.D.Lewis B. Cullman Professor of Molecular, Cellular, and Dev. Biol. Chemistry, PharmacologyCenter for Molecular DiscoveryYale University
Dennis Wright, Ph.D.Professor of Medicinal ChemistryNPDD InitiativeUCONN School of PharmacyUniversity of Connecticut
Dennis Wright, Ph.D.Professor of Medicinal ChemistryNPDD InitiativeUCONN School of PharmacyUniversity of Connecticut
PITCH: Who?
BackgroundWest Liberty State BS (Chemistry)Ohio University Ph.D. (Chemistry)Stanford Postdoc TrainingUCONN Joined Faculty in 2006
Experience• New Pathways in Drug Discovery (NPDD)
-Co-Founder
• Promiliad, Inc.-Co-Founder
• Synaptic Dynamics, Inc.-Co-Founder
PITCH: Who?
Craig M. Crews, Ph.D.Lewis B. Cullman Professor of Molecular, Cellular, and Dev. Biol. Chemistry, PharmacologyCenter for Molecular DiscoveryYale University
BackgroundU.Va. BA (Chemistry)Harvard Ph.D. (Biochemistry)Harvard Postdoc TrainingYale Joined Faculty in 1995
Experience• Yale Center for Molecular Discovery (YCMD)
-Founder/Executive Director
• Proteolix, Inc.-Co-Founder
• Arvinas, Inc.-Founder -Chief Scientific Officer
PITCH: Where?
Yale Center for Molecular Discovery (YCMD)Yale West Campus (former Bayer Pharmaceuticals)
PITCH: Where?
•Established in 2003
•Occupies building B27 with ~10,000 sf of laboratory and office space
•9.5 staff: 7 Ph.D., 2 M.S., 1.5 B.S.
•332 Projects in past 5 years with investigators from 25 Yale departments
•Numerous prominent publications
•Providing target identification, small molecule siRNA screening, and medicinal chemistry services
•Multiple corporate interactions and start-ups
Craig M. Crews, Ph.D.MCDB/Chemistry/Pharmacology
Janie Merkel, Ph.D.Director of Biology
Denton Hoyer, Ph.D.Director of Chemistry
• 9.5 Full Time Employees– 5 Biology– 3 Chemistry– 1.5 Administrative
• Experience in Academia & Industry:
PITCH: Where?
Overview of Capabilities
• Biology– Assay Development– High Content Imaging– Screening (siRNA and small molecule)
• Chemistry– Structure-Activity Modeling– Medicinal Chemistry– Compound Synthesis & Analoging
• Assisting with Patent Writing
16
PITCH: Where?
YCMD Resources• Liquid Handling & Robotics
– 96-, 384-, 1536-well plate compatibility– Sterile or Non-Sterile Environments
• Multiple Types of Readouts– At molecule level: Protein-protein, Enzymatic assays– Cell-based, Organism-based assays– High Content Screening - Highly subsidized costs
• Medicinal, Computational & Synthetic Chemistry– Synthetic planning & execution/outsourcing– Structure and Ligand-based drug design– Optimization of ligand potency and pharmacokinetics
• Experience with Multiple Therapeutic Areas– Oncology, Neurodegenerative, Infectious Diseases,
Inflammation, Cardiovascular…
PITCH: Where?
Demetrios Braddock, Department of Pathology
R. A
. Alb
right
et a
l Blo
od, (
2012
) 120
:443
2-44
40.
Assay for Inhibitors of NPP4 Activity
X-Ray Structure of Target
Classical High Throughput Screening
Structure-Based Design
Follow-OnImprovement
Novel Compositionof Matter
Proof of Concept(Repurposing)
PITCH: Where?
NPDD: A Drug Discovery Network
New Pathwaysto
Drug Discovery
ExternalPartners
UCONNHealth
UCONNStorrs The NPDD is a cross-college initiative
dedicated to drug discovery and development with faculty from Pharmaceutical Sciences, Chemistry, MCB and UCH/CICATS
PITCH: Where?
UCONN School of Pharmacy
The SOP provides an exciting, highly interactiveenvironment for experimental therapeutics withscientists from a broad range of backgrounds unitedby an interest in drug discovery and development.We are organized into three disciplines…
Pharmaceutics: expertise in small molecule formulation, formulation of biologics and drug delivery
Medicinal Chemistry: expertise in drug design, drug target structure and mechanism of action
Pharmacology/Toxicology: expertise in liver toxicology, metabolism and stem cell biology
Medicinal Chemistry Capabilities
High-Throughput Screening
Structure-Based Drug Design
Medicinal Chemistry
Drug design/SAR Complex
molecule/parallel synthesis
Stereoselective synthesis
In vitro metabolism Physico-chemical
property determination
Automated handling 150K lead library Pharmacological
Screens (LOPAC) Target and Phenotypic
screens
X-ray crystallography Biomolecular NMR Docking Virtual Screening Rational Design
Drug Target Studies at UCONN Health
Protein Expression Protein Purification Protein Characterization High Field NMR (800 MHz) Other Biophysical Studies
External Advisory Board
EvaluationUCONN
Yale
AssaySubmission
Due: October 1
PITCH: How?
External Advisory Board
EvaluationUCONN
Yale
AssaySubmission
Bill LaRochelle, (Sr.Dir, Roche Sequencing SolutionsBrian Dixon, (CEO, BioRelix)Peter Farina, (SVP, Boehringer Ingelheim)Amy Burd, (Exe. Dir. Res Strategy, Leukemia & Lymphoma Society)Henry Showell (Sr. Res Fellow, Pfizer)
PITCH: How?
Live Presentations to the EAB10am-1:30pm October 30Yale Center for Molecular Discovery (YCMD)West Haven, CT
Originating Lab or CRO
AssayDevelopment
AssaysScreened
Virtual HitExpansion
[in vivo Testing]
BusinessPlan
Pitch
External Advisory Board
Evaluation
SAR/Med Chem
YCMD UCONNPharm
UCONN
Yale
AssaySubmission
New Leaf Ventures
Elm Street Ventures
OrbiMed Ventures
Canaan Partners Ventures
Other VCs/PharmaVenture Funds?
Out-license?
YCMD
UCONNProtein
ProductionCore
PITCH: How?
36 AssaysDeveloped
30 AssaysScreened
24 Virtual HitExpansions
12 SAR/Med Chem
8 BusinessPlans
8 Pitches# AssaysSubmitted?
Three Year Goals
PITCH: When?
Deadlines:
Submission of Slidedeck PITCH Application: October 1
PITCH: When?
Deadlines:
Submission of Slidedeck PITCH Application: October 1
Faculty Presentation to External Advisory Board: October 30th (at the YCMD)
PITCH: When?
Deadlines:
Submission of Slidedeck PITCH Application: October 1
Faculty Presentation to External Advisory Board: October 30th (at the YCMD)
Notification of Awards: Mid November
Project Title
Investigators
30
To see TIPS and FAQS for each slide, please look at this template in Notes view.
31
Two Year Goal Statement
Your two year goal will frame the following assessment.
• Brief background for team members and their roles on this project.
• Include relevant past experience, if any.• Identify unfilled roles needed.
32
Project Team
Briefly, introduce background science.
What is the problem worth solving?
What is your solution? Why is it novel?33
Scientific Background and Opportunity
Describe additional research data needed but which is outside the scope and capability of the investigator’s laboratory.
34
Research Plan
1. Describe your target and biological pathway
2. Does biochemical assay exist?
3. Does a cell-based readout exist?
4. What are assay readouts for all assays (e.g. luminescence, fluorescence intensity, image-based, others)?
5. What is your level of experience with the assays?
6. Are all critical reagents for the assays currently available?35
Assay Feasibility Assessment
1. Target location(s): extracellular, intracellular, CNS, etc. and tissue type.
2. Can the protein be reliably expressed and purified? How?
3. Does crystal structure of target exist, resolution and RCSB code. If no, what are the closest homologs with crystal structure coordinates?
4. Predicted binding pocket affinity of target (YCMD determined); i.e., is the target druggable?
5. Are small molecule inhibitors known?
6. Synthetic accessibility (conducted after HTS analysis)36
Med. Chem. Feasibility Assessment
1. Is the biology (i.e. pathway) well characterized?
2. Has modulation of the pathway been shown to correlate with changes in disease burden (e.g. phenotype of KO mice, relevant animal studies, GWAS)
3. Is there precedent for the MOA for similar disease targets?
4. Is there a reliable and predictive animal model that has a history in translating compounds to the clinic?
5. Does a clinically relevant biomarker exist?
6. Competition: Examine approved claims (efficacy and safety) of competitors. Examine the competitive environment for compounds currently in development.37
Clinical Correlation Assessment
1-2 slides addressing
Scope of unmet medical need• Number people affected by disease (target population)• Current standard of care and market size (commercial
potential)• Unique needs of the target population• Phase II proof of mechanism and patient stratification
strategy
38
Clinical Need/Potential Market
• 1 slide describing the desired characteristics of the proposed therapeutic for the intended indication
• What is the specific value of your drug/approach to patients? What advantages does it offer over existing or competing approaches? How your product meets the needs of your global market based upon performance features, costs, robustness, etc.
39
Targeted Product Attributes
1 slide addressing OCR/T2 disclosure and patentability status
40
Intellectual Property Position
Contact Craig Crews (Yale) or Dennis Wright (UCONN)
Craig [email protected](203) 432-9364
Dennis [email protected](860) 486-9451
Questions about the Program?
Thank You