SLIDE 1 Craig M. Crews, Ph.D.
Lewis B. Cullman Professor of Molecular, Cellular, and Developmental Biology Chemistry, Pharmacology Center for Molecular Discovery Yale University
Dennis Wright, Ph.D.
Professor of Medicinal Chemistry NPDD Initiative UCONN School of Pharmacy University of Connecticut
SLIDE 2
PITCH: What?
SLIDE 3
An Collaboration between Yale and UCONN to Help Academic Projects Cross the Valley of Death
PITCH: What?
SLIDE 4 PITCH: What?
- Provide a streamlined translational pathway for researchers to
convert their discoveries to new therapeutics
SLIDE 5 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
SLIDE 6 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
SLIDE 7 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
SLIDE 8 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
SLIDE 9 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
SLIDE 10 PITCH: Who?
Craig M. Crews, Ph.D.
Lewis B. Cullman Professor of Molecular, Cellular, and Dev. Biol. Chemistry, Pharmacology Center for Molecular Discovery Yale University
Dennis Wright, Ph.D.
Professor of Medicinal Chemistry NPDD Initiative UCONN School of Pharmacy University of Connecticut
SLIDE 11 Dennis Wright, Ph.D.
Professor of Medicinal Chemistry NPDD Initiative UCONN School of Pharmacy University of Connecticut
PITCH: Who?
Background
West Liberty State BS (Chemistry) Ohio University Ph.D. (Chemistry) Stanford Postdoc Training UCONN Joined Faculty in 2006
Experience
- New Pathways in Drug Discovery (NPDD)
- Co-Founder
- Promiliad, Inc.
- Co-Founder
- Synaptic Dynamics, Inc.
- Co-Founder
SLIDE 12 PITCH: Who?
Craig M. Crews, Ph.D.
Lewis B. Cullman Professor of Molecular, Cellular, and Dev. Biol. Chemistry, Pharmacology Center for Molecular Discovery Yale University
Background
U.Va. BA (Chemistry) Harvard Ph.D. (Biochemistry) Harvard Postdoc Training Yale Joined Faculty in 1995
Experience
- Yale Center for Molecular Discovery (YCMD)
- Founder/Executive Director
- Proteolix, Inc.
- Co-Founder
- Arvinas, Inc.
- Founder
- Chief Scientific Officer
SLIDE 13 PITCH: Where?
Y ale Center for Molecular Discovery (YCMD)
Y ale West Campus (former Bayer Pharmaceuticals)
SLIDE 14 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
SLIDE 15
– 5 Biology – 3 Chemistry – 1.5 Administrative
Industry: PITCH: Where?
SLIDE 16 Overview of Capabilities
– Assay Development – High Content Imaging – Screening (siRNA and small molecule)
– Structure-Activity Modeling – Medicinal Chemistry – Compound Synthesis & Analoging
- Assisting with Patent Writing
16
PITCH: Where?
SLIDE 17 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?
SLIDE 18 Demetrios Braddock, Department of Pathology
- R. A. Albright et al Blood, (2012) 120:4432-4440.
Assay for Inhibitors of NPP4 Activity X-Ray Structure of Target Classical High Throughput Screening Structure-Based Design
Follow-On Improvement Novel Composition
Proof of Concept (Repurposing)
PITCH: Where?
SLIDE 19
NPDD: A Drug Discovery Network
New Pathways to Drug Discovery External Partners UCONN Health UCONN Storrs 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?
SLIDE 20
UCONN School of Pharmacy
The SOP provides an exciting, highly interactive environment for experimental therapeutics with scientists from a broad range of backgrounds united by 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
SLIDE 21
Medicinal Chemistry Capabilities
High-Throughput Screening Structure-Based Drug Design Medicinal Chemistry
Drug design/ SAR Complex molecule/ parallel synthesis Stereoselective synthesis I n 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
SLIDE 22
Drug Target Studies at UCONN Health
Protein Expression Protein Purification Protein Characterization High Field NMR (800 MHz) Other Biophysical Studies
SLIDE 23 External Advisory Board Evaluation
UCONN Yale Assay Submission Due: October 1
PITCH: How?
SLIDE 24 External Advisory Board Evaluation
UCONN Yale Assay Submission
Bill LaRochelle, (Sr.Dir, Roche Sequencing Solutions Brian 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 EAB 10am-1:30pm October 30 Yale Center for Molecular Discovery (YCMD) West Haven, CT
SLIDE 25 Originating Lab or CRO Assay Development Assays Screened Virtual Hit Expansion [in vivo Testing] Business Plan Pitch
External Advisory Board Evaluation
SAR/ Med Chem YCMD UCONN Pharm UCONN Yale Assay Submission New Leaf Ventures Elm Street Ventures OrbiMed Ventures Canaan Partners Ventures Other VCs/Pharma Venture Funds? Out-license? YCMD UCONN Protein Production Core
PITCH: How?
SLIDE 26 36 Assays Developed 30 Assays Screened 24 Virtual Hit Expansions 12 SAR/ Med Chem 8 Business Plans 8 Pitches # Assays Submitted?
Three Year Goals
SLIDE 27
PITCH: When?
Deadlines: Submission of Slidedeck PITCH Application: October 1
SLIDE 28
PITCH: When?
Deadlines: Submission of Slidedeck PITCH Application: October 1 Faculty Presentation to External Advisory Board: October 30th (at the YCMD)
SLIDE 29
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
SLIDE 30 Project Title
Investigators
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To see TIPS and FAQS for each slide, please look at this template in Notes view.
SLIDE 31 31
Two Year Goal Statement
Your two year goal will frame the following assessment.
SLIDE 32
- Brief background for team members and their roles
- n this project.
- Include relevant past experience, if any.
- Identify unfilled roles needed.
32
Project Team
SLIDE 33 Briefly, introduce background science. What is the problem worth solving? What is your solution? Why is it novel?
33
Scientific Background and Opportunity
SLIDE 34 Describe additional research data needed but which is outside the scope and capability of the investigator’s laboratory.
34
Research Plan
SLIDE 35 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
SLIDE 36 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
SLIDE 37 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
SLIDE 38 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
SLIDE 39
- 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
SLIDE 40 1 slide addressing OCR/T2 disclosure and patentability status
40
Intellectual Property Position
SLIDE 41
Contact Craig Crews (Yale) or Dennis Wright (UCONN)
Craig Crews craig.crews@yale.edu (203) 432-9364 Dennis Wright dennis.wright@yale.edu (860) 486-9451
Questions about the Program?
SLIDE 42 Contact Janie Merkel (YCMD) janie.merkel@yale.edu (203) 737-3080
42
Questions about the Application?
SLIDE 43
Thank You
