Partnership to accelerate novel treatments for heart valve disease Mayo Clinic, NIH/NCATS, Sanofi, University of Minnesota, Nanosyn Jordan D. Miller, PhD Innovator Presentation
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Heart Valve Function
Heart Valve Function
Heart Valve Function Can be the earliest sign of heart valve disease
Heart Valve Function
Heart Valve Function
10 million people will have aortic valve stenosis
Current Treatment Options Valve Replacement Transcatheter Approaches
For the rest of the talk An unlikely story Discovery Opportunity Pivots Partnerships
Goals 5 Years Ago DNA
K99/R00 Grant Nitric oxide signaling in valve disease
K99/R00 Grant Nitric oxide signaling Successful Therapeutically limited * WT DDAH1 +/
K99/R00 Grant Nitric oxide signaling Successful Therapeutically limited Not Pharma Not medicinal chemistry group
Typical Academic Model DNA
New NIH Program New Therapeutic Uses for Existing Drugs One year proof of concept (UH2) Cell Animal Human (Phase I) Two year clinical trial (UH3) Human (Phase II)
New NIH Program List of ~30 drugs Provided by Pharma partners Known safety profile formulation
New NIH Program List of ~30 drugs What is the likelihood that one would hit our target?
New NIH Program List of ~30 drugs What is the likelihood that one would hit our target?
New NIH Program
New NIH Program
New NIH Program Nitric Oxide N O Ataciguat Ataciguat N sgc O Oxidative Stress Ataciguat Ox sgc Valve Calcification
Shift in Mindset DNA
Our New Goal DNA
<1 year to get to human studies Historical view Science Medicine
New View Diverse skillsets Diverse ways of thinking Shared common goal Patient needs
New View Initial UH2/UH3 Team Jordan D. Miller, PhD (PI) Scientist Hartzell V. Schaff, MD (Co-PI) Surgeon Maurice Enriquez-Sarano, MD (Co-PI) Cardiologist
Our Proposed Approach UH2 Phase UH3 Phase Cells Mice Human (Phase I) Human (Phase II) Proof of Concept Tolerance/ Proof of Concept Effectiveness/Efficacy
Historical Model PI/Mayo Sanofi NIH
After the Grant Started PI/Mayo Sanofi NIH
After the Grant Started Brought Expertise Mayo Previous experience with drug Cross-reference IND Trial design/refinement Sanofi Industry insights NIH
Everything was underway A new twist Launchpad for Enterprise Innovation that is Evidence-based Customer -focused
Two key insights After 10 weeks Repurposing has limited value Limited Patent Life New Drugs in Phase II
New Key Partnerships Novel drug development Academia Industry
UH2/UH3 Where are we now? Completing Phase I and planning Phase II Drug development Identified 2 lead compounds (one with each partner) Planning refinement
An expensive process $500k January 2015 Scalable Screening Assays Novel Hits Compound Refinement July 2016 $3 5M Cell based Assays Animal Models Phase I Safety Trials Phase II Efficacy Trials
Challenges Funding for new leads Regulatory endpoints Business development strategies Public awareness of valve disease Screening Strategies for early diagnosis
Heart valve disease Major unmet needs Summary
Summary Heart valve disease Major unmet needs Requires new strategy Multidisciplinary teams Unique partnerships Patients FDA
Heart valve disease Summary Major unmet needs Requires new strategy Brings forth new challenges
Heart valve disease Summary Major unmet needs Requires new strategy Brings forth new challenges Training current and next generation
Summary Tremendously exciting time for translational research Looking for new partners at all levels
Team Mayo Clinic Miller Laboratory Bin Zhang, MD Carolyn Roos, MS Michael Hagler Heyu Zhang, MD/PhD Nassir Thalji, MB ChB Leslie Smith Brandon Dunagan Maurice Enriquez-Sarano, MD Hartzell Schaff, MD Rakesh Suri, MD/DPhil Jenny Weiss Marcia Andresen Reid Mark Wentworth Juliana St-Helene Kraft Launchpad for Enterprise Todd Morrill, PhD NIH Christine Colvis, PhD Bonnie Dunn, PhD, Bobbie-Ann Austin, PhD Frank Evans, PhD Sanofi Julia Gershkovich Karl Denkel, PhD Michael Halpern Christoph Gaudin, MD Many others University of Minnesota IDTT Michael Walters, PhD Jon Hawkinson, PhD Henry Wong, PhD Gunda Georg, PhD Nanosyn