Leaders in Pharmaceutical Business Intelligence (LPBI) Group

• Chairman, Department of Medicine, Physician-in-Chief, Brigham and Women’s Hospital
• Hersey Professor of the Theory and Practice of Medicine, Soma Weiss, MD Distinguished Chair in Medicine, Harvard Medical School

1. What is the state of play and the future of CVD
2. Why Drugs are behind vs Devices
3. Precision Medicine in CVD
4. Nutraceuticals – more regulations??
5. Insights that surprised you at FDA
6. Redesign the FDA – Areas?
7. Patient participacition post approval

• Commissioner (former), Food and Drug Administration

1. CVD – drugs vs Devices
2. Drugs are less exciting while devices are booming
3. Effective therapies of generic drugs is remarkable
4. Reimbursement system is messed up
5. DIfferent drugs have equal effects and ROI is not there, Pharma are pursuing different areas
6. Checkpoints drugs in Oncology has no analogy in CVD
7. Enrollment in Clinical Trials: In oncology, patients flock to Trials – that is not the case with CVD Trials
8. Precision Medicine is over inflated, it is demonstrated in Oncology, “in CVD, I wish to hear from you”
9. System Biology and Drugs
10. FDA – one drug is a success for several attempts, several is large
11. FDA is not interested in the Mechanism, they are interested in identidying the population, demonstrate safety and efficacy no adverse events
12. Investment in Devices looks better vs CVD Drugs, Biologics are different
13. Food supplement for Prostate, some are harmful – Law forbid regulation of Nurtaceuticals not good for public health
14. Academic centers: Duke and Partners are far advanced in HC landscape
15. FDA works with CMS – demonstration of Value in Drugs – Pragmatic randomized Trials
16. Total cost, better spent
17. FDA is a Science-based Organization – tremendous people, amazing work – learned the regulation over time
18. Political Corporation have same status like individual for First Amendment
19. Regulate Cosmetics and Nurtaceuticals
20. Ecosystem: Products, Patient Advocacy Groups and Regulators — better alignment
21. Cooperation and interaction among agencies: NIH, FDA
22. Speeding the process if Patients are involved earlier – Pragmatic study design
23. CVD – reassurance the patient

• Director, Translational Research Center, Massachusetts General Hospital
• Professor of Medicine Harvard Medical School

1. CVD Success stories NOT by Cardiologists
2. Metabolic Drugs Clinical Trials: Outcome Trials – 4% each trial is $2Billion thousand of Patients
3. Trial design
4. Technologies
5. Quality control in Clinical Trial in Russia, Gorgie – no metabolites in blood
6. Biomarkers Predictor of responses

• SVP, Global Head of Regenerative Medicine Unit, Head of Scientific Affairs, Japan, Takeda

1. Stem Cells Skin cells or blood cells and converted to other cells
2. development of Cell-based therapy for Cardiac myocytes: propiatory method to purify myocytes
3. In Japan, Cardiac transplant in very small cases – Alternative for Heart Transplant for HF – development of gene therapy and stem cell converted to myocytes
4. Govenrment initiative to develop regenerative medicine, procedure can be improved,
5. approval for EF improval – conditional Approval given by Government on 100 patients
6. Severe HF — cell therapy and procedure is consider
7. Osaka University, cell transplantatio – in Acadedmic Center
8. If efficacy and safety — continuous improvement – inject the cell be applied to more patient beyond CVD applications
9. Post approval registry, call patient back every few month, HF continuos Monitoring

• CMO, Verily

1. Tools to make the Patient the center of the Trial and engaged
2. Information arrives in Real Time with Analytics – value derived from Dashboard design
3. Multidimensional Data
4. Definition of Disease – not as a point once a year but continual
5. Real Time monitoring, deep IT design, each Patient has own Portal, monitoring takes major resources, Large Informatics companies, screen ECG of huge populations
6. FDA interested in NEW tools, data that comes from individual
7. Biomarkers: Biosignals broader, connection Genomics and physiology – Neurlology
8. CVD – BP druds and QT prolongation
9. User-centric Design – Patient-center, data infrastructure for MDs

• SVP, Global CMO, Novo Nordisk

1. 2016 – three drug studies CVD and DM – Insulin: (1) Post market on Safety, (2) Preapproval assessement (3) Insulin study assess data without compromising the continuation of the study (CVRT)
2. Engaging Patients and Investigators – Global Trials varies by Regions – Global Experts, Local Experts and RN as Coordinators — worked very well
3. CVD Outcome Trials – engaging patients
4. Intermediate Analysis: conduct and protect the Intermediate results no disclosure till Trial is completed
5. Identify the right site id a challenge
6. Multiple pathway related to CVD – Biomarkers difficult to find as insightful
7. In Israel data integrity is the highest
8. Innovative Medical Initiative – Novo, Lilly, Sanofi — DM data comparison

• SVP & CSO, PAREXEL International – CRO

1. Adaptive Trials vs Traditional Cardio (no windows) – intermediate evaluation
2. Adaptive Trials: Flexibility 50% of Phase III Fails – Adaptive design offer more values
3. OMICS revolution – innovative revolution
4. Umbrella Design: different treatment for single indication
5. Platform design – infrastructure design is inefficient vs Platform: Number of Drugs Several indications
6. Interaction with FDA: They are open to Adaptive design wiht Power, survival rate window adaptive,
7. Tufts data and PAREXEL: Adoption 30% of new design for Phase III: maintain blindness
8. Data Surveillence during the Trial administration – look at data cycle time, monitor margins during the study Red flags identified before end of study
9. Biomarkers in Early Translational Research – down stream processes to identify and validate

• Reporter, CNBC

• CEO, Boston Scientific

Geography – Global vs 10 years ago US focus

Pipeline strategy – Diversified: Neurology, CVD, Endoscopy – innovation cycle very strong

• Symatec – valve company – M&A – strengthen Strategy on TAVR
• AF product
• Deeper Stimulation for Parkinson
• Mitral Valve Strategy: Venture bets with VC for repair and replacement
• TAVR – volunteer recall back in Europe – P&A – fully deployed valve synergies with Symatec
• Digital tool
• GHX – B to B Healthcare Exchange – automate procurement, innovate the portfolio – supply chain cost reduction
• 30 VC investment – microelectronics, AD Neuro-modulation, Obesity, Immunology
• Sensors – prediction of HF – two devices: diagnostics-side to reduce hospital readmission – GO HOME with Alert system to avoid ER, diagnostics
• Cnsolidation: growing very well: Drive Category leadership – Hospitals want to deal with three suppllier.
• Partner of Choice for Partners
• Acquisitions: Early stage and more mature
• Challenges in Emerging Markets:

1. Brazil – different that China or India
2. China – more regulation for approval
3. India – price very low – not to offer more expensive stents

• Cyber security – Investment in this domain to secure data – not a market reaction to this issue
• Reimbursement: Clinical path to get Approved – Upfront effort to align approval with Reimburement
• FDA responsive to 2nd time improvement Clinical trial designed
• Microelectronics new direction: Endoscopy GI Pulmonary,
• SPINAL CORD STIMULATION: GU, GI (Crohn), Neuromodulation: Depression, Pain, Parkinson

• President, Brigham Health
• Professor of Medicine, Harvard Medical School

1. What innovative projects at NHLBI
2. Young Investigators
3. Large Cohort studies: Framingham Study, 1958 – CVD Risk for: Policy: Lowering BP and Cholesterol
4. CVD hot areas
5. Value-based Care

• Director, NHLBI

1. Enabling other the pursuit of Science for Public Good
2. Ecosystem – the Government arm –
3. ROI – funds Projects
4. KI – New Program – funding PIs – investigators initiatives – Next generation of Scholars
5. 50% of KI converts to ROI
6. Reduction in CVD is an ROI in research in CVD Biology and Drug development and Devices
7. 2018 NIH Funding – last two years increase in budget, cuts may or may not occur
8. Opportunity to reinvent Longitudinal Cohort Studies with insertion of Genomics sequencing – 7,000 Whole Genome – target 100,000
9. Concepts of Data Commons – Sharing ONE resource for distributed Analytics: Reusability, interoperability, API
10. CVD – portfolio to include Minority Population disease prevalent
11. Translation of Science, concept mechanism
12. Epigenomics and Patho-biology DB and changes over time -a rare resource
13. Science is to be done for the Public Good, commonwealth of the entire nation – Accessibility of Genome Data after the National goal of sequencing the Genome
14. 20% investigators take up 50% of the grants and squeeze out the younger generation
15. Pragmatic optimist in this position, scientists innovate for Patients

• SVP and US Medical Leader, Eli Lilly and Company

1. Obesity and DM2 – direct (Heart Disease Arthritis) and indirect cost (quality of life and productivity)
2. What is most exciting
3. What is the challenges
4. Best ideas
5. NASH
6. Microbiome
7. Food Science

• SVP and CSO, CVMET, Pfizer, Cambridge

1. Cardiometabolic in same department with Neurodegenerative Disease – affected by metabolic state
2. Behavior modification does not work – 1:1 care is too expensive
3. therapeutics needed for obesity
4. Which drugs will be translatable
5. NASH – most die with Heart disease – if NASH treated no death??

• Global VP, Cardiovascular, Renal and Metabolism AstraZeneca

1. Renal condition CKD
2. CVD
3. comorbidity
4. Drug perspective: White fat in not inert, signalling
5. combination of drug
6. compounds that have impact on CV system
7. Three Barriers: (1) Science, (2) access to medicines (3) holistic approach: Nephrology needs to use DM drugs, Cardiologist other drugs than cardiac drugs
8. NASH – it is a REAL disease, impact on Patient

• CEO, Zafgen

1. Inhibiting enzyme in obisity for weight reduction
2. Inflammation burden, lipid, thrombotic events
3. NASH
4. Fat and glucose metabolism – integrated physiologic view
5. Cardiovascular Outcomes: lack of harm vs showing benefit caused by emerging therapies
6. Food and obesity

• Director, Obesity, Metabolism & Nutrition Institute, Massachusetts General Hospital
• Associate Professor, Harvard Medical School

1. MGH-GI, Bariatric Surgery, effect on comorbidity Vascular Pressure –>> Hypertrophy, conduction and Arryhythmia
2. Obesity in 6 Countries not only in US, Urban and Rural
3. CVD occurs in Asia in absence of Obesity
4. Bariatric surgery is not a public solution – it affects the gut different that drugs do
5. what get a person to obesity and waht maintain the obesity
6. complications of obisity – abnormal target of stores
7. move from the ideas of calories consumption vs Brain function
8. Develop drug against the complications vs against the obesity itself: Science of Obesity not understood,
9. Voluntary obesity vs life style – stigma against obesity, heterogenous disease
10. Microbiome – effect size is small master regulator are interactive Pro-biotics needs to be invented

Bruce Spiegelman, PhD

• Stanley J. Korsmeyer Professor of Cell Biology and Medicine, Dana Farber Cancer Institute, Harvard Medical School

1. Molecular development of fat molecule and in exercise impart on energy expansion,
2. Capture the molecules that participate in exercise to be given to bedridden patients
3. Obesity is a disease of energy imbalance – Food Intake and Energy expenditure – BEIGE FAT cells that expend energy
4. Molecular involvement: Exercise causes neurogenesis: ALS, Parkinson, AD
5. Exercise affect, Heart, Brain and cognition
6. Science had budget challenge, Biotech, Pharma: CVD Outcomes studies
7. R&D has challenges to get traction
8. Microbiome – natural context  provide modest benefit, some effects

• Chief of Cardiovascular Medicine, Brigham and Women’s Hospital
• Associate Professor of Medicine, Harvard Medical School

• Chief, Cardiology Division, Massachusetts General Hospital
• Professor of Medicine, Harvard Medical School