Vasilios Papademetriou is a cardiologist and professor of medicine at Georgetown University who has collaborated extensively with the biomedical industry. He discusses several career pathways for medical students in the biomedical industry, including doing clinical trials sponsored by industry, serving on advisory boards, and collaborating on research. He provides examples of physicians who have successfully worked with industry to develop new drugs and devices.

1. Vasilios Papademetriou, MD, DSc, FACC, FACP, FAHA
Professor of Medicine (Cardiology)
Georgetown University
Washington DC
Options for Medical
Students to Follow: The
Biomedical Industries
Pathway

2. › I am a cardiologist-Interventional
› Professor of Medicine ( Cardiology)
› Director of Cardiovascular Research for > 25 years
› Have done basic research ( early on)- NIH,VA Medical Center
› Lately ClinicalTrials ( Mostly)
– Collaborated with the industry
– Part of several NIH ,VA sponsored trials
› For the last 5 years I served as a member of the Cardio renal Panel
of the FDA ( Approval of new drugs)
– Rivaroxaban
– Droxidopa etc
A few things about myself

3. › Develop New Drugs
› Develop New Devices
– Diagnostic
– Interventional
– Sensors
– Imaging
Aim of the Industry

4. New Drugs
 Discovery and Development
 Test many compounds
 Mechanism of action
 Rout of administration etc
 Preclinical Research
 In vitro and in vivo
 Dosing and toxicity in animal models
 Clinical Research
 FDA Review
 FDA Post-Marketing Safety
Monitoring
Clinical Research
 Phase 1
 Dosage & safety
 20 to 100 healthy volunteers
 Phase 2
 Efficacy & side effects
 Several 100s of people
 Phase 3
 Efficacy and adverse events
 300 to 3,000 people
 Phase 4
 Safety and efficacy
 Several 1000s of people
RESEARCH & DEVELOPMENT
Only 1:10 new drugs makes it to the FDA and cost can be up to one BILLION $

5. New Devices
 Device discovery and concept
 Preclinical research-Prototype
 Pathway to approval
 FDA Review
 FDA Post_ Marketing
Monitoring
Pathway to approval
 FDA established risk-based
classification system
 Class I
 Class II
 Class III
 Safety and Efficacy
 Proof of concept/First in man study
 Controlled trials
 Placebo or sham control studies
 Outcome data
DEVICE DEVELOPMENT PROCESS

6. Foreign Medical Graduates:
Options in Biomedical Industries
Work for the Industry
Maximize your potential
Optimize chances for success
Collaborate with the
industry
Graduates of the EUC

7. › As a Physician working in private practice or Academia
– Clinical Research ( Phase I,II,III or IV studies)
– Investigator initiated projects – sponsored by the industry
– Basic research of interest to the industry
› Serve on advisor boards
– Help the industry understand clinical implications of their studies
– Design the right kind of research
– Interpret the results of clinical trials
› Steering committees
– Direct and supervise clinical studies
– Analyze results
– Publish research papers
Collaborate with the industry
(Part time job)

8. › Physicians of DCRI
– Robert Calif
› Brigham and Women's
Research Center
– Mark Pfeffer
› Contributed to the
development of many of the
drugs we use today:
– ACE inhibitors
– Beta blockers
– Statins
– Diabetes drugs
Collaborating with the industry

9. • Pre clinical testing
• Toxicity studies
Drug Development
• First in human study
• Proof of efficacy and safety
Proof of concept
• Pivotal study
• Phase I, II, III and IV studies
Clinical Development Program
› Research & Development
– Invent and test new therapies
– Design and Direct Clinical
Trials
› Direct Marketing
– Education
– Promotion
Working for the Industry as a Physician

10.  Afferent and Efferent Renal fibers
Can affect blood pressure control
 Afferent fibers originate from the
kidney and transfer signals to the
brain
 After processing can affect the
function of the heart, the blood
vessels and the kidney
 Efferent fibers transfer signals from
the brain to the kidney and can affect
Na and fluid absorption, plasma renin
activity and aldosterone production
SYMPATHETIC RENAL DENERVATION CONCEPT
Papademetriou et al. Circulation 2014;129:1440-51

11. FIRST IN MAN STUDY: SYMPLICITY HTN-1
-14 -21 -22 -24 -27-10 -10 -11 -11 -17
-50
-40
-30
-20
-10
0
10
1 month
(n=41)
3 months
(n=39)
6 months
(n=26)
9 months
(n=20)
12 months
(n=9)
Mean
Change in
Blood
Pressure
(mmHg)
Presented with
95% Confidence
Intervals
Systolic
Diastolic
Lancet 2009

12. RENAL DENERVATION SYSTEMS WITH CE MARK
APPROVAL IN EUROPE

13. ST JUDE MEDICAL RENAL DENERVATION SYSTEM

14. STAGES OF RENAL DENERVATION
Papademetriou, Tsioufis, Doumas…… Circulation 2014;129:1440-51

15. LESION PATTERNS USING THE ENLIGHTEN
SYSTEM

16. NOREPINEPHRINE REDUCTION
16
 Renal nerve ablation using the EnligHTN ablation system shows significant reduction in k idney NE
at the 30 and 90 day time points vs. Sham PTA Balloon (N=30 k idneys)
65% reduction

17. Average systolic blood pressure
during control (CON) and for 8 weeks after renal
denervation
Correlation between SBP and mean
and renal tissue norepinephrine (NE)
levels
CATHETER-BASED RADIOREFREQUENCY RENAL DENERVATION LOWERS
BLOOD PRESSURE
IN OBESE HYPERTENSIVE DOGS
Each bar represents the average of 7 days of blood pressure
measurements, 18 hours a day
NEPI change: -42%

18. ENLIGHTN I: 12 MONTH DATA
Papademetriou V, Tsioufis C,,,,,,,,Hypertension 2014
Worthley S, Tsioufis C……Papademetriou V; EHJ 2013

19.  Almost two decades ago the 4S first showed that simvastatin effectively
improve survival in patients with cardiovascular disease (CVD), and initiated
a revolution in the treatment of atherosclerotic heart disease
 Results with other statins confirmed and enhanced these results
 Other newer and/or novel compounds were abandoned either because of lack
of efficacy or unacceptable side effects
 Recently ezetimibe-in the IMPROVE-IT study- showed further improvement of
outcomes when added to a statin.
 Yet the incremental reduction of LDL-C was modest and additional benefits
small, but the study confirmed the impression that “ Lower is better”
That’s where PCSK9 come into play
MANAGEMENT OF DYSLIPIDEMIAS AND PCSK9
INHIBITORS

20. “Are considered a breakthrough in the
management of dyslipidemias because”
Are safe and
Very-very effective
WHY ARE PSCK9 INHIBITORS IMPORTANT?

21. SAFE BECAUSE ARE HUMANIZED MONOCLONAL
ANTIBODIES

22. HOW LDL PARTICLES ARE CLEARED

23. PSCK9 TAGS LDL-R FOR DESTRUCTION

24. EVOLOCUMAB BINDS TO PCSK9
PREVENTING IT FROM BINDING THE LDL RECEPTORS

26. CARRIERWITHTHE INDUSTRY
 Graduated from the School of
Pharmacy
 Graduated from Medical school
 Specialized in Internal Medicine
 Practiced for 10 years
 Finally Joined Astra Zeneca as a
Scientist-Medical Leeson
 Works in that position ever since
 Lives a comfortable-fulfilling
Interesting life
Medical Leeson specialist withAstra Zeneca

27. BRIGHT EXAMPLES
 Aris Baras MD
 Graduated from London high School
 Duke college
 Duke Medical
 Worked on his MD/MBA dual degree at
Duke University.As an undergraduate at
Duke, he studied biology and economics.
Aris has been fascinated with pursuing
biomedical discoveries and the
development of life-saving therapies since
he was in high school. One of Aris’ mentors
has been Dr. RoyVagelos, former CEO and
chairman of Merck. Aris lives in Durham,
North Carolina with his wife, Lia, and their
son, Parker.School
 Joined Regeneron 2years ago, his already a
multimillioneur
Through my association with Dr. RoyVagelos, I
started working with the translational medicine
team at Regeneron. One of the group’s functions
is to thoroughly vet drug candidates before
embarking on risky and expensive investments in
clinical development programs

28. LEADING WITHINTHE INDUSTRY
 Graduated Medical School in Athens
Greece
 Scholarship at the NIH.Worked and
discovered the gene for Parkinson’s
disease
 Recruited by Novartis and worked as a
researcher for a few years on Gene
targeted therapies
 Recruited to start his own biotech
company
 FormedVANDA pharm
 Developed and sold first drug for $570
million
Vanda Pharmaceuticals
Reports Preliminary Fourth
Quarter and FullYear 2015
Results and 2016 Financial
Guidance
- Fourth quarter 2015 HETLIOZ® net
product sales are expected to be
approximately $15.1 million
- 2015Total revenues are expected to be
approximately $109.9 million
- 2016Total revenues are expected to be
between $143 and $153 million

29. REACHINGTHETOP
 GeorgeYancopoulos, MD, PhD of
Greek origin, Founding scientist,
President and CEO of Regeneron.
 Graduated from Columbia Un and
Joined Regeneron in 1989
 11th most highly cited scientists in the
word in the 1990s
 He was the PI and got approval of 4
drugs ( aflibercept, ziv-
aflibercept,rilonacept and alirocumab)
 He is now the highest paid Chief
executive
 His Company is worth more than $48
billion
The quality of Regeneron science has
been recognized in the academic scientific
community as well as through a very
tangible metric: our four FDA-approved
products, as well as every one of our
clinical candidates, were discovered and
validated in Regeneron's labs. Regeneron
Genetics Center ,Target Discovery , Drug
Candidate Platforms, Protein Production -