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Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Device Development: Past, Present and Future
1
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
MY CONFLICTSOF INTEREST ARE
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Approaches to Establish Funding
• Angel
• Venture
• Corporate
2
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Angel Funding
• Pros
– Less Expensive
– Industry Expertise
– Provides Upstart to build value and more leverage
• Cons:
– Hassle Factor
– One/Two Round Only
• When does it make sense?
– Less Cash intensive opportunities
– Low regulatory hurdles
– Fast-followers
– First-timers putting an experienced executive team together
3
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Venture Funding
• Pros
– Deep Pockets
– Professional Expertise
– Extensive Business Network
• Cons
– More Expensive
– Return / Liquidity Requirements
– In-Depth Due Diligence
• When does it make sense?
– Large Opportunities
– Markets > $500 million
– Cash and time intensive
– First-timers unable to assemble a solid executive team together
4
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Corporate Funding
• Pros:
– Less Expensive
– Value Add
– Credibility
• Cons:
– Hidden Agenda/Special Rights
– Questionable Follow-On Dollars
– Exit Strategy Limited
– Business Alignment
• When does it make sense?
– Funding Needs beyond VC’s
– Close to commercialization…looking for a commercial partner
5
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Funding Stages
CompanyStage ConceptConcept Company Company Sales /
Profits Sales / Profits Liquidity Liquidity
Product Devtand
Commercialization
FundingType
SeedStage
(Series A)
Startup(Series B)
Expansion(Series C)
Mezzanine(Series D)
IPO or Merger
RISKHigher Lower
$$$ VALUE $$$Lower Higher
6
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
ImportantStartup Rule
#1
The more $$ you spend
The more $$’s you have to raise
The more of your opportunity you
have to sell
The less return
you provide
to investors
… 7
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
The Team &
The Company
• Management:– Do You Have a CEO?
– Is He/She Qualified, Experienced as CEO?
– Can They Raise Money?
• Team:– Functional Disciplines?
– No-compromise on hiring great people?
– Team Chemistry?
Bottom Line:
•Risk in the team….COSTLY
•The timing of the right functional teams coming together ….CRITICAL TO SUCCESS
8
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
• Intense Competition
• Intellectual Property
• Capital Requirement
• Engineering
• Regulatory Environment
9
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Anatomy of a Start-up…
IPO
FDA Approval; Product Launch
Distribution Agreement
Hired CEO; Key management in placeFDA submission
Animal studies completed; Start clinical trials
Prototype completed; Funds raised
Patents Disclosed
Time (years)
Val
uat
ion
($
)
10
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
• Timing is everything
• It is often, but not always best to be first
• Some markets change quickly; others very slowly
• New market development is expensive
Window of Opportunity
11
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
• Rigor of randomized clinical trials
• Clinical adoption
• Ease of use
• Learning curves
12
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Goals of Startups
Balancing
13
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Understanding of the Opportunity
Novel Idea Iterative Idea
Investment Dollars Needed Higher Lower
Time to Liquidity Longer Shorter
Biggest RisksTechnical/Clinical
Market adoption timeliness
Execution timeliness and quality
Competition
Most Important for SuccessIP protection
Customer willingness to change/adopt
Experienced team
Laser focus
Adoption Curve Longer Shorter
Likely Exit Value Higher Lower
Importance of Expense Control Moderate - high Very high
14
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Golden Rules
• Device or procedure must be simple to apply an can be adopted by the average practitioner
• Invention addresses an otherwise unmet clinical need
• Device regulatory path is associated with a “reasonable” chance for success in an otherwise well defined study with a finite sample size
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
19891997
19992000
20022003
2004
20052006
16
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
1977
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Coronary Angioplasty (PTCA) Andreas Gruntzig
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
1977
1984
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Directional Coronary Atherectomy (DCA)John Simpson
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Rotational Atherectomy (PTCRA)David Auth
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
1989
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Coronary StentingJulio Palmaz
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
1989
1997
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
In- Stent Restenosis
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Brachytherapy
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
19891997
1999
2000
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Drug Eluting Stents
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Event-Free Survival at Two Years Event-Free Survival at Two Years following procedure following procedure
Freedom from
events (%)
50
60
70
80
90
100
0 120 240 360 480 600 720
Sir-MACE
Ctl-MACE
Days after initial procedure
92%
76%
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
ARTS I: Three-year outcome after Stenting vs. CABG for the Treatment of Multivessel Disease
. 100
99
98
97
96
95
94
93
92
91
900 120 240 360 480 600 720 840 960 1080 1200
Days since randomization
% S
urv
ival
Stent
CABG
Van Domburg, et al., Circ. 2004:109, 1114-20
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
19891997
1999
2000
2002
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Percutaneous Treatment of Carotid Artery Stenosis
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Percutaneous Aortic Valve TherapyAlain Cribier
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Percutaneous Valve Therapy Edwards LifeSciences
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Self-expandingNitinol
multi-level frame
Porcine pericardium Tissue Valve
Disposable Loading System
Delivery Catheter 18 French 12 Fr body
The CoreValve Revalving™ SystemSelf-Expanding Support Frame
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
19891997
19992000
2002
2003
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Percutaneous “Mitral” Valve Repair
• Coronary Sinus Annuloplasty
• Edge-to-Edge Repair
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Coronary Sinus AnnuloplastyEdwards LifeScience
HandleHandleSliding Knob
Sliding Knob
Location of Implant
(Internal)
Location of Implant
(Internal)
Distal AnchorDistal AnchorProximal AnchorProximal Anchor
BridgeBridge
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Mitral Valve Edge-to-Edge Repair
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
19891997
19992000
20022003
2004
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Atrial fibrillation is a major source of cardiogenic embolism-related
stroke
Source: Neurology, 1978; Stroke, 1985; European Heart Journal, 1987; Lancet, 1987
• 500,000 strokes per year
• AHA estimates that 15 – 20% of strokes/year are related to AF
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
WATCHMAN® Device
• Frame: Nitinol (shape memory)– Contour shape accommodates most LAA anatomy– Barbs engage the LAA tissue
• Fabric Cap: Polyethyl terephthalate (PET) Fabric– Prevents harmful emboli from exiting during the healing process
Barbs
160 µ PET fabric • Device available in various sizes:– 21, 24, 27, 30 and 33 mm
(diameter)
– Device diameter is measured
across face of device
– Device Length = Device Diameter
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Left Atrial Appendage Closure
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
19891997
19992000
20022003
2004
2005
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
The Next Frontier in Coronary Stenting
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Treating Bifurcation LesionsLimitations of Current DES
– Stents are tubular structures • not intended for Y-shaped
anatomy
– Side branch jailing– Limited ostial coverage
(“Gaps”)– Technically demanding– Multiple layers of metal– Increasing risk of thrombosis– Myriad of Techniques
Gap
MultipleLayers
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
The TAXUS PetalTM
Boston Scientific Coroporation
Stent Advantages– Special stent feature to cover
ostium of side branch (~2mm)– Reduces / eliminates side branch
“gap”– May reduce frequency of 2nd stent– Placing 2nd stent, when
necessary, is technically more straight forward
Delivery System Advantages– Side Branch wire lumen aids in
alignment at ostium– Side branch “pre-wired”, no need
to re-access through stent– Final Petal size determined by
post dilatation balloon
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Chronic Total Occlusion (CTO)
.
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
History of Interventional Cardiology
19771984
1988
19891997
19992000
20022003
2004
2005
2006
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Why Degradable Stents?
• No late adverse events– Late thrombosis– Hypersensitivity reactions
(chronic inflammation)
– Stent fractures
• Does not restrict arterial remodeling
• Permits non-invasive imaging of artery
• Permits bypass surgery in future
Degradable Stents
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Bioabsorbable Stent Design
.
Core: Polymer A
Undercoat: Polymer B
Topcoat: Polymer B
Drug Layer: Polymer B + Sirolimus Coating Layers
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Multi-Layer, Combination Drug Delivery
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Biodegradable Stents
• Could also be the ideal vehicle for several other applications: non-obstructive vulnerable plaque, gene transfer for infract repair and angiogenesis…..
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
“Biodegradable Stents:
They Do Their Job and Disappear”
- Ron Waksman
Maurice Buchbinder, MD Foundation for Cardiovascular Medicine
Future Opportunities in Interventional Cardiology
Peripheral Vascularization
-Claudication
-Limb Salvage
-Angiogenesis
Structural Heart/ Stroke Prevention
-PFO/ASD Closure
-Left Atrial Appendage closure
- Atrial Fib. Ablation
Cerebral Revascularization
-Carotid Stenting
-Embolic Protection Devices
-Acute Stroke Intervention
Congestive Heart Failure
-Resynchronization Therapy
-Impulse Modulation
-Implantable Pressure Regulators