Maurice Buchbinder, MD Foundation for Cardiovascular Medicine History of Device Development: Past,...

Maurice Buchbinder, MD Foundation for Cardiovascular Medicine

History of Device Development: Past, Present and Future

MY CONFLICTSOF INTEREST ARE

Approaches to Establish Funding

• Angel

• Venture

• Corporate

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

Venture Funding

• Pros

– Deep Pockets

– Professional Expertise

– Extensive Business Network

• Cons

– More Expensive

– Return / Liquidity Requirements

– In-Depth Due Diligence

– Large Opportunities

– Markets > $500 million

– Cash and time intensive

– First-timers unable to assemble a solid executive team together

Corporate Funding

• Pros:

– Less Expensive

– Value Add

– Credibility

• Cons:

– Hidden Agenda/Special Rights

– Questionable Follow-On Dollars

– Exit Strategy Limited

– Business Alignment

– Funding Needs beyond VC’s

– Close to commercialization…looking for a commercial partner

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

ImportantStartup Rule

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

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

• Intense Competition

• Intellectual Property

• Capital Requirement

• Engineering

• Regulatory Environment

Anatomy of a Start-up…

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)

• 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

• Rigor of randomized clinical trials

• Clinical adoption

• Ease of use

• Learning curves

Goals of Startups

Balancing

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

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

History of Interventional Cardiology

19771984

19891997

19992000

20022003

20052006

Coronary Angioplasty (PTCA) Andreas Gruntzig

Directional Coronary Atherectomy (DCA)John Simpson

19771984

Rotational Atherectomy (PTCRA)David Auth

19771984

Coronary StentingJulio Palmaz

19771984

In- Stent Restenosis

Brachytherapy

19771984

19891997

Drug Eluting Stents

Event-Free Survival at Two Years Event-Free Survival at Two Years following procedure following procedure

Freedom from

events (%)

0 120 240 360 480 600 720

Sir-MACE

Ctl-MACE

Days after initial procedure

ARTS I: Three-year outcome after Stenting vs. CABG for the Treatment of Multivessel Disease

900 120 240 360 480 600 720 840 960 1080 1200

Days since randomization

Van Domburg, et al., Circ. 2004:109, 1114-20

19771984

19891997

Percutaneous Treatment of Carotid Artery Stenosis

Percutaneous Aortic Valve TherapyAlain Cribier

Percutaneous Valve Therapy Edwards LifeSciences

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

19771984

19891997

19992000

Percutaneous “Mitral” Valve Repair

• Coronary Sinus Annuloplasty

• Edge-to-Edge Repair

Coronary Sinus AnnuloplastyEdwards LifeScience

HandleHandleSliding Knob

Sliding Knob

Location of Implant

(Internal)

Location of Implant

(Internal)

Distal AnchorDistal AnchorProximal AnchorProximal Anchor

BridgeBridge

Mitral Valve Edge-to-Edge Repair

19771984

19891997

19992000

20022003

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

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

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

Left Atrial Appendage Closure

19771984

19891997

19992000

20022003

The Next Frontier in Coronary Stenting

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

MultipleLayers

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

Chronic Total Occlusion (CTO)

19771984

19891997

19992000

20022003

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

Bioabsorbable Stent Design

Core: Polymer A

Undercoat: Polymer B

Topcoat: Polymer B

Drug Layer: Polymer B + Sirolimus Coating Layers

Multi-Layer, Combination Drug Delivery

Biodegradable Stents

• Could also be the ideal vehicle for several other applications: non-obstructive vulnerable plaque, gene transfer for infract repair and angiogenesis…..

“Biodegradable Stents:

They Do Their Job and Disappear”

- Ron Waksman

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

Maurice Buchbinder, MD Foundation for Cardiovascular Medicine History of Device Development: Past,...

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