Next GenerationCardiac Assist Devices

Society for Medical Innovation and Technology11-14 May 2006

Pebble Beach, Monterey, CA, USA

presented to

Jeffrey L. Helfer

- Overview -

2 •

Heart Failure…Our Focus

Each year, about 1 million people die from HF in the U.S.

To achieve a significant improvement in outcome requires a paradigm shift in treatment methods

There are many medical approaches for treating heart failure – all of which have serious limitations!

• Conventional emergency resuscitation• Traditional drug therapy• Ventricular Assist Devices (VADs)• Intra-aortic balloon pumps (IABP)• Transplant and Total artificial heart

3 •

The Paradigm Shift

A safer and more effective treatment that addresses both short term support and recovery:

• Short-term support, e.g. minimize ischemic damage

• Longer-term support (when necessary) to enable recovery of the heart and (ultimately) removal of the device/therapy

A therapy that is also;

• Cost effective (total procedure cost)

• Broadly available - not just at specialized cardiac centers

• Reimbursable under existing guidelines

• Permits effective delivery of multiple therapeutic agents

4 •

The Product

How it Works (Gen-1 Product)

• Polymer cup that slips over the heart

• Installed via a small chest incision.

• Attached to and driven by a small external pump

• Sustains natural pulsatile flow

This technology has already saved human lives

Approach: Utilize the best blood pump ever developed – the native human heart!

5 •

Unique Product Capabilities

1. No contact with circulating blood (Avoids clotting and stroke, bleeding, and infection)

2. Systolic and diastolic support to both ventricles (Treats many types of heart failure)

3. Enhanced myocardial perfusion (Minimizes ischemic injury)

4. Normal pulsatile flow (More effective reperfusion)

5. Supports all sizes of hearts in many acute and chronic diseases

6. Rapid, technically simple installation and removal (Available at virtually all hospitals)

7. A “healing environment” that includes means to deliver multiple therapies directly to the heart

6 •

Clinical and Pre-clinical Results

1. Supported 45-year old for 2 days following massive myocardial infarction with no damage to the heart.

2. Supported 71-year old for 2 days following heart surgery with no damage to the heart or by-pass grafts.

3. Supported 56-year old for 2-1/2 days as bridge to successful transplantation with no damage to native heart.

4. Supported 18-year old for 7-1/2 days until heart healed from a viral myocarditis with no damage to the heart.

5. Supported 44-year old for 84 days with normal neurologic function with no damage to the heart.

In addition to human studies, over 700 animal experiments have been conducted to develop and patent the means to safely and effectively support human hearts while simultaneously providing a wide array of additional operational, diagnostic, and therapeutic capabilities.

7 •

Rapid Myotech Circulatory Support System (CSS) intervention (e.g. post-MI) can limit the extent and degree of ischemia in cardiac tissue and limit infarct size:

• Reduce LV/RV workload so that marginally perfused myocardium can survive

• Enhance cardiac reperfusion

- Increased coronary flow

- Maintain perfusion pressure by preventing shock

- Improved thrombolysis due to enhanced delivery of lysis agents

• Increase blood O2 concentration

- Increasing perfusion volume of the lungs

- Decrease myocardial O2 requirements by cooling the heart

- Summary -

A Rx for Acute Heart Failure

8 •

High potential for recovery of normal cardiac function: - Immediate pumping support

- Offload mechanical stress on the heart the basic mechanism that triggers the complex remodeling cascade

- Adaptive constraint maintains low mechanical stress

- Enhanced drug therapy capability

- Mechanical “training” of a weakened heart

Nearly certain to promote re-remodeling

Treats multiple HF conditions, including diastolic and RV failure

Little potential for short-term or long-term complications.

Full implantability possible

- Summary -

A Rx for Chronic Heart Failure

Manage chronic HF

by better managing acute HF

9 •

- Briefly -

Infarct Expansion in Ventricle

LV Before Infarct LV After Infarct

During acute MI, the initial loss of contractile tissues adversely affects workload and wall stress on the remaining viable myocardium, providing a

“substrate” for progressive ventricular enlargement.

10 •

For each 25-mL increment in

end-systolic volume, the risk

for death increased

exponentially over that of

other survivors of myocardial

infarction with preserved left

ventricular volume.

- Briefly -

Relative Risk for Death in MI Survivors

Factors that influence ventricular remodeling after MI can be modified to improve clinical outcome.

Limiting the extent of ventricular remodeling in asymptomatic patients after MI can be considered as preventive therapy for symptomatic congestive heart failure.

White HD, Norris RM, Brown MA, et al.: Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987, 76: 44–51.

11 •

1. Cardiac-directed

- Delivery of agents directly to the heart

- Local concentrations that cannot be achieved, maintained or tolerated systemically

2. Continuous delivery (optimize pharmacokinetics)

3. Enhanced transfer rates

- “Open channels” to the myocardium

- The normal mechanism for delivering agents/signals to cells

4. Supportive micro-environment (delivery of nutrients)

Drug Delivery Capability

Improved regional effects with less adverse systemic reaction

12 •

Combined Drug-Device Therapies

Near-termApplications

- Anti-arrhythmic drugs

- Membrane stabilizing drugs (e.g. steroids)

- High dose beta blockers

- ACE inhibitors

- Calcium ion antagonists

Intermediate-termApplications

- Para-hormones

- Agents directed against negative aspects of HF o MMP inhibition

o Ischemic damage

o Cell apoptosis

- Calcium sensitizers

- Endothelin receptor agonists

Longer-term Applications/Therapies

- Gene therapy

- Growth factors

- Stem cell therapy

Increased use of existing drugs

Reduced regulatory hurdles for new indications

of existing drugs

Enable adoption of new agents

13 •

The Results

14 •

Anticipated Indications for Use

Acute ResuscitationImportant rapid recovery during cardiac emergencies and maintaining cardiac output for short periods of time. Significantly expanded market segment.

Bridge-to-RecoveryProvides short-term support while the heart heals from moderate injury. A very important and growing market.

Bridge-to-TransplantKeeps patients alive until a new heart is available.

Destination TherapyPermanent support. Huge potential for MYOTECH since other current design VAD problems severely limit usage. Significantly expanded market segment.

Therapeutic RecoveryLonger-term support from serious disease or injury. The potential for many hearts to recover, allowing device removal. A new market segment.

15 •

Appendices

16 •

Current Cardiac Assist Device Technology

BenefitsSystolic support of a single ventricle

Increase coronary perfusion and oxygen delivery via increased systemic pressure

Patient mobility

ProblemsPerforates the heart and great vessels

High risk of patient complications due to clotting and stroke, bleeding, and infection

Average procedure cost: $205,8001

Limited applications at specialized transplant and cardiac centers

[1] Oz. M., Annetine, C., Miller L. et al., Left Ventricular Assist Devices as permanent Heart Failure Therapy: The price of progress, Annals of Surgery. 238(4): 577-83, October 2003.

17 •

Validation of the Cardiac Assist Device Market

Ventricular Assist Devices or “VADs” have already been shown to be superior to medical management for the treatment of heart failure.

REMATCH patient survival data

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60.0%

80.0%

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1 3 5 7 9 11 13 15 17 19 21 2325 2729 31

Month

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rviv

al r

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OMM Patients LVAD Patients

The huge investment in VAD technologies continues to be

a great indication of the potential of this market -

despite serious short term and long term complications,

While the therapeutic benefit of VADs is exciting, complications severely restrict their use