TM

Recovering Hearts. Saving Lives.

The Door to Unload (DTU) STEMI Safety & Feasibility Pilot Trial
November 2018

Recovering Hearts. Saving Lives.

 LEGAL DISCLAIMERS
This presentation includes select slides presented by Navin Kapur, MD, executive director of the CardioVascular
Center for Research and Innovation at Tufts Medical Center, at the American Heart Association Scientific Sessions
2018 in Chicago. The complete slide presentation, Door to Unload (DTU) STEMI Safety & Feasibility Pilot Trial, is
available in the Abiomed investor website at http://investors.abiomed.com/events-presentations.
Impella® heart pumps are not FDA approved for use in STEMI patients without cardiogenic shock.
This presentation contains forward-looking statements, including statements regarding development of Abiomed's existing and new products, the Company's progress toward commercial growth, and
future opportunities, the Company’s guidance for future financial performance and expected regulatory approvals. Each forward-looking statement contained in this presentation is subject to risks and
uncertainties that could cause actual results to differ materially from those projected in such statement, including uncertainties associated with development, testing and related regulatory approvals;
the potential for future losses; the impact of complex manufacturing processes and high quality requirements; dependence on limited sources of supply; competition; technological change; government
regulation; third-party reimbursement to the Company’s customers; litigation matters; future capital needs and uncertainty of additional financing, and other risks and challenges detailed in the
Company's filings with the Securities and Exchange Commission, including the most recently filed Annual Report on Form 10-K and Quarterly Report on Form 10-Q. Readers are cautioned not to
place undue reliance on any forward-looking statements, which speak only as of the date of this presentation. The Company undertakes no obligation to publicly release the results of any revisions to
these forward-looking statements that may be made to reflect events or circumstances that occur after the date of this presentation or to reflect the occurrence of unanticipated events, whether as a
result of new information, future events or otherwise, unless otherwise required by law.

U.S. Food and Drug Administration Approvals

• The Impella 2.5 and Impella CP are indicated for providing temporary (< 6 hours) ventricular support during elective or urgent high risk percutaneous coronary interventions (PCI) performed in
hemodynamically stable patients with severe coronary artery disease, when a heart team, including a cardiac surgeon, has determined high risk PCI is the appropriate therapeutic option. Use
of the Impella 2.5 and the Impella CP in these patients may prevent hemodynamic instability which can result from repeat episodes of reversible myocardial ischemia that occur during planned
temporary coronary occlusions and may reduce peri- and post-procedural adverse events.
• The Impella 2.5, Impella CP, Impella 5.0, and Impella LD Catheters, in conjunction with the Automated Impella Controller, are temporary ventricular support devices intended for short term use
(≤4 days for the Impella 2.5 and Impella CP, and ≤6 days for the Impella 5.0 and Impella LD) and indicated for the treatment of ongoing cardiogenic shock that occurs immediately (<48 hours)
following acute myocardial infarction or open heart surgery, or in the setting of cardiomyopathy, including peripartum cardiomyopathy, or myocarditis as a result of isolated left ventricular
failure that is not responsive to optimal medical management and conventional treatment measures.* The intent of the Impella Support Systems therapy is to reduce ventricular work and to
provide the circulatory support necessary to allow heart recovery and early assessment of residual myocardial function.
• The Impella RP® is indicated for providing circulatory assistance for up to 14 days with a body surface area ≥ 1.5 m2 who develop acute right heart failure or decompensation following left
ventricular assist device implantation, myocardial infarction, heart transplant, or open-heart surgery.

For safety information associated with Abiomed’s technologies, visit www.protectedpci.com/hcp/information/isi and www.cardiodenicshock.com/hcp/information/isi.

The ABIOMED logo, ABIOMED, Impella 2.5, Impella CP, Impella RP, Impella 5.0, Impella LD and Symphony are registered trademarks of Abiomed, Inc. in the U.S.A. and
certain foreign countries. Impella ECP, Impella 5.5, Impella BTR, cVAD Registry and Recovering hearts. Saving lives. is a trademark of Abiomed, Inc.

Recovering Hearts. Saving Lives.

 3
Loaded heart during AMI Unloaded heart during AMI

CO CO
LA LA
Stretch Stretch
MAP MAP pVAD Support
LVEDP LVEDP
LVEDV LVEDV
Wall
Wall Stress Stress
MVO2
MVO2 AAR AAR

Cardioprotective Effects of Unloading

Decreased myocardial oxygen consumption
Reduced acute infarct size and subsequent scar size
Activation of cardioprotective signaling (i.e., SDF1a/CXCR4 and RISK pathway)
Hemodynamic stabilization through reperfusion-dependent arrhythmia
Increased cardiac microvascular perfusion into infarct zone
Bridge through reperfusion-induced myocardial stunning
 Preclinical Development of the DTU Concept
2012 2018
TandemHeart Impella CP Impella CP Impella CP Impella CP
Delayed Reperfusion Delayed Reperfusion Cardioprotective Biology Preclinical Pilot DTU-STEMI Pilot Trial
(Circulation 2013) (JACC HF 2015) (JACC 2018) (JACC 2018) (Circulation 2018)

Trans-valvular LV Unloading Limits Myocardial Ischemia and

Promotes a Cardioprotective Shift in Myocardial Biology
Esposito, Zhang, Qiao and Kapur et al JACC 2018 4
The Rationale for the DTU Pilot Before the Pivotal
DTU Pivotal
100
DTU
Infarct Size / Area at Risk (%)

?
Pilot
80

60

40

20

0
Reperfusion 15 min 30 min Unloading After
Alone Reperfusion
Unloading + Delayed
Esposito, Zhang, Qiao and Kapur et al JACC 2018 Reperfusion 5
Door To Unload: STEMI Pilot Trial: Central Hypothesis

Compared to LV unloading and immediate reperfusion,

LV unloading followed by a 30 minute delay to
reperfusion is feasible and safe as defined by:

o Successful enrollment and protocol completion (Feasibility)

o No increase in major adverse cardiovascular or cerebral

events (MACCE Safety)

o No increase in infarct size between groups (Safety)

6
 Results: Procedural Characteristics
Clinical Variable U-IR (n=25) U-DR (n=25)* p-value
LAD Culprit, n (%) 25 (100) 24 (100) NS
Proximal LAD Lesion Location, n (%) 17 (68) 19 (76) NS
Mid LAD Lesion Location, n (%) 8 (32) 5 (21) NS
Successful Impella CP Implant, n (%) 25 (100) 25 (100) NS
Pre-PCI TIMI Flow (After Impella CP Activation) NS
Pre-Intervention TIMI Flow 0-1, n (%) 16 (64) 10 (40) NS
Pre-Intervention TIMI Flow 2-3, n (%) 9 (36) 15 (60) NS
Post-Intervention TIMI Flow NS
Post-Intervention TIMI Flow 3, n (%) 25 (100) 24 (100) NS

* 1 patient had no coronary obstruction LAD = Left anterior descending artery

TIMI = Thrombolysis In Myocardial Infaction 7
Results: Successful enrollment & protocol completion
Zero Bailout PCI in the U-DR Group
Unload to Balloon Time (Minutes)

45
U-DR
40
U-IR
35
30 minutes of
30 LV Unloading
25
20
15
10
5
0
Enrolled Patients
8
 DTU-STEMI Results: 3-5 Day CMR Parameters
Infarct Size vs Myocardial Salvage Microvascular
Total LV Mass (%) Index (%) Obstruction (%)
40 80 10
35 70 9
8
30 60
7
25 50 6
20 40 5
15 30 4
3
10 20
2
5 10 1
0 0 0
U-IR U-DR CRISP U-IR U-DR CRISP U-IR U-DR CRISP
AMI AMI AMI

Unloading and delaying reperfusion for 30 minutes did

not increase infarct size 9
 DTU-STEMI Results: Exploratory Subgroup Analysis
Infarct Size / Total LV Mass (%) Infarct Size / Area at Risk (%)
40 100
*
30 80

60 15
20
19 16
40
10
20

0 0
Total STE>4 STE>5 STE>6 Total STE>4 STE>5 STE>6

U-DR U-IR

10
 What did we learn from this Pilot Study?
• The Door-To-Unload in STEMI Pilot Trial demonstrates for the first time
that LV unloading using the Impella CP device with a 30-minute delay
before reperfusion is safe and feasible within a relatively short DTB
Time.

• No prohibitive safety signals that would preclude proceeding to a larger

pivotal study of LV unloading and delaying reperfusion for 30 minutes
were identified.

• Compared to LV unloading and immediate reperfusion, LV unloading and

delaying reperfusion for 30 minutes does not increase infarct size.

• Among patients with sum STE>6mm, infarct size normalized to the area
at risk was significantly lower with 30 minutes of LV unloading before
reperfusion compared to LV unloading and immediate reperfusion.
11
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TERMS AND ACRONYMS: STEMI-DTU PRESENTATION

• STEMI – ST segment Elevation Myocardial Infarction – an EKG pattern that identifies acute coronary occlusion, sometimes referred to as a tombstone pattern
• U-IR – Unloading with immediate reperfusion - Impella placed for ventricular unloading in the setting of STEMI care followed immediately by PPCI
• U-DR – Unloading with delayed reperfusion - Impella placed for ventricular unloading in the setting of STEMI care followed by a longer period of unloading before PPCI (in STEMI DTU
duration was prespecified as 30 minutes)
• Primary PCI or PPCI – A coronary interventional procedure usually with coronary stenting (PCI) performed in the setting of a STEMI
• Unloading – Reduction of mechanical power expenditure (PVA x HR)1 of the ventricle to minimize myocardial oxygen consumption (MVO2) and reduce hemodynamic forces that lead to
ventricular remodeling and, in MI, to reduce infarct size
• MACCE – Major adverse cardiac and cerebral events – (a composite endpoint of death, MI, stroke or repeat revascularization)
• Infarct Size /Total LV Mass (%) – An imaging evaluation usually with CMR to assess the % of the entire heart which has sustained an infarction – larger infarct % correlates with greater
post MI sequela
• Infarct Size / Area at Risk (%) – An imaging evaluation usually with CMR to assess the % of the portion of the heart that was ischemic or in jeopardy which has sustained an infarction -
larger infarct % correlates with greater post MI sequela
• Myocardial Salvage Index (%) (MSI) – A calculated assessment of the amount of heart salvaged – calculated as 1- Infarct Size/ Area at risk – a greater MSI correlates with greater
amount of infarct area that was rescued from infarction by the intervention
• Microvascular Obstruction (%) – Or no-reflow phenomenon is an established complication of coronary reperfusion therapy for acute myocardial infarction; recognized as a poor
prognostic indicator and marker of subsequent adverse LV remodeling, evaluation by CMR is particularly useful in
• STE or ∑STE – Sum score of ST segment elevation – a measurement made by adding the maximal ST segment elevation in mm on each of the 12 ECG leads to assess the extent of
myocardium in jeopardy
• CMR – Cardiac magnetic resonance imaging also Cardiac MR or Cardiac MRI

• TIMI Flow – A scoring system from 0 – 3 of the coronary flow rates estimated visually on angiography developed by investigators at Thrombolysis in Myocardial Infarction Study Group.
TIMI 0 flow (no perfusion) refers to the absence of any antegrade flow beyond a coronary occlusion. TIMI 1 flow (penetration without perfusion) is faint antegrade coronary flow beyond
the occlusion, with incomplete filling of the distal coronary bed. TIMI 2 flow (partial reperfusion) is delayed or sluggish antegrade flow with complete filling of the distal territory. TIMI 3 is
normal flow which fills the distal coronary bed completely
• LVEF – Left ventricular ejection fraction – the amount of volume of blood ejected from the heart each beat expressed as a percent of the diastolic volume
• LVEDP – Left ventricular end diastolic pressure in mmHg
• MAP – Mean arterial pressure in mmHg
• CRISP-AMI – A study evaluating use of Intra-aortic balloon pump (IABP) placed before reperfusion in Anterior STEMI – results failed to show a benefit compared to PPCI alone with a
trend toward larger infarcts with IABP – published in JAMA. 2011;306(12):1329-1337