TRYTON EXTENDED ACCESS REGISTRY

The Tryton IDE trial was a randomized (1:1), multi-center, active control,
non-inferiority clinical trial to compare the Tryton stent with drug eluting
stent (DES) to Provisional stent with DES in subjects with bifurcation disease.
The goal was to demonstrate that the Tryton stent is safe and effective for its
intended use. The primary endpoint was Target Vessel Failure (TVF) 9 months
post-procedure. TVF is a composite endpoint consisting of three components:
cardiac death, target vessel myocardial infarction (MI), and target vessel
revascularization (TVR). The powered secondary endpoint was percent diameter
stenosis of the side branch 9 months post-procedure. The trial was the first
randomized trial specifically conducted in the bifurcation disease area. The
trial did not meet its primary endpoint; the TVF rate for the Tryton arm was
17.4% compared to 12.8% for the Provisional arm, non-inferiority p=0.417. There
are two main causes for this. First, upon examining the components, the main
determinant of not meeting non-inferiority was the rate of target vessel MI;
however, the vast majority of these events were clinically silent, transient
elevations in peri-procedural CK-MB enzymes. Second, upon examining the size of
the side branch vessel by the core lab, it was discovered that approximately
60% of treated subjects had a side branch vessel of less than 2.5 mm by QCA
(inclusion criterion 10b, Side branch reference vessel diameter must be >=2.5 mm
to <= 3.5 mm by visual estimate). This was due primarily to participating
investigators inadvertently overestimating the size of the side branch vessel
by greater than the anticipated 10% increase relative to the angiographic core
lab determination. When a subset of subjects with side branch vessel of at
least 2.25 mm (10% less than the 2.5 mm visual estimation inclusion criterion)
was examined, the TVF rate in the Tryton arm was 11.3% relative to 15.6% in the
Provisional arm (the upper 95% confidence limit excludes the prospectively
determined non-inferiority delta chosen for the full cohort). The data suggest
smaller side branches reflect less myocardium at risk and raise the possibility
of clinically silent restenosis, impacting clinically driven TVR rates. In
addition, patients with smaller side branches assigned to the Tryton arm were
subjected to far greater over-stretch, which may lead to increased
peri-procedural CKMB elevation (study defined MI) and restenosis. The powered
secondary endpoint of in-segment % diameter stenosis in the side branch at 9
months was 31.6% for the Tryton stent and 38.6% for the Provisional Control, (p
= 0.002), demonstrating superiority for the Tryton stent in the complete ITT
population, thus meeting the pre-specified powered secondary (efficacy)
endpoint. In a similar analysis of the angiographic cohort of patients with
side branch vessel diameters at least 2.25mm by QCA, the in-segment % diameter
stenosis of the side branch at 9 months was 30.4% for Tryton stents and 40.6%
for Provisional controls (p= 0.004), demonstrating superiority of Tryton for
the pre-specified efficacy endpoint in this subset of patients as well. * A
critical long-term consequence for patients with side branch disease is
restenosis at the ostium, which means the patient has symptoms and may need
re-intervention in the ostium of the side branch. A decrease in % diameter
stenosis in the side branch reduces the likelihood of that which is an
important benefit to the patient. Another potential benefit of Tryton is
maintaining that access to the side branch for future downstream treatment. In
order to confirm the acceptable safety profile of the Tryton Side Branch Stent
as demonstrated in the >=2.25mm SB RVD subset of the primary IDE study, Tryton
will prospectively collect additional clinical data on approximately 133
subjects in the EXTENDED Access Registry. Tryton believes that an open-label
registry approach is appropriate in the Tryton stent setting. While the Tryton
trial did not meet its primary endpoint, due to clinically silent, transient
peri-procedural elevations in CK-MB enzymes, the clinical literature has
debated whether CK-MB enzyme elevations are clinically meaningful, as the
majority of these events were not associated with clinical sequelae. In
addition, the specific threshold for concern has also been debated in the
literature, with values of 3x, 5x, 8x, and even 10x the normal level proposed.
Aside from the transient CK-MB enzymes, the safety profile of the Tryton stent
appears acceptable, with no cardiac death out to 9 months, low stent thrombosis
and low TVR. The TRYTON EXTENDED Access Registry is therefore focused on the
peri-procedural CK-MB elevations and will compare Tryton rates of
peri-procedural events to a performance goal derived from the performance of
the provisional stenting control group from the >=2.25mm SB RVD subset of the
primary IDE study. As well the incidental enrollment of subjects outside of the
>2.5 mm side branch visual RVD intended study population will be monitored.
Changes to the EXTENDED Access Registry protocol are centered around the study
design changes that remove the active control, (randomization) as the registry
is a single arm study with the endpoint focused on Periprocedural Target Vessel
Failure (TVF) of cardiac death and myocardial infarction (Q wave and non Q
wave) at 48hours as a follow-up to the original IDE study. The registry study
will only require 30 day and 1 year telephone follow-up therefore, removes the
need for longer-term follow-up of 6,and 9 months and 2, 3, 4 and 5-year time
points. Additionally, the registry has no angiographic or IVUS interventions as
no sub studies are required. All pre-procedure and post procedure lab testing
and screening remains the same and the Tryton treatment algorithm remain the
same with additional detail in the predilatation steps only. Several changes to
grammar and miscellaneous terminology have been corrected throughout.

To assure the continued safety and effectiveness of the Tryton Side Branch
Stent* with main branch approved DES in the treatment of de novo native
coronary artery bifurcation lesions with side branch diameter ranging from >=2.5
mm to <=3.5 mm and main branch diameter ranging from >=2.5 mm to <=4.0 mm

TRYTON EXTENDED Access is designed to enroll up to 133 subjects treated with
the Tryton Side Branch Stent* with main branch approved DES for treatment of
native coronary artery bifurcation disease.

Treatment with the Tryton Side Branch StentTM plus approved main branch DES

Known risks are associated with balloon inflation and stent implantation,
including death (0.2 - 0.5%), heart attack (4 - 5%), or emergency surgery
(0.5%). Other risks include (but are not limited to): • Cardiac events such as
inadequate or impaired blood flow to the heart causing chest pain or discomfort
(angina or angina symptoms), impaired pumping ability of the heart,
re-narrowing of a treated heart artery, collection of blood around the lining
of the heart, injury or tear in a heart artery, tear or puncture in a heart
wall, weakening and bulging in a heart artery, or an unexpected need for
immediate heart surgery. • Irregularities in the heart rhythm such as very
fast or slow beating of the upper and/or the lower heart chambers, or
disorganized beating of the lower heart chambers. • Stent events such as
failure to place it in the desired spot in the heart artery, clot or
obstruction within the stent, unintended movement of the stent in the heart
artery, losing the stent in the circulation as it is placed, inadequate
expansion or fit of the stent in the heart artery. • Respiratory events such as
impaired ability of the lungs to provide oxygen for body tissues, fluid
build-up in the lungs, or breathing difficulties. • Blood vessel events such as
bleeding or blood collection at catheter entry site/s in groin, high or low
blood pressure, abnormal area or weakness in wall of artery, abnormal
connection between an artery and vein in the groin, injury or tear in artery in
groin leading to the heart, air, tissue debris, or blood clot that moves to
smaller vessels away from the heart and may block flow, spasm in a vessel. •
Brain or nervous system events such as stroke, impaired brain function that
improves over time, nerve injury in brain or in other body parts. • Bleeding
events such as bruising, bleeding from the catheter groin site/s, or bleeding
in other body parts requiring a blood transfusion or other treatment. • Kidney
events such as impaired kidney function or kidney failure. • Allergic or immune
system events such as sensitivities or body reactions to medications given such
as contrast dye, heparin, aspirin, Plavix, drug/polymer in the stent or other
drugs the doctor prescribes for treating the heart artery; or fever or
infection.