#### 2 Summary of Safety and Effectiveness 

#### 2.1 Summary of Safety and Effectiveness

+------------+---------------------------------------------------------+
| #          | > The Summary of Safety and Effectiveness (SS&E) is     |
| #### Summa | > based upon information available at the time of this  |
| ry of Safe | > submission.                                           |
| ty and Eff | >                                                       |
| ectiveness | > Included in the SS&E are:                             |
|            |                                                         |
|            | 1.  General Information                                 |
|            |                                                         |
|            | 2.  Indications for Use                                 |
|            |                                                         |
|            | 3.  Contraindications                                   |
|            |                                                         |
|            | 4.  Warnings                                            |
|            |                                                         |
|            | 5.  Precautions                                         |
|            |                                                         |
|            | 6.  Device Description                                  |
|            |                                                         |
|            | 7.  Alternative Practices and Procedures                |
|            |                                                         |
|            | 8.  Marketing History                                   |
|            |                                                         |
|            | 9.  Adverse Events                                      |
|            |                                                         |
|            | 10. Summary of Studies                                  |
|            |                                                         |
|            | -   Non-Clinical Studies                                |
|            |                                                         |
|            | ```{=html}                                              |
|            | <!-- -->                                                |
|            | ```                                                     |
|            | -   Summary of Clinical Investigations                  |
|            |                                                         |
|            | 11. Conclusions Drawn from Studies                      |
|            |                                                         |
|            | 12. Panel Recommendation                                |
|            |                                                         |
|            | 13. CDRH Decision                                       |
|            |                                                         |
|            | 14. Approval Specifications                             |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ##### 1.   |                                                         |
|  General I |                                                         |
| nformation |                                                         |
+------------+---------------------------------------------------------+

+---------------------+------------------------------------------------+
| Device Generic Name | Drug Eluting Stent                             |
+---------------------+------------------------------------------------+
| Device Trade Name   | CYPHER^TM^ Sirolimus-eluting Stent mounted on  |
|                     | either RAPTOR^TM^ Over-the-Wire or             |
|                     | RAPTORRAIL^TM^ Rapid Exchange delivery system  |
+---------------------+------------------------------------------------+
| Applicant's Name    | > Cordis Corporation                           |
| and Address         | >                                              |
|                     | > 7 Powder Horn Drive                          |
|                     |                                                |
|                     | Warren, NJ 07059                               |
+---------------------+------------------------------------------------+
| PMA Number          | > P0200026                                     |
+---------------------+------------------------------------------------+
| Date of Panel       | > 10/22/02                                     |
| Recommendation      |                                                |
+---------------------+------------------------------------------------+
| Date of Notice of   | > TBD                                          |
| Approval to         |                                                |
| Applicant           |                                                |
+---------------------+------------------------------------------------+

+------------+---------------------------------------------------------+
| ##### 2.   | > The CYPHER Sirolimus-eluting Stent is indicated for   |
|  Indicatio | > improving coronary luminal diameter in patients with  |
| ns for Use | > symptomatic ischemic disease due to discrete de novo  |
|            | > lesions (30mm in length) in native coronary arteries  |
|            | > with reference vessel diameter of 2.25 mm to 5.00 mm. |
|            | >                                                       |
|            | > The CYPHER^TM^ Sirolimus-eluting Stent has been shown |
|            | > to significantly reduce binary restenosis,            |
|            | > angiographic late loss at 8 months and repeat target  |
|            | > lesion revascularization and target vessel failure at |
|            | > 9 months. Long-term outcome (beyond 24 months) for    |
|            | > this permanent implant is unknown at present.         |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ##### 3    | > CYPHER Sirolimus-eluting Stent is generally           |
| . Contra-i | > contraindicated in the following patient types:       |
| ndications |                                                         |
|            | -   Patients in whom antiplatelet and/or                |
|            |     > anticoagulation therapy is contraindicated.       |
|            |                                                         |
|            | -   Patients judged to have a lesion that prevents      |
|            |     > complete inflation of an angioplasty balloon.     |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ##### 4    | > CYPHER Sirolimus-eluting Stent warnings are as        |
| . Warnings | > follows:                                              |
|            |                                                         |
|            | -   Do not use if the inner package is opened or        |
|            |     > damaged.                                          |
|            |                                                         |
|            | -   The use of this device carries the associated risks |
|            |     > of subacute thrombosis, vascular complications,   |
|            |     > and/or bleeding events.                           |
|            |                                                         |
|            | -   The device should not be used in patients with a    |
|            |     > known hypersensitivity to sirolimus, 316L         |
|            |     > stainless steel, polymethacrylates or polyolefin  |
|            |     > copolymers.                                       |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ##### 5. P | > CYPHER Sirolimus-eluting Stent precautions are as     |
| recautions | > follows:                                              |
|            |                                                         |
|            | -   Only physicians who have received adequate training |
|            |     > should perform implantation of the stent.         |
|            |                                                         |
|            | -   Stent placement should only be performed at         |
|            |     > hospitals where emergency coronary artery bypass  |
|            |     > graft surgery can be readily performed.           |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| #          | -   Subsequent stent blockage may require repeat        |
| #### 5. Pr |     dilatation of the arterial segment containing the   |
| ecautions, |     stent. The long-term outcome following repeat       |
|  continued |     dilatation of endothelialized stents is not well    |
|            |     characterized.                                      |
|            |                                                         |
|            | -   To avoid the possibility of dissimilar metal        |
|            |     corrosion, do not implant stents of different       |
|            |     materials in tandem where overlap or contact is     |
|            |     possible.                                           |
|            |                                                         |
|            | -   Do not use Ethiodol[^1] or Lipiodol contrast media. |
|            |                                                         |
|            | ```{=html}                                              |
|            | <!-- -->                                                |
|            | ```                                                     |
|            | -   Do not expose the delivery system to organic        |
|            |     > solvents, such as alcohol or detergents.          |
+------------+---------------------------------------------------------+
| #####      | > **Stent Handling -- Precautions**                     |
|            |                                                         |
|            | -   **For single use only.** Do not resterilize or      |
|            |     > reuse this device. Note the "Use By" date on the  |
|            |     > product label.                                    |
|            |                                                         |
|            | -   **Do not remove the stent from the delivery balloon |
|            |     > -- removal may damage the stent and/or lead to    |
|            |     > stent embolization.**                             |
|            |                                                         |
|            | -   **Do not induce a vacuum on the delivery system     |
|            |     > prior to reaching the target lesion.**            |
|            |                                                         |
|            | -   Special care must be taken not to handle or in any  |
|            |     > way disrupt the stent on the balloon. This is     |
|            |     > most important while removing the catheter from   |
|            |     > the packaging, placing it over the guidewire, and |
|            |     > advancing it through the large-bore rotating      |
|            |     > hemostatic valve and guiding catheter hub.        |
|            |                                                         |
|            | -   Stent manipulation (e.g., rolling the mounted stent |
|            |     > with your fingers) may loosen the stent from the  |
|            |     > delivery system balloon and cause dislodgment.    |
|            |                                                         |
|            | -   Use only the appropriate balloon inflation media.   |
|            |     > Do not use air or any gaseous medium to inflate   |
|            |     > the balloon as this may cause uneven expansion    |
|            |     > and difficulty in deployment of the stent.        |
+------------+---------------------------------------------------------+
| #####      | > **Stent Placement -- Precautions**                    |
|            |                                                         |
|            | -   **Do not prepare or pre-inflate the balloon prior   |
|            |     > to stent deployment other than as directed. Use   |
|            |     > the balloon purging technique described in the    |
|            |     > Operator's Manual Section included in this        |
|            |     > document.**                                       |
|            |                                                         |
|            | -   Guiding catheters used must have lumen sizes that   |
|            |     > are suitable to accommodate the stent delivery    |
|            |     > system, see Device Description section.           |
|            |                                                         |
|            | -   Do not induce a negative pressure on the delivery   |
|            |     > catheter prior to placement of the stent across   |
|            |     > the lesion. This may cause premature dislodgment  |
|            |     > of the stent from the balloon.                    |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| #          | > **Stent Placement -- Precautions (continued)**        |
| #### 5. Pr |                                                         |
| ecautions, | -   Although the stent delivery balloon catheter is     |
|  continued |     > strong enough to expand the stent without         |
|            |     > rupture, a circumferential tear of the carrier    |
|            |     > balloon distal to the stent and prior to complete |
|            |     > expansion of the stent could cause the balloon to |
|            |     > become tethered to the stent, requiring surgical  |
|            |     > removal. In case of rupture of the balloon, it    |
|            |     > should be withdrawn and, if necessary, a new      |
|            |     > balloon catheter exchanged over the guidewire to  |
|            |     > complete the expansion of the stent.              |
|            |                                                         |
|            | -   Implanting a stent may lead to a dissection of the  |
|            |     > vessel distal and/or proximal to the stented      |
|            |     > portion and may cause acute closure of the vessel |
|            |     > requiring additional intervention (CABG, further  |
|            |     > dilatation, placement of additional stents, or    |
|            |     > other intervention).                              |
|            |                                                         |
|            | -   Do not expand the stent if it is not properly       |
|            |     > positioned in the vessel. (See Stent/System       |
|            |     > Removal -- Precautions.)                          |
|            |                                                         |
|            | -   Placement of the stent has the potential to         |
|            |     > compromise side branch patency.                   |
|            |                                                         |
|            | -   Balloon pressures should be monitored during        |
|            |     > inflation. **Do not exceed rated burst pressure   |
|            |     > as indicated on the product label.** Use of       |
|            |     > pressures higher than those specified on the      |
|            |     > product label may result in a ruptured balloon    |
|            |     > with possible intimal damage and dissection.      |
|            |                                                         |
|            | -   **Do not attempt to pull an unexpanded stent back   |
|            |     > through the guiding catheter, as dislodgment of   |
|            |     > the stent from the balloon may occur. Remove as a |
|            |     > single unit per instructions in Stent/System      |
|            |     > Removal -- Precautions.**                         |
|            |                                                         |
|            | -   Stent retrieval methods (use of additional wires,   |
|            |     > snares and/or forceps) may result in additional   |
|            |     > trauma to the coronary vasculature and/or the     |
|            |     > vascular access site. Complications may include   |
|            |     > bleeding, hematoma, or pseudoaneurysm.            |
|            |                                                         |
|            | -   Ensure full coverage of the entire                  |
|            |     > lesion/dissection site so that there are no gaps  |
|            |     > between stents.                                   |
+------------+---------------------------------------------------------+
| #####      | > **Stent System Removal -- Precautions**               |
|            | >                                                       |
|            | > Should **unusual resistance** be felt **at any time** |
|            | > during either lesion access or removal of the stent   |
|            | > delivery system before stent implantation, the entire |
|            | > system **should be removed as a single unit.**        |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| #          | > **When removing the Delivery System as a single       |
| #### 5. Pr | > unit:**                                               |
| ecautions, |                                                         |
|  continued | -   Do not retract the delivery system into the guiding |
|            |     > catheter.                                         |
|            |                                                         |
|            | -   Advance the guidewire into the coronary anatomy as  |
|            |     > far distally as safely possible.                  |
|            |                                                         |
|            | -   Tighten the rotating hemostatic valve to secure the |
|            |     > stent delivery system to the guiding catheter;    |
|            |     > then remove the guiding catheter and stent        |
|            |     > delivery system as a **single unit.**             |
|            |                                                         |
|            | > Failure to follow these steps or applying excessive   |
|            | > force to the stent delivery system can potentially    |
|            | > result in loss or damage to the stent or stent        |
|            | > delivery system.                                      |
|            | >                                                       |
|            | > If it is necessary to retain the guidewire in         |
|            | > position for subsequent artery/lesion access, leave   |
|            | > the guidewire in place and remove all other system    |
|            | > components.                                           |
+------------+---------------------------------------------------------+
| #####      | > **Post Implant -- Precautions**                       |
|            |                                                         |
|            | -   Great care must be exercised **when crossing a      |
|            |     > newly deployed stent** with an intravascular      |
|            |     > ultrasound (IVUS) catheter, a coronary guidewire  |
|            |     > or balloon catheter to avoid disrupting the stent |
|            |     > geometry.                                         |
|            |                                                         |
|            | -   Do not perform a **magnetic resonance imaging**     |
|            |     > (MRI) scan on a patient after stent implantation  |
|            |     > until the stent has completely endothelialized    |
|            |     > (eight weeks) to minimize the potential for       |
|            |     > migration. The stent may cause artifacts in MRI   |
|            |     > scans due to distortion of the magnetic field.    |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ##### 6    | > The device description is provided in tabular format. |
| . Device D |                                                         |
| escription |                                                         |
+------------+---------------------------------------------------------+

## 

+-----------------+-------------------------+-------------------------+
| Description     | CYPHER                  | CYPHER                  |
|                 | Sirolimus-eluting Stent | Sirolimus-eluting Stent |
|                 | on                      | on                      |
|                 |                         |                         |
|                 | Raptor Over-the-Wire    | RaptorRail Rapid        |
|                 | SDS                     | Exchange SDS            |
+-----------------+-------------------------+-------------------------+
| Available Stent | 8, 13, 18, 23, 28 & 33  | 8, 13, 18, 23, 28 & 33  |
| Lengths,        |                         |                         |
| unexpanded      |                         |                         |
| (mm):           |                         |                         |
+-----------------+-------------------------+-------------------------+
| Available Stent | 2.25, 2.50, 2.75, 3.00, | 2.25, 2.50, 2.75, 3.00, |
| Diameters (mm): | 3.50, 4.00, 4.50 and    | 3.50, 4.00, 4.50 and    |
|                 | 5.00                    | 5.00                    |
+-----------------+-------------------------+-------------------------+
| Stent Material: | Electropolished         |                         |
|                 | stainless steel (316L), |                         |
|                 | laser-cut from seamless |                         |
|                 | tubing in a sinusoidal  |                         |
|                 | pattern coated with a   |                         |
|                 | polymer and Sirolimus   |                         |
|                 | mixture.                |                         |
+-----------------+-------------------------+-------------------------+
| Stent Geometry: | Six circumferential     |                         |
|                 | cells (2.25 mm --       |                         |
|                 | 3.00 mm stents),        |                         |
|                 |                         |                         |
|                 | Seven circumferential   |                         |
|                 | cells (3.50 -- 4.00 mm  |                         |
|                 | stents) or              |                         |
|                 |                         |                         |
|                 | Nine circumferential    |                         |
|                 | cells (4.50 -- 5.00 mm  |                         |
|                 | stents).                |                         |
+-----------------+-------------------------+-------------------------+
| Nominal Stent   | 1 mm or less for stents |                         |
| Foreshortening: | \<4.00mm in diameter or |                         |
|                 | \<18 mm in length       |                         |
|                 |                         |                         |
|                 | 2 mm or less for stents |                         |
|                 | [\>]{.underline} 4.00mm |                         |
|                 | in diameter and         |                         |
|                 | [\>]{.underline} 18mm   |                         |
|                 | in length               |                         |
+-----------------+-------------------------+-------------------------+
| Delivery System | 145 cm                  | 137 cm                  |
| Usable Length:  |                         |                         |
+-----------------+-------------------------+-------------------------+
| Delivery System | Y-Connector (Side arm   | Single access port to   |
| Y-Adapter       | for access to balloon   | the inflation lumen. A  |
| Ports:          | inflation/deflation     | guidewire exit port is  |
|                 | lumen. Straight arm is  | located at 28 cm from   |
|                 | continuous with shaft   | the tip. Designed for   |
|                 | inner lumen -- designed | guidewire guidewire     |
|                 | for guidewire           | [\<]{.underline}        |
|                 | [\<]{.underline}        | 0.014\" (0.36 mm).      |
|                 | 0.014\" (0.36 mm).)     |                         |
+-----------------+-------------------------+-------------------------+
| Stent Delivery  | Single-layer nylon,     |                         |
| Balloon:        | nominally 2 mm longer   |                         |
|                 | than stent. Mounted     |                         |
|                 | stent length and        |                         |
|                 | location is defined by  |                         |
|                 | 2 platinum-iridium      |                         |
|                 | radiopaque marker       |                         |
|                 | bands.                  |                         |
+-----------------+-------------------------+-------------------------+
| Balloon         | Nominal pressure for    |                         |
| Inflation       | diameters 2.25 --       |                         |
| Pressure:       | 4.00mm: 11 atm          |                         |
|                 | (1115kPa)               |                         |
|                 |                         |                         |
|                 | Nominal pressure for    |                         |
|                 | diameters 4.50 --       |                         |
|                 | 5.00mm: 10 atm          |                         |
|                 | (1031kPa)               |                         |
|                 |                         |                         |
|                 | Rated Burst Pressure:   |                         |
|                 | 16 atm (1621 kPa)       |                         |
+-----------------+-------------------------+-------------------------+
| Guiding         | 0.067\" (1.7 mm) for    | [\>]{.underline} 0.056" |
| Catheter Inner  | 2.25 -- 4.00 mm         | (1.4 mm) for 2.25 --    |
| Diameter:       |                         | 3.00 mm                 |
|                 | 0.078" (1.98mm) for     |                         |
|                 | 4.00 -- 5.00 mm         | 0.067\" (1.7 mm) for    |
|                 |                         | 3.50 -- 4.00 mm         |
|                 |                         |                         |
|                 |                         | 0.078\" (1.98mm) for    |
|                 |                         | 4.50 -- 5.00 mm         |
+-----------------+-------------------------+-------------------------+
| Catheter Shaft  | 3.3F proximally,        | 2.3F proximally,        |
| Outer Diameter: |                         |                         |
|                 | 2.7F distally.          | 2.6F distally ( up to   |
|                 |                         | 3.00 mm),               |
|                 |                         |                         |
|                 |                         | 2.9F distally ( \> 3.00 |
|                 |                         | mm).                    |
+-----------------+-------------------------+-------------------------+

+------------+---------------------------------------------------------+
| #####      | > Treatment of patients with coronary artery disease    |
|  7. Altern | > including in-stent restenosis may include exercise,   |
| ative Prac | > diet, drug therapy, percutaneous coronary             |
| tices and  | > interventions and coronary artery bypass surgery.     |
| Procedures |                                                         |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| #####      | > The CYPHER Sirolimus-eluting Stent is approved in     |
| 8. Marketi | > Argentina, Australia, Brazil, Czech & Slovak          |
| ng History | > Republic, the European Community, Hong Kong, India,   |
|            | > Malaysia, Mexico, Pakistan, Peru, Philippines,        |
|            | > Russia, Singapore, South Africa, Thailand, Uruguay,   |
|            | > Venezuela, and Vietnam.                               |
|            | >                                                       |
|            | > As of September 1, 2002, approximately 20,000 CYPHER  |
|            | > Sirolimus-eluting Stents have been distributed        |
|            | > outside the United States. No products have been      |
|            | > withdrawn from the market in any country for any      |
|            | > reason.                                               |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ###        | ### Observed Adverse Events                             |
| ## 9. Adve |                                                         |
| rse Events | A total of 1058 patients were enrolled in a             |
|            | multi-center, double-blind, randomized clinical trial   |
|            | (SIRIUS trial) to evaluate the use of the Cordis CYPHER |
|            | Sirolimus-eluting Stent for treatment of symptomatic    |
|            | ischemic coronary artery disease.                       |
|            |                                                         |
|            | > Additionally, data are provided on the RAVEL trial    |
|            | > (multi-center, double-blind, randomized, 238          |
|            | > patients).                                            |
+------------+---------------------------------------------------------+

+-----------------+-------+-------+-------+-------+-------+-------+
| **Major Adverse |       |       |       |       |       |       |
| Cardiac Events, |       |       |       |       |       |       |
| In-Hospital vs. |       |       |       |       |       |       |
| Ou              |       |       |       |       |       |       |
| t-of-Hospital** |       |       |       |       |       |       |
+-----------------+-------+-------+-------+-------+-------+-------+
|                 | **S   |       |       | **    |       |       |
|                 | IRIUS |       |       | RAVEL |       |       |
|                 | (N=   |       |       | (N    |       |       |
|                 | 1058) |       |       | =238) |       |       |
|                 | to    |       |       | to    |       |       |
|                 | 270   |       |       | 365   |       |       |
|                 | D     |       |       | D     |       |       |
|                 | ays** |       |       | ays** |       |       |
+-----------------+-------+-------+-------+-------+-------+-------+
|                 | **Si  | **BX  | **All | **    | **BX  | **All |
|                 | rolim | V     | Patie | Sirol | V     | Patie |
|                 | us-el | ELOCI | nts** | imus- | ELOCI | nts** |
|                 | uting | TY™** |       | el    | TY™** |       |
|                 | Bx    |       | **(N  | uting |       | *     |
|                 | V     | **(   | =1058 | Bx    | *     | *(N=2 |
|                 | ELOCI | N=525 | Patie | V     | *(N=1 | 38)** |
|                 | TY™** | Patie | nts** | ELOCI | 18)** |       |
|                 |       | nts** |       | TY™** |       |       |
|                 | **(   |       | **N   |       |       |       |
|                 | N=533 | **    | =1064 | *     |       |       |
|                 | Patie | N=531 | Lesio | *(N=1 |       |       |
|                 | nts** | Lesio | ns)** | 20)** |       |       |
|                 |       | ns)** |       |       |       |       |
|                 | **    |       |       |       |       |       |
|                 | N=533 |       |       |       |       |       |
|                 | Lesio |       |       |       |       |       |
|                 | ns)** |       |       |       |       |       |
+-----------------+-------+-------+-------+-------+-------+-------+
| **In-Hospital   | 13    | 8     | 21    | 3     | 3     | 6     |
| Complication**  | (     | (     | (     | (     | (     | (     |
|                 | 2.4%) | 1.5%) | 2.0%) | 2.5%) | 2.5%) | 2.5%) |
| MACE (Death, Q  |       |       |       |       |       |       |
| wave or non-Q   | 1     | 0     | 1     | 0     | 0     | 0     |
| wave MI, Em     | (     | (     | (     | (     | (     | (     |
| CABG, TLR)\*    | 0.2%) | 0.0%) | 0.1%) | 0.0%) | 0.0%) | 0.0%) |
|                 |       |       |       |       |       |       |
| Death           | 12    | 8     | 20    | 3     | 3     | 6     |
|                 | (     | (     | (     | (     | (     | (     |
| Myocardial      | 2.3%) | 1.5%) | 1.9%) | 2.5%) | 2.5%) | 2.5%) |
| Infarction      |       |       |       |       |       |       |
|                 | 2     | 0     | 2     | 2     | 1     | 3     |
| -   Q-wave      | (     | (     | (     | (     | (     | (     |
|                 | 0.4%) | 0.0%) | 0.2%) | 1.7%) | 0.8%) | 1.3%) |
| -   Non Q-wave  |       |       |       |       |       |       |
|                 | 10    | 8     | 18    | 1     | 2     | 3     |
| Emergent CABG   | (     | (     | (     | (     | (     | (     |
|                 | 1.9%) | 1.5%) | 1.7%) | 0.8%) | 1.7%) | 1.3%) |
| Target Lesion   |       |       |       |       |       |       |
| Re              | 0     | 0     | 0     | 0     | 0     | 0     |
| vascularization | (     | (     | (     | (     | (     | (     |
|                 | 0.0%) | 0.0%) | 0.0%) | 0.0%) | 0.0%) | 0.0%) |
| -   TL CABG     |       |       |       |       |       |       |
|                 | 1     | 0     | 1     | 0     | 0     | 0     |
| -   TL RPTCA    | (     | (     | (     | (     | (     | (     |
|                 | 0.2%) | 0.0%) | 0.1%) | 0.0%) | 0.0%) | 0.0%) |
| MACE            |       |       |       |       |       |       |
|                 | 0     | 0     | 0     | 0     | 0     | 0     |
| Target Vessel   | (     | (     | (     | (     | (     | (     |
| Re              | 0.0%) | 0.0%) | 0.0%) | 0.0%) | 0.0%) | 0.0%) |
| vascularization |       |       |       |       |       |       |
| not involving   | 1     | 0     | 1     | 3     | 3     | 6     |
| Target Lesion   | (     | (     | (     | (     | (     | (     |
|                 | 0.2%) | 0.0%) | 0.1%) | 2.5%) | 2.5%) | 2.5%) |
| -               |       |       |       |       |       |       |
|  TV/non-TL-CABG | 0     | 0     | 0     | 1(    | 1(    | 2     |
|                 | (     | (     | (     | 0.8%) | 0.8%) | (     |
| -               | 0.0%) | 0.0%) | 0.0%) |       |       | 0.8%) |
|  TV/non-TL-PTCA |       |       |       | 3     | 3(    |       |
|                 | 0     | 0     | 0     | (     | 2.5%) | 6(    |
| Target Vessel   | (     | (     | (     | 2.5%) |       | 2.5%) |
| Failure         | 0.0%) | 0.0%) | 0.0%) |       | 0     |       |
|                 |       |       |       | 0     | (     | 0     |
| Stent           | 0     | 0     | 0     | (     | 0.0%) | (     |
| Thrombosis      | (     | (     | (     | 0.0%) |       | 0.0%) |
|                 | 0.0%) | 0.0%) | 0.0%) |       | 0     |       |
| Sub-acute       |       |       |       | 0     | (     | 0     |
| Closure         | 13    | 8     | 21    | (     | 0.0%) | (     |
|                 | (     | (     | (     | 0.0%) |       | 0.0%) |
| CVA             | 2.4%) | 1.5%) | 2.0%) |       | 0     |       |
|                 |       |       |       | 0     | (     | 0     |
|                 | 0     | 0     | 0     | (     | 0.0%) | (     |
|                 | (     | (     | (     | 0.0%) |       | 0.0%) |
|                 | 0.0%) | 0.0%) | 0.0%) |       |       |       |
|                 |       |       |       |       |       |       |
|                 | 0     | 0     | 0     |       |       |       |
|                 | (     | (     | (     |       |       |       |
|                 | 0.0%) | 0.0%) | 0.0%) |       |       |       |
|                 |       |       |       |       |       |       |
|                 | 1     | 4     | 5     |       |       |       |
|                 | (     | (     | (     |       |       |       |
|                 | 0.2%) | 0.8%) | 0.5%) |       |       |       |
+-----------------+-------+-------+-------+-------+-------+-------+
| **              | 26    | 93    | 119   | 4     | 20    | 24    |
| Out-of-Hospital | (     | (1    | (1    | (     | (1    | (1    |
| Complications** | 4.9%) | 7.7%) | 1.2%) | 3.3%) | 6.9%) | 0.1%) |
|                 |       |       |       |       |       |       |
| MACE (Death, Q  | 4     | 3     | 7     | 2     | 2     | 4     |
| wave or non-Q   | (     | (     | (     | (     | (     | (     |
| wave MI, Em     | 0.8%) | 0.6%) | 0.7%) | 1.7%) | 1.7%) | 1.7%) |
| CABG, TLR)\*    |       |       |       |       |       |       |
|                 | 3     | 9     | 12    | 1     | 3     | 4     |
| Death           | (     | (     | (     | (     | (     | (     |
|                 | 0.6%) | 1.7%) | 1.1%) | 0.8%) | 2.5%) | 1.7%) |
| Myocardial      |       |       |       |       |       |       |
| Infarction      | 2     | 2     | 4     | 0     | 0     | 0     |
|                 | (     | (     | (     | (     | (     | (     |
| -   Q-wave      | 0.4%) | 0.4%) | 0.4%) | 0.0%) | 0.0%) | 0.0%) |
|                 |       |       |       |       |       |       |
| -   Non Q-wave  | 1     | 7     | 8     | 1     | 3     | 4     |
|                 | (     | (     | (     | (     | (     | (     |
| Emergent CABG   | 0.2%) | 1.3%) | 0.8%) | 0.8%) | 2.5%) | 1.7%) |
|                 |       |       |       |       |       |       |
| Target Lesion   | 0     | 0     | 0     | 1     | 16    | 17    |
| Re              | (     | (     | (     | (     | (1    | (     |
| vascularization | 0.0%) | 0.0%) | 0.0%) | 0.8%) | 3.6%) | 7.1%) |
|                 |       |       |       |       |       |       |
| -   TL CABG     | 21    | 87    | 108   | 1     | 0     | 1     |
|                 | (     | (1    | (1    | (     | (     | (     |
| -   TL RPTCA    | 3.9%) | 6.6%) | 0.2%) | 0.8%) | 0.0%) | 0.4%) |
|                 |       |       |       |       |       |       |
| Target Vessel   | 3     | 8     | 11    | 0     | 16    | 16    |
| Re              | (     | (     | (     | (     | (1    | (     |
| vascularization | 0.6%) | 1.5%) | 1.0%) | 0.0%) | 3.6%) | 6.7%) |
| not involving   |       |       |       |       |       |       |
| Target Lesion   | 19    | 83    | 102   | 0     | 1     | 1     |
|                 | (     | (1    | (     | (     | (     | (     |
| -               | 3.6%) | 5.8%) | 9.6%) | 0.0%) | 0.8%) | 0.4%) |
|  TV/non-TL-CABG |       |       |       |       |       |       |
|                 | 17    | 25    | 42    | 2     | 21    | 23    |
| -               | (     | (     | (     | (     | (1    | (     |
|  TV/non-TL-PTCA | 3.2%) | 4.8%) | 4.0%) | 1.7%) | 7.8%) | 9.7%) |
|                 |       |       |       |       |       |       |
| Target Vessel   | 3     | 7     | 10    | 0     | 0     | 0     |
| Failure         | (     | (     | (     | (     | (     | (     |
| (Primary        | 0.6%) | 1.3%) | 0.9%) | 0.0%) | 0.0%) | 0.0%) |
| Endpoint\*)     |       |       |       |       |       |       |
|                 | 15    | 19    | 34    | 0     | 0     | 0     |
| Stent           | (     | (     | (     | (     | (     | (     |
| Thrombosis      | 2.8%) | 3.6%) | 3.2%) | 0.0%) | 0.0%) | 0.0%) |
|                 |       |       |       |       |       |       |
| Sub-acute       | 34    | 103   | 137   | 0     | 0     | 0     |
| Closure         | (     | (1    | (1    | (     | (     | (     |
|                 | 6.4%) | 9.6%) | 2.9%) | 0.0%) | 0.0%) | 0.0%) |
| Late Thrombosis |       |       |       |       |       |       |
|                 | 1     | 1     | 2     | 0     | 0     | 0     |
| CVA             | (     | (     | (     | (     | (     | (     |
|                 | 0.2%) | 0.2%) | 0.2%) | 0.0%) | 0.0%) | 0.0%) |
|                 |       |       |       |       |       |       |
|                 | 1     | 0     | 1     |       |       |       |
|                 | (     | (     | (     |       |       |       |
|                 | 0.2%) | 0.0%) | 0.1%) |       |       |       |
|                 |       |       |       |       |       |       |
|                 | 1     | 3     | 4     |       |       |       |
|                 | (     | (     | (     |       |       |       |
|                 | 0.2%) | 0.6%) | 0.4%) |       |       |       |
|                 |       |       |       |       |       |       |
|                 | 4     | 5     | 9     |       |       |       |
|                 | (     | (     | (     |       |       |       |
|                 | 0.8%) | 1.0%) | 0.9%) |       |       |       |
+-----------------+-------+-------+-------+-------+-------+-------+
| CI --           |       |       |       |       |       |       |
| Confidence      |       |       |       |       |       |       |
| Interval        |       |       |       |       |       |       |
|                 |       |       |       |       |       |       |
| Difference =    |       |       |       |       |       |       |
| Sirolimus -- Bx |       |       |       |       |       |       |
| VELOCITY™ SE =  |       |       |       |       |       |       |
| sqrt(p1\*q      |       |       |       |       |       |       |
| 1/n1+p2\*q2/n2) |       |       |       |       |       |       |
| CI = Diff       |       |       |       |       |       |       |
| [+]{.underline} |       |       |       |       |       |       |
| 1.96\*SE        |       |       |       |       |       |       |
|                 |       |       |       |       |       |       |
| \* Primary      |       |       |       |       |       |       |
| endpoint for    |       |       |       |       |       |       |
| SIRIUS trial.   |       |       |       |       |       |       |
+-----------------+-------+-------+-------+-------+-------+-------+

+-----------------------------------+-----------------------------------+
| **Table First-in-Man: Clinical    |                                   |
| Events**                          |                                   |
|                                   |                                   |
| **All Patients Treated with Slow  |                                   |
| Release Formulation (N = 30)**    |                                   |
+-----------------------------------+-----------------------------------+
| **Parameters**                    | **Counts (%)**                    |
+-----------------------------------+-----------------------------------+
| In Hospital                       | 2/30 (6.7%)                       |
|                                   |                                   |
| Any MACE^1^                       | 1/30 (3.3%)                       |
|                                   |                                   |
| Death                             | 1/30 (3.3%)                       |
|                                   |                                   |
| MI^2^                             | 0/30 (0.0%)                       |
|                                   |                                   |
| Target Lesion Revascularization   | 0/30 (0.0%)                       |
|                                   |                                   |
| CABG                              | 0/30 (0.0%)                       |
|                                   |                                   |
| PTCA                              | 1/30 (3.3%)                       |
|                                   |                                   |
| Target Vessel Revascularization   |                                   |
| not involving the TL              |                                   |
+-----------------------------------+-----------------------------------+
| Out of Hospital (1 month)         | 0/30 (0.0%)                       |
|                                   |                                   |
| Any MACE^1^                       | 0/30 (0.0%)                       |
|                                   |                                   |
| Death                             | 0/30 (0.0%)                       |
|                                   |                                   |
| MI^2^                             | 0/30 (0.0%)                       |
|                                   |                                   |
| Target Lesion Revascularization   | 0/30 (0.0%)                       |
|                                   |                                   |
| CABG                              | 0/30 (0.0%)                       |
|                                   |                                   |
| PTCA                              | 0/30 (0.0%)                       |
|                                   |                                   |
| Target Vessel Revascularization   |                                   |
| not involving the TL              |                                   |
+-----------------------------------+-----------------------------------+
| Out of Hospital (24 months)       | 1/30 (3.3%)                       |
|                                   |                                   |
| Any MACE^1^                       | 0/30 (0.0%)                       |
|                                   |                                   |
| Death                             | 0/30 (0.0%)                       |
|                                   |                                   |
| MI^2^                             | 1/30 (3.3%)                       |
|                                   |                                   |
| Target Lesion Revascularization   | 0/30 (0.0%)                       |
|                                   |                                   |
| CABG                              | 1/30 (3.3%)                       |
|                                   |                                   |
| PTCA                              | 1/30 (3.3%)                       |
|                                   |                                   |
| Target Vessel Revascularization   |                                   |
| not involving the TL              |                                   |
+-----------------------------------+-----------------------------------+
| Combined (24 months)              | 3/30 (10.0%)                      |
|                                   |                                   |
| Any MACE^1^                       | 1/30 (3.3%)                       |
|                                   |                                   |
| Death                             | 1/30 (3.3%)                       |
|                                   |                                   |
| MI^2^                             | 1/30 (3.3%)                       |
|                                   |                                   |
| Target Lesion Revascularization   | 0/30 (0.0%)                       |
|                                   |                                   |
| CABG                              | 1/30 (3.3%)                       |
|                                   |                                   |
| PTCA                              | 2/30 (6.7%)                       |
|                                   |                                   |
| Target Vessel Revascularization   |                                   |
| not involving the TL              |                                   |
+-----------------------------------+-----------------------------------+
| ^1^ MACE is a composite endpoint  |                                   |
| comprised of deaths, WHO defined  |                                   |
| non-Q wave myocardial infarction, |                                   |
| Q-wave myocardial infarction, or  |                                   |
| target lesion revascularization.  |                                   |
|                                   |                                   |
| ^2^ MI includes WHO defined non-Q |                                   |
| wave myocardial infarction and    |                                   |
| Q-wave myocardial infarction.     |                                   |
+-----------------------------------+-----------------------------------+

+-----------+----------------------------------------------------------+
| #####     | > **Potential Adverse Events**                           |
|           | >                                                        |
| #####     | > Adverse events (in alphabetical order) which may be    |
|           | > associated with the implantation of a coronary stent   |
|           | > in coronary arteries:                                  |
|           | >                                                        |
|           | > > • Allergic reaction                                  |
|           | >                                                        |
|           | > > • Aneurysm                                           |
|           | >                                                        |
|           | > > • Arrhythmias                                        |
|           | >                                                        |
|           | > > • Cardiac tamponade                                  |
|           | >                                                        |
|           | > > • Death                                              |
|           | >                                                        |
|           | > > • Dissection                                         |
|           | >                                                        |
|           | > > • Drug reactions to antiplatelet agents /            |
|           | > > anticoagulation agents / contrast media              |
|           | >                                                        |
|           | > > • Emboli, distal (tissue, air, or thrombotic emboli) |
|           | >                                                        |
|           | > > • Embolization, stent                                |
|           | >                                                        |
|           | > > • Emergency CABG                                     |
|           | >                                                        |
|           | > > • Failure to deliver the stent to the intended site  |
|           | >                                                        |
|           | > > • Fever                                              |
|           | >                                                        |
|           | > > • Fistulization                                      |
|           | >                                                        |
|           | > > • Hemorrhage                                         |
|           | >                                                        |
|           | > > • Hypotension/Hypertension                           |
|           | >                                                        |
|           | > > • Infection and pain at the intended site            |
|           | >                                                        |
|           | > > • Myocardial infarction                              |
|           | >                                                        |
|           | > > • Myocardial ischemia                                |
|           | >                                                        |
|           | > > • Occlusion                                          |
|           | >                                                        |
|           | > > • Prolonged angina                                   |
|           | >                                                        |
|           | > > • Pseudoaneurysm                                     |
|           | >                                                        |
|           | > > • Renal failure                                      |
|           | >                                                        |
|           | > > • Restenosis of stented segment (greater than 50%    |
|           | > > obstruction)                                         |
|           | >                                                        |
|           | > > • Rupture of native and bypass graft                 |
|           | >                                                        |
|           | > > • Stent compression                                  |
|           | >                                                        |
|           | > > • Stent migration                                    |
|           | >                                                        |
|           | > > • Stroke                                             |
|           | >                                                        |
|           | > > • Thrombosis (acute, subacute, or late)              |
|           | >                                                        |
|           | > > • Ventricular fibrillation                           |
|           | >                                                        |
|           | > > • Vessel spasm                                       |
|           | >                                                        |
|           | > > • Vessel perforation                                 |
|           | >                                                        |
|           | > Although systemic effects of sirolimus are not         |
|           | > anticipated, see Physicians' Desk Reference[^2] for    |
|           | > more information concerning potential adverse effects  |
|           | > observed with RAPAMUNE^3^                              |
|           |                                                          |
|           | ^2^ Physicians' Desk Reference, published by Medical     |
|           | Economics Company, Inc. at Montvale, NJ.                 |
|           |                                                          |
|           | > ^3^ Rapamune is a registered trademark of Wyeth        |
|           | > Pharmaceuticals.                                       |
+-----------+----------------------------------------------------------+

+------------+---------------------------------------------------------+
| ####       | > *In vitro* studies were conducted to support the      |
| # 10. Summ | > design and performance for the CYPHER                 |
| ary of Non | > Sirolimus-eluting Stent mounted on either the         |
| -clinical  | > RAPTOR^TM^ Over the Wire (OTW) stent delivery system  |
| Laboratory | > or the RAPTORRAIL^TM^ Rapid Exchange (RX) stent       |
|  Studies - | > delivery system. All testing was performed in         |
| - *In vitr | > accordance with an established protocol. The results  |
| o* Testing | > of the tests revealed that the CYPHER                 |
|            | > Sirolimus-eluting Stent mounted on either the         |
|            | > RAPTOR^TM^ Over the Wire stent delivery system or the |
|            | > RAPTORRAIL^TM^ Rapid Exchange stent delivery system   |
|            | > performed in accordance with established              |
|            | > specifications. The details of the testing are        |
|            | > included in the next section.                         |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ###        | > The following are the details for the *in vitro*      |
| ## Details | > studies conducted to support the design and           |
|  of *in vi | > performance for the CYPHER Sirolimus-eluting Stent    |
| tro* Tests | > mounted on either the RAPTOR^TM^ Over the Wire stent  |
|            | > delivery system or the RAPTORRAIL^TM^ Rapid Exchange  |
|            | > stent delivery system.                                |
+------------+---------------------------------------------------------+

+-------------+------------------------------------------------+-------+
| Test        | Description of Test                            | Re    |
|             |                                                | sults |
+-------------+------------------------------------------------+-------+
| Material    | Material analysis and testing for surface      | Pass  |
| Analysis    | impurities was conducted on the stainless      |       |
|             | steel tubing used to fabricate the stents.     |       |
+-------------+------------------------------------------------+-------+
| Mechanical  | Testing was performed to characterize the      | Pass  |
| Properties  | tensile strength and percent elongation of the |       |
|             | tubing sizes used to fabricate the stents.     |       |
+-------------+------------------------------------------------+-------+
| Corrosion   | Corrosion testing was performed as part of the | Pass  |
|             | fatigue testing on the stents to analyze the   |       |
|             | stent for resistance to corrosion.             |       |
+-------------+------------------------------------------------+-------+
| Stent Free  | The percent change in free or open area and    | Pass  |
| Area &      | stent foreshortening were tested for the       |       |
| dimensional | stents.                                        |       |
| changes     |                                                |       |
| (fore       |                                                |       |
| shortening) |                                                |       |
+-------------+------------------------------------------------+-------+
| Stent       | The stent uniformity testing was conducted on  | Pass  |
| Uniformity  | the stent. It was calculated by subtracting    |       |
| Testing     | the maximum outer diameter measurement of the  |       |
|             | stent from the minimum outer diameter          |       |
|             | measurement of the stent and dividing this     |       |
|             | result by the labeled inner diameter of the    |       |
|             | stent, than multiplying by 100%. This testing  |       |
|             | compares the stent diameter measurements along |       |
|             | the expanded stent length.                     |       |
+-------------+------------------------------------------------+-------+
| Radial      | The radial strength of the stent was tested to | Pass  |
| (hoop)      | ensure it could withstand radial compression.  |       |
| Strength    |                                                |       |
+-------------+------------------------------------------------+-------+
| Fatigue     | An accelerated 10-year fatigue equivalent and  | Pass  |
| Testing     | finite element analysis (FEA) was conducted on |       |
|             | the stent to demonstrate the ability of this   |       |
|             | stent design to maintain structural integrity. |       |
+-------------+------------------------------------------------+-------+
| Stent       | The recoil of the stent was tested to quantify | Pass  |
| Recoil      | the amount of diameter reduction experienced   |       |
|             | after the inflated balloon no longer supports  |       |
|             | the stent. The recoil is calculated by         |       |
|             | subtracting the internal stent diameter after  |       |
|             | balloon deflation from the internal diameter   |       |
|             | on the inflated balloon.                       |       |
|             |                                                |       |
|             | The foreshortening of the stent was tested to  |       |
|             | determine the amount of length reduction the   |       |
|             | stent may experience after it is expanded to   |       |
|             | the rated burst pressure. The foreshortening   |       |
|             | is calculated by subtracting the expanded      |       |
|             | length from the crimped length.                |       |
+-------------+------------------------------------------------+-------+

+-------------+-----------------------------------------------+--------+
| **Test**    | **Description of Test**                       | **Res  |
|             |                                               | ults** |
+=============+===============================================+========+
| Magnetic    | The interaction between the implanted stent   | Pass   |
| Resonance   | and magnetic resonance imaging was evaluated. |        |
| Imaging     |                                               |        |
+-------------+-----------------------------------------------+--------+
| Stent       | The stent expansion testing was conducted on  | Pass   |
| Expansion/  | the stent as part of fatigue testing. The     |        |
|             | test was conducted to determine whether the   |        |
| Crack       | plastic deformation experienced by the stent  |        |
| Initiation  | in going from its initial to final position   |        |
|             | could give rise to crack initiation.          |        |
+-------------+-----------------------------------------------+--------+
| Dimensional | Testing was conducted on the stent, delivery  | Pass   |
| V           | systems and stent/delivery systems to verify  |        |
| erification | they meet their dimensional specifications.   |        |
+-------------+-----------------------------------------------+--------+
| Maximum     | Testing was conducted on the stent/delivery   | Pass   |
| Pressure    | system to determine the burst pressure rating |        |
| (Burst:     | for the delivery systems. The results         |        |
| 95%, 99.9%) | demonstrate statistically with 95% confidence |        |
|             | at least 99.9% of the balloons will not       |        |
|             | experience loss of integrity at or below the  |        |
|             | rated burst pressure.                         |        |
+-------------+-----------------------------------------------+--------+
| Stent       | Testing was performed on the stent/delivery   | Pass   |
| Diameter    | systems to verify that the stent would expand |        |
| vs. Balloon | to within ten percent of the labeled diameter |        |
| Inflation   | in the working pressure range for the         |        |
| Pressure    | delivery system.                              |        |
| (           |                                               |        |
| Compliance) |                                               |        |
+-------------+-----------------------------------------------+--------+
| Bond        | The delivery systems were tested to quantify  | Pass   |
| Strength    | the tensile strength of each catheter joint   |        |
|             | (balloon distal seal/tip, balloon proximal    |        |
|             | seal, hub to catheter shaft bond and          |        |
|             | transition seal) and meets specifications.    |        |
+-------------+-----------------------------------------------+--------+
| Diameter    | The delivery systems were tested to determine | Pass   |
| and Profile | the diameter of the catheter shaft, profile   |        |
|             | of the balloons and inflated diameter of the  |        |
|             | balloons to ensure that the actual diameter   |        |
|             | matches the labeled diameters.                |        |
+-------------+-----------------------------------------------+--------+
| Balloon     | The delivery systems were tested to verify    | Pass   |
| De          | that the balloon could be withdrawn from the  |        |
| flatability | deployed stent within a specified time.       |        |
+-------------+-----------------------------------------------+--------+
| Balloon     | Testing was conducted on the stent/delivery   | Pass   |
| Inflation   | systems to verify the device successfully     |        |
| and         | deploys the stent and that the balloon        |        |
| Deflation   | deflates within a specified time.             |        |
| Time        |                                               |        |
+-------------+-----------------------------------------------+--------+
| Multiple    | Testing was conducted on the stent/delivery   | Pass   |
| Inflations  | systems to determine the ability of the       |        |
|             | delivery system to withstand multiple         |        |
|             | consecutive inflation cycles to the rated     |        |
|             | burst pressure without failure.               |        |
+-------------+-----------------------------------------------+--------+
| Catheter    | Testing was conducted on the stent/delivery   | Pass   |
| Body        | systems to determine the ability of the       |        |
| Maximum     | adhesive bond (hub/shaft), the catheter shaft |        |
| Pressure    | and the transition seal to withstand the      |        |
|             | rated burst pressure.                         |        |
+-------------+-----------------------------------------------+--------+
| Tip Pulling | Testing was conducted on the delivery systems | Pass   |
| and         | to verify that the force required to break    |        |
| Torquing    | the joints and/or materials in the distal end |        |
|             | of the catheter is sufficiently large to      |        |
|             | assure the integrity of the tip during        |        |
|             | pulling, pushing or torquing maneuvers.       |        |
+-------------+-----------------------------------------------+--------+
| Stent       | Testing was conducted on the stent/delivery   | Pass   |
| Retention   | system to determine the tensile force         |        |
|             | required to move the crimped stent away from  |        |
|             | the original crimped position.                |        |
+-------------+-----------------------------------------------+--------+
| Crossing    | Testing was conducted on the stent/delivery   | Pass   |
| Profile     | systems to determine the crossing profile of  |        |
|             | the system.                                   |        |
+-------------+-----------------------------------------------+--------+
| Drug        | Testing was conducted on the stent to verify  | Pass   |
| Content/    | the drug content meets specifications for     |        |
|             | both finished goods release and stability     |        |
| Impurities  | testing.                                      |        |
+-------------+-----------------------------------------------+--------+
| Residual    | Testing was conducted on the stent to verify  | Pass   |
| Solvents    | the residual levels of the solvents used in   |        |
|             | manufacturing meet specifications.            |        |
+-------------+-----------------------------------------------+--------+
| Elution     | Testing was performed on the stent to         | Pass   |
|             | evaluate the release performance of the stent |        |
|             | meets specifications.                         |        |
+-------------+-----------------------------------------------+--------+
| Particulate | Testing was performed to evaluate the coating | Pass   |
| Testing     | for particulates that could be generated by   |        |
|             | the coating or stent deployment.              |        |
+-------------+-----------------------------------------------+--------+
| Polymer     | Testing was conducted to establish the        | Pass   |
| Stability   | 10-year equivalent chemical and mechanical    |        |
|             | stability for CYPHER^TM^ Sirolimus eluting    |        |
|             | Stent coating materials.                      |        |
+-------------+-----------------------------------------------+--------+

+------------+---------------------------------------------------------+
| ##         | > [SDS Components and Stent-contacting Packaging        |
| ### 10. Su | > Materials]{.underline}                                |
| mmary of N | >                                                       |
| on-clinica | > Tests were conducted to support the biocompatibility  |
| l Laborato | > of the SDS systems and stent-contacting packaging     |
| ry Studies | > materials. GLP biocompatibility tests and USP         |
|  -- Biocom | > Enhanced Physiochemical Testing were performed in     |
| patibility | > accordance with ISO 10993-1 on the SDS components and |
|            | > stent-contacting materials. In all of these tests     |
|            | > systems, the materials were non-reactive and produced |
|            | > no greater response than the negative control         |
|            | > employed in each test system.                         |
|            | >                                                       |
|            | > [Polymer and Stent Materials]{.underline}             |
|            | >                                                       |
|            | > Tests were conducted to support the biocompatibility  |
|            | > of the polymer and stent materials. Biocompatibility  |
|            | > testing was conducted in accordance with ISO 10993-1  |
|            | > on ethylene oxide-sterilized, polymer-coated 316L     |
|            | > stainless steel stents or polymer-coated 316L         |
|            | > stainless steel coupons. In addition, thrombogenicity |
|            | > of polymer-coated stents was evaluated through a      |
|            | > series of porcine feasibility implant studies.        |
|            | > Complement activation, leukocyte migration (*in       |
|            | > vitro* and *in vivo*), and muscle implant (3- and     |
|            | > 30-day in rat, 7-and 14-day in rabbit) tests were     |
|            | > also performed on polymer-coated stents. In all of    |
|            | > these tests, the polymer-coated stainless steel was   |
|            | > non-reactive and produced no greater response than    |
|            | > the negative control employed in each test system.    |
+------------+---------------------------------------------------------+
|            | > [CYPHER Sirolimus-eluting Stents]{.underline}         |
|            | >                                                       |
|            | > Tests were conducted to support the biocompatibility  |
|            | > of the sirolimus-eluting coronary stent. The safety   |
|            | > and biocompatibility were assessed in conjunction     |
|            | > with a series of feasibility studies evaluating the   |
|            | > efficacy of sirolimus-eluting stents in porcine,      |
|            | > rabbit and canine models of stent-mediated vascular   |
|            | > injury. The intravascular safety and biocompatibility |
|            | > were also evaluated in a six-month GLP safety study   |
|            | > in pigs. The results of these tests support the       |
|            | > biocompatibility of the sirolimus-eluting stent.      |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ###        | > Shelf life testing was conducted to support a         |
| ## 10. Non | > 12-month shelf life for the CYPHER Sirolimus-eluting  |
| -clinical  | > Stent. In addition, an on-going stability program has |
| Laboratory | > been established that will generate site specific     |
|  Studies - | > stability data.                                       |
| - Shelf Li |                                                         |
| fe Studies |                                                         |
+------------+---------------------------------------------------------+

+------------+---------------------------------------------------------+
| ##### 10.  | > Animal testing was conducted to support the safety    |
|  Non-clini | > and efficacy of the CYPHER Sirolimus-eluting Stent    |
| cal Labora | > mounted on either the RAPTOR^TM^ Over the Wire stent  |
| tory Studi | > delivery system or the RAPTORRAIL^TM^ Rapid Exchange  |
| es -- Anim | > stent delivery system.                                |
| al Studies | >                                                       |
|            | > [GLP Efficacy Studies]{.underline}                    |
|            | >                                                       |
|            | > The ability of sirolimus to reduce intimal            |
|            | > hyperplasia in response to stent implantation was     |
|            | > evaluated in a series of GLP studies in a porcine     |
|            | > model of stent-mediated vascular injury. The studies  |
|            | > included: a six-month biocompatibility study of the   |
|            | > fast-eluting (1X) and slow-eluting (1XTC)             |
|            | > formulations; a 30 day study of the 1XTC formulation  |
|            | > produced under validated clinical manufacturing       |
|            | > conditions; a 90 day re-endothelialization study of   |
|            | > the 1XTC formulation and a 30 day study of the 1XTC   |
|            | > formulation with varying doses of sirolimus.          |
|            | > Collectively, these studies indicate that sirolimus   |
|            | > consistently reduces neointimal hyperplasia following |
|            | > implantation in normal pig coronary arteries or       |
|            | > rabbit iliac arteries and suggest that sirolimus may  |
|            | > be useful in preventing restenosis in humans when     |
|            | > delivered from a polymeric stent coating.             |
|            | >                                                       |
|            | > [*In Vivo* Elution of Sirolimus]{.underline}          |
|            | >                                                       |
|            | > The *in vivo* elution rate of sirolimus from the      |
|            | > polymer formulation was evaluated in several          |
|            | > feasibility studies and in several GLP studies.       |
|            | >                                                       |
|            | > [Feasibility Studies]{.underline}                     |
|            | >                                                       |
|            | > Feasibility studies were conducted with sirolimus     |
|            | > formulated at various concentrations in the polymer   |
|            | > matrix and coated on Cordis coronary stents with or   |
|            | > without a topcoat. These tests served as a basis for  |
|            | > device design and dose selection for our clinical     |
|            | > investigations.                                       |
+------------+---------------------------------------------------------+

+-------------+--------------------------------------------------------+
| ##### 10. S | > Conclusion SIRIUS study:                             |
| ummary of S | >                                                      |
| tudies -- C | > In suitable patients, elective Sirolimus-eluting Bx  |
| linical Inv | > VELOCITY™ stent placement in native coronary *de     |
| estigations | > novo* lesions resulted in significantly lower        |
|             | > angiographic in-stent late loss (0.17 mm vs. 1.00    |
|             | > mm, difference \[95% CI\] -0.83 \[-0.92, -0.74\]) at |
|             | > 8 month follow-up and significantly lower cumulative |
|             | > incidence of the primary endpoint target vessel      |
|             | > failure (TVF) (8.6% vs. 21.0%, difference \[95% CI\] |
|             | > -12.3% \[-16.5%, -8.1%\]) at 270 days post procedure |
|             | > as compared to uncoated Bx VELOCITY™ stent control.  |
|             | > In the Sirolimus arm, 8-month follow-up angiography  |
|             | > revealed: mean in-stent % diameter stenosis was      |
|             | > significantly reduced (10.5% vs. 40.1%, difference   |
|             | > \[95% CI\] -29.6% \[-32.8%, -26.4%\]), in-stent      |
|             | > binary restenosis was significantly reduced (3.2%    |
|             | > vs. 35.4%, difference \[95% CI\] -32.2% \[-37.6%,    |
|             | > -26.9%\]); mean in-lesion % diameter stenosis was    |
|             | > significantly reduced (23.6% vs. 43.3%, difference   |
|             | > \[95% CI\] -19.6% \[-22.5%, -16.7%\]), in-lesion     |
|             | > binary restenosis was significantly reduced (8.9%    |
|             | > vs. 36.3%, difference \[95% CI\] -27.4% \[-33.2%,    |
|             | > -21.5%\]); and there was no evidence of an           |
|             | > edge-effect 5 mm proximal or distal to the stent.    |
|             | > Neointimal hyperplasia (NIH) volume by intravascular |
|             | > ultrasound (IVUS) was also significantly reduced in  |
|             | > the Sirolimus arm (4.1 mm^3^ vs. 56.8 mm^3^,         |
|             | > difference \[95% CI\] -52.7 \[-62.3, -43.1\]). The   |
|             | > reductions described above lead to a highly          |
|             | > significant reduction in incidence of target lesion  |
|             | > revascularization (TLR) at 270 days (4.1 vs. 16.6%,  |
|             | > difference \[95% CI\] -12.4% \[-16.0%, -8.8%\]).     |
|             | >                                                      |
|             | > Conclusion RAVEL study:                              |
|             | >                                                      |
|             | > In suitable patients, elective Sirolimus-eluting Bx  |
|             | > VELOCITY™ stent placement in native coronary *de     |
|             | > novo* lesions resulted in significantly lower        |
|             | > angiographic in-stent late loss (0.0mm vs. 0.8 mm,   |
|             | > difference \[95% CI\] --0.8 \[-0.9, -0.7\]) at 6     |
|             | > month follow-up and significantly lower major        |
|             | > adverse cardiac events (MACE) (5.8% vs. 18.6%,       |
|             | > difference \[95% CI\] --12.8% \[-21.0%, -4.6%\]) at  |
|             | > 365 days post-procedure as compared to uncoated Bx   |
|             | > VELOCITY™ stent control. In the Sirolimus arm,       |
|             | > 6-month follow-up angiography revealed: mean %       |
|             | > diameter stenosis was significantly reduced (14.7    |
|             | > vs. 36.7, difference \[95% CI\] -22.0 \[-25.6,       |
|             | > -18.4\]); there were no instances of binary          |
|             | > restenosis \[[\>]{.underline} 50% diameter           |
|             | > stenosis\] with observed rates of 0.0% vs. 26.6%,    |
|             | > difference \[95% CI\] --26.6% \[-34.9%, -18.3%\]);   |
|             | > and there was no evidence of an edge effect 5 mm     |
|             | > proximal or distal to the stent. Percent volume      |
|             | > obstruction in-stent by intravascular ultrasound     |
|             | > (IVUS) was also significantly reduced in the         |
|             | > Sirolimus arm (1.1 vs. 26.1, difference \[95% CI\]   |
|             | > -25.0 \[-30.3, -19.7\]). The reductions in the       |
|             | > Sirolimus arm led to a highly significant reduction  |
|             | > in incidence of target lesion revascularization      |
|             | > (TLR) at 365 days (0.8% vs. 13.6%, difference \[95%  |
|             | > CI\] -12.7% \[-19.1%, -6.3%\].                       |
+-------------+--------------------------------------------------------+

+-------------+--------------------------------------------------------+
| #####       | > Conclusion First-In-Man Study:                       |
|             | >                                                      |
|             | > In 45 suitable patients, elective sirolimus-eluting  |
|             | > Bx VELOCITY^TM^ stent placement in native coronary   |
|             | > de novo lesions resulted in 100% procedure success.  |
|             | > At 18 to 24 months, the in-stent mean percent        |
|             | > diameter stenosis (%DS) ranged from 1.4% to 13.1%    |
|             | > and mean in-stent late loss ranged from 0.09 mm to   |
|             | > 0.28 mm. Loss of stent volume (obstruction volume)   |
|             | > by neointima ranged from means of 2.27% to 7.53% by  |
|             | > Intravascular Ultrasound (IVUS) at 18 to 24 months.  |
|             | > The overall MACE rate at 24 months was 11.1% (5/45); |
|             | > 1 patient (2.2%) expired at 3 days, 3 patients       |
|             | > (6.7%) had a target lesion revascularization, and 2  |
|             | > patients (4.4%) had a WHO defined non-Q wave         |
|             | > myocardial infarction. Of the patients treated with  |
|             | > the slow release formulation (n=30), the overall     |
|             | > MACE rate at 24 months was 10.0% (3/30); 1 patient   |
|             | > (3.3%) expired at 3 days, 1 patient (3.3%) had a     |
|             | > target lesion revascularization, and 1 patient       |
|             | > (3.3%) had a WHO defined non-Q wave myocardial       |
|             | > infarction.                                          |
+-------------+--------------------------------------------------------+

+------------------------+-------+-------+-------+------+---------+---+
| **Table SIRIUS:        |       |       |       |      |         |   |
| Principal              |       |       |       |      |         |   |
| Effectiveness and      |       |       |       |      |         |   |
| Safety Results (to 270 |       |       |       |      |         |   |
| Days)**                |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| **All Patients         |       |       |       |      |         |   |
| Treated**              |       |       |       |      |         |   |
+------------------------+-------+-------+-------+------+---------+---+
| **Effectiveness        | *     | **Bx  | **All | **   | **Diffe | * |
| Measures**             | *Siro | VELOC | Patie | Rela | rence** | * |
|                        | limus | ITY** | nts** | tive |         | P |
|                        | -elut |       |       | Ri   | **\[95% | - |
|                        | ing** | **(   | **(N  | sk** | CI\]**  | V |
|                        |       | N=525 | =1058 |      |         | a |
|                        | **Bx  | Patie | Patie | **\  |         | l |
|                        | VELOC | nts** | nts** | [95% |         | u |
|                        | ITY** |       |       | CI   |         | e |
|                        |       | **    | **N   | \]** |         | * |
|                        | **(   | N=531 | =1064 |      |         | * |
|                        | N=533 | Lesio | Lesi  |      |         |   |
|                        | Patie | ns)** | ons** |      |         |   |
|                        | nts** |       |       |      |         |   |
|                        |       |       |       |      |         |   |
|                        | **    |       |       |      |         |   |
|                        | N=533 |       |       |      |         |   |
|                        | Lesio |       |       |      |         |   |
|                        | ns)** |       |       |      |         |   |
+------------------------+-------+-------+-------+------+---------+---+
| Lesion Success         | 99.8% | 1     | 99.9% | 1.00 | -0.2%   | 1 |
|                        | (532  | 00.0% | (     | \[0  | \       | . |
| Device Success         | /533) | (531  | 1063/ | .99, | [-0.6%, | 0 |
|                        |       | /531) | 1064) | 1.   | 0.2%\]  | 0 |
| Procedure Success\*    | 97.9% |       |       | 00\] |         | 0 |
|                        | (522  | 98.7% | 98.3% |      | -0.7%   |   |
| Post-Procedure         | /533) | (524  | (     | 0.99 | \       | 0 |
| in-Stent Minimal Lumen |       | /531) | 1046/ | \[0  | [-2.3%, | . |
| Diameter (MLD, in mm)  | 97.4% |       | 1064) | .98, | 0.8%\]  | 4 |
|                        | (519  | 98.5% |       | 1.   |         | 7 |
| Mean [+]{.underline}SD | /533) | (517  | 97.9% | 01\] | -1.1%   | 7 |
| (N)                    |       | /525) | (     |      | \       |   |
|                        | 2.6   |       | 1036/ | 0.99 | [-2.8%, | 0 |
| Range (min, max)       | 7[+]{ | 2.6   | 1058) | \[0  | 0.6%\]  | . |
|                        | .unde | 8[+]{ |       | .97, |         | 2 |
| Post-Procedure         | rline | .unde | 2.6   | 1.   | 0.00    | 8 |
| In-Stent Percent       | }0.40 | rline | 8[+]{ | 01\] | \       | 1 |
| Diameter Stenosis      | (528) | }0.42 | .unde |      | [-0.05, |   |
| (%DS)                  |       | (526) | rline | N/A  | 0.05\]  | 0 |
|                        | (     |       | }0.41 |      |         | . |
| Mean [+]{.underline}SD | 1.71, | (     | (     | N/A  | -0.6%   | 9 |
| (N)                    | 4.22) | 1.41, | 1054) |      | \       | 7 |
|                        |       | 4.25) |       | N/A  | [-1.6%, | 8 |
| Range (min, max)       | 5.4   |       | (     |      | 0.4%\]  |   |
|                        | %[+]{ | 6.    | 1.41, | N/A  |         | 0 |
| Post-Procedure         | .unde | 0%[+] | 4.25) |      | -0.01\  | . |
| in-Lesion Minimal      | rline | {.und |       | N/A  | [-0.07, | 2 |
| Lumen Diameter (MLD,   | }8.2% | erlin | 5.7   |      | 0.04\]  | 2 |
| in mm)                 | (528) | e}7.9 | %[+]{ | N/A  |         | 2 |
|                        |       | (526) | .unde |      | -0.1%   |   |
| Mean [+]{.underline}SD | (-3   |       | rline | N/A  | \       | 0 |
| (N)                    | 4.5%, | (-3   | }8.1% |      | [-1.2%, | . |
|                        | 2     | 0.3%, | (     | N/A  | 1.0%\]  | 6 |
| Range (min, max)       | 8.1%) | 3     | 1054) |      |         | 2 |
|                        |       | 4.7%) |       | N/A  | 0.81    | 7 |
| Post-Procedure         | 2.3   |       | (-3   |      | \[0.71, |   |
| In-Lesion Percent      | 8[+]{ | 2.4   | 4.5%, | N/A  | 0.92\]  | 0 |
| Diameter Stenosis      | .unde | 0[+]{ | 3     |      |         | . |
| (%DS)                  | rline | .unde | 4.7%) | 0.09 | -29.6%  | 7 |
|                        | }0.45 | rline |       | \[0  | \[      | 9 |
| Mean [+]{.underline}SD | (529) | }0.46 | 2.3   | .06, | -32.8%, | 9 |
| (N)                    |       | (526) | 9[+]{ | 0.   | -       |   |
|                        | (     |       | .unde | 14\] | 26.4%\] | \ |
| Range (min, max)       | 0.00, | (     | rline |      |         | < |
|                        | 4.00) | 1.16, | }0.46 | 0.24 | 0.55    | 0 |
| Eight-Month Follow-up  |       | 3.75) | (     | \[0  | \[0.45, | . |
| In-Stent Minimal Lumen | 16.1  |       | 1055) | .18, | 0.65\]  | 0 |
| Diameter (MLD, in mm)  | %[+]{ | 16.2  |       | 0.   |         | 0 |
|                        | .unde | %[+]{ | (     | 34\] | -19.6%  | 1 |
| Mean [+]{.underline}SD | rline | .unde | 0.00, |      | \[      |   |
| (N)                    | }9.7% | rline | 4.00) | N/A  | -22.5%, | \ |
|                        | (529) | }8.5% |       |      | -       | < |
| Range (min, max)       |       | (526) | 16.2  | N/A  | 16.7%\] | 0 |
|                        | (-    |       | %[+]{ |      |         | . |
| Eight-Month Follow-up  | 5.5%, | (-    | .unde | N/A  | -0.83   | 0 |
| In-Stent Percent       | 10    | 2.9%, | rline |      | \       | 0 |
| Diameter Stenosis      | 0.0%) | 4     | }9.1% | N/A  | [-0.92, | 1 |
| (%DS)                  |       | 9.1%) | (     |      | -0.74\] |   |
|                        | 2.5   |       | 1055) | N/A  |         | \ |
| Mean [+]{.underline}SD | 0[+]{ | 1.6   |       |      | -0.57   | < |
| (N)                    | .unde | 8[+]{ | (-    | N/A  | \[-066, | 0 |
|                        | rline | .unde | 5.5%, |      | -0.48\] | . |
| Range (min, max)       | }0.58 | rline | 10    |      |         | 0 |
|                        | (348) | }0.80 | 0.0%) |      | -32.2%  | 0 |
| Eight-Month Follow-up  |       | (353) |       |      | \[      | 1 |
| In-Lesion Minimal      | (     |       | 2.0   |      | -37.6%, |   |
| Lumen Diameter (MLD,   | 0.00, | (     | 9[+]{ |      | -       | \ |
| in mm)                 | 4.05) | 0.00, | .unde |      | 26.9%\] | < |
|                        |       | 3.70) | rline |      |         | 0 |
| Mean [+]{.underline}SD | 10.5% |       | }0.81 |      | -27.4%  | . |
| (N)                    | [+]{. | 40.1% | (701) |      | \[      | 0 |
|                        | under | [+]{. |       |      | -33.2%, | 0 |
| Range (min, max)       | line} | under | (     |      | -       | 1 |
|                        | 16.7% | line} | 0.00, |      | 21.5%\] |   |
| Eight-Month Follow-up  | (348) | 25.3% | 4.05) |      |         | \ |
| In-Lesion Percent      |       | (353) |       |      | 1.6     | < |
| Diameter Stenosis      | (-3   |       | 25.4% |      | \[0.9,  | 0 |
| (%DS)                  | 3.2%, | (-1   | [+]{. |      | 2.2\]   | . |
|                        | 10    | 0.3%, | under |      |         | 0 |
| Mean [+]{.underline}SD | 0.0%) | 10    | line} |      | -52.7   | 0 |
| (N)                    |       | 0.0%) | 26.1% |      | \       | 1 |
|                        | 2.1   |       | (701) |      | [-62.3, |   |
| Range (min, max)       | 5[+]{ | 1.6   |       |      | -43.1\] | \ |
|                        | .unde | 0[+]{ | (-3   |      |         | < |
| Eight-Month Late Loss  | rline | .unde | 3.2%, |      | 12.8%   | 0 |
| In-Stent (mm)          | }0.61 | rline | 10    |      | \[8.7%, | . |
|                        | (349) | }0.72 | 0.0%) |      | 16.9%\] | 0 |
| Mean [+]{.underline}SD |       | (353) |       |      |         | 0 |
| (N)                    | (     |       | 1.8   |      | 12.8%   | 1 |
|                        | 0.00, | (     | 7[+]{ |      | \[8.4%, |   |
| Range (min, max)       | 3.76) | 0.00, | .unde |      | 17.2%\] | \ |
|                        |       | 3.45) | rline |      |         | < |
| Eight-Month Late Loss  | 23.6% |       | }0.72 |      | 12.6%   | 0 |
| In-Lesion (mm)         | [+]{. | 43.3% | (702) |      | \[7.9%, | . |
|                        | under | [+]{. |       |      | 17.3%\] | 0 |
| Mean [+]{.underline}SD | line} | under | (     |      |         | 0 |
| (N)                    | 16.4% | line} | 0.00, |      | 12.0%   | 1 |
|                        | (349) | 22.4% | 3.76) |      | \[7.6%, |   |
| Range (min, max)       |       | (353) |       |      | 16.5%\] | \ |
|                        | (-    |       | 33.5% |      |         | < |
| Eight-Month In-Stent   | 8.3%, | (     | [+]{. |      |         | 0 |
| Binary Restenosis      | 10    | 4.3%, | under |      |         | . |
|                        | 0.0%) | 10    | line} |      |         | 0 |
| Eight-Month In-Lesion  |       | 0.0%) | 22.0% |      |         | 0 |
| Binary Restenosis      | 0.1   |       | (702) |      |         | 1 |
|                        | 7[+]{ | 1.0   |       |      |         |   |
| Eight-Month Minimum    | .unde | 0[+]{ | (-    |      |         | \ |
| Lumen Area (mm^3^)     | rline | .unde | 8.3%, |      |         | < |
|                        | }0.44 | rline | 10    |      |         | 0 |
| Mean [+]{.underline}SD | (346) | }0.70 | 0.0%) |      |         | . |
| (N)                    |       | (350) |       |      |         | 0 |
|                        | (-    |       | 0.5   |      |         | 0 |
| Range (min, max)       | 1.23, | (-    | 9[+]{ |      |         | 1 |
|                        | 2.65) | 0.80, | .unde |      |         |   |
| Eight-Month NIH Volume |       | 3.12) | rline |      |         | \ |
| (mm^3^)                | 0.2   |       | }0.72 |      |         | < |
|                        | 4[+]{ | 0.8   | (696) |      |         | 0 |
| Mean [+]{.underline}SD | .unde | 1[+]{ |       |      |         | . |
| (N)                    | rline | .unde | (-    |      |         | 0 |
|                        | }0.48 | rline | 1.23, |      |         | 0 |
| Range (min, max)       | (347) | }0.67 | 3.12) |      |         | 1 |
|                        |       | (350) |       |      |         |   |
| TLR-Free at 270 days†  | (-    |       | 0.5   |      |         | \ |
|                        | 0.93, | (-    | 2[+]{ |      |         | < |
| TVR-Free at 270 days†  | 2.24) | 0.93, | .unde |      |         | 0 |
|                        |       | 2.78) | rline |      |         | . |
| TVF-Free at 270 days†  | 3.2%  |       | }0.65 |      |         | 0 |
|                        | (11   | 35.4% | (697) |      |         | 0 |
| MACE-Free at 270 days† | /348) | (125  |       |      |         | 1 |
|                        |       | /353) | (-    |      |         |   |
|                        | 8.9%  |       | 0.93, |      |         | \ |
|                        | (31   | 36.3% | 2.78) |      |         | < |
|                        | /349) | (128  |       |      |         | 0 |
|                        |       | /353) | 19.4% |      |         | . |
|                        | 5     |       | (136, |      |         | 0 |
|                        | .4[+] | 3     | 701)  |      |         | 0 |
|                        | {.und | .9[+] |       |      |         | 1 |
|                        | erlin | {.und | 22.6% |      |         |   |
|                        | e}2.1 | erlin | (159  |      |         | \ |
|                        | (99)  | e}1.9 | /702) |      |         | < |
|                        |       | (76)  |       |      |         | 0 |
|                        | (1,   |       | 4     |      |         | . |
|                        | 13)   | (1,   | .7[+] |      |         | 0 |
|                        |       | 11)   | {.und |      |         | 0 |
|                        | 4     |       | erlin |      |         | 1 |
|                        | .1[+] | 56.   | e}2.2 |      |         |   |
|                        | {.und | 8[+]{ | (175) |      |         | \ |
|                        | erlin | .unde |       |      |         | < |
|                        | e}5.9 | rline | (1,   |      |         | 0 |
|                        | (45)  | }31.7 | 13)   |      |         | . |
|                        |       | (42)  |       |      |         | 0 |
|                        | (0,   |       | 29.   |      |         | 0 |
|                        | 21)   | (8,   | 5[+]{ |      |         | 1 |
|                        |       | 124)  | .unde |      |         |   |
|                        | 95.7% |       | rline |      |         |   |
|                        |       | 82.9% | }34.6 |      |         |   |
|                        | 93.6% |       | (87)  |      |         |   |
|                        |       | 80.8% |       |      |         |   |
|                        | 91.1% |       | (0,   |      |         |   |
|                        |       | 78.6% | 124)  |      |         |   |
|                        | 92.7% |       |       |      |         |   |
|                        |       | 80.7% | 89.3% |      |         |   |
|                        |       |       |       |      |         |   |
|                        |       |       | 87.1% |      |         |   |
|                        |       |       |       |      |         |   |
|                        |       |       | 84.9% |      |         |   |
|                        |       |       |       |      |         |   |
|                        |       |       | 86.7% |      |         |   |
+------------------------+-------+-------+-------+------+---------+---+
| **Safety Measures**    |       |       |       |      |         |   |
+------------------------+-------+-------+-------+------+---------+---+
| In-Hospital MACE\*     | 2.4%  | 1.5%  | 2.0%  | 1.60 | 0.9%    | 0 |
|                        | (13   | (8    | (21/  | \[0  | \       | . |
| Out-of-Hospital MACE   | /533) | /525) | 1058) | .67, | [-0.8%, | 3 |
| to 270 days\*          |       |       |       | 3.   | 2.6%\]  | 7 |
|                        | 4.9%  | 17.7% | 11.2% | 80\] |         | 9 |
| MACE to 270 days\*     | (26   | (93   | (119/ |      | -12.8%  |   |
|                        | /533) | /525) | 1058) | 0.28 | \[      | \ |
| TVF to 270 days        |       |       |       | \[0  | -16.6%, | < |
| (Primary Endpoint)\*   | 7.1%  | 18.9% | 12.9% | .19, | -9.1%\] | 0 |
|                        | (38   | (99   | (137/ | 0.   |         | . |
| Stent Thrombosis to 30 | /533) | /525) | 1058) | 40\] | -11.7%  | 0 |
| days                   |       |       |       |      | \[      | 0 |
|                        | 8.6%  | 21.0% | 14.7% | 0.38 | -15.7%, | 1 |
| Late Thrombosis to 270 | (46   | (110  | (156/ | \[0  | -7.7%\] |   |
| days                   | /533) | /525) | 1058) | .27, |         | \ |
|                        |       |       |       | 0.   | -12.3%  | < |
| Subacute Closure       | 0.2%  | 0.2%  | 0.2%  | 53\] | \[      | 0 |
|                        | (1    | (1    | (2/   |      | -16.5%, | . |
| Cerebrovascular        | /533) | /525) | 1058) | 0.41 | -8.1%\] | 0 |
| Accident (CVA) to 270  |       |       |       | \[0  |         | 0 |
| days                   | 0.2%  | 0.6%  | 0.4%  | .30, | 0.0%    | 1 |
|                        | (1    | (3    | (4/   | 0.   | \       |   |
| Major Bleeding         | /533) | /525) | 1058) | 56\] | [-0.5%, | \ |
| Complications          |       |       |       |      | 0.5%\]  | < |
|                        | 0.2%  | 0.0%  | 0.1%  | 0.98 |         | 0 |
| Major (Hemorrhagic)    | (1    | (0    | (1/   | \[0  | -0.4%   | . |
| Vascular Complications | /533) | /525) | 1058) | .06, | \       | 0 |
|                        |       |       |       | 15.  | [-1.1%, | 0 |
| Hematological          | 0.9%  | 1.7%  | 1.3%  | 73\] | 0.4%\]  | 1 |
| Dyscrasia to 270 days  | (5    | (9    | (14/  |      |         |   |
|                        | /533) | /525) | 1058) | 0.33 | 0.2%    | 1 |
|                        |       |       |       | \[0  | \       | . |
|                        | 3.4%  | 3.4%  | 3.4%  | .04, | [-0.2%, | 0 |
|                        | (18   | (18   | (36/  | 2.   | 0.6%\]  | 0 |
|                        | /533) | /525) | 1058) | 81\] |         | 0 |
|                        |       |       |       |      | -0.8%   |   |
|                        | 1.5%  | 2.3%  | 1.9%  | >    | \       | 0 |
|                        | (8    | (12   | (20/  |  \-- | [-2.2%, | . |
|                        | /533) | /525) | 1058) | > \[ | 0.6%\]  | 3 |
|                        |       |       |       | \--, |         | 7 |
|                        | 0.8%  | 0.8%  | 0.8%  | > \  | -0.1%   | 1 |
|                        | (4    | 4     | (8/   | --\] | \       |   |
|                        | /533) | /525) | 1058) |      | [-2.2%, | 1 |
|                        |       |       |       | 0.55 | 2.1%\]  | . |
|                        |       |       |       | \[0  |         | 0 |
|                        |       |       |       | .19, | -0.8%   | 0 |
|                        |       |       |       | 1.   | \       | 0 |
|                        |       |       |       | 60\] | [-2.4%, |   |
|                        |       |       |       |      | 0.9%\]  | 0 |
|                        |       |       |       | 0.98 |         | . |
|                        |       |       |       | \[0  | 0.0%    | 2 |
|                        |       |       |       | .52, | \       | 9 |
|                        |       |       |       | 1.   | [-1.1%, | 5 |
|                        |       |       |       | 87\] | 1.0%\]  |   |
|                        |       |       |       |      |         | 1 |
|                        |       |       |       | 0.66 |         | . |
|                        |       |       |       | \[0  |         | 0 |
|                        |       |       |       | .27, |         | 0 |
|                        |       |       |       | 1.   |         | 0 |
|                        |       |       |       | 58\] |         |   |
|                        |       |       |       |      |         | 0 |
|                        |       |       |       | 0.98 |         | . |
|                        |       |       |       | \[0  |         | 3 |
|                        |       |       |       | .25, |         | 7 |
|                        |       |       |       | 3.   |         | 6 |
|                        |       |       |       | 92\] |         |   |
|                        |       |       |       |      |         | 1 |
|                        |       |       |       |      |         | . |
|                        |       |       |       |      |         | 0 |
|                        |       |       |       |      |         | 0 |
|                        |       |       |       |      |         | 0 |
+------------------------+-------+-------+-------+------+---------+---+
| Numbers are %          |       |       |       |      |         |   |
| (counts/sample size)   |       |       |       |      |         |   |
| or Mean                |       |       |       |      |         |   |
| [+]{.underline} SD. CI |       |       |       |      |         |   |
| = Confidence Interval  |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Relative Risk =        |       |       |       |      |         |   |
| Sirolimus/Bx VELOCITY  |       |       |       |      |         |   |
| SE = Calculated in SAS |       |       |       |      |         |   |
| Using Mantel-Haenszel  |       |       |       |      |         |   |
| Method                 |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| CI =                   |       |       |       |      |         |   |
| RR\*exp([+             |       |       |       |      |         |   |
| ]{.underline}1.96\*SE) |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| All event data were    |       |       |       |      |         |   |
| adjudicated by the     |       |       |       |      |         |   |
| independent Clinical   |       |       |       |      |         |   |
| Events Committee       |       |       |       |      |         |   |
| (CEC). All QCA data    |       |       |       |      |         |   |
| were assessed by the   |       |       |       |      |         |   |
| Angiographic Core      |       |       |       |      |         |   |
| Laboratory. All IVUS   |       |       |       |      |         |   |
| data were assessed by  |       |       |       |      |         |   |
| the IVUS Core          |       |       |       |      |         |   |
| Laboratory.            |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Lesion Success (Lesion |       |       |       |      |         |   |
| Based) -- The          |       |       |       |      |         |   |
| attainment of \<50%    |       |       |       |      |         |   |
| residual stenosis (by  |       |       |       |      |         |   |
| QCA), using any        |       |       |       |      |         |   |
| percutaneous method    |       |       |       |      |         |   |
| (if QCA was not        |       |       |       |      |         |   |
| available, the visual  |       |       |       |      |         |   |
| estimate of diameter   |       |       |       |      |         |   |
| stenosis was used).    |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Device Success (Lesion |       |       |       |      |         |   |
| Based) -- Achievement  |       |       |       |      |         |   |
| of a final residual    |       |       |       |      |         |   |
| diameter stenosis of   |       |       |       |      |         |   |
| \<50% (by QCA) using   |       |       |       |      |         |   |
| the assigned device    |       |       |       |      |         |   |
| only (if QCA was not   |       |       |       |      |         |   |
| available, the visual  |       |       |       |      |         |   |
| estimate of diameter   |       |       |       |      |         |   |
| stenosis was used).    |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Procedure Success      |       |       |       |      |         |   |
| (Lesion Based) --      |       |       |       |      |         |   |
| Achievement of a final |       |       |       |      |         |   |
| diameter stenosis of   |       |       |       |      |         |   |
| \<50% (by QCA) using   |       |       |       |      |         |   |
| any percutaneous       |       |       |       |      |         |   |
| method, without the    |       |       |       |      |         |   |
| occurrence of death, Q |       |       |       |      |         |   |
| wave or WHO-defined    |       |       |       |      |         |   |
| non-Q wave MI, or      |       |       |       |      |         |   |
| repeat                 |       |       |       |      |         |   |
| revascularization of   |       |       |       |      |         |   |
| the target lesion      |       |       |       |      |         |   |
| during the hospital    |       |       |       |      |         |   |
| stay (if QCA was not   |       |       |       |      |         |   |
| available, the visual  |       |       |       |      |         |   |
| estimate of diameter   |       |       |       |      |         |   |
| stenosis was used).    |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| In-Lesion (Within      |       |       |       |      |         |   |
| Segment) -- In-lesion  |       |       |       |      |         |   |
| measurement was        |       |       |       |      |         |   |
| defined as the         |       |       |       |      |         |   |
| measurements either    |       |       |       |      |         |   |
| within the stented     |       |       |       |      |         |   |
| segment or within 5 mm |       |       |       |      |         |   |
| proximal or distal to  |       |       |       |      |         |   |
| the stent edges.       |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| In-Stent (Within       |       |       |       |      |         |   |
| Stent) -- In-stent     |       |       |       |      |         |   |
| measurement was        |       |       |       |      |         |   |
| defined as the         |       |       |       |      |         |   |
| measurement within the |       |       |       |      |         |   |
| stented segment.       |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| NIH = Neointimal       |       |       |       |      |         |   |
| Hyperplasia            |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| \*Events rates in this |       |       |       |      |         |   |
| table included the WHO |       |       |       |      |         |   |
| definition of non-W    |       |       |       |      |         |   |
| wave MI.               |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| WHO-defined non-Q wave |       |       |       |      |         |   |
| MI -- Elevation of     |       |       |       |      |         |   |
| post-procedure CK      |       |       |       |      |         |   |
| levels to \>2 times    |       |       |       |      |         |   |
| normal with elevated   |       |       |       |      |         |   |
| CKMB in the absence of |       |       |       |      |         |   |
| new pathological Q     |       |       |       |      |         |   |
| waves.                 |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| † The following        |       |       |       |      |         |   |
| survival estimates are |       |       |       |      |         |   |
| by Kaplan-Meier        |       |       |       |      |         |   |
| Methods with standard  |       |       |       |      |         |   |
| error estimates by     |       |       |       |      |         |   |
| Peto formula:          |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| TLR-Free -- No target  |       |       |       |      |         |   |
| lesion                 |       |       |       |      |         |   |
| revascularization      |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| TVR-Free -- No target  |       |       |       |      |         |   |
| vessel                 |       |       |       |      |         |   |
| revascularization.     |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| TVF-Free -- No cardiac |       |       |       |      |         |   |
| death, Q-wave or       |       |       |       |      |         |   |
| WHO-defined non-Q wave |       |       |       |      |         |   |
| MI, or target vessel   |       |       |       |      |         |   |
| revascularization.     |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| MACE-Free -- No death, |       |       |       |      |         |   |
| Q wave or WHO-defined  |       |       |       |      |         |   |
| non-Q wave MI, or      |       |       |       |      |         |   |
| target vessel          |       |       |       |      |         |   |
| revascularization.     |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Major Adverse Cardiac  |       |       |       |      |         |   |
| Events (MACE) -- A     |       |       |       |      |         |   |
| composite endpoint     |       |       |       |      |         |   |
| comprised of death, Q  |       |       |       |      |         |   |
| wave or WHO-defined    |       |       |       |      |         |   |
| non-Q wave MI, or      |       |       |       |      |         |   |
| target vessel          |       |       |       |      |         |   |
| revascularization.     |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Target Vessel Failure  |       |       |       |      |         |   |
| (TVF) -- A composite   |       |       |       |      |         |   |
| endpoint comprised of  |       |       |       |      |         |   |
| cardiac death, Q-wave  |       |       |       |      |         |   |
| or WHO-defined non-Q   |       |       |       |      |         |   |
| wave MI, or target     |       |       |       |      |         |   |
| vessel                 |       |       |       |      |         |   |
| revascularization      |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Stent Thrombosis -- A  |       |       |       |      |         |   |
| 30-day endpoint        |       |       |       |      |         |   |
| including subacute     |       |       |       |      |         |   |
| closure or unexplained |       |       |       |      |         |   |
| death or Q wave MI.    |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Late Thrombosis --     |       |       |       |      |         |   |
| Myocardial infarction  |       |       |       |      |         |   |
| occurring \>30 days    |       |       |       |      |         |   |
| after the index        |       |       |       |      |         |   |
| procedure and          |       |       |       |      |         |   |
| attributable to the    |       |       |       |      |         |   |
| target vessel with     |       |       |       |      |         |   |
| angiographic           |       |       |       |      |         |   |
| documentation          |       |       |       |      |         |   |
| (site-reported or by   |       |       |       |      |         |   |
| QCA) of thrombus or    |       |       |       |      |         |   |
| total occlusion at the |       |       |       |      |         |   |
| target site and        |       |       |       |      |         |   |
| freedom from an        |       |       |       |      |         |   |
| interim                |       |       |       |      |         |   |
| revascularization of   |       |       |       |      |         |   |
| the target vessel.     |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Subacute (Subarupt)    |       |       |       |      |         |   |
| Closure -- Abrupt      |       |       |       |      |         |   |
| closure that occurred  |       |       |       |      |         |   |
| after the index        |       |       |       |      |         |   |
| procedure was          |       |       |       |      |         |   |
| completed (and the     |       |       |       |      |         |   |
| patient left the       |       |       |       |      |         |   |
| catheterization        |       |       |       |      |         |   |
| laboratory) and before |       |       |       |      |         |   |
| the 30-day follow-up   |       |       |       |      |         |   |
| endpoint.              |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Cerebrovascular        |       |       |       |      |         |   |
| Accident (CVA) --      |       |       |       |      |         |   |
| Sudden onset of        |       |       |       |      |         |   |
| vertigo, numbness,     |       |       |       |      |         |   |
| aphasia, or dysarthria |       |       |       |      |         |   |
| due to vascular        |       |       |       |      |         |   |
| lesions of the brain   |       |       |       |      |         |   |
| such as hemorrhage,    |       |       |       |      |         |   |
| embolism, thrombosis,  |       |       |       |      |         |   |
| or rupturing aneurysm, |       |       |       |      |         |   |
| that persisted \>24    |       |       |       |      |         |   |
| hours.                 |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Major Bleeding         |       |       |       |      |         |   |
| Complications --       |       |       |       |      |         |   |
| Bleeding requiring     |       |       |       |      |         |   |
| transfusions or        |       |       |       |      |         |   |
| associated with        |       |       |       |      |         |   |
| hemoglobin drop \>5g.  |       |       |       |      |         |   |
|                        |       |       |       |      |         |   |
| Major (hemorrhagic)    |       |       |       |      |         |   |
| Vascular Complication  |       |       |       |      |         |   |
| -- Hematoma at access  |       |       |       |      |         |   |
| site \>5 cm; false     |       |       |       |      |         |   |
| aneurysm; AV fistula;  |       |       |       |      |         |   |
| retroperitoneal bleed; |       |       |       |      |         |   |
| peripheral             |       |       |       |      |         |   |
| ischemia/nerve injury; |       |       |       |      |         |   |
| any transfusion        |       |       |       |      |         |   |
| required was reported  |       |       |       |      |         |   |
| as a vascular          |       |       |       |      |         |   |
| complication unless    |       |       |       |      |         |   |
| clinical indication    |       |       |       |      |         |   |
| clearly other than     |       |       |       |      |         |   |
| catheterization        |       |       |       |      |         |   |
| complication; and      |       |       |       |      |         |   |
| vascular surgical      |       |       |       |      |         |   |
| repair.                |       |       |       |      |         |   |
+------------------------+-------+-------+-------+------+---------+---+

+------------------+-------------+------------+---------+-------------+
| **Table RAVEL:   |             |            |         |             |
| Principal        |             |            |         |             |
| Effectiveness    |             |            |         |             |
| and Safety       |             |            |         |             |
| Results (to 365  |             |            |         |             |
| days)**          |             |            |         |             |
|                  |             |            |         |             |
| **All Patients   |             |            |         |             |
| Treated          |             |            |         |             |
| (N=238)**        |             |            |         |             |
+------------------+-------------+------------+---------+-------------+
| **Effectiveness  | **Sirolimu  | **Bx       | **R     | **D         |
| Measures**       | s-Eluting** | V          | elative | ifference** |
|                  |             | ELOCITY™** | Risk**  |             |
|                  | **Bx        |            |         | **\[95%     |
|                  | VELOCITY™** | *          | **\[95% | CI\]**      |
|                  |             | *(N=118)** | CI\]**  |             |
|                  | **(N=120)** |            |         |             |
+------------------+-------------+------------+---------+-------------+
| Procedure        | 96.7%       | 93.1%      | 1.04    | 3.6%        |
| Success          | (116/120)   | (108/116)  | \[0.98, | \[-2.1%,    |
|                  |             |            | 1.10\]  | 9.2%\]      |
| Binary           | 0.0%        | 26.6%      |         |             |
| Restenosis Rate  | (0/109)     | (29/109)   | N/A     | -26.6%      |
|                  |             |            |         | \[-34.9%,   |
| MLD              | 2.43        | 2.41       | N/A     | -18.3%\]    |
| Post-procedure   | ­[+]{        | [+]{.      |         |             |
| in-stent (mm)    | .underline} | underline} | N/A     | 0.01        |
|                  | 0.41        | 0.40       |         | \[-0.09,    |
| mean             | (N=120)     | (N=116)    | N/A     | 0.12\]      |
| [+]{.underline}  |             |            |         |             |
| SD (n)           | (1.53,      | (1.29,     | N/A     | -2.1        |
|                  | 3.49)       | 3.30)      |         | \[-3.7,     |
| (min., max.)     |             |            | N/A     | -0.5\]      |
|                  | 11.9        | 14.0       |         |             |
| \% DS            | [+]{        | [+]{.      |         | 0.78        |
| Post-procedure   | .underline} | underline} |         | \[0.64,     |
| in stent (mm)    | 5.9 (N=120) | 6.8        |         | 0.93\]      |
|                  |             | (N=116)    |         |             |
| mean             | (-0.5,      |            |         | -22.0       |
| [+]{.underline}  | 27.5)       | (-4.0,     |         | \[-25.6,    |
| SD (n)           |             | 45.0)      |         | -18.4\]     |
|                  | 2.42        |            |         |             |
| (min., max.)     | [+]{        | 1.64       |         | -0.81       |
|                  | .underline} | [+]{.      |         | \[-0.93,    |
| MLD 6 month f/u  | 0.49        | underline} |         | -0.70\]     |
| in-stent (mm)    | (N=109)     | 0.59       |         |             |
|                  |             | (N=109)    |         | -25.0       |
| mean             | (1.55,      |            |         | \[-30.3,    |
| [+]{.underline}  | 3.53)       | (0.00,     |         | -19.7\]     |
| SD (n)           |             | 2.85)      |         |             |
|                  | 14.7        |            |         |             |
| (min., max.)     | [+]{        | 36.7       |         |             |
|                  | .underline} | [+]{.      |         |             |
| %DS 6 month f/u  | 6.9 (N=109) | underline} |         |             |
| in-stent (mm)    |             | 18.0       |         |             |
|                  | (-0.5,      | (N=108)    |         |             |
| mean             | 34.7)       |            |         |             |
| [+]{.underline}  |             | (4.0,      |         |             |
| SD (n)           | -0.01       | 100.0)     |         |             |
|                  | [+]{        |            |         |             |
| (min., max.)     | .underline} | 0.80       |         |             |
|                  | 0.33        | [+]{.      |         |             |
| Late loss 6      | (N=109)     | underline} |         |             |
| month f/u (mm)   |             | 0.53       |         |             |
|                  | (-1.14,     | (N=108)    |         |             |
| mean             | 0.94)       |            |         |             |
| [+]{.underline}  |             | (-0.40,    |         |             |
| SD (n)           | 1.1         | 2.58)      |         |             |
|                  | [+]{        |            |         |             |
| (min., max.)     | .underline} | 26.1       |         |             |
|                  | 2.5 (N=56)  | [+]{.      |         |             |
| Volume           |             | underline} |         |             |
| obstruction      | (0.0, 16.9) | 20.2       |         |             |
| in-stent (mm)    |             | (N=54)     |         |             |
|                  | 99.2%       |            |         |             |
| mean             | \[97.1%,    | (0.0,      |         |             |
| [+]{.underline}  | 100.0%\]    | 77.3)      |         |             |
| SD (n)           |             |            |         |             |
|                  | 98.3%       | 86.0%      |         |             |
| (min., max.)     | \[95.4%,    | \[77.5%,   |         |             |
|                  | 100.0%\]    | 94.6%\]    |         |             |
| TLR-free at 365  |             |            |         |             |
| days\*           | 95.8%       | 84.3%      |         |             |
|                  | \[91.2%,    | \[75.3%,   |         |             |
| TVR-free at 365  | 100.0%\]    | 93.3%\]    |         |             |
| days\*           |             |            |         |             |
|                  | 94.1%       | 80.3%      |         |             |
| TVF-free at 365  | \[88.7%,    | \[70.7%,   |         |             |
| days\*           | 99.4%\]     | 90.0%\]    |         |             |
|                  |             |            |         |             |
| MACE-free at 365 |             | 81.2%      |         |             |
| days\*           |             | \[71.7%,   |         |             |
|                  |             | 90.7%\]    |         |             |
+------------------+-------------+------------+---------+-------------+
| **Safety         | 2.5%        | 2.5%       | 0.98    | 0.0%        |
| Measures**       | (3/120)     | 93/118)    | \[0.20, | \[-4.0%,    |
|                  |             |            | 4.77\]  | 3.9%\]      |
| MACE in-hospital | 3.3%        | 16.9%      |         |             |
|                  | (4/120)     | (20/118)   | 0.20    | -13.6%      |
| MACE             |             |            | \[0.07, | \[-21.1%,   |
| out-hospital at  | 5.8%        | 18.6%      | 0.56\]  | -6.1%\]     |
| 365 days         | (7/120)     | (22/118)   |         |             |
|                  |             |            | 0.31    | -12.8%      |
| MACE at 365 days | 0.0%        | 0.0%       | \[0.14, | \[-21.0%,   |
|                  | (0/120)     | (0/118)    | 0.70\]  | -4.6%       |
| Sub-acute        |             |            |         |             |
| occlusion        | 0.0%        | 0.0%       | 0.33    | 0.0%        |
|                  | (0/120)     | (0/118)    | \[0.03, | \[\--,\--\] |
| Stent thrombosis |             |            | 3.11\]  |             |
|                  | 0.0%        | 0.0%       |         | 0.0%        |
| Late thrombosis  | (0/120)     | (0/118)    |         | \[\--,\--\] |
|                  |             |            |         |             |
| CVA at 365 days  | 0.0%        | 0.0%       |         | 0.0%        |
|                  | (0/120)     | (0/118)    |         | \[\--,\--\] |
| Major Bleeding   |             |            |         |             |
| at 365 days      | 0.8%        | 2.5%       |         | 0.0%        |
|                  | (1/120)     | (3/118)    |         | \[\--,\--\] |
|                  |             |            |         |             |
|                  |             |            |         | -1.7%       |
|                  |             |            |         | \[-5.0%,    |
|                  |             |            |         | 1.6%\]      |
+------------------+-------------+------------+---------+-------------+
| Numbers are %    |             |            |         |             |
| (                |             |            |         |             |
| counts/available |             |            |         |             |
| field sample     |             |            |         |             |
| size) or mean    |             |            |         |             |
| [+]{.underline}  |             |            |         |             |
| 1 standard       |             |            |         |             |
| deviation.       |             |            |         |             |
|                  |             |            |         |             |
| CI -- confidence |             |            |         |             |
| interval CI --   |             |            |         |             |
| Diff             |             |            |         |             |
| [+]{.underline}  |             |            |         |             |
| 1.96 \* SE       |             |            |         |             |
|                  |             |            |         |             |
| SD -- Standard   |             |            |         |             |
| deviation SE --  |             |            |         |             |
| sqrt             |             |            |         |             |
| (p1\*q1/n1 +     |             |            |         |             |
| p2\*q2/n2)       |             |            |         |             |
|                  |             |            |         |             |
| Procedure        |             |            |         |             |
| success --       |             |            |         |             |
| Successful       |             |            |         |             |
| implantation of  |             |            |         |             |
| study device,    |             |            |         |             |
| attainment of \< |             |            |         |             |
| 30% diameter     |             |            |         |             |
| stenosis by      |             |            |         |             |
| angiographic     |             |            |         |             |
| core lab.        |             |            |         |             |
| Quantitative     |             |            |         |             |
|                  |             |            |         |             |
| Coronary         |             |            |         |             |
| Angiography      |             |            |         |             |
| (QCA)            |             |            |         |             |
| determination,   |             |            |         |             |
| and freedom from |             |            |         |             |
| in-hospital      |             |            |         |             |
| MACE.            |             |            |         |             |
|                  |             |            |         |             |
| %DS -- Percent   |             |            |         |             |
| diameter         |             |            |         |             |
| stenosis --      |             |            |         |             |
| value calculated |             |            |         |             |
| as               |             |            |         |             |
| 100\*(1-MLD/RVD) |             |            |         |             |
| using the mean   |             |            |         |             |
| values from two  |             |            |         |             |
| orthogonal views |             |            |         |             |
| (when possible)  |             |            |         |             |
| by Quantitative  |             |            |         |             |
| Coronary         |             |            |         |             |
| Angiography      |             |            |         |             |
| (QCA). A 100% DS |             |            |         |             |
| was imputed for  |             |            |         |             |
| total occlusions |             |            |         |             |
| if no RVD values |             |            |         |             |
| were             |             |            |         |             |
| avai             |             |            |         |             |
| lable.Restenosis |             |            |         |             |
| Rate -- Percent  |             |            |         |             |
| lesions with a   |             |            |         |             |
| follow-up        |             |            |         |             |
| percent diameter |             |            |         |             |
| stenosis is      |             |            |         |             |
| [\>]{.underline} |             |            |         |             |
| 50%.             |             |            |         |             |
|                  |             |            |         |             |
| \* The following |             |            |         |             |
| survival         |             |            |         |             |
| estimates are by |             |            |         |             |
| Kaplan-Meier     |             |            |         |             |
| methods.         |             |            |         |             |
| Standard Error   |             |            |         |             |
| estimates from   |             |            |         |             |
| Peto formula.    |             |            |         |             |
|                  |             |            |         |             |
| TLR--free -- No  |             |            |         |             |
| target lesion    |             |            |         |             |
| r                |             |            |         |             |
| evascularization |             |            |         |             |
|                  |             |            |         |             |
| TVR-free -- No   |             |            |         |             |
| target vessel    |             |            |         |             |
| r                |             |            |         |             |
| evascularization |             |            |         |             |
|                  |             |            |         |             |
| TVF-free -- No   |             |            |         |             |
| cardiac death,   |             |            |         |             |
| target vessel    |             |            |         |             |
| related          |             |            |         |             |
| myocardial       |             |            |         |             |
| infarction or    |             |            |         |             |
| target vessel    |             |            |         |             |
| r                |             |            |         |             |
| evascularization |             |            |         |             |
|                  |             |            |         |             |
| MACE-free -- No  |             |            |         |             |
| death,           |             |            |         |             |
| myocardial       |             |            |         |             |
| infarction,      |             |            |         |             |
| target lesion    |             |            |         |             |
| CABG or target   |             |            |         |             |
| lesion Re-PTCA   |             |            |         |             |
|                  |             |            |         |             |
| In hospital MACE |             |            |         |             |
| -- Death,        |             |            |         |             |
| myocardial       |             |            |         |             |
| infarction       |             |            |         |             |
| (Q-wave and non  |             |            |         |             |
| Q-wave), target  |             |            |         |             |
| lesion CABG or   |             |            |         |             |
| target lesion    |             |            |         |             |
| r                |             |            |         |             |
| evascularization |             |            |         |             |
| prior to         |             |            |         |             |
|                  |             |            |         |             |
| > hospital       |             |            |         |             |
| > discharge as   |             |            |         |             |
| > determined by  |             |            |         |             |
| > the            |             |            |         |             |
| > independent    |             |            |         |             |
| > Clinical       |             |            |         |             |
| > Events         |             |            |         |             |
| > Committee.     |             |            |         |             |
|                  |             |            |         |             |
| Out-hospital     |             |            |         |             |
| MACE - Death,    |             |            |         |             |
| myocardial       |             |            |         |             |
| infarction       |             |            |         |             |
| (Q-wave and non  |             |            |         |             |
| Q-wave), target  |             |            |         |             |
| lesion CABG or   |             |            |         |             |
| target lesion    |             |            |         |             |
| r                |             |            |         |             |
| evascularization |             |            |         |             |
| after            |             |            |         |             |
|                  |             |            |         |             |
| > hospital       |             |            |         |             |
| > discharge      |             |            |         |             |
| > through the    |             |            |         |             |
| > 180 days       |             |            |         |             |
| > contact as     |             |            |         |             |
| > determined by  |             |            |         |             |
| > the            |             |            |         |             |
| > independent    |             |            |         |             |
| > Clinical       |             |            |         |             |
| > Events         |             |            |         |             |
| > Committee.     |             |            |         |             |
|                  |             |            |         |             |
| Late loss --     |             |            |         |             |
| Difference MLD   |             |            |         |             |
| after device --  |             |            |         |             |
| MLD at           |             |            |         |             |
| follow-up.       |             |            |         |             |
|                  |             |            |         |             |
| MACE -- Major    |             |            |         |             |
| Adverse Cardiac  |             |            |         |             |
| Events: death,   |             |            |         |             |
| myocardial       |             |            |         |             |
| infarction       |             |            |         |             |
| (Q-wave and non  |             |            |         |             |
| Q-wave), target  |             |            |         |             |
| lesion CABG or   |             |            |         |             |
| target lesion    |             |            |         |             |
|                  |             |            |         |             |
| > re             |             |            |         |             |
| vascularization. |             |            |         |             |
|                  |             |            |         |             |
| Major Bleeding   |             |            |         |             |
| Events -- Any    |             |            |         |             |
| intracranial     |             |            |         |             |
| bleeding,        |             |            |         |             |
| cardiac          |             |            |         |             |
| tamponade,       |             |            |         |             |
| bleeding events  |             |            |         |             |
| associated with  |             |            |         |             |
| a decrease in    |             |            |         |             |
| hemoglobin \>    |             |            |         |             |
| 5.0 g/dL,        |             |            |         |             |
|                  |             |            |         |             |
| > transfusion or |             |            |         |             |
| > surgical       |             |            |         |             |
| > repair.        |             |            |         |             |
|                  |             |            |         |             |
| MI -- Myocardial |             |            |         |             |
| Infarction:      |             |            |         |             |
| Necrosis of the  |             |            |         |             |
| myocardium, as a |             |            |         |             |
| result of        |             |            |         |             |
| interruption of  |             |            |         |             |
| the blood supply |             |            |         |             |
| to the area as   |             |            |         |             |
| in coronary      |             |            |         |             |
| thrombosis. For  |             |            |         |             |
| this study,      |             |            |         |             |
| myocardial       |             |            |         |             |
| infarction was   |             |            |         |             |
| categorized in   |             |            |         |             |
| Q-wave and       |             |            |         |             |
| non-Q-wave.      |             |            |         |             |
|                  |             |            |         |             |
| Sub-acute        |             |            |         |             |
| occlusion -- New |             |            |         |             |
| reduced (TIMI 0  |             |            |         |             |
| or 1) flow at    |             |            |         |             |
| the target       |             |            |         |             |
| vessel as a      |             |            |         |             |
| result of        |             |            |         |             |
| mechanical       |             |            |         |             |
| obstruction,     |             |            |         |             |
| such as          |             |            |         |             |
| dissection or    |             |            |         |             |
| luminal          |             |            |         |             |
|                  |             |            |         |             |
| > thrombus,      |             |            |         |             |
| > occurring      |             |            |         |             |
| > after          |             |            |         |             |
| > completion of  |             |            |         |             |
| > the index      |             |            |         |             |
| > procedure but  |             |            |         |             |
| > within thirty  |             |            |         |             |
| > days of stent  |             |            |         |             |
| > deployment.    |             |            |         |             |
|                  |             |            |         |             |
| Stent Thrombosis |             |            |         |             |
| -- Complete      |             |            |         |             |
| thirty-day       |             |            |         |             |
| ischemic         |             |            |         |             |
| endpoint         |             |            |         |             |
| including death, |             |            |         |             |
| Q-wave MI or     |             |            |         |             |
| subabrupt        |             |            |         |             |
| closure          |             |            |         |             |
| requiring        |             |            |         |             |
| re               |             |            |         |             |
| vascularization. |             |            |         |             |
|                  |             |            |         |             |
| Late Thrombosis  |             |            |         |             |
| -- Late          |             |            |         |             |
| Thrombosis was   |             |            |         |             |
| myocardial       |             |            |         |             |
| infarction       |             |            |         |             |
| attributable to  |             |            |         |             |
| the target       |             |            |         |             |
| vessel with      |             |            |         |             |
| angiographic     |             |            |         |             |
| documentation    |             |            |         |             |
| (site-reported   |             |            |         |             |
| or               |             |            |         |             |
|                  |             |            |         |             |
| > by QCA) of     |             |            |         |             |
| > thrombus or    |             |            |         |             |
| > total          |             |            |         |             |
| > occlusion at   |             |            |         |             |
| > the target     |             |            |         |             |
| > site \> 30     |             |            |         |             |
| > days after the |             |            |         |             |
| > index          |             |            |         |             |
| > procedure in   |             |            |         |             |
| > the absence of |             |            |         |             |
| > an intervening |             |            |         |             |
| > r              |             |            |         |             |
| evascularization |             |            |         |             |
| >                |             |            |         |             |
| > of the target  |             |            |         |             |
| > vessel.        |             |            |         |             |
|                  |             |            |         |             |
| MLD -- mean      |             |            |         |             |
| minimal luminal  |             |            |         |             |
| diameter (mm)    |             |            |         |             |
| from two         |             |            |         |             |
| orthogonal views |             |            |         |             |
| using            |             |            |         |             |
| Quantitative     |             |            |         |             |
| Coronary         |             |            |         |             |
| Angiography      |             |            |         |             |
| (QCA).           |             |            |         |             |
|                  |             |            |         |             |
| RVD -- Reference |             |            |         |             |
| Vessel Diameter: |             |            |         |             |
| Average of       |             |            |         |             |
| normal segments  |             |            |         |             |
| proximal and     |             |            |         |             |
| distal to the    |             |            |         |             |
| target lesion    |             |            |         |             |
| from two         |             |            |         |             |
| orthogonal views |             |            |         |             |
| (when            |             |            |         |             |
|                  |             |            |         |             |
| available) using |             |            |         |             |
| QCA              |             |            |         |             |
|                  |             |            |         |             |
| TL -- target     |             |            |         |             |
| lesion TV --     |             |            |         |             |
| target vessel    |             |            |         |             |
+------------------+-------------+------------+---------+-------------+

+-------------------------------------------+--------------------------+
| **Table First-in-Man: Effectiveness and   |                          |
| Safety Results**                          |                          |
|                                           |                          |
| **All Patients Treated with Slow Release  |                          |
| Formulation (N=30 Patients, 30 Lesions)** |                          |
+-------------------------------------------+--------------------------+
| **Effectiveness Measures**                | **Sirolimus-Eluting Bx   |
|                                           | VELOCITY**               |
|                                           |                          |
|                                           | **(N=30 Patients, N=30   |
|                                           | Lesion)**                |
+-------------------------------------------+--------------------------+
| Procedure Success (QCA)                   | 100.0% (30/30)           |
|                                           |                          |
| 18-month In-Stent % DS -- Slow Release    | 3.2% [+]{.underline}     |
| Netherlands                               | 13.1% (10)               |
|                                           |                          |
| Mean [+]{.underline} SD (N)               | 1.4% [+]{.underline}     |
|                                           | 5.9% (14)                |
| 24-month In-Stent %DS -- Slow Release     |                          |
| Brazil                                    | 0.20 [+]{.underline}     |
|                                           | 0.24 (10)                |
| Mean [+]{.underline} SD (N)               |                          |
|                                           | -0.09 [+]{.underline}    |
| 18-Month In-Stent Late Loss (mm) -- Slow  | 0.24 (14)                |
| Release Netherlands                       |                          |
|                                           | 2.27% [+]{.underline}    |
| Mean [+]{.underline} SD (N)               | 2.09% (7)                |
|                                           |                          |
| 24-month In-Stent Late Loss (mm) -- Slow  | (0.08%, 5.09%)           |
| Release Brazil                            |                          |
|                                           | 7.53% [+]{.underline}    |
| Mean [+]{.underline} SD (N)               | 7.27% (8)                |
|                                           |                          |
| 18-month Obstruction Volume (%) -- Slow   | (0.01%, 18.29%)          |
| Release Netherlands                       |                          |
|                                           | 3.3% (1/30)              |
| Mean [+]{.underline} SD (N)               |                          |
|                                           |                          |
| Range (min, max)                          |                          |
|                                           |                          |
| 24-month Obstruction Volume (%) -- Slow   |                          |
| Release Brazil                            |                          |
|                                           |                          |
| Mean [+]{.underline} SD (N)               |                          |
|                                           |                          |
| Range (min, max)                          |                          |
|                                           |                          |
| 24-month Target Lesion Revascularization  |                          |
| (TLR)                                     |                          |
+-------------------------------------------+--------------------------+
| **Safety Measures**                       |                          |
+-------------------------------------------+--------------------------+
| In Hospital MACE Events                   | 6.7% (2/30)              |
|                                           |                          |
| Out-of-Hospital MACE Events to 24 months  | 3.3% (1/30)              |
|                                           |                          |
| Combined (In and Out-of-Hospital) MACE    | 10.0% (3/30)             |
| Events to 24 months                       |                          |
+-------------------------------------------+--------------------------+
| Numbers are % (counts available field     |                          |
| sample size) or Mean [+]{.underline}      |                          |
| Standard Deviation.                       |                          |
|                                           |                          |
| Procedure Success -- The attainment of a  |                          |
| final in-stent diameter stenosis of \<50% |                          |
| (by QCA) in the absence of death,         |                          |
| emergent CABG, Myocardial Infarction, or  |                          |
| TLR prior to hospital discharge.          |                          |
|                                           |                          |
| QCA -- Quantitative Coronary Angiography  |                          |
| by Corelab                                |                          |
|                                           |                          |
| %DS -- Percent Diameter Stenosis          |                          |
|                                           |                          |
| MACE is a composite endpoint comprised of |                          |
| deaths, WHO defined non-Q wave myocardial |                          |
| infarction, Q-wave myocardial infarction, |                          |
| or target lesion revascularization.       |                          |
+-------------------------------------------+--------------------------+

+-------------+--------------------------------------------------------+
| ##### 1     | > Based on the non-clinical and clinical studies       |
| 1. Conclusi | > presented in this section, it is reasonable to       |
| ons Drawn f | > conclude that the benefits of this device for the    |
| rom Studies | > target population outweigh the risk of illness or    |
|             | > injury when used as indicated in accordance with the |
|             | > instructions for use.                                |
+-------------+--------------------------------------------------------+

+-------------+--------------------------------------------------------+
| ##### 12    | > TBD                                                  |
| . Panel Rec |                                                        |
| ommendation |                                                        |
+-------------+--------------------------------------------------------+

+-------------+--------------------------------------------------------+
| #           | > TBD                                                  |
| #### 13. CD |                                                        |
| RH Decision |                                                        |
+-------------+--------------------------------------------------------+

+-------------+--------------------------------------------------------+
| ##### 14. A | > TBD                                                  |
| pproval Spe |                                                        |
| cifications |                                                        |
+-------------+--------------------------------------------------------+

[^1]: ^1^ Ethiodol is a trademark of Guerbet S.A.

[^2]: ^2^