CONFIDENTIAL | IND #32,617; IDE # G990038 INVESTIGATOR’S BROCHURE Ll Deleath System Kit for Liver Chemotherapy (Doxorubicin and Melphalan) Administration and Filtration Investigator’s Brochure Date: July 24, 1998 Updated December 1, 2004 Updated — December 10, 2007 Sponsor: Deleath Systems, Inc. Rockefeller Center 600 Fifth Avenue 23" Floor New York, NY 10020 December 10, 2007 1IND # 32,617; IDE # G990038 INVESTIGATOR’S BROCHURE Purpose of Investigator’s Brochure ‘This Investigator’s Brochure includes information useful for investigators participating in clinical trials using the Delcath System Kit for Chemotherapy (Doxorubicin and Mclphalan) Administration and Filtration. ‘The Deleath System Kit is investigational, and as such may only be used as part of an FDA approved protocol under Deleath’s IDE/IND. This Investigator’s Brochure is for information purpose only and does not take the place of an approved protocol in any manner or part. December 10, 2007 2CONFIDENTIAL 2,617; IDE # 6990038 INVESTIGATOR’S BROCHURE PoOoD> v. vi. vi. APPENDIX A - Manufacturer’s Labeling for Doxorubicin APPENDIX B ~ Manufacturer’s Labeling for Melphalan .. TABLE OF CONTENTS INTRODUCTION. PRE-CLINICAL § HUMAN EXPERIENCE WITH DOXORUBICW..... HUMAN EXPERIENCE WITH MELPHALAN Phase I Dose Range Finding Study....... Phase II Multiple Histology Study Phase III Melanoma Study... Gastrointestinal Toxicity Extraction Efficiency of Deleath System Filters. DELCATH SYSTEM KIT. ..co0on PRECAUTIONS AND WARNINGS... BIBLIOGRAPRY...... December 10, 2007 3| Defeath ‘CONFIDENTIAL IND # 32,617; IDE # G990038 INVESTIGATOR’S BROCHURE 1 INFRODUCTION The Delcath System is under investigation for use in the arterial delivery of doxorubicin or melphalan to the liver, with subsequent filtration of the drug after it passes through the liver and before it enters the systemic circulation, in order to reduce potential systemic toxicity. The Deleath System Kit utilizes a series of catheters and filters to target drug delivery to the liver and filter it out bofore it reaches systemic circulation (see below). Sood Pow sh J Fitere Deloath Double. Balloon Catheter Flow Probe —>| Pump Heed - Odleath { Irteducer Sot ‘The hepatic artery drug infusion catheter (lower right in picture) is inserted through the skin into one of the femoral arteries and advanced into the hepatic artery so that the tip is positioned to deliver drug to the liver. Utilizing the Deleath Introducer Set, the Deleath Double Balloon Catheter (lower left) is inserted through the skin into @ femoral vein and advanced through the inferior vena cava to the liver. The balloons on the Deleath Double Balloon Catheter are inflated 50 as to isolate the blood flowing out of the liver, preventing its circulation to the rest of the body. Doxorubicin or melphalan is infused into the liver through the infusion catheter. That portion of the drag which is not taken up by the liver and tumors flows with the blood out of the body through the Deleath Double Balloon Catheter. This blood is pumped by an exteraal blood December 10, 2007 4Delcath ‘CONFIDENTIAL | IND # 32,617; IDE # G990038 INVESTIGATOR’S BROCHURE pump through charcoal filters. The filtered blood retums to the patient through a venous return sheath (upper left). At the end of the procedure, normal circulation is restored. Deleath has an open IDE with FDA's Center for Devices & Radiological Health (*CDRH”) for the study of “Delcath System Kit for Liver Chemotherapy (doxorubicin or melphalan) Administration and Filtration”. Deleath also has an open IND with FDA's Center for Drug ‘Evaluation and Review (“CDER”) to study doxorubicin and melphalan for its use with the Deleath System Kit, ‘The Delcath System Kit is intended to reduce the systemic concentration of the chemotherapeutic agents (i.¢., doxorubicin or melphalan) in the current clinical studies. After the drug has been delivered intra-arterially to the liver and passed through this target organ, the Deleath system ‘facilitates the removal of the drug before it enters systemic circulation. Following hepatic arterial delivery of the chemotherapeutic agent and organ perfusion, the Deleath System Kit diverts the hepatic effluent blood flow through extracorporeal filters to decrease the levels of the agent in the patient's blood. This filtration process occurs before high levels of the agent can reach systernic circulation and cause severe adverse effects normally observed with chemotherapy. ‘The Deleath System Kit is intended for use only in patients with unresectable liver cancer (ie., hepatoma and metastatic tumors in the liver) in the current clinical studies. In most cases, liver ‘cancer is rapidly fatal within several months of diagnosis. The liver is one of the most common ‘organs to which cancer originating from outside the liver will metastasize. Management of hepatic metastases is therefore an important aspect in the treatment of disseminated neoplastic conditions. Most liver cancer patients, regardless of whether the source of their cancer is primary or metastatic, become severely debilitated by liver failure before they eventually die of their disease. For many of these patients, the use of conventional intravenous chemotherapy is of marginal benefit. This is because the hematologic toxicity caused by systemic exposure of conventional chemotherapy compromises, to a significant degree, the patient's health resulting in morbidity, lower quality of life and, in some cases, rapid death. Certain side effects, such as the cardiomyopathy associated with the use of doxorubicin, are irreversible. The Deleath System Kit may benefit terminally ill patients by decreasing side effects while still delivering high-dose doxorubicin or melphalan where it is needed ~ at the local liver tumor site. December 10, 2007 5Deleath CONFIDENTIAL | IND #32,617; IDE # 6990038 INVESTIGATOR’S BROCHURE. Ul, — PRE-CLINICAL STUDIES WITH DOXORUBICIN A seties of porcine and rabbit studies were conducted with the Deleath Double Balloon Catheter. ‘The System was capable of shunting the blood flow from the hepatic vein to an extracorporeal circuit outside the body and two charcoal hemoperfusion filters (in a parallel configuration) were capable of removing a high percentage of the drug flowing into the hepatic effluent that was not absorbed by the liver. In some experiments, non-target tissue samples and systemic plasma samples both showed the presence of significantly less doxorubicin than did samples taken in the absence of extracorporeal filtration. Hepatic tissues showed minimal changes at high doses of doxorubicin or no damage at all, Hypotension which may result from the mechanical reduction ‘of blood return via the inferior vena cava by the double belloon catheter and extraction of endogenous catecholamines by the extracorporeal filters was managed with intravenous fluids and pressor agents, Highlights from these animal studies are presented below. August! (1994) treated swine with 3 mg/kg doxorubicin administered over 90 minutes. Hepatic venous isolation was accomplished with the Delcath Double Balloon Catheter. The hepatic venous blood was routed through an extracorporeal circuit and returned via the jugular vein for a total of 240 minutes. Group 1 (n= 3) had the drug administered as an hepatic artery infusion (HAD and hepatic venous blood passed through activated charcoal filters and Group 2 (n= 3) had the drug administered systemically with no filtration in the extracorporeal circuit. Hemodynamic, pharmacokinetic and doxorubicin/doxorubicinol cardiac tissue concentrations were measured, ‘The following observations were made: 1) In both groups, the mean arterial blood pressure during hepatic venous isolation was maintained with the infusion of fluids (40-50 cc/kg/hr). In Group 1, epinephrine (0.1-0.3 ug/kg/min) was also infused to replace pressor agents removed by the filters, 2) Mean hepatic blood flow during hepatic isolation decreased by approximately 15% for both groups. 3) Mean filter extraction efficiency {equal to (Ci - Co\Ci where C, is the concentration of doxorubicin in the blood pre-filter and Co is the concentration of doxorubicin post-filtration} ranged from 0.82 to 0.92 for Group 1. 4) As shown in Table 1 below, hepatic isolation with filtration decreased systemic levels of doxorubicin (Group 1 levels were 16 times lower than Group 2) and increased hepatic venous levels. This may translate into better tumor exposure and less systemic adverse events in humans. 5) As shown in Table 2 below, hepatic isolation with filtation decreased cardiac exposure to doxorubicin (Group | cardiac tissue levels were 1/16 less than in Group 2) and doxorubicinol (Group 1 cardiac levels were more than 1/4 less than in Group 2). This may translate into better cardio protection in humans. December 10, 2007 6Delcath CORFIDENTIAL IND #32,617; IDE # G990038 INVESTIGATOR’S BROCHURE Table 1 Mean AUCs AUC (amole « min/ml) f infusion | ‘Hepatic Vein * After Filters Le Systemic Group 1 (HAT and 113 + 320 12.6 + 4.82 16.9 + 8.43! filtration) Group 2 (Systemic infusion wo filtration) | - 83.64 22.1 Not Applicable | 270 + 112" Ps ootr Table 2 ‘Mean Tissue Concentrations (nmole/gm of cardiec tissue) of Doxorubicin and Doxorubicinol AUC (nmote + min/ml) Group.1.(HAr end °° Grou = Coispoind : filtration) “infision'w/o ‘Dita ny Doxorubicin 0.444 02 | 739 + 4.21 16.8 Doxorubicinol <0.001 0,004 + 0.007 4 August” (1995) treated additional swine with 0.5, 1.0, 5.0, and 9.0 mg/kg doxorubicin administered over 90 minutes. Hepatic venous isolation was accomplished with the Delcath Double Balloon Catheter. The hepatic venous blood was routed through an extracorporeal circuit and retumed via the jugular vein for a total of 240 minutes. Group 1 had the drug administered HAI and hepatic venous blood passed through activated charcoal filters, and Group 2 had the drug administered systemically with no filtration in the extracorporeal circuit. Hemodynamic and pharmacokinetic measurements were taken. Findings, in addition to those listed above include: 1) _Of the 34 swine studied, 2 died of technical problems, and 4 died of acute doxorubicin toxicity. These 4 animals received higher doses of doxorubicin and did not have the benefit of filtration, 2) Filter extraction ranged from .74 - 911 and did not vary with time or dose. December 10, 2007 7Defcai CONFIDENTIAL IND #32,617; IDE # G990038 INVESTIGATOR’S BROCHURE, 3) During either hepatic or systemic infusion, hepatic extraction and clearance were positive. At 60 minutes into the infusion, the hepatic extraction ranged from 0.74 to 0.91 and the clearance ranged irom 596 to 880 ml/min, and these parameters were not dose related. 4) After cessation of both the hepatic and systemic infusions (0 to 90 minutes after completion of infusion), the hepatic extraction and clearance were negative, suggesting the liver serves as a reservoir and then releases the doxorubicin over time. 5) Doxorubicinol was present in the blood in concentrations < 5% of doxorubicin. The metabolite, aglycone, was seen less frequently that doxorubicino!, especially at the lower doses. Curley’ (1991) conducted an experiment in swine with hepatic isolation with the Deleath Double Balloon Catheter and activated charcoal filtration in an extracorporeal circuit. One animal received 3 mg/kg of doxorubicin and another received 9 mg/kg, Two animal were not given drug but were observed for hemodynamic assessment. Two additional animals received cisplatin and mitomycin C, but the pharmacokinetic data will not be presented here. ‘The following observations were noted: 1) There was a pre-filter to post-filter reduction in doxorubicin of 97% and 92% for the 3 and 9 mykg dose of doxorebicin, respectively. 2) As shown in Table 3, when the animals were first placed on the extracorporeal by-pass without the filtration, there was no significant change in systolic and diastolic blood pressure; however, there was an 18% increase in heart rate and a 20% decrease in cardiac output. 3) Also shown in Table 3, during filtration, there was a) a drop in systolic and diastolic blood ‘pressure, b) a 50% reduction in cardiac output, and c) a concomitant decrease in left heart filling pressure compared to baseline. (With the addition of filtration, there was no change in the pressure required to maintain flow in the bypass circuit. ‘The rapid decline in blood pressure, cardiac output and left heart filling pressure was rapidly reversed by continuous intravenous infusion of phenylephrine [2-5 j.g/kg/sin].) December 10, 2007 8cath CONFIDENTIAL IND # 32,617; IDE # G990038 INVESTIGATOR’S BROCHURE Table 3 ‘Hemodynamic Effects of Complete Hepatic Venous Isolation and Extracorporeal Chemofiltration Ep aiaee Se BR BP dias! ARES: co! “Ppewe™ Pre-pumprun | 93.00+8.51 | 50.0048.32 | 91.67+5.01 | 5.7441.36 | 6.6743.88 On pump, no filtration 87.17 £16.52 | 48.67 410.63 | 112.67 +1652 | 4474097 | 4.004219 On pump with filtration 50.50 + 6.987 | 27.1745.317| 93.33+5.72 | 2.804040? | 0.674 0.827 End of pump run 91.67 + 48,33 + 107.67 + 21.40 | 5.244+1.60 | 6.00+2.83 [__ 19.08 12.08 1) BP syst~ sys Dood presute, BP dts = dale blond presse, HR = heat rate, CO = earte outa, PCWP = pulmonary wedge pressure, Means fom 6 animal. 2) P00) Student test pre-pump vs. on pup with tation December 10,2007 9CONFIDENTIAL IND # 32,617; IDE # G990038 INVESTIGATOR’S BROCHURE. Lowy* (1996)/Curley’ (1993) conducted an experiment in swine to assess hepatobiliary toxicity and survival after HAI of doxorubicin (10 minute infusions of 1 or 3 mg/kg) with hepatic isolation with the Delcath Double Balloon Catheter and activated charcoal filtration in an extracorporeal circuit, ‘The following observations were noted: 1) The procedure was well tolerated. 2) Average peak hepatic venous doxorubicin levels were 2000 ng/sl and $800 ng/ml for the 1 and 3 mg/kg doses, while the average peak systemic doxorubicin levels were 200 ng/ml and 210 ng/ml for the | and 3 mg/kg doses, indicating systemic protection with hepatic venous isolation ‘and filtration. 3) Animals treated with 1 mg/kg doses had no significant change in serum liver tests (alkaline phosphatase, bilirubin, espartate aminotransferase and alanine emino-transferase) in the 14 days afier HAI doxorubicin, Animals treated with 3 mg/kg doses had no significant change in serum liver tests, except for transient elevations in aspartate aminotransferase. 4) Pathologic evaluation revealed that 50% of the animals treated at each dose had minimal periportal inflammation without other changes in liver architecture. The remaining animals had normal livers, indicating there was no significant acute hepatobiliary toxicity. 5) There were no significant changes in serum values for leukocytes, hemoglobin, platelets, or glucose. There was a decrease in total protein, albumin and caleium immediately after the procedure. Lowy! (1996)/Curley* (1993) performed another experiment in a rabbit liver tumor madel (VX~ 2) examining infusion of doxorubicin via HAI and portal vein (PVD, with and without hepatic isolation/activated charcoal filtration. Rabbits without the benefit of hepatic isolation/filtration received 5 minute infusions of 0.5, 1.0, 1.5, or 2.0 mg/kg of doxorubicin to determine meximum tolerated dose (MTD) and antitumor response at the MTD. The remaining animals, with the benefit of hepatic isolation/filtration, received cither 3.0 or 5.0 mg/kg of doxorubicin to determine plasma and tissue levels of drug, and antitumor response. The following observations were noted: 1) HAJ and PVI animals without hepatic isolation and filtration at the 2.0 mg/kg doses died of chemotherapy-related systemic toxicities, and animals with hepatic isolation and filtration at doses of 3.0 and 5.0 mg/kg survived, indicating systemic protection with hepatic venous isolation and filtration. 2) Rabbits with hepatic isolation and filtration had a 90% decrease in drug levels pre- to post- filter, similar to results reported by August!**, December 10, 2007 10~ Defcath ee CONFIDENTIAL IND # 32,617; IDE # G990038 INVESTIGATOR’S BROCHURE 3) As shown in Table 4, HAI produced 4 fold increase in intratumor doxorubicin Jevels than PVI, suggesting that HAI is a better route of administration for the VX-2 tumor and possibly for human tumors of the liver. 4) Additionally, Table 4 suggests that hepatic isolation with filtration provides greater doxorubicin protection to heart and kidney tissues. Again, this is similar to results for cardiac tissue presented by August! 5) Animals treated with 1.5 mg/kg showed disease progression in the liver at 7 and 14 days post treatment. Animals treated at the higher dose of 3 mg/kg showed significant tumor necrosis at 7 and 14 days and no progression in the liver, indicating enhanced tumor cytotoxicity. There was also no evidence of inflammation or alteration in normal hepatic architecture at the 3 mg/kg dose. Table 4 Tissue Doxorubicin Content 30 minutes after HAI or PVI at 3 mg/kg Doxorubicin With or Without Hepatic Isolation/Activated Charcoal Filtration : ‘Treatment HAL with hepatic isolation and filtration 38.1266 | 40.9274 3641.07 HAI without isolation and filtration 447490 | 40.2455 | 332431 | 8174172 PVI with hepatic isolation and filtration 28.7422 9.9 42.0 B31P 72222 PVI without isolation and | filtration 23.6440 | 98423 | 4834136 | 654274 1) Nanogzame dosorbicials of tue 2) P< 0.00 forherti eoain/raon vs. eaten without kept oationtitcation by Stents pied two-aed st 3) P £0.01 for hepatic sla traion vs, einent without hepatic alton fivation by Shidem'spived, toda est Ravikumar 1994” evaluated the extraction of catecholamines by the filters during the Delcath System procedure in swine. Catecholamine levels are shown in Table 5 at baseline, during the Deleath procedure without filtration (on-bypass), during filtration, and at the conclusion of the procedure. This experiment demonstrated that the activated charcoal filters extract catecholamines from the blood. December 10, 2007 WwDeleath z CONFIDENTIAL IND # 32,617; IDE # 6990038 INVESTIGATOR’S BROCHURE Table 5 Catecholamine Levels in Swine During the Deleath Procedure “Tine Ditring * “Epinephrine pel Norepinephrine pelint = Deloath Progeduce +7 SPietiieeii'o :Postillter’ “Prefer... Postfilter Baseline 28 nat 25 nat Baseline on bypass 37 nat 91 na® 2 mimutes with filtration na 6 175 29 5 mimutes with filtration 82, 0 150 3 10 minutes with filtration i | 264 15. 15 minutes with filtration 4 | 287 n 30 minutes with filtration 52 | 420 18 End of procedure. nat na? “Not Applicable December 10,2007 12GONFIDENTIAL IND # 32,617; IDE # 6990038 INVESTIGATOR’S BROCHURE IM HUMAN EXPERIENCE WITH DOXORUBICIN Early clinical trials of the Delcath System Kit were held at two major institutions for the purpose of generating data to support Delcath’s Phase HII clinical programm: U._ Yale University School of Medicine ‘Two similar but separate protocols conducted by two different Investigators O M.D. Anderson Cancer Center ‘One protocol with one Investigator From 1991 through December 1996, 30 patients entered the Phase [-II trials, which have bees conducted under the joint aegis of Deleath’s IDE G890047 and IND 32,617. Additionally, 3 patients at the Chelsea and Westminster Hospital were treated with the Deleath System and doxorubicin in a study conducted outside the US (non-IND/non-IDE). In total, there have been 79 catheterizations and 77 treatments with doxorubicin and the Deleath System. NOTE: Under a separate 5-FU and Deleath System protocol, 15 patients received 37 catheterizations and 36 treatments with 5-FU at two centers, “The summary in this section has been organized as follows: (A) PATIENT POPULATION - An overview of patients treated with doxorubicin and the patients’ characteristics are presented. (B) PHARMACOKINETIC MEASUREMENTS - Results ere summarized for the filtration of drug (doxorubicin) from the hepatic effluent, (© ADVERSE EVENTS - Summaries of adverse events for the Phase I-II Deleath doxorubicin ‘rials are presented in tabular and deseriptive form. A description of device-related events for the 5-FU trials is also provided. (D) RESPONSE AND SURVIVAL - Results are for the Phase I-11 Deleath doxorubicin ‘rials are summarized. (@) PATIENT POPULATION Characteristics of the population treated with doxorubicin and the Delcath System are shown in Tables 6 (demographics), 7 (tumor types), and 8 (dosing information). ‘Twenty males and thirteen females were enrolled. Ages ranged from 36 to 78 at the time of enrollment. The largest group of patients had hepatocellular carcinoma. The next most common tumor type was malignant melanoma metastatic to the liver. A number of patients were treated at more than one dose level and others received multiple doses at the same level. Courses ranged from | to 10 per patient, with and average of 2.5 courses per patient. December 10, 2007 13~ ‘CONFIDENTIAL IND #32617; IDE # G990038 INVESTIGATOR’S BROCHURE Table 6 ‘Demographic Features of Patients Enrolled ao ‘Yale MD: Chelsea [Poi Data By Study oo ‘Anderson ~ |" Westminster’ | ~-Overa Number Male 13 6 1 20 Number Female 6 5 rl 13 Median Age 58.5 62 33 58 Mean Age ST 7 52.6 STs Age Range 36-78 37-72 49-53 36-78 Table 7 ‘Tumor Types in Enrolled Patients SOT vale] Me. Asderson: 8 0 Chelsea T= | Westminster: Hepatocellular Melanoma ‘Melanoma Breast Colon Adenocarcinoma Adenocarcinoma Panereas Unknown Unknown, 1 Adenocarcinoma Adenocarcinoma ‘Small Cell Sarcoma Small Bowel 2 eoe Sarcoma. Total Retroperitoneum December 10, 2007 14CONFIDENTIAL INVESTIGATOR’S BROCHURE, Table 8 Number of Doxorubicin Doses by Dose Level and Study Site in 33 Patients Study. Site: ‘Total Dose'Level meg/n? ike 50 8 0 0 8 60 0 6 0 6 5 4 0 0 4 90 17 2 4 26 120 28 Re 0 33 Total 57 16 4 7 B) PHARMACOKINETIC MEASUREMENTS During the Phase [-Il studies, plasms concentrations were measured at eight points in time, commencing at mid-infusion and concluding at 90 minutes after the start of infusion. At each of the first seven sample times, blood was drawn at three locations: unfiltered hepatic effluent blood, filtered hepatic effluent blood, and systemic blood (radial artery). The sample at 90 minutes was of systemic blood only. Peak plasma concentration (Cmax), the highest level attained at any time following the start of drug infusion or bolus administration; and area under the concentretion/time curve (AUC), another widely accepted indicator of cytotoxic potential, have been calculated for 16 Yale patients (tables 10A and 10B). ‘The extraction efficiency of the filters in the Delcath System was calculated as a difference between pre- and post-filter blood levels. The mean reduction was 67.5% in the AUC, with 95% confidence limits of 64.3% and 70.8%. The mean reduction was 73.1% at the time of Cmax, with 95% confidence limits of 69.8% and 76.5%. When comparing the systemic AUC of intravenously administered doxorubicin (bolus infusion listed in the literature) with that of the Deleath System, there is a reduction in overall systemic exposure (Table 9). This permitted higher doses of doxorubicin via the Deleath System than could have been given with IV bolus administration, Further definition of doxorubicin (and doxorubicinol) plasma levels will be gained in the upcoming Phase III trials. December 10, 2007 15Delcath ~ CONFIDENTIAL IND #32,617; IDE # 6990038 INVESTIGATOR’S BROCHURE Table 9 Systemic AUC - IV Bolus Doxorubicin Administration and the Deleath System Average Systenjic AUC t Yale Site - Deloath System: GiMeminit 15 mg/m? 53.8° “ 25 mg/m? 167.5? = 30 mg/m? 98.4 -140,08 10" ~ 50 mg/m* 146.5 - 212.6% 7" 29.44 6.9% 60 mem? 204.2'5 ~ 75 mg/m? 268.0 - 710.416 '6 13.1 £68" 90 mg/m? ci 65.3 + 25.6% 46.0 + 15.3* +9595 confidence init December 10,2007 16CONFIDENTIAL IND #52,617; IDE # G990038 INVESTIGATOR’S BROCHURE Table 108 Yale University Doxorubicin Study ‘Summary of Drug Filtration Data (AUC) SOP ARES Under Tine Concentration: ‘Tnfisiont! 5 Ty cae Alb feo IuMemini) Filter od Pree Bose. | Syatemie. | iicienay BS i Fes oBiker )SBMer 7 e L ‘WB | 1 06/14/91) 15/45 60.115 24.262 SL858 59.6% 1 ‘WB 2 (07/05/91; 50 15/45 70.412 14.353, 20.637 79.6% 1 WB | 3 (08/09/91) 50 15/45 116.622 21.025 23.487 82.0% 1 WB | 4 08/30/91) _50 15/45 165.125 13.003 26.210 92.1% | 2 AV | 1 (07/26/91) SO 15/45 81,828 | 28.208 33.375, 65.5% 2_| av|2 logon so_| is/4s | 77.292 | 17.768 | 30.505 | 77.0% 3 DW] 1 [11/06/91] 50 30/60 67.475, 21.565 27.230 68.0% 3 DW | 2 j1125/91| 50 30/60 65.230 | 21,370 22.285 67.2% 4 ID | 1 (03/25/92) 75 30/60 5.830 1.830 9.780 68.6% 4 ID | 2 [04/15/92) 75 30/60 37.715 11.455 21.665 69.6% 4 | ww] 3 losis. 75 | 30/60 | 82805 | 8610} 21.025 | 89.6% 4 ID | 4 (05/27/92|_75 30/60 40.200 8.445 9.195 79.0%. 3 | DB] 1 osi992| 90 | 30/60 | 37.445 [76.495 | 42.200 w/a 5 DB} 2 07/31/92} 90 30/60 81.895, 33.115 37.175 59.6% 5 DB} 3 09/09/92} 90 30/60 58,905, 25.950 28.955 55.9% 5 DB} 4 [10/19/92) 90 30/60 54.305, 13.310 16.260 75.5% 5 | DB|s 1207/92] 90 | 30/60 | 193.175 | 49.815 | 85.060 | 74.2% 5 DB | 6 (01/20/93) 90 30/60 158.610 57,435 104.870. 63.8% 6 GD] 1 {07/29/92[ 90 30/60 25.975 10.560 22.270 59.3% 6 GD {2 08/19/92] 90 30/60 67.170, 16.355, 37.300 75.7%, 8 GS | 1 10/21/92! 90 30/60 417.370 | 100.685 179.495 75.5% 8 GS | 2 |11/11/92|__90 30/60 117,335, 66.245 176.790 | 43.5% 9 {Mm [1 _fov/isi93| 120 | 30/60_| 273.400 | 109.315 | 146.375 | 60.0%. 10 | MEW) i (05/10/93! 120 30/60 68.900 11.193, 12.981 83.8% | 10_| MEW| 2 |osrai/93|_120_| 30/60 | 57.858 | 19.303 | 33.907 | 66.6%. Pil MM/1- {10/18/94} 120 30/45 64.070 | 22.185 24.975, 65.4% PL MM} 2_= {11/08/94) 120 30/60 75.270 | 28.305 31.235 62.4% PL MM! 3 |12/06/94| 120 30/60 84.375, 25.830 44.425 69.4% Pi | MM|4 {12/8/94 120 | 30/60 | 126.075 | 19.910 | 23.035 | 84.2% Pl MM/5_ {01/30/95| 120 30/60 167.675 31.915 33.835 81.0% pi | mm 6 joz/2g/95| 120 | 30/60 | 162.160 | 35.585 | 22.190 | 78.1% Pi | MM|7 |os/os/95) 120 | 30/45 | 104445 | 23.280 | 24.005 ) 77.7% PI MM] 8 = [05/03/95] 120 30/45 114.025 | 20.790 29.685 81.8% Pl MM/]9 = |06/13/95| 120 30/45 62.645 15,370 15,285 75.5% P1_| mm|10_|osog/9s| 120 | 30/45 | 167.205 | 32.825 | 27.260 | 80.4% December 10, 2007 7