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HomeTrak System for Monitoring Organ Transplant Maintenance Therapy HomeTrak System for Monitoring Organ Transplant Maintenance Therapy

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HomeTrak System Outline of Presentation

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HomeTrak System Therapeutic Drug Monitoring of Immunosuppressants (TDM-IS) The Overall Process

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HomeTrak System Equivalence to Venous Samples

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Tacrolimus n=161 tests 1.8% mean absolute difference Rapamycin n= 67 tests 2.9% mean absolute difference Cyclosporin n=70 tests 1.2% mean absolute difference NOTE: current ongoing data comparison shows capillary vs. venous Everolimus correlation exceeds Sirolimus correspondence Altman-Bland Analysis demonstrates Equivalence of capillary to venous blood in testing

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Example Comparisons in Consecutive Individual Patient Tests LC-MS/MS analysis with Waters Acquity / Quattro Micro system TMS BioScience in collaboration with Tulane Abdominal Transplant Program 2007 IRB Study

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HomeTrak System Advantages

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Frequent monitoring of immunosuppressant drugs levels is essential for proper transplant care HomeTrak Advantages At-home sampling allows frequent monitoring - cases of noncompliance or difficulty in achieving proper drug levels

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Emerging Goals in Transplantation Reduce Side Effects of Immunosuppressant Medication Therapy Preservation of Kidney Function Decrease Risk of Cardiovascular Disease & Diabetes Drug Levels must be CLOSELY monitored - Frequent and Flexible Testing is absolutely necessary - TMS BioScience Labs HomeTrak accomplishes this Critical Goal With recently improved short-term outcomes, emerging long-term goals in organ transplantation include minimization of CNI immunosuppressant (IS) drug toxicities, with special emphasis on reducing nephrotoxicity and other direct cardiovascular effects of currently used agents BY TRANSITIONING THERAPY to mTOR INHIBITORS such as EVEROLIMUS.

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Secondary Diseases are Major Causes of Death in Transplant Patients Emerging Goals in Transplantation

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HomeTrak System Use for Emerging Goals in Transplantation Therapy HomeTrak facilitates frequent drug monitoring assists low dose CNI treatment (minimization) Surveillance of patient medication adherence Transition to mTOR therapy in chronic allograft nephropathy from CNI treatment The addition of creatinine & BUN renal profile assists team in monitoring kidney function Liver enzymes can detect hepatic injury HomeTrak facilitates frequent drug monitoring assists low dose CNI treatment (minimization) Surveillance of patient medication adherence Transition to mTOR therapy in chronic allograft nephropathy from CNI treatment The addition of creatinine & BUN renal profile assists team in monitoring kidney function Liver enzymes can detect hepatic injury

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HomeTrak System Special Utility of HomeTrak Tandem Mass Spectrometry Instrument (MS/MS) Most Accurate Analytic Method- lowest limit of detection Most Specific Method no metabolite interference Alternative Sampling Strategy Allows analysis of small blood sample volumes Small sample volumes allow at-home fingerstick sampling Timely Results Reporting High through-put platform hundreds of tests / 24 hours 2 minute / test produces rapid results for clinicians

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HomeTrak System Additional Tests to TDM-IS Serum is separated by a proprietary process in TMS BioScience Labs Creatinine & BUN renal profile and adjustment of medication dosage (clearance) Liver Enzymes SGOT & SGPT liver injury Other serum tests can be performed (custom) Serum Biomarkers (research) may be assayed Serum is separated by a proprietary process in TMS BioScience Labs Creatinine & BUN renal profile and adjustment of medication dosage (clearance) Liver Enzymes SGOT & SGPT liver injury Other serum tests can be performed (custom) Serum Biomarkers (research) may be assayed

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Venous vs. Capillary Samples Clinical Chemistry Creatinine & BUN Normal volunteers NaEDTA collection simultaneous venous & capillary Alfa-Wassermann - ACE Alera Clinical Chemistry Analyzer TMS BioScience Labs - internal data on file --- Venous --- Capillary Equivalence of HomeTrak Venous vs Capillary samples in Renal Tests

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Venous vs Capillary Samples for Renal Profile Tests Normal volunteers NaEDTA collection simultaneous venous & capillary Alfa-Wassermann - ACE Alera Clinical Chemistry Analyzer TMS BioScience internal data on file

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HomeTrak System Additional Tests CBC with differential (complete blood count) done by desk-top flow cytometry provides anemia analysis, white cell count & automatic differential, and platelet count monitor blood system effects of immunosuppressants BK viral load copy # in blood by qRT-PCR (AB 7500) to screen for viral nephropathy (CMV, EB, JC, other screens in development) CBC with differential (complete blood count) done by desk-top flow cytometry provides anemia analysis, white cell count & automatic differential, and platelet count monitor blood system effects of immunosuppressants BK viral load copy # in blood by qRT-PCR (AB 7500) to screen for viral nephropathy (CMV, EB, JC, other screens in development)

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At-Home Sample Collection a simple & straightforward process > 98.6% success in patient performance in 80+ patients evaluated

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Micro Collection Tubes ~ 6 drops of Blood Patients provided adequate volume sample without clots in 99.4% of 260 HomeTrak samples sent in

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Serum Separation for Clinical Chemistry microcentrifuge technique with proprietary cell collection method Serum assayed for Creatinine, BUN, SGOT, SGPT, ALP, others

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HomeTrak Optional Test Menu Hgb A1C, cholesterol & triglycerides HDL, LDL, and other clinical chemistries Other serum enzymes: Alkaline Phophatase, etc. Therapeutic levels of numerous drugs, antifungals, antivirals, neuroleptics, etc. Biomarkers and DNA tests of interest Optional testing included in patent application

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HomeTrak System Patent Applied For Includes Additional tests and Optional tests Patent assignment to inventor: Pleasant F. Hooper, MD

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HomeTrak Sample Stability Temperature exposure of whole blood samples Immunosuppressants -stabile in blood 25 C for 7 days confirmed in other published studies IS withstand 35 C for 48 hours no loss of test accuracy this is also demonstrated in the literature. Shipping of blood samples without cooling packs is appropriate and functional proven in practice Serum based clinical test stability for 48 hours at normal and elevated temps. - HomeTrak results mirror clinic results Shipping of blood samples without cooling packs is appropriate and functional proven in HomeTrak history

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HomeTrak Sample Stability at Temperatures 25-35 C for 48 Hours Liver enzyme tests minimal loss at 24 hours 25 C - less accurate at 48 hours or elevated temps

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HomeTrak Experience IRB - 33 patients (> 98% participation of clinic and in hospital patients asked) 97% completed study- 95.7% of samples adequate improved over study 42 patients monitored in demonstration project over 18 months included tacrolimus, cyclosporin, and sirolimus therapy (prior to US approval of everolimus) 97.4% completed the monitoring course many reports of preference of fingerstick (patients with history of dialysis have poor veins)

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HomeTrak Experience Current HomeTrak utilization has increased dramatically over last 6 months due to Zortress (everolimus) prescribing for CNI transition and CRAD study of diabetes in everolimus + low dose CNI (cyclosporin) protocol Currently no widely available immunoassay for Zortress (everolimus) mass spectrometry reference testing is the method in place Send out to reference labs by patients discharged to home reveals problems with results reporting

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HomeTrak Experience Similar problem existed for Rapamune (sirolimus) in 2008 mass spectrometry only available test method 7 day turn around time for send outs Very low utilization of Rapamune at Tulane TMS BioScience began providing rapid results for Rapamune testing Jan. 2008 June 2008 Rapamune utilization increased by 72.6% over use in Jan. A six month increase driven by rapid results reporting = practical dosing !!

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HomeTrak Experience Currently monitoring 12 patients on Zortress 5 are post-surgery dose titrations length of monitoring as far as 4 months postop all patients have successfully performed HomeTrak and are still being monitored by HomeTrak initial sampling is bi-weekly, then weekly, then twice monthly. 7 patients have been transitioned to Zortress after CNI therapy they are 1 to 2 years post-transplant Patients homes are from 60 miles to 134 miles from transplant center 2 state distribution

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HomeTrak Experience HomeTrak is targeted service to transplant programs the patients sample is sent directly to testing facility (TMS lab) the samples are immediately tested due to priority in work load (dedicated monitoring laboratory) results are reported directly to transplant team by secure email and fax transmission (nurses request) and are now being posted to a secure website for review. Avoids the delay in having results entered into hospital LIMS systems internal delays, lost reports

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Website Results Reporting Smart phone and iPad accessible

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HomeTrak Experience Potential Difficulties Potential Problem solutions: Patient education to correct collection method, adequate sample volume and proper time of collection (trough level critical) this is a minimal incidence issue (< 3.6% of samples) and less than 1% of patients experience problems. Video training DVD helps and direct teaching during clinic visits Home Health visiting nurse programs are under development to aid in patient teaching

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HomeTrak Experience Potential Difficulties Problem areas: Missed delivery or delayed delivery of samples this occurs infrequently (< 2.6% of samples) and patient education and carrier consultation are effective corrections Exposure of samples to temperature extremes we have high temperature summer months and potential for high temperature exposure using thermal strip indicators in 10 samples sent during midsummer = no sample > 30C encountered

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Clinical Interest in HomeTrak Fingerstick monitoring has attracted attention by clinicians We have received many inquires and correspondence about HomeTrak

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HomeTrak Summary HomeTrak is a novel method to monitor transplant therapy initial dosing or transition to new therapy Convenient, no extra patient cost, with high patient preference and healthcare team acceptance & proven performance in use at Tulane transplant Can be deployed anywhere in the nation Addresses the problem of Zortress monitoring proven effective in Tulane experience (Rapamune testing scenario from 2008) Central dedicated laboratory with rapid reporting and internet access for healthcare team.