The 4Kscore blood test for risk of aggressive prostate cancer

The 4Kscore blood test for risk of aggressive prostate cancer

Prostate cancer tests When to use the 4Kscore Test? Screening Prior to 1 st biopsy Prior to negative previous biopsy Prognosis in Gleason 6 for aggressive disease* Monitoring (AS or after therapy) 4Kscore Test * If the 4Kscore Test was run prior to the biopsy

Early detection of aggressive prostate cancer Challenges Serum PSA has a high false positive rate Over 1 million prostate biopsies performed annually in US 75% biopsies will have low-grade, indolent (Gleason 6) or no prostate cancer Serious complications of biopsies include infection and hospitalization Overtreatment- 75% of Gleason 6 indolent cancers at prostate biopsy are confirmed at radical prostatectomy Recommendation by USPSTF to stop PSA screening misses an opportunity to detect and treat men with high grade (Gleason 7), the aggressive form of prostate cancer

The 4Kscore Test The only blood test that accurately identifies risk for aggressive prostate cancer Aggressive prostate cancer is defined by both high-grade disease and long term clinical outcomes (rate of prostate cancer metastases) Based on 10 years of work by scientists at Memorial Sloan-Kettering Cancer Center and evaluated in over 30,000 men in 8 clinical studies and validated in a prospective, blinded prebiopsy study of 1,012 men in US (October 2013 to April 2014)

The 4Kscore Test is based on 10 years of clinical research from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Key ERSPC Reference Cohort Population Number Subjects AUC Aggressive Prostate Cancer BMC Medicine 2008 6:19 Göteborg Unscreened 740 0.90 BMC Cancer 2010 10:635 France Unscreened 262 0.87 J Clin Oncol 2010 28:2493 Rotterdam Unscreened 2914 0.84 Eur Urol 2013 64:693 Rotterdam Screened 392 0.81 Cancer 2010 116 (11) 2612 Göteborg Screened 1241 0.83 Clin Can Res 2010 16(12) 3232 Rotterdam Screened 1501 0.80 BJC 2010 103:708 Rotterdam Prior Biopsy 925 0.87

What is the 4Kscore Test? Components OPKO ALGORITHM Results OPKO { 4 kallikrein levels Total PSA Free PSA Intact PSA hk2 + Age, DRE, and prior biopsy status % risk of having aggressive prostate cancer for an individual patient

Prospective, blinded, multicenter US study validates 4Kscore Test 1,012 patients enrolled in 26 centers for validation (Oct. 2013 to Apr. 2014) Men scheduled for biopsy regardless of PSA, age, DRE status, prior biopsy TRUS Biopsy of 10 cores Excluded for treatments known to influence PSA levels OPKO Lab developed and performed the 4Kscore test Pathology conducted according to the established practice at each center 26 Clinical study sites

Gleason score distribution in Prospective US Study Gleason Grade N % All Cancers N = 470 % All Patients N = 1,012 Summary Negative 542 -- 53.6% 6 239 50.9% 23.6% 7 (3+4) 108 23.0% 10.7% 77.2% Negative Negative or Gleason or 6 prostate Gleason cancer 6 7 (4+3) 59 12.6% 5.8% 8 35 7.4% 3.5% 9 26 5.5% 2.6% Aggressive 22.8% (Gleason High-Grade 7) prostate cancer 10 3 0.6% 0.3%

The 4Kscore Test has the accuracy of a prostate biopsy for aggressive prostate cancer Sensitivity 4Kscore AUC = 0.82 1 AUC = area under the curve Larger AUC = better accuracy for predicting aggressive prostate cancer PSA AUC = 0.69 1 AUC of other tests when applied to aggressive disease AUC = 0.5 PHI = 0.70, 0.67 2,3 PCA3 = 0.68 4 1. Parekh, D et al 2014 submitted 2. Catalona et al. J Urol. 2011 185(5): 1650 1 - Specificity 3. Wang, W et al Scientific Reports 4:1-8 2014 4. Chevli, K et al J Urol 191:1743 2014;;

The risk of aggressive prostate cancer predicted by the 4Kscore Test is confirmed by prostate biopsy 239 aggressive prostate cancers detected in 1,012 subjects Actual Aggressive prostate cancer detected by biopsy Predicted

4Kscore Test is more accurate than total PSA alone in predicting aggressive prostate cancer in subset of men with PSA 16-20ng/mL Total PSA DRE 4Kscore Test Result Biopsy Result 16.1 Normal 69% 7 16.4 Normal 1% Negative 16.4 Normal 8% Negative 16.6 Normal 50% 6 17.1 Normal 80% 9 17.3 Normal 89% 7 17.5 Normal 87% 8 17.6 Abnormal 98% 8 18.1 Abnormal 88% 9 18.4 Abnormal 87% 7 18.5 Normal 14% Negative 18.5 Abnormal 94% 7 19.0 Normal 3% Negative 19.5 Normal 0% Negative 19.7 Abnormal 96% 7 19.8 Abnormal 83% 8 20.0 Abnormal 98% 9

The 4Kscore Test predicts the probability of distant metastases within 20 years 4Kscore Test Biomarkers > 7.5% 4Kscore Test Biomarkers > 7.5% (N = 922, 38%) 5 year 10 year 15 year 20 year = 2.4% = 5.6% = 9.9% = 16.4% 4Kscore Test Biomarkers 7.5% (N = 1510, 62%) 4Kscore Test Biomarkers 7.5% 5 year 10 year 15 year 20 year = 0% = 0.2% = 1.0% = 1.8% Vasterbötten Intervention Project study J Clin Oncol 32:5s, 2014 (suppl; abstr 5081)

Clear result reporting Patient Information informed decision making Clinician Information Robert Blade, M.D. Urology Associates 1234 Medical Arts Dr. Anytown, MN 37180 Phone: (808) 677-0000 Fax: (808) 677-0000 Clinical & Specimen Information Prior Biopsy: Yes Age: 76 DRE: Neg. Received: Whole blood in K 2 EDTA 4Kscore Test Result & Interpretation FINAL REPORT Total PSA and Free PSA Results Name: John Doe Gender: M Chart No: 87485524 DOB: 04/30/1938 Accession #: FKS-000001 Collected: 05/01/2014 Received: 05/02/2014 Total PSA: 6.23 (Reference Range 0.0 4.0 ng/ml) F/T PSA Ratio: 21% (Reference Range > 25%) The patient s 4Kscore Test result is 5% At a 4Kscore Test result of 5%, about 1 in 20 men biopsied would have high-grade prostate cancer. Based on your 4Kscore Test result, your probability for having a high-grade cancer is 5%. This means that if 100 men with your same 4Kscore Test result were to have a prostate biopsy, 5 out of the 100 men would have a finding of high-grade prostate cancer upon biopsy. = 95% chance that the biopsy does not find a high-grade prostate cancer. 4Kscore Test Result 1% 5% 10% 15% 20% 25% 30% 40% 50% 60% 70% 80% 90% 95% 100 20 10 6.7 5 4 3.3 2.5 2 < 2 Number of men to biopsy to find one high-grade prostate cancer = 5% chance that the biopsy finds a high-grade prostate cancer. The 4Kscore Test result is a personal risk of a high-grade prostate cancer of Gleason score 7 or higher on prostate biopsy. Other clinical information along with the 4Kscore Test result should be considered in the discussion between the urologist and the patient in the process of making the most informed decision about undergoing biopsy. 4Kscore = Personal Positive Predictive Value Test Description: The 4Kscore Test was developed by OPKO Lab and is performed by OPKO Lab at its CLIA-accredited laboratory. The 4Kscore Test is calculated from the results of four in-vitro diagnostic immunoassays: Total PSA, Free PSA, Intact PSA, and Human Kallikrein (hk2), plus patient age, reported DRE result, and history of prior biopsy. The 4Kscore Test result is reported as a probability of high-grade cancer with a range of less than 1% to greater than 95%. Additional Comments: None

The 4Kscore Test Summary Clinical utility was validated based on a decade of clinical research in over 30,000 men in Europe and the United States Identifies the actual risk of aggressive prostate cancer for the individual patient High grade prostate cancer pathology Poor prostate cancer clinical outcomes within 20 years Has high sensitivity and high negative predictive value for aggressive prostate cancer The only blood test that accurately identifies risk for aggressive prostate cancer