The 4Kscore® blood test for risk of aggressive prostate cancer

Early detection of aggressive prostate cancerChallenges

• 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- 67% 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 22,000 men in 12 clinical studies and validated in a prospective, blinded prebiopsy study of 1,012 men in US

• Included in the 2015 NCCN Guidelines for Prostate Cancer Early Detection

2015 NCCN Prostate Cancer Early Detection Guidelines

What is the 4Kscore Test?

Components Results

Total PSA

Free PSAIntact PSA hK2

+ Age, DRE, and prior biopsy status

Proprietary to OPKO {

% risk of havingaggressive prostate

cancer for an individual patient

4Kscore Test: 10 years of clinical research conducted by Memorial Sloan Kettering Cancer Center and leading international cancer centers

Prospective, blinded, multicenter US study validates 4Kscore Test

• 1,012 patients enrolled in 26 academic and community practices

• Referred for biopsy regardless of age, PSA, clinical findings or prior biopsy status

• Minimum of 10 core TRUS-guided biopsies performed

• The 4Kscore Test was performed at OPKO Lab, Nashville, TN

• Pathology conducted according to the established practice at each center

• Presented in the 2014 AUA Plenary Session and published in European Urology (http://dx.doi.org/10.1016/j.eururo.2014.10.021) Epub Ahead of Print

26 Clinical study sites

Gleason score distribution in Prospective US Study

Negative or Gleason 6 prostate cancer

Aggressive (Gleason ≥ 7)

prostate cancer

The 4Kscore Test has the greatest accuracy for predicting aggressive prostate cancer

Sensitivity

1 - Specificity

AUC = 0.5

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

PHI = 0.72, 0.67 2,3

PCA3 = 0.68 4

1. Parekh, D et al. http://dx.doi.org/10.1016/j.eururo.2014.10.021(Epub Ahead of Print)2. Catalona et al. J Urol. 185:1650 2011

3. Wang, W et al. Scientific Reports 4:1-8 20144. 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

4Kscore Test is more accurate than total PSA alone in predicting aggressive prostate cancer in subset of men with PSA 16-20ng/mL

Improving the Specificity of Screening for Lethal Prostate Cancer Using Prostate-specific Antigen and a Panel of Kallikrein Markers: A Nested Case–Control Study Stattin, P et al. http://dx.doi.org/10.1016/j.eururo.2015.01.009(Epub Ahead of Print)

4Kscore Test Biomarkers> 7.5% (N =1510, 62%)

4Kscore Test Biomarkers≤ 7.5% (N = 922, 38%)

5 year10

year15

year20

year

= 2.4%= 5.6%= 9.9%= 16.4%

5 year10 year15 year20 year

= 0%= 0.2%= 1.0%= 1.8%

4Kscore> 7.5%

all men PSA ≥ 3

4Kscore≤ 7.5%

all men PSA ≥ 3

The 4Kscore Test predicts the probability of distant metastases within 20 years

Clear result reporting for informed decision making

4Kscore =Personal Positive Predictive Value

The 4Kscore Test Summary

• Included in the 2015 NCCN Guidelines for Prostate Cancer Early Detection

• Clinical utility was validated based on a decade of research in over 22,000 men in Europe and the United States

• Identifies the 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