Critical diagnostics introducing the aspect plus™ st2 test.

1. Introducing the Aspect-PLUS™ ST2 Test
James V. Snider, Ph.D.
President
Critical Diagnostics
Heart Failure 2015

3. Why produce a FAST assay for ST2?
• Using the 1st generation ELISA many things were
accomplished
• ST2 is CE marked for sale in the EU and is cleared by
the US FDA, CFDA and KFDA as an aid in risk
stratification of patients with heart failure.
• Included in the 2013 ACCF/AHA guidelines for heart
failure patient management.
• In 2014 the AMA issued a unique CPT code for ST2,
83006, and in January 2015 CMS issued a favorable
coverage/payment decision.
• April 2015 the AJC published the International ST2
Consensus Panel paper summarizing the clinical value
of ST2.
– Twelve chapters and over 80 pages summarizing the support for
clinical use of ST2 across all 4 stages of heart failure.

4. ST2 Clinical Value
• In published research studies ST2 is
consistently the most robust prognostic
marker reported
• With its low RCV it is ideally suited for patient
monitoring
• ST2 is not adversely effected by typical
confounders such as renal dysfunction and
obesity
• Emerging evidence shows the utility of using
ST2 to personalize patient therapy

5. Serial ST2 Measurements:
Basel ADHF Cohort
Breidhardt, et al. 2013, J. Card. Failure

6. ST2 Predicts Therapy ResponseCumulativesurvival
Days
BB treated ST2 responder
untreated ST2 responder
untreated ST2 non-responder
BB treated ST2 non-responder
p=0.62
p=0.1
• Risk is not absolute!
• It can be attenuated!!
Breidhardt, et al. 2013, J. Card. Failure
RR=2.8

7. ST2 Therapeutic Response:
PROTECT Study
Non- Rarely Mostly Full
CV events by ST2 time in response
% time in response
%withCVevents
0.00.20.40.60.81.0
Non-responder
Rarely responder
Mostly responder
Full responder
N=46 N=28 N=30 N=41
Summary:
• Time in ST2 response (<35
ng/ml) is closely tied to
outcomes in chronic HF due
to LVSD.
• The prognostic value of
sST2 is independent of
relevant covariates,
including NT-proBNP.
• “Only sST2 appeared to
provide incremental
prognostic information and
reflect changes in
myocardial remodeling over
time.”
Gaggin et al. 2014, JACC HF

8. Cardiovascular events by baseline sST2 and final
achieved β-blocker (BB) dose
Gaggin H et al. Circ Heart Fail 2013;6:1206-1213 Copyright © American Heart Association, Inc. All rights reserved.
p = 0.09
P < 0.001
for trend

9. Stage B NYHA Class I HF Progression
Biomarker Levels and Therapy in Subsequent Visits
1 2 3 4 5 6 7
0
10
20
30
40
50
60
70
80
90
0
100
200
300
400
500
600
700
800
900
ST2(ng/mL)
NT-proBNP(pg/mL)
β blocker
increased
β blocker
increased
ACE-inhibitor
increased
Visits

10. Aspect-PLUS™ ST2 Test
• Quantitative
fluorescent lateral flow
immunoassay format
• System is comprised of
a disposable, single use
cassette and a
fluorescent reader
• Uses EDTA plasma as
the test specimen
• Result in 20 minutes
• Analytical performance
comparable to the
Presage® ST2 Assay

11. Aspect-PLUS™ ST2 Test:
Performance
Parameter Presage® ST2 Assay Aspect-PLUS™ ST2 Test
Limit of Quantitation (LoQ) 2.4 ng/ml 12.5 ng/ml
Linearity Limit 200 ng/ml 257 ng/ml
Intra-Assay Precision 4.0% 10.4%
Inter-Assay Precision 6.4% 13.6%
Hook Effect No hook effect up to 200 ng/ml No hook effect up to 2000 ng/ml
Interfering Substances
No effect observed from 5 endogenous and 49 therapeutic
substances
Specimen EDTA or heparin plasma, serum EDTA plasma
Specimen volume 0.020 ml 0.035 ml
Method Concordance:
Passing-Bablok regression
No significant deviation from linearity (y = 1.01x + 5.8, p=0.75, ).
And a correlation coefficient (R) of 0.92.

12. Conclusions
• ST2 is established as a powerful biomarker
tool for personalization and optimization of
heart failure patient care
• The Aspect-PLUS™ ST2 Test is the first
rapid test providing a cost effective solution
for ST2 testing
• The Aspect-PLUS™ ST2 Test is comparable
to the established Presage® ST2 Assay and
meets the requirements for IVD analytical
performance.