Visit http://www.Agendia.com to learn more about MammaPrint, the only FDA approved breast cancer recurrence test.

1. The Importance of a
Treatment and ER
Independent Assay

2. MammaPrint® is treatment
and ER-independent
 Nearly half of patients (49%) of patients do not comply
with 5 years of Tamoxifen therapy (Owusu et. al., JCO
2008)
 Aromatase inhibitors are in use and untested in
prognostic profiles and also have a compliance issue
(Partridge et. al., JCO 2008)
 Concern with “correctness” of ER interpretation by IHC
(Badve et. al., JCO 2008)

3. MammaPrint® validated on an
untreated patient population
Gene expression profile
identifies “low risk”
and “high risk” tumors
With MammaPrint there are no Tamoxifen compliance issues

4. Some patients may be masking as “low risk”
21 Gene Assay validated on
Tamoxifen treated patients
Profile identifies recurrence
risk assuming 5 years of
Tamoxifen compliance

5. What does “low risk” mean?
 MammaPrint® “Low Risk”: 90% metastasis-free without
any adjuvant treatment over the following 10 years
(NEJM 2002/JNCI 2006).
 The majority of “Low Risk” patients are ER positive, but
a few actually have high risk profiles and can be
expected to have a more ominous clinical course.
 Interestingly, 5-6% of “Low Risk” patients are ER
negative.
 With ER+ patients receiving hormonal therapy, a further
50% risk reduction can be achieved in the “Low Risk”
group, thus MammaPrint “Low Risk” means >95% 10
year metastasis-free survival.

6. 0%
10%
20%
30%
40%
0 10 20 30 40 50 100
For other signatures, “Low Risk” can be as high as
14% recurrence following Hormonal Treatment
Rate of Distant Recurrence by 21-Gene Recurrence
Score in the Clinical Validation Study
Low Risk Intermediate
Risk
High Risk
Rate
95% Confidence Interval
AverageRateofDistantRecurrenceat10Years
after5YearsofTamoxifenTreatment
Recurrence Score
MammaPrint “Low Risk”

7. MammaPrint® Delivers a Definitive
High Risk or Low Risk Result
CLASSIFICATION THRESHOLD
Low Risk
Signature
High Risk
Signature
No Intermediate Results

8. Ease of Interpretation:
MammaPrint® Test Result

9. Criteria for an Ideal Genomic Assay
 Highest Integrity of genomic material
 Selection of an unbiased gene set
 Highest quality clinical data with assay performance
independent of hormone receptor status or compliance with
treatment
 Risk parameters consistent with treatment thresholds for
chemotherapy
 Ease of interpretation
 FDA compliance to insure safety and efficacy
 Predictive data to provide clinical relevance to prognosis
 Data from prospective randomized clinical trials showing
effect on treatment outcomes

10. Regulatory Compliance – FDA IVDMIA

11. 231 reporter genes (incl. 70-gene profile) in nine-fold
465 normalization genes in three-fold
539 control genes in three-fold
XPrint Software
Algorithm
Risk Assessment
(“High” Risk or
“Low” Risk)
5,600 sources
MammaPrint® IVDMIA Microarray

12. What does FDA Regulation mean?
FDA clearance entails:
 Clinical (Claims) Validation
 Clinical Utility
 Technical Validation - Precision, Accuracy,
Reproducibility
 Software Validation
Demonstration that the assay is both safe (to use)
and effective (clinically valid and useful)

13. Alternative to FDA regulation
“Home brew” exemption per CLIA
 No assessment of clinical validity
 No assessment of clinical utility
 No assessment of assay reproducibility
CLIA only means running your lab according
to prescribed Federal standards

14. FDA Clearance of MammaPrint®
Study Purpose Details Comments
1
Nature
Development
70-gene profile
2002
78 patients, LN0, <55yrs
6.4% adjuvant treatment
Within 5 year metastasis risk by
profile multivariate OR 18
2
NEJM
Validation
70-gene profile
2002
151 patients
5.2% adjuvant treatment
Metastasis-free at 10 yrs:
low risk 87%,high risk: 44%
5 yrs: low risk 93%,high risk
56%
3
MammaPrint
Development
MammaPrint
2006
reproducibility of (1) and
(2) on MammaPrint
Highly reproducible
MammaPrint as a diagnostic tool
4
TRANSBIG
Independent
European
validation
2006
302 patients
no adjuvant treatment
Metastasis-free at 10 yrs:
low risk 88%,high risk: 71%
5 yrs: low risk 96%,high risk
83%

15. Reproducibility of 70-Gene
Prognostic Assay – 99%
70-Gene Prognostic Assay Experiment 1
70-GenePrognosticAssayExperiment2

16. Clinical Reproducibility of 70-Gene
Prognostic Assay – 99%
70-GenePrognosticAssayOutcome

17. FDA clears MammaPrint® &
Agendia’s molecular fixative
 February 2007:
MammaPrint granted
FDA first and only IVDMIA
Clearance
 June 2007: FDA Clears
RNARetain molecular
fixative enabling ambient
temperature shipping
These data led to the first FDA clearance for an IVDMIA.