WISE ChoiceThe Harmony Prenatal Test (NIPT) is based on a very simple promise. Our promise is to provide clinicians across the world and pregnant women of any age with a simple, non-invasive screen for common chromosomal abnormalities, such as trisomy 21.

Respected clinicians rely on the timely and accurate results that we deliver every day.

Some of the claims being made by participants in the NIPT field lately have been based on limited published data. We seek to set the record straight and continue to provide you with the clear, precise, and accurate information you have come to expect from us.

Within please find

• a comparison of blinded validation studies and published false positive rates

• relative PPV values within average and higher-risk populations

• why we measure fetal fraction in every sample we receive

From the way we run our test, to the way we handle your samples, accuracy and quality are our top priorities. We pride ourselves on providing you and your patients the experience you deserve.

We thank you for your continued support and hope to meet your needs for years to come.

Sincerely,

Ken Song, MD Co-founder Ariosa Diagnostics

Ken Song, MD

Quality Leadership

CLEAR ANSWERS TO QUESTIONS THAT MATTER

Not all NIPT Providers are the same. The focus of Ariosa Diagnostics’ dedicated staff is to provide clear answers to questions that matter. The Harmony Prenatal Test is built on an exceptional foundation of solid clinical studies.Table 1

Exceptional Positive Predictive Value (PPV)PPV for any screening test will depend upon the incidence of the condition within a specific population and the false positive rate of the test. Figure 2 The Harmony Prenatal Test’s low false positive rate of less than 0.1% for trisomy 21 also allows us to deliver exceptional PPV.12, 28 The Harmony Test is the wise choice for clinicians that wish to efficiently deliver clarity, maximize PPV, and minimize false alarms in both high and lower risk populations.12, 28

A Global LeaderSince entering the market in 2012, access to the Harmony Prenatal Test has expanded swiftly. In 2015, we began the process of transferring our technology to enable the Harmony Test to be run locally. Since 2016, Life Genomics has been a local Harmony provider in Europe, located in Sweden.

CLEAR ANSWERS TO QUESTIONS THAT MATTER

over 100 countries

900,000+ pregnancies

In the last two years alone, clinicians in over 100 countries have trusted the Harmony Test to provide clear prenatal health information on over 900,000 pregnancies.2

5% FPR(First Trimester

Screening)29

0.75% FPR

0.2% FPR

<0.1% FPR(Harmony)3, 12

6%4%

Figure 2 Theoretical PPV for Trisomy 21 in Average & High Risk Populations *

0 20 40 60 80 100Percent

67%54%

93%80%

35%24%

* Theoretical PPV above calculated based on prevalence of trisomy 21 of 1/417 (“average risk” population) and 1/249 (“high risk” population) at differing false positive rates (FPRs).

“high risk”“average risk”

Accurate Fetal Fraction? Yes, please.

Professional societies like ACOG and SMFM recognize that sufficient fetal fraction is essential for accurate NIPT results.22 For this reason, we measure, report, and incorporate fetal fraction into every test result. 8, 30 Harmony uses a unique targeted technology that differentiates and quantifies maternal and fetal DNA using single nucleotide polymorphisms (SNPs).8, 30 By measuring and incorporating fetal fraction into every Harmony Prenatal Test report, we deliver exceptionally accurate results that include an individualized risk score.

A recent report showed that three of five commercial NIPT test providers reported a normal female fetus in samples from women who were not even pregnant.23 For this same set of samples, The Harmony Prenatal Test correctly reported insufficient fetal cell-free DNA to report a risk assessment result. When other NIPT providers do not measure fetal fraction, their results may be incorrectly based on the DNA of the mother. We clearly note the percent fetal fraction contained in samples, right at the top of every Harmony Prenatal Test patient report.

Focused on Patient Benefits

Patient and Provider InformationPATIENT NAME:

DATE OF BIRTH:(MM/DD/YYYY)

MRN:

LABORATORY ID: OTHER ID:

GESTATIONAL AGE:

# OF FETUSES: IVF STATUS:

COLLECTION DATE (MM/DD/YYYY) : RECEIVED DATE (MM/DD/YYYY) :

ACCOUNT #:

CLINIC NAME:

REFERRING/ORDERING CLINICIAN:

REFERRING/ORDERING CLINICIAN FAX #:

OTHER CLINICIAN:

OTHER CLINICIAN FAX #:

REPORT DATE:(MM/DD/YYYY)

Questions:

clientservices@ariosadx.com

US: (855) 927-4672

Intl: +1 (925) 854-6246

Jane Doe

01/01/1970

1234567890123456789

AD12345678-PAT 00123456789012345XZY

10 wks 5 days

1 non-IVF pregnancy

07/20/2015 07/21/2015

7654321

The Clinic Offering Test

Ordering Physician MD

123-456-7890

Genetic Counselor MA, CGC

987-654-3210

07/28/2015

Laboratory Director: Jack Ji, PhD, FACMG

CLIA # 05D2032812 STATE # CLF 341864TP-00115-F1 Rev 13.0

Test Results

CHROMOSOME RESULT PROBABILITY RECOMMENDATION

TEST DESCRIPTION The Harmony™ Prenatal Tests measure the relative proportion of chromosomes to aid in the riskassessment of fetal trisomies 21, 18, and 13. The laboratory developed tests perform a directedanalysis of cell-free DNA (cfDNA) in maternal blood and incorporate the fetal fraction of cfDNA intest results. Test results also incorporate maternal age (or egg donor age) and gestational agerelated risk based on information provided on the test requisition form. Tests have beenvalidated in singleton and twin pregnancies of at least 10 weeks gestational age. Tests are neitherintended nor validated for diagnosis or for use in pregnancies with more than two fetuses,mosaicism, partial chromosome aneuploidy, translocations, or maternal aneuploidy. Harmonydoes not detect neural tube defects. Twin results reflect the probability that the pregnancyinvolves at least one affected fetus. Analysis of cfDNA does not always correlate with fetalgenotype. Not all aneuploid fetuses will be classified as high risk and some euploid fetuses willhave a high risk result. The Harmony Prenatal Tests are not diagnostic tests and results should beconsidered with other clinical criteria and communicated in a setting that includes appropriatecounseling.

CLINICAL DATA

Detection Rate

> 99%(95% CI: 97.9-99.8%)

97.4%(95% CI: 93.4-99.0%)

93.8%(95% CI: 79.9-98.3%)

False Positive Rate

< 0.1%(95% CI: 0.02-0.07%)

< 0.1%(95% CI: 0.01-0.05%)

< 0.1%(95% CI: 0.01-0.06%)

Detection and false positive (discordant result) rates based on risk cut-off of 1/100 (1%) and onsingleton, non egg donor pregnancies. Because these conditions are rare, limited numbers of

aneuploidy twin and egg donor pregnancies have been evaluated. The negative predictive valuefor Trisomy 21, 18, and 13 is greater than 99%. Positive predictive value (PPV) varies by

prevalence. The probability result reported is not equivalent to the PPV. For more informationregarding PPV refer to: http://www.ariosadx.com

REFERENCES: Sparks AB et al. Am J Obstet Gynecol 2012; 206:319.e1–9; Norton ME et al. Am J Obstet Gynecol 2012; 207:137.e1–8; Nicolaides KH et al. Am J Obstet Gynecol 2012; 207:374.e1–6; Ashoor G et al. Ultrasound Obstet Gynecol 2013; 41(1):21–5;Verweij EJ et al. Prenat Diagn 2013; 33:996–1001; Gil MM et al. Fetal Diagn Ther 2013; 35:1-6; Juneau K et al. Fetal Diagn Ther 2014; 36:282–6; Norton ME et al. N Engl J Med 2015; 372:1589–97; Data on file.

The Harmony Prenatal Tests are intended for clinical use and should not be regarded as investigational or for research. The tests have been developed, and the performance characteristics determined, by the AriosaDiagnostics Clinical Laboratory, which is certified under the Clinical Laboratory Improvement Act of 1988 (CLIA) as qualified to perform high complexity clinical testing. The Harmony Prenatal tests have not been cleared orapproved by the U.S. Food and Drug Administration.

Fetal cfDNA Percentage: 10.5%

21

Trisomy 21 (T21) Low Risk Less than 1/10,000 (0.01%) Review results with patient

18

Trisomy 18 (T18) Low Risk Less than 1/10,000 (0.01%) Review results with patient

13

Trisomy 13 (T13) Low Risk Less than 1/10,000 (0.01%) Review results with patient

1. As of September, 2015. Internal data on file. 2. As of May, 2015. Internal data on file. 3. Norton et al. Am J Obstet Gynecol. 2012 Aug;207(2):137.e1-8. 4. Nicolaides et al. Am J Obstet Gynecol. 2012 Nov;207(5):374.e1-6. 5. Ashoor et al. Ultrasound Obstet Gynecol. 2013 Jan;41(1):21-5. 6. Verweij et al. Prenat Diagn. 2013 Oct;33(10):996-1001. 7. Ashoor et al. Am J Obstet Gynecol. 2012 Apr;206(4):322.e1-5. 8. Sparks et al. Am J Obstet Gynecol. 2012 Apr;206(4):319.e1-9. 9. Gil et al. Fetal Diagn Ther. 2014;35:204-11. 10. Nicolaides et al. Fetal Diagn Ther. 2014;35(1):1-6. 11. Hooks et al. Prenat Diagn. 2014 May;34(5):496-9. 12. Norton et al. N Engl J Med. 2015 Apr 23;372(17):1589-97 13. Nicolaides et al. Prenat Diagn. 2013 Jun;33(6):575-9. 14. Pergament et al. Obstet Gynecol. 2014 Aug;124(2 Pt 1):210-8.

15. Sehnert et al. Clin Chem. 2011 Jul;57(7):1042-9. 16. Bianchi et al. Obstet Gynecol. 2012 May;119(5):890-901. 17. Bianchi et al. N Engl J Med. 2014 Feb 27;370(9):799-808. 18. Illumina website - Sept 14, 2015: http://bit.ly/1iDhSOd 19. Ehrich et al. Am J Obstet Gynecol. 2011 Mar;204(3):205.e1-11. 20. Palomaki et al. Genet Med. 2011 Nov;13(11):913-20. 21. Palomaki et al. Genet Med. 2012 Mar;14(3):296-305. 22. Cell-free DNA Screening for fetal aneuploidy. Committee opinion No. 640. American College of Obstetricians & Gynecologists. Obstet Gynecol 2015; 126:e31-7.23. Takoudes and Hamar. Ultrasound Obstet Gynecol. 2015 Jan;45(1):112.24. Illumina website - Sept 14, 2015: http://bit.ly/1Kpo6rz 25. Sequenom website - Sept 14, 2015: http://bit.ly/1Oi6VPI26. Panorama website - Sept 14, 2015: http://bit.ly/1P53jOt

27. Wax et al. J Clin Ultrasound. 2015 Jan;43(1):1-6.28. Stokowski, et al. Prenat Diagn. 2015 Sep 1. doi: 10.1002/pd.4686.29. ACOG Committee of Practice Bulletin No. 77. Obstet Gynecol 2007; 109:217-2730. Juneau et al. Fetal Diagn Ther. 2014;36(4):282-6.31. Dondorp et al. Eur J Hum Genet. 2015 Apr 1. doi: 10.1038/ejhg.2015.56. [Epub ahead of print]32. Mazloom et al. Prenat Diagn. 2013 Jun;33(6):591-7. 33. Canick et al. Prenat Diagn. 2013 Jul;33(7):667-7434. Porreco et al. Am J Abstst Gynecol. 2014 Oct;211(4)365.e12.35. Samango-Sprouse et al. Prenat Diagn. 2013 Jul;33(7):643-9

CLEAR ANSWERS TO QUESTIONS THAT MATTER

Reducing False Positives Over 90 Times Compared to FTS12

First Trimester Screening False Positives = 854 The Harmony Prenatal Test False Positives = 9

From our inception, Ariosa® has focused on serving the prenatal screening needs of pregnant women with exceptional accuracy. Harmony is the leading non-invasive prenatal test that assesses the risk of trisomy 21, 18, and 13 in pregnant women of any age or risk category.* In the largest blinded, prospective head-to-head comparative study to date, published in the New England Journal of Medicine, the Harmony Test significantly outperformed First Trimester Screening (FTS) that measures maternal serum for biochemical markers for trisomy 21 within the general pregnancy population.12

In this landmark NEXT (Non-Invasive Examination of Trisomy) Study, Harmony’s detection rate for Trisomy 21 was >99%, compared with 79% for traditional FTS. The Harmony test’s false positive rate was 0.06% compared to 5.4% for traditional screening.12

Studies show that the Harmony’s false positive rate is also lower than those of most major NIPT providers.Table 1

NIPT Leadership

Extensively Validated The Harmony Prenatal Test has been validated in published blinded clinical studies conducted on more than 22,000 pregnant patients.3-12, 28 In 2015, our data set was three times as large as all the major NIPT screening providers combined.

As blinded clinical studies are the appropriate standard for validation, the science supporting the Harmony Prenatal Test is in a class by itself.

Total Patients Tested in Blinded Validation Studies

Illumina® verifi™ = 2,510 15-17

Sequenom® MaterniT21® = 6,280 19-21, 32-34

Natera™ Panorama™ = 1,306 13, 14

Harmony > 22,000 validated results 3-12, 28

* Providers of generic NIPT tests often do not have any blinded validation studies.

* Both under 35 and over 35 age groups, studies have included women ages 18-48

 Illumina®/

Verinata® verifi ™Sequenom®

MaterniT21®Natera™

Panorama™Generic

Illumina® NIPT

Claimed Cumulative False Positive Rates (T21, T18, T13)

Less than 0.1%28 0.21%24 0.8%25 Less than

0.1%26 0.21%18

False Positive Rate Claims (for T21, T18, T13) Based Upon

Published Clinical Validation Studies

Limited Published Clinical Validation Studies, Unpublished Data

Limited Published Clinical Validation Studies

LimitedPublished Clinical Validation Studies

Unpublished Data

Table 1

PUBLISHED CLINICAL VALIDATION STUDIES1

Figure 1

12

3-12, 28, 30

3

15-17

6

19-21, 32-34

3

13, 14, 35

0

Illumina®/ Verinata® verifi ™

Sequenom®

MaterniT21®

Natera™

Panorama™

Generic Illumina® NIPT

CLEAR ANSWERS TO QUESTIONS THAT MATTER

Harmony BenefitsFAST: Lab results in as little as a week from time of receipt.

EARLY: Can be performed as early as 10 weeks gestation.

ACCURATE: Exceptional accuracy in pregnant women of any age or risk. Results proven in published blinded studies of over 22,000 delivered a false-positive rate for trisomy 21 of less than 0.1%.28

SAFE: A simple blood draw may minimize invasive procedures caused by false positive results.27

TRUSTED: Clinicians in over 100 countries have trusted the Harmony Test to provide clear prenatal health information on 900,000+ pregnancies.2

CLEAR ANSWERS TO QUESTIONS THAT MATTER

For both Monosomy X and the Sex Chromosome Aneuploidy Panel, fetal sex will not be reported unless the Fetal Sex box is checked separately. However if the result indicates a high risk for sex chromosome aneuploidy, then this risk assessment will indirectly provide information regarding fetal sex. The Harmony Prenatal test is not available for more than 2 fetuses.

The Harmony Prenatal Test is validated for use in singleton, twin, and IVF pregnancies, including self and non-self egg donor pregnancies.9

The following test options are also available from the same blood draw:

Fetal Sex

Provides information regarding fetal sex. Assessment of fetal sex does not include risk assessment of sex chromosome aneuploidy. In twin pregnancies, a female result applies to both fetuses; a male result applies to one or both fetuses.

Monosomy X Provides monosomy X risk assessment, but no information regarding other sex chromosome aneuploidies.

Sex Chromosome Aneuploidy Panel

Provides assessment of risk of X and Y chromosome aneuploidies, including monosomy X, XXX, XXY, XYY and XXYY.

22q11.2 Provides assessment of 22q11.2 deletion syndrome (DiGeorge syndrome).

SINGLETON EGG DONOR & IVF

TWINS

Harmony Prenatal Test

Evaluates the risk of fetal trisomy 21, trisomy 18 and trisomy 13.

AVAILABLE FOR

Draw a maternal blood sample at 10 weeks or later in pregnancy

Submit sample to Life Genomics through one of our clinical partners.

Lab results in as little as a week from time of receipt.12 131

Visit us at nipt.se For assistance email info@lifegenomics.se or call Life Genomics Laboratory +46 708 58 33 72

Three Simple Steps to Clarity

Test Options

COMBINED FALSE POSITIVE

RATE28

< 0.1%Trisomies 21,18, 13

FETAL FRACTION

MEASUREMENT

100%of all eligible

samples

DETECTION RATE 28

Trisomy 21

>99%False negative rate <1%

CLEAR ANSWERS TO QUESTIONS THAT MATTER

Ref: MM-00665-101515-Rev1.0LG-H-NLT-Rev1.0

The Harmony® Prenatal Test was developed by Ariosa Diagnostics (San Jose, California, USA). The Harmony® reagents and Ariosa cell-free DNA System (AcfS) software used as part of the Harmony Prenatal Test are CE Marked under the IVD Directive 98/79/EC. Harmony is a non-invasive prenatal test (NIPT) based on cell-free DNA analysis. The results are intended for prenatal screening and are not intended to be the sole basis for diagnosis. Harmony does not screen for potential chromosomal or genetic conditions other than those expressly identified in this document. Before making any treatment decisions, all women should discuss their results with their healthcare provider, who can recommend confirmatory, diagnostic testing where appropriate.

HARMONY and HARMONY design are trademarks of Ariosa Diagnostics, Inc. in the US. HARMONY is a trademark of Roche in other countries. All other trademarks are the property of their respective owners.

© 2016 Life Genomics AB. All Rights Reserved.