BE PROACTIVE. SCREEN TODAY. PROTECT TOMORROW.

Transcription

1 BE PROACTIVE. SCREEN TODAY. PROTECT TOMORROW.

2 THE LEADER IN FERTILITY & REPRODUCTIVE GENETIC SCREENING EvolveGene was founded by world leaders in preventive and personalized healthcare, with over 25 years of experience in human reproduction, genetic screening and Assisted Reproductive Technology (ART) research. Our research team has published over 250 clinical papers in fertility and genetic research, with over 8,000 related citations, along with over 20 worldwide patents in reproductive technology. Our goal is to provide our valued customers with the most comprehensive Genetic Screening with viable healthcare solutions for your family and for future generations. EVOLVEGENE PRE-CONCEPTION GENETIC SCREENS EVOLVE FERTILITY GENETIC SCREENS Male FertilityReady TM Screen...Cat # MFGS or Cat # MFGB Female FertilityReady TM Screen...Cat # FFGS or Cat # FFGB POF FertilityReady TM Screen (Premature Ovarian Failure)...Cat # FPOS or Cat # FPOB EVOLVE CARRIER GENETIC SCREENS FamilyReady TM Carrier Screen...Cat # CFRS or Cat # CFRB j-familyready TM Carrier Screen...Cat # JFRS or Cat # JFRB DonorReady TM Carrier Screen...Cat # DRCS or Cat # DRCB EVOLVEGENE PRENATAL GENETIC SCREENS BLUE BOX SALIVA RED BOX BLOOD EVOLVE NONINVASIVE PRENATAL GENETIC TESTING EarlyPregnancy TM NIPT Screen... Cat # NIPT EarlyPregnancy TM Plus NIPT Screen... Cat # PLUS Reveal TM Gender Screen... Cat # REVE GOLD BOX BLOOD Support@EvolveGene.com US/Canada: Fax:

3 4 The Evolve Advantage 6 Evolve Genetic Fertility Screens 10 Evolve Genetic Carrier Screens 14 Complimentary Genetic Counseling 15 Pre-IVF Genetic Screening 16 Evolve Genetic NIPT Screens 18 Research Innovations 3

4 Advanced & Accurate Screening Highest detection rates >99% sensitivity/specificity for most genes screened Reporting Reliable Results Testing performed at a state-of-the-art CLIA-licensed & CAP-certified clinical laboratory Specialized in Reproduction The first & leading genetic screens to assess reproductive health The Evolve Advantage Rapid Turn Around Times For most Screens: 2 weeks (or less!) Superior Technology Latest Next Gen Sequencing Molecular Chromosome Analysis Deletion/Duplication Analysis Complete & Relevant Testing Well-researched and prevalent genetic disorders Panels based on professional guidelines Easy Integration into Clinical Care Seamless logistics Access to expert support Complimentary Genetic Counseling Pre-test & post-test consultations 3 Simple Steps to Screen! 1. REGISTER Patients register through the online portal; healthcare providers sign requisition form 2. COLLECT & SEND SAMPLE Either blood or saliva is accepted and courier services deliver samples for analysis 3. RESULTS Throughout the process alerts keep you informed, and within days understandable reports are made available

5 EVOLVEGENE SCREENS Accurate and Advanced Genetic Screening Evolve Genetic Fertility Screens Evolve Genetic Carrier Screens Evolve Genetic NIPT Screens 5

6 EVOLVE GENETIC FERTILITY SCREENS The Leaders in Genetic Fertility Screening Offering the following genetic fertility screens to help determine the genetic causes of infertility in males and females. Evolve Female FertilityReady TM Screen Evolve Male FertilityReady TM Screen Evolve POF FertilityReady TM Screen Genetics is a key component of infertility. Genetic factors influencing fertility include numerical or structural chromosome alterations and genetic mutations. Through advanced genetic technologies, EvolveGene brings actionable and reliable results to improve the chances of reproductive success. Professional medical societies including the American Congress of Obstetricians and Gynecologists (ACOG), the American Urological Association (AUA), and the American Society for Reproductive Medicine (ASRM) recommend females and males with infertility have genetic screening.

7 EVOLVE FERTILITYREADY TM SCREENS The First & Leading Genetic Screens To Assess Reproductive Health Know Your Reproductive Potential Today! Superior genetic screening using the latest Next Generation Sequencing (NGS) technology for P Gene Sequencing P Deletion Duplication Analysis P Molecular Chromosome Analysis FertilityReady TM Screens provide comprehensive insight into the genetic makeup of a person and allow for a more personalized and refined diagnosis and the opportunity for tailored fertility treatments. Specialized gene panels for men and women designed by world leading geneticists and fertility experts. 10% BRINGING A NEW PERSPECTIVE TO INFERTILITY CARE Who should have the Evolve Female FertilityReady TM Screen? Testing Indications: Approximate number of female infertility cases with a genetic factor. Personal or family history of infertility Diminished ovarian reserves (DOR) Premature ovarian failure (POF) Recurrent implantation failure (RIF) Hypogonadotropic hypogonadism (HH) Recurrent pregnancy loss (RPL) Women who are considering delaying having children until after age 35 Women who are considering ART, especially IVF. Who should have the Evolve Male FertilityReady TM Screen? Testing Indications: 15% 30% Personal or family history of infertility Hypogonadotropic hypogonadism (HH) Oligospermia (low sperm count) Azoospermia (absent sperm count) Known genetic causes responsible for male infertility. REF // Foresta C. et al. (2002) Guidelines for the appropriate use of genetic tests in infertile couples. Eur J Hum Genet. 10: Sullivan, S. et al. (2011) FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med. 29: Venkatesh T. et al. (2014) New insights into the genetic basis of infertility. Appl Clin Genet. 7:

8 EVOLVE POF FERTILITYREADY TM SCREEN POF: One of the Most Common Causes of Diminished Female Fertility Premature ovarian failure (POF) also known as primary ovarian insufficiency (POI) is a condition of low or poor reserve of oocytes relative to a given age. Evolve POF FertilityReady TM Screening is intended for any woman with features of POF or a family history of the condition. Features of POF Oligomenorrhea or amenorrhea Elevated levels of serum gonadotropins Low estradiol levels Many women with POF are either misdiagnosed or not diagnosed until their mid-30s when they experience difficulty conceiving a child. The Evolve POF FertilityReady TM Screen is the most comprehensive test specifically for the genetic causes of POF. Using NGS technology for Gene Sequencing + Deletion/Duplication Analysis Accurate Fragile X FMR1 CGG Repeat Analysis. Know Your FMR1 CGG Repeat Number 5-44 repeats: normal repeats: intermediate repeats: premutation >200 repeats: full mutation 1 in 150 women are Fragile X FMR1 premutation carriers* * Women with FMR1 premutations are not only at a high risk of developing POF but they also have an increased risk of having a child with Fragile X syndrome due to the premutation expanding to a full mutation. REF // Chapman C. et al. (2015) The genetics of premature ovarian failure: current perspectives. Int J Womens Health. 7: Goswami D. et al. (2007) Premature ovarian failure. Horm Res. 68: Lozano R. et al. (2014) Fragile X spectrum disorders. Intractable Rare Dis Res. 3:

9 #1 IN GENETIC FERTILITY SCREENING HFM1 ESR1 CATSPER1 AR FSHR HDS17B4 CFTR BLM ZP1 NOBOX FertilityReady TM Genes GALT EIF2B3 FOXL2 POF1B LHCGR AURKC EIF2B2 BMP15 USP9Y LHB EIF2B4 FIGLA FSHB CYP17A1 DIAPH2 FMR1 NR5A1 EIF2B5 CYP19A1 LMNA GDF9 PSMC3IP EVOLVE FERTILITYREADY SCREENS Validated & Supported by clinical research with extensive literature review of >4,000 publications May help reduce repeated IVF failures Rapid turn-around times & reliable results High accuracy & detection rates >99% for most genes screened Gene Panels Available Upon Request Nearly all testing options available to order as a single test! INTRODUCING: EVOLVE DSD SCREEN An advanced genetic screen to detect Disorders of Sexual Development (DSD) Designed by world leading geneticists and fertility experts, Evolve DSD Screen provides an in-depth assessment for genes that impact ovarian and testicular development of male and female external genitalia. DSDs can range in severity from gonadal abnormalities to complete discordance between chromosomal and phenotypic sex. Evolve DSD Screen is a pre-adolescence test that can detect these genetic causes disrupting sex determination and sex differentiation using NGS technology with Gene Sequencing + Deletion/ Duplication Analysis. REF // Hughes IA. et al. (2006) Consensus statement on management of intersex disorders. J Pediatr Urol. 3: Thomas K. et al. (2017) Child and Adolescent Health From 1990 to 2015 : Findings From the Global Burden of Diseases, Injuries, and Risk Factors 2015 Study. JAMA Pediatr. Epub. 9

10 EVOLVE GENETIC CARRIER SCREENS EVOLVE FAMILYREADY TM CARRIER SCREEN Accurate & Comprehensive expanded carrier screen for the most relevant disorders for all ethnicities. It s a simple checkup at the genetic level that every couple should consider variants in >150 genes targeted + full sequencing Females only: Fragile X testing of FMR1 by CGG trinucleotide repeat expansion + reflex AGG interruption analysis for carriers of intermediate alleles and premutations with <100 CGG repeats Deletion/duplication analysis >20 genes (e.g. CFTR, DMD, MECP2, HBA1, HBA2) Spinal Muscular Atrophy SMN1 copy number detection THE LATEST TECHNOLOGY FOR SEQUENCING + DELETION/ DUPLICATION ANALYSIS Del/Dup Analysis NGS EvolveGene Others* *Data as per recent marketing materials. Other refers to laboratories offering similar carrier screens. The Evolve FamilyReady TM Carrier Screen provides in-depth carrier screening with accurate data-proven results using NGS and PCR. Traditional carrier screening involves sequencing, only EvolveGene takes a critical 2nd step with deletion/duplication analysis that is missed by other methods, for the most complete carrier screening in the market. Impact of Genetic Disorders Evolve FamilyReady TM Carrier Screen is a comprehensive genetic carrier screen for the most medically relevant genetic disorders that can significantly impact the health of an individual. The genetic disorders can be categorized into 3 groups, note genetic disorders can belong to one, two, or all three categories. Can be managed early in life and are treatable (e.g. PKU and Wilson Disease) Chronic and require lifelong management (e.g. Sickle Cell Anemia and Fragile X Syndrome) Life-threatening with no curative treatments (e.g. Cystic Fibrosis and Duchenne Muscular Dystrophy)

11 SELECT GENE PANEL of the FAMILYREADY TM SCREEN View the Complete Listing at EvolveGene.com DISORDER... GENE Alphathalassemia...HBA1/HBA2 Argininosuccinate Lyase Deficiency...ASL Aspartylglycosaminuria...AGA Ataxia-Telangiectasia...ATM Beta-Hemoglobinopathies...HBB Beta-Ketothiolase Deficiency...ACAT1 Biotinidase Deficiency...BTD Bloom Syndrome...BLM Canavan Disease...ASPA Choroideremia...CHM Congenital Adrenal Hyperplasia (CAH)...CYP21A2 Costeff Optic Atrophy Syndrome...OPA3 Cystic Fibrosis...CFTR Dihydropyrimidine Dehydrogenase Deficiency...DPYD Duchenne Muscular Dystrophy...DMD Fabry Disease...GLA Factor XI Deficiency...F11 Familial Dysautonomia...IKBKAP Galactosemia...GALT Gaucher Disease...GBA Glucose-6-Phosphate Dehydrogenase Deficiency...G6PD Glutaric Acidemia Type 1...GCDH Growth Hormone Deficiency, Isolated...GHRHR Heme Oxygenase 1 Deficiency...HMOX1 Hemochromatosis...HFE Hemophilia B...F9 Hereditary Fructose Intolerance...ALDOB Homocystinuria, CBS-deficient...CBS Hyperinsulinism...ABCC8 Inclusion Body Myopathy 2...GNE Isovaleric Acidemia...IVD Joubert Syndrome 2...TMEM216 Krabbe Disease...GALC Long Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency... HADHA Maple Syrup Urine Disease Type 1A...BCKDHA Maple Syrup Urine Disease Type 1B...BCKDHB Maple Syrup Urine Disease Type 2...DBT Medium Chain Acyl-CoA Dehydrogenase Deficiency...ACADM Muscle-Eye-Brain Disease...POMGNT1 Nemaline Myopathy...NEB Nijmegen Breakage Syndrome...NBN Oculocutaneous Albinism Type 1...TYR Ornithine Transcarbamylase Deficiency...OTC Phenylalanine Hydroxylase Deficiency (PKU)...PAH Polycystic Kidney Disease, Autosomal Recessive...PKHD1 Retinoschisis, Juvenile...RS1 Salla Disease (a.k.a Sialic Acid Storage Disease)...SLC17A5 Sandhoff Disease...HEXB Segawa Syndrome...TH Short Chain Acyl-CoA Dehydrogenase Deficiency...ACADS Smith-Lemli-Opitz Syndrome...DHCR7 Tay-Sachs Disease (a.k.a. Hexosaminidase A Deficiency)...HEXA Usher Syndrome Type 1F...PCDH15 Usher Syndrome Type 3...CLRN1/ USH3A Very Long Chain Acyl-CoA Dehydrogenase Deficiency...ACADVL Wilson Disease...ATP7B Zellweger Spectrum Disorder Type 1...PEX1 X-Linked Inheritance: Female Parent When a female is a carrier for an X-linked disorder, if she has a daughter, there is a 50% chance she will be a carrier. If she has a son, there is a 50% chance he will be affected by the X-linked disorder. An example of an X-linked disorder is Hemophilia. NORMAL NORMAL 25% MALE CARRIER 25% FEMALE NORMAL 25% CARRIER AFFECTED 25% Autosomal Recessive Inheritance: Both Parents Carriers If both parents are carriers, there is a 25% chance with each pregnancy for sons or daughters to be affected with the genetic disorder. An example of an autosomal recessive disorder is Spinal Muscular Atrophy. NORMAL 25% MALE CARRIERS CARRIERS 50% FEMALE AFFECTED 25% X-Linked Inheritance: Male Parent When a male is a carrier for an X-linked disorder, if he has a daughter, there is a 100% chance she will be a carrier. If he has a son, there is virtually a 0% chance he will be affected by the X-linked disorder. An example of an X-linked disorder is G6PD Deficiency. CARRIER MALE FEMALE NORMAL CARRIER CARRIER NORMAL NORMAL 11

12 Society Guidelines and Recommendations Evolve Genetic Carrier Screens are comprehensive tests that screen for relevant genetic disorders including both the American College of Obstetricians and Gynecologists (ACOG) and the American College of Medical Genetics (ACMG) recommended diseases for individuals of reproductive age or who are considering using donors in ART. ACOG recently released two updated Committee Opinions on carrier screening. Carrier Screening in the Age of Genomic Medicine (#690) stated ethnic-specific, panethnic, and expanded carrier screening are acceptable strategies for pre-pregnancy and prenatal carrier screening. Carrier Screening for Genetic Conditions (#691) states information about genetic carrier screening should be provided to every pregnant woman. Research has shown that individuals, especially those undergoing fertility care, have used information from carrier screening to make a clinical decision regarding their reproductive health. EVOLVE j-familyready TM CARRIER SCREEN Specialized carrier screen specifically for genetic disorders found in those of Jewish descent including those from Ashkenazi and Sephardic populations. Individuals of Jewish descent are at increased risk to be carriers for conditions such as Fanconi Anemia, Bloom Syndrome, and Nonsyndromic hearing loss. EVOLVE DONORREADY TM CARRIER SCREEN Advanced carrier screen developed for sperm and egg donors with optional molecular chromosome analysis. Donors who are carriers need not necessarily be excluded if the reproductive partner has had appropriate carrier screening 2 Testing Methods with 1 Comprehensive Test! Targeted & Full Sequencing Females only: Fragile X testing of FMR1 by CGG trinucleotide repeat expansion + reflex AGG interruption analysis for carriers of intermediate alleles and premutations with <100 CGG repeats Deletion/Duplication Analysis Select genes (e.g. CFTR, HBA1, HBA2) Spinal Muscular Atrophy SMN1 copy number detection Optional molecular chromosome analysis Aneuploidies Aneusomies The American Society of Reproductive Medicine (ASRM) recommends carrier screening for donors. All donors should be tested for cystic fibrosis at minimum. REF // Benn P. et al. (2014) Obstetricians and gynecologists practice and opinions of expanded carrier testing and noninvasive prenatal testing. Prenat Diagn. 34: Edwards J. et al. (2015) Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol. 125: Franasiak J. et al. (2016) Expanded carrier screening in an infertile population: how often is clinical decision making affected? Genet Med. Epub. Recommendation for gamete and embryo donation (2013) Practice Committee of the American Society for Reproductive Medicine and the Practice Committee of the Society for Assisted Reproductive Technology. Fertil Steril Jan; 99(1):47-62.

13 Ethnicity Changes The Chance Of Being A Carrier Some genetic disorders are more common in certain populations. As the chart below demonstrates, your patient s ethnicity alone can put them at an increased risk of being a carrier of a severe recessive genetic disorder. Most people cannot state their ethnicities correctly. With that in mind, our Carrier Screens have been expertly developed to include the most relevant genetic disorders for all ethnic groups. African American Ashkenazi Jewish Asian POPULATION GENETIC DISORDER CARRIER FREQUENCY Beta-Thalassemia Cystic Fibrosis Sickle Cell Disease Cystic Fibrosis Gaucher Disease Tay-Sachs Disease Alpha-Thalassemia Beta-Thalassemia Cystic Fibrosis 1 in 75 1 in 61 1 in 10 1 in 24 1 in 15 1 in 25 1 in 20 1 in 50 1 in 94 European Cystic Fibrosis 1 in 25 French Canadian Tay-Sachs Disease 1 in 30 Hispanic/Latino Beta-Thalassemia Cystic Fibrosis 1 in 40 1 in 58 Mediterranean Beta-Thalassemia Cystic Fibrosis 1 in 25 1 in

14 COMPLIMENTARY GENETIC COUNSELING READY TO ANSWER ALL YOUR QUESTIONS Each EvolveGene Screen includes complimentary genetic counseling for both pre-test consultations and post-test support. Board-certified genetic counselors can responsibly explain the risk, benefits, and limitations of a genetic screen. Results will be explained in the context of the patient s fertility, family, and medical history. Accessible & Convenient Available for patients and healthcare providers based on your schedule Compassionate Consults No matter what the concern, our experts are there to listen Detailed Medical History Allows results to be explained in the context of a patient s personal and family history No Communication Barriers Offering telemedicine services in over 250+ languages Care Continuity Support for patients and clinics along the entire genetic screening process from beginning to end Disclosure Documentation A summary results letter is written for every consult discussing clinical assessment and impact

15 PRE-IVF GENETIC SCREENING WHAT IS PRE-IVF GENETIC SCREENING? Pre-IVF Genetic Screening is a package that includes any FertilityReady TM Screen + a FamilyReady TM Screen for a comprehensive reproductive health assessment at the genetic level. To uncover the causes of infertility & the future risk of inherited disorders. RELIABLE AND ACTIONABLE RESULTS: GIVING OPTIONS TO PLAN Pre-IVF Genetic Screening provides information to help plan and make informed decisions for the healthiest family possible. Only available with EvolveGene. SALIVA collection device is easy to use & FDA Cleared for DNA collection Convenient testing from home! 15

16 EVOLVE GENETIC NIPT SCREENS Providing valuable insights into chromosome health at the first opportunity. Technologically Superior & Scientifically Sound Evolve noninvasive prenatal test (NIPT) Screens are highly accurate to detect multiple fetal chromosomal aneuploidies using maternal blood. MATERNAL BLOODSTREAM P Lowest Technical Failure Rate at 0.1% P Individualized Positive Predictive Value + Fetal Fraction Detection Rates Reported P Latest Next Generation Sequencing (NGS) technology FETAL DNA MATERNAL DNA EVOLVE REVEAL TM GENDER SCREEN Reveal TM Gender Screen is a NIPT that has been specifically designed to analyze only the sex chromosomes for sex determination. Available for singleton & twin pregnancies EVOLVE EARLYPREGNANCY TM NIPT SCREEN The gold standard in NIPT Includes the standard EarlyPregnancy TM NIPT Screen panel for the most prevalent chromosome abnormalities with optional sex chromosome aneuploidies (SCAs) detection available for singleton pregnancies and optional presence of Y chromosome available for twin pregnancies. EVOLVE EARLYPREGNANCY TM PLUS NIPT SCREEN NIPT performance is better than traditional maternal serum prenatal screening and is now a prenatal screening option for all women, regardless of maternal age or risk, including pregnancies conceived by in-vitro fertilization (IVF) and assisted reproductive technologies (ART). Screening can be performed as early as 10 weeks in a pregnancy, with reliable results available just days after your sample is received! An expanded NIPT panel Includes the standard EarlyPregnancy TM NIPT Screen panel with optional detection for SCAs and microdeletion disorders. For an additional $50 fee, NIPT can be upgraded to all chromosome analysis (including SCAs). Available for singleton pregnancies

17 You can focus on patient care while we focus on the science. THE STANDARD EARLYPREGNANCY TM NIPT PANEL CONDITION SENSITIVITY* OBSERVED SENSITIVITY** SPECIFICITY* OBSERVED SPECIFICITY** Trisomy 21 > % 99.8% 99.77% Trisomy % 99.6% 99.69% Trisomy % >99.9% 99.84% * Prenatal test performance data ** Observed sensitivity and specificities were calculated using available outcome data with the cohort size adjusted for the proportion of positive cases with confirmed outcomes. The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) issued a joint Practice Bulletin including Cell-free DNA screening or NIPT as part of the screening options for all pregnancies, to allow for patients to make an informed choice based on their values and goals. According to the bulletin, all pregnant women should be offered aneuploidy screening or diagnostic testing (with informed consent), regardless of maternal age or risk factors. It is also recommended that the option should be discussed with women who achieved IVF pregnancies following preimplantation genetic screening. REF // ACOG (2016) Practice Bulletin No. 163 Screening for Fetal Aneuploidy. Obstet Gynecol. Published Electronically. Illumina (2012) Analytical Validation of the verifi prenatal test: Enhanced Test Performance for Detecting Trisomies 21, 18, and 13 and the Option for Classification of Sex Chromosome Status. Lo Y. et al. (1997) Presence of fetal DNA in maternal plasma and serum. Lancet. 350:

18 RESEARCH INNOVATIONS Leading Genetic Fertility Research To New Frontiers At EvolveGene, we are continuing our 25+ years of experience in the field of reproductive medicine in conjunction with our distinguished scientific team composed of leading embryologists, geneticists and fertility experts to bring meaningful research backed products and services to the field. Through our experience, expertise and passion we are committed to advancing the field of infertility care and reproductive medicine and helping to improve reproductive success around the world. Noninvasive Genetic Screening through Liquid Biopsy EvolveGene is currently undertaking IRB-approved research projects led by our scientific team aimed at developing novel solutions for noninvasive genetic screening in the field of In Vitro Fertilization (IVF).

19 BECOME AN EVOLVEGENE CLINIC MEMBER TODAY Membership is free & benefits include: Automatic replenishment of Evolve kits to clinics Subscription to our Fertility Genetics magazine and newsletters Access to Expert Scientific Speakers available for technical workshops and seminars with patients and clinics Eligibility for Complimentary Evolve kits upon registration Low patient Out-of-Pocket Costs with financial assistance available as necessary Scientific speakers and genetic counseling support can be scheduled on request by contacting EvolveGene specialists. If you are interested in making your clinic part of the EvolveGene Member program, please us at RAPID, RELIABLE & STRAIGHTFORWARD GENETIC SCREENING

20 Questions? Canada/US: Intl.: USA EvolveGene, LLC th St N., Unit A St. Petersburg, FL USA Canada EvolveGene Inc Norwich St E Guelph, ON N1H 2G6 Canada Belgium EvolveGene Industriepark Noord 23 Beernem 8730 Belgium Hong Kong EvolveGene Rm 2115, 21/F Blk C Wah Lok Ind Center, No. 31 Shan Mei Street Sha Tin N.T. Hong Kong EvolveGene Evolve_Folder_ Evolve_Folder_