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MyRisk®, FirstGene®, Prequel®, and Foresight® studies among 10 datasets to be shared by MyriadSALT LAKE CITY, Sept. 18, 2024 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in genetic testing and precision medicine, today announced it will showcase 10 studies highlighting its advancements in oncology and reproductive genetic testing at the National Society of Genetic Counselors (NSGC) 43rd Annual Conference, which will take place from Sept. 17-21, 2024, in New Orleans, LA. The research will highlight the value of genetic and genomic testing in patient care and will cover the company’s MyRisk Hereditary Cancer Test, FirstGene Multiple Prenatal Screen, Prequel Prenatal Screen and Foresight Carrier Screen. “At Myriad, we’re committed to partnering with genetic counselors in an effort to make genetic testing more accessible, affordable and easier to use for all patient populations,” said Susan Manley, Senior Vice President of Medical Services, Myriad Genetics. “We’re excited to share our new research with the genetic counselor community at this year’s NSGC Conference and to showcase how our latest advancements may help better inform personalized care and improve outcomes for patients.” Myriad’s latest innovations and support services will be on display at booth #119 and through a series of poster presentations at the conference. Myriad’s Presentation Schedule Wednesday, Sept. 18, 2024, from 12:15-2:00pm and 5:45-7:00pm CDT Poster CAN91: Age at Diagnosis of Breast Cancer for Women with Pathogenic Variants in BARD1, RAD51C, and RAD51DSummary: This study shows that the median age of breast cancer diagnosis with pathogenic variants (PVs) in BARD1, RAD51C, and RAD51D is similar to that of other breast cancer genes. Additionally, it shows that a significant number of PV carriers are diagnosed prior to the recommended screening age of 40 years. Poster PRE323: Outcomes in pregnancies that screened positive for rare autosomal aneuploidies (RAAs) Summary: By linking prenatal cell-free DNA results to insurance claims data, this study provides evidence that RAA-screen positive patients have higher rates of miscarriage and preterm birth as compared to RAA-screen negative patients. Poster PRE333: Complications and outcomes of pregnancies screening positive for microdeletions 22q11.2, 15q11.2, 1p36, 4p, or 5pSummary: This study shows that microdeletion screen-positive pregnancies may experience higher rates of ultrasound abnormalities and pregnancy complications. Poster PRE347: Validation of fetal and maternal recessive disease genotyping with FirstGene: a combined, non-invasive prenatal cfDNA assay for fetal aneuploidy, recessive diseases, and serological screeningSummary: This study indicates that the FirstGene screen accurately identifies fetal SNV and INDELs for recessive conditions. Poster PRE349: Validation of fetal and maternal spinal muscular atrophy (SMA) and hemoglobin (Hb) Bart’s screening with FirstGene, a combined, non-invasive prenatal cfDNA assay for fetal aneuploidy, recessive diseases, and serological screening Summary: This study indicates that the FirstGene screen accurately identifies maternal and fetal SMA and Hb Bart’s disease status. Poster PRE351: Validation of fetal RHD copy number calling in FirstGene, a combined, non-invasive prenatal cfDNA assay for fetal aneuploidy, recessive diseases, and serological screeningSummary: This study indicates that the FirstGene assay accurately determines fetal RHD copy number in RhD-negative pregnant patients. Thursday, Sept. 19, 2024, from 12:00-3:00pm and 4:30-6:30pm CDT Poster PRE324: A comparison of carrier rates derived from different data sourcesSummary: This study shows high concordance in carrier rates between Myriad’s database and gnomAD data. Poster PRE344: Investigating cancer diagnosis codes after atypical findings on noninvasive prenatal cell-free DNA (pcfDNA) screeningSummary: This study indicates that patients with an autosomal monosomy or multiple aneuploidies on pcfDNA have a higher risk of a cancer diagnosis than those without. Poster PRE348: Validation of fetal aneuploidy detection with FirstGene: a combined, non-invasive prenatal cfDNA assay for fetal aneuploidy, recessive diseases, and serological screeningSummary: This study indicates that fetal aneuploidy screening on the FirstGene assay is comparable to that of standalone WGS-based pcfDNA screening with fetal fraction amplification. Lunch Symposium: At 12:45pm CDT, Myriad will host a lunch symposium titled ‘How genetic counselors can integrate breast cancer risk assessment programs into surgical, primary care, OB/GYN, and imaging clinics’, moderated by Myriad’s Susan Manley. Myriad will also have a virtual presentation, Characteristics and Cancer Incidence in MITF p.E318K Carriers, available for viewing on the NSGC online experience platform. This study shows that MITF carriers have an increased risk of melanoma, but not renal cancer, as several other studies have suggested. For more information about Myriad’s presence at NSGC, please visit: https://myriad.com/nsgc2024/. Updates will also be shared across Myriad’s LinkedIn and X channels throughout the conference. About Myriad GeneticsMyriad Genetics is a leading genetic testing and precision medicine company dedicated to advancing health and well-being for all. Myriad develops and offers genetic tests that help assess the risk of developing disease or disease progression and guide treatment decisions across medical specialties where genetic insights can significantly improve patient care and lower healthcare costs. For more information, visit www.myriad.com. Safe Harbor StatementThis press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company's commitment to partnering with genetic counselors in an effort to make genetic testing more accessible, affordable and easier to use for all patient populations and how the company’s latest advancement may help better inform personalized care and improve outcomes for patients. These “forward-looking statements” are management’s expectations of future events as of the date hereof and are subject to known and unknown risks and uncertainties that could cause actual results, conditions, and events to differ materially and adversely from those anticipated. Such factors include those risks described in the company’s filings with the U.S. Securities and Exchange Commission, including the company’s Annual Report on Form 10-K filed on February 28, 2024, as well as any updates to those risk factors filed from time to time in the company’s Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. Myriad is not under any obligation, and it expressly disclaims any obligation, to update or alter any forward-looking statements, whether as a result of new information, future events or otherwise except as required by law. Investor ContactMatt Scalo(801) 584-3532IR@myriad.com Media ContactGlenn Farrell(385) 318-3718PR@myriad.com

VYN201 demonstrated positive effect on key biomarkers relevant to vitiligo Data supports VYN201’s rapid onset of action and previously announced positive clinical results Program is on track for Phase 2b initiation in Q2 Jan. 10, 2024 (GLOBE NEWSWIRE) -- VYNE Therapeutics Inc. (Nasdaq: VYNE) (“VYNE” or the “Company”), a clinical-stage biopharmaceutical company developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions, today announced new biomarker data from the previously completed Phase 1b trial in patients with nonsegmental vitiligo. The data show that BET inhibitor, VYN201, had a positive effect on multiple disease-associated biomarkers. Positive clinical data from the Phase 1b trial were announced in October 2023. The trial was a 16-week open-label study assessing the safety, tolerability, pharmacokinetics, and exploratory efficacy of once-daily topical VYN201 in 29 patients with a clinical diagnosis of active nonsegmental vitiligo, in three dose cohorts (0.5%, 1.0% and 2.0% strengths). Enrolled subjects had two, non-facial active vitiligo lesions. One lesion, selected for treatment with VYN201, had skin tissue biopsies taken prior to first application of VYN201 and after 8 weeks of treatment. Biopsies were analyzed to quantify the effect of VYN201 on specific biomarkers related to inflammation associated with vitiligo, melanocyte proliferation, and melanogenesis. Exploratory data from the 1.0% and 2.0% cohorts showed that VYN201 treatment demonstrated biological activity and a positive effect on certain key biomarkers relevant to vitiligo disease severity and progression. The magnitude of biomarker modulation was more pronounced in the 2.0% dose cohort than in the 1.0% dose cohort, indicative of an emerging dose-response. Results from the biomarker analyses include the following: Downregulation of Matrix metalloproteinase-9 (MMP-9) levels: VYN201 induced the downregulation of MMP-9 in biopsied lesional skin after 8 weeks of treatment compared to baseline. MMP-9 is an inflammatory biomarker associated with the detachment and subsequent loss of melanocytes from skin in vitiligo and is elevated in patients with vitiligo. At Week 8, there was a median reduction in MMP-9 of 40.8% in lesional skin compared to baseline for subjects in the 2.0% cohort. Upregulation of melanocyte-related transcription factors (MRTFs): VYN201 induced the upregulation of multiple MRTFs, including SRY-box transcription factor 10 (SOX10), Lymphoid-enhancing factor-1 (LEF1), β-Catenin and Microphthalmia associated transcription factor (MITF), after 8 weeks of treatment compared to baseline. Each of these markers are linked to the proliferation of melanocytes, recovery in melanogenesis, and subsequent re-pigmentation of skin. In the 2.0% cohort, SOX10, LEF1, β-Catenin and MITF transcription factors had median increases of 36.1%, 90.2%, 16.5% and 15.2% in their respective expression levels in lesional skin compared to baseline. “VYN201’s potential to reduce melanocyte detachment by downregulating MMP-9 and by upregulating the expression of proteins relevant to melanocyte proliferation and melanogenesis is promising, and I look forward to the continued advancement of VYN201 as a potential differentiated therapy for vitiligo,” said Amit Pandya, M.D., former President of the Global Vitiligo Foundation and Dermatologist, Department of Dermatology, Palo Alto Foundation Medical Group. “We are encouraged by these new biomarker data from the Phase 1b trial for VYN201, building on our recently announced positive clinical results,” said David Domzalski, President and CEO of VYNE. “We’ve made considerable progress in advancing this program, and we look forward to initiating a Phase 2b trial evaluating VYN201 in patients with both active and stable nonsegmental vitiligo in the second quarter of this year.” The loss of functional melanocytes in vitiligo is associated with the generation of inflammatory mediators that facilitate melanocyte detachment in skin.1 This cellular detachment occurs due to the disrupted surface distribution of adhesion molecule E-cadherin and the release of soluble E-cadherin.2 E-cadherin cleavage may be induced by several metalloproteinases including MMP-9. MMP-9 is secreted by the keratinocytes in response to various proinflammatory cytokines such as IFN-γ and TNF-α.3 The Wnt/β-catenin pathway plays an essential role in pigmentation by regulating both melanocyte differentiation and melanogenesis through the action of MITF.4 β-catenin is increased by the binding of Wnt proteins to their receptors, leading to transport of β-catenin into the nucleus, where it regulates transcription of MITF through interactions with several transcription factors that include LEF1 and SOX10. MITF also regulates transcription of downstream genes key for melanin synthesis and melanocyte cell development. Vitiligo is a chronic autoimmune depigmenting disorder of the skin, characterized by the loss of pigment producing cells known as melanocytes. Vitiligo is the most common depigmenting skin condition, with a prevalence estimated at 0.5-2.0% of the world population.5 There is currently only one FDA-approved product for the treatment of vitiligo. Nonsegmental vitiligo is the most common type of vitiligo. VYN201 is a pan-bromodomain BET inhibitor designed to be locally-administered as a “soft” drug to address diseases involving multiple, diverse inflammatory cell signaling pathways while providing low systemic exposure. To date, VYN201 has produced consistent reductions in pro-inflammatory and disease-related biomarkers and improvements in disease severity, and demonstrated local activity in several preclinical models (using several different routes of administration). BET proteins play a key role in regulating gene transcription via epigenetic interactions (“reading”), and recent research has determined a key role for these proteins in regulating B cell and T cell activation and subsequent inflammatory processes. As epigenetic readers, BET proteins regulate the recruitment of transcriptional factors that are key to the production of several pro-inflammatory cytokines. BET inhibitors have the potential to treat a range of immuno-inflammatory and fibrotic diseases by blocking pro-inflammatory cytokine transcription with additional potential in myeloproliferative neoplastic disorders. 1. Picardo, M. et al. Nat. Rev. Dis. Primer 1, 15011 (2015). 2. Delmas, V. & Larue, L. Exp. Dermatol. 28, 662–666 (2019). 3. Boukhedouni, N. et al. JCI Insight 5, 133772 (2020). 4. Zhao SJ et al, Clin Cosmet Investig Dermatol. Sep 1;14:1089-11031 (2021). 5. Rosmarin et al, Lancet (2020);396:110-120. VYNE’s mission is to improve the lives of patients by developing proprietary, innovative and differentiated therapies for the treatment of immuno-inflammatory conditions. The Company’s unique and proprietary bromodomain & extra-terminal (BET) domain inhibitors, which comprise its InhiBET™ platform, include a locally administered pan-BD BET inhibitor (VYN201) and an orally available BD2-selective BET inhibitor (VYN202) that were licensed from Tay Therapeutics Limited. 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Researchers have discovered key insights into the molecular basis of skin color variations among African populations. Their findings broaden the understanding of human evolution and the genetics underpinning contemporary human skin color diversity. Researchers from the University of Pennsylvania have discovered key insights into the molecular basis of skin color variations among African populations. Their findings, published in Nature Genetics, broaden the understanding of human evolution and the genetics underpinning contemporary human skin color diversity. "Despite the abundant genetic diversity within African populations, they have been historically underrepresented in genetic studies," says senior author Sarah Tishkoff, a Penn Integrates Knowledge University Professor with appointments in the Perelman School of Medicine and School of Arts & Sciences. "Our findings offer novel information about the genetic basis and evolutionary history of skin color diversity, contributing to a clearer depiction of human evolution." The story of human evolution is as rich and diverse as the adaptations found across the world's populations, Tishkoff says. She notes that, among many adaptive traits, skin color stands out as one of the most well-known. Darker skin tones, prevalent in equatorial regions, serve as nature's very own sunblock, evolving over millennia to shield these populations from the sun's intense ultraviolet radiation. Conversely, lighter pigmentation, as seen in populations closer to the poles, is an adaptation to mitigate the risks of insufficient sun exposure by maximizing vitamin D production, which is triggered by UV exposure. "Our approach involved genome-wide association studies of skin color from more than 1,500 eastern and southern African individuals as well as scanning the genome to identify genetic variants that are highly differentiated between lightly-pigmented Khoesan-speaking San population and other darkly pigmented Africans and may play a role in local adaptation in that population," says Yuanqing Feng, first author of the paper and a postdoctoral researcher in the Tishkoff Lab. The researchers note that pigmentation is a complex trait influenced by hundreds of variants scattered across the genome, with the majority situated in noncoding regions. These noncoding variants may affect the expression of genes located up to one million bases away. The vast number of mutations associated with skin color and the uncertainty surrounding the target genes regulated by these mutations make it particularly arduous for researchers to find the precise genetic mechanisms governing this trait. Feng and collaborators used massively parallel reporter assays to discern the regulatory activities of thousands of variants. This high-throughput technique narrowed down the thousands of candidates to 165 functional variants. To identify the target genes of these functional variants, Feng further constructed high-resolution chromatin interaction maps in melanocytic cells using chromatin conformation capture assays. "This is a high-resolution 3D genome map in melanoma cells that will be valuable for gene regulation studies in pigmentation and melanoma biology," Feng says. Using CRISPR/Cas9-based genome editing, the researchers discovered that mutations in an enhancer of OCA2, a gene associated with albinism, could lead to a 75% reduction in melanin levels when compared to control cells. Within the same OCA2 enhancer, the researchers identified two closely located regulatory variants, estimated to be 1.2 million years old and 57 thousand years old, with the latter coinciding with the period of human migration from Africa. "This case illustrates the continuous evolution of human skin color, and it's remarkable to observe the significant effects on skin pigmentation attributed to a single enhancer," Feng says. San people have relatively lighter pigmentation compared to other African populations and possess the oldest genetic lineages in humans. While it is hypothesized that the light skin color of the San may result from adaptation to a southern African environment, the genetic underpinnings of this adaptation remain elusive. The researchers pinpointed several crucial regulatory variants near MITF, LEF1, and TRPS1 that contribute to the skin color adaptation observed in the San. "MITF, LEF1, and TRPS1 are involved in signaling pathways regulating both melanocyte differentiation and hair development," Tishkoff says. "This suggests that the variants influencing the lighter skin pigmentation observed in the San people may also contribute to their distinctive hair morphology." Notably, the variant near TRPS1 associated with lighter skin color is at nearly 100% frequency in the San and in most non-Africans, whereas the variant associated with darker skin color is common in most other African populations and in the darkly pigmented Melanesian population, a striking example of global adaptations to UV exposure." Additionally, the researchers found a novel gene impacting human skin pigmentation, CYB561A3, which regulates iron homeostasis and influences melanin levels in melanocytic cells. "To our knowledge, the role of CYB561A3 in skin pigmentation has not been reported before. Intriguingly, there have been reports linking intravenous iron infusion to skin hyperpigmentation. Given that CYB561A3 encodes an iron reductase, I am curious about the role of this protein in this process," Tishkoff says. "Our findings underscore the complexity of genetic factors influencing skin color and the benefits of including ethnically diverse and underrepresented populations in genetic studies," she says. "Conducting functional studies on the impact of noncoding variants will enhance our comprehension of the genetics underlying complex human traits and disease risk." "The populations included in this study are from remote regions of Africa and required the use of a mobile lab set up in the field sites," Tishkoff says. "The collaboration with our partners in Africa was key to the success of this research project." In future research, the Tishkoff lab would like to use its innovative functional genomics approach to identify more genetic variants contributing to human pigmentation and other adaptive traits in a larger sample of ethnically diverse Africans. Sarah Tishkoff is the David and Lyn Silfen University Professor in Genetics and Biology and a Penn Integrates Knowledge University Professor with appointments in the Perelman School of Medicine's Department of Genetics and Department of Medicine and in the School of Arts & Sciences' Department of Biology at the University of Pennsylvania. Yuanqing Feng is a postdoctoral fellow in the Tishkoff lab at Penn. Other authors include Ning Xie, Chao Zhang, Fang Zhang, and Matthew E.B. Hansen of Penn; Fumitaka Inoue of Kyoto University; Shaohua Fan of Fudan University; Thomas Nyambo of Hubert Kairuki Memorial University; Sununguko Wata Mpoloka and Gaonyadiwe George Mokone of the University of Botswana; Charles Fokunang and Alfred K. Njamnshi of the University of Yaoundé; Gurja Belay of Addis Ababa University; Michael S. Marks of the Children's Hospital of Philadelphia Research Institute; Elena Oancea of Brown University; and Nadav Ahituv of the University of California, San Francisco. This research was supported by the National Institutes of Health (grants R35GM134957-01, 3UM1HG009408-02S1, 1R01GM113657-01, 5R01AR076241-02, and 1S10OD010786-01) and the Penn Skin Biology and Disease Resource-based Center (Grant NIH P30-AR069589).