CIDEB

NIH data show that globally less than 2% of genetic information being studied today originates from people of African ancestry1 The newly established Diaspora Human Genomics Institute (DHGI) will manage the Together for CHANGE initiative, which aims to increase available genomic data for people of African ancestry and enhance representation in STEM careers NASHVILLE, Tenn. and TARRYTOWN, N.Y. and WILMINGTON, Del. and BAGSVAERD, Denmark and BASEL, Switzerland, Oct. 18, 2023 (GLOBE NEWSWIRE) -- Meharry Medical College, along with partners Regeneron Genetics Center® (RGC™), AstraZeneca, Novo Nordisk, and Roche, today announced the launch of the Together for CHANGE™ (“Changing Healthcare for People of African Ancestry through an InterNational Genomics & Equity”) initiative to create better health care and outcomes for all. The Together for CHANGE initiative seeks to address inequities in STEM careers and research with a two-pronged approach. First, the Diaspora Human Genomics Institute (DHGI) will establish a grant program to support research and educational capacity in genomics and related fields at Meharry Medical College, as well as broader STEM programs in racially diverse communities for grade school-aged children. Second, in close consultation with the local Black community through listening sessions and ongoing input, the DHGI will help facilitate the building of the largest African ancestry genomics research database, composed of de-identified genomic and phenotypic data from up to 500,000 volunteer participants. Meharry Medical College, one of the oldest and largest historically Black academic health sciences centers in the U.S., is a co-founder and academic convener of this initiative. The DHGI, a newly chartered non-profit organization, will serve as the governing organization for Together for CHANGE. Data collected from the Together for CHANGE initiative will be secured and managed by the DHGI to ensure the integrity and transparency of all activities of the initiative. Additionally, the DHGI will form an ethics committee with leaders from the Black community to provide stewardship of the data. Accenture will also provide support as a strategic partner to the DHGI as the program rolls out. “Historically, African Americans have been – and continue to be – underrepresented in scientific and medical research, as well as in STEM careers, negatively impacting both health outcomes and career opportunities for this population,” said James E.K. Hildreth Sr., Ph.D., M.D., President and Chief Executive Officer, Meharry Medical College. “Working with our local community and biopharmaceutical partners, we are eager to bring to life a vision of more equitable health care through the Together for CHANGE initiative.” Meharry worked with Regeneron Genetics Center to convene three founding partners for the initiative, AstraZeneca, Novo Nordisk, and Roche, and welcome participation from additional partners. Each organization intends to make contributions worth $20 million during the initiative, with Regeneron Genetics Center also undertaking and funding the sequencing of genetic samples. The DHGI launch is underway, with more information about study participation and grants to be available later this year. “People of African ancestry have been underrepresented in genomics studies, which leads to clinical genetic testing that has less reference data and less confident testing results,” said Aris Baras, M.D., Senior Vice President, Regeneron, and Head of Regeneron Genetics Center. “At RGC, we know that genetic databases function best as global resources when they reflect humanity’s broad spectrum of ethnic and genetic diversity, so that the resulting research and medical innovation may benefit all populations. With one of the most diverse genomic datasets in the world, we are immensely proud to spearhead this impactful initiative that aims to shift the makeup of available genetic data and better equip promising students and researchers to create much-needed medicines of the future.” “We are proud to be part of this collaborative initiative that will strengthen our understanding of human disease and unlock scientific discovery, prioritizing inclusive science to reduce healthcare disparities for under-represented populations. This will enable us to develop medicines that reflect the needs of a diverse patient population,” said Sharon Barr, Executive Vice President of BioPharmaceuticals R&D at AstraZeneca. “The STEM career pipeline is lacking in Black professionals whose presence will bring more diverse thoughts to solving research problems, which will better inform care for people of African ancestry, as well as inspire others to pursue scientific and medical careers,” said Lyndon Mitnaul, Ph.D., Executive Director, Research Initiatives, RGC. “Even though similar proportions of Black and white students start to pursue STEM degrees, far fewer Black students succeed in achieving them. This initiative is intentionally designed to inspire new Black scientists and changemakers.”2 “Through this initiative, several new programs will be launched to nurture young people throughout their educational pathways, including the creation of a DNA Learning Center, mentorships, and a Master of Science program in Genetic Counseling. In addition, researchers from historically Black colleges and universities and Africa will have access to the first-ever reference genome of African ancestry people to build collaborative projects at the intersection of genomics and health equity research that will ensure that the breakthroughs represent a healthier future for everyone, including the global Black communities that have historically been ignored,” said Anil Shanker, Ph.D., Senior Vice President for Research and Innovation, Meharry Medical College. “This partnership provides a unique opportunity to work closely with the community to build on human genomics datasets and ensure they become truly representative of a global population, ultimately enhancing research and improving health outcomes. Diversity is a fundamental part of inclusive innovative health solutions. By building a robust STEM pipeline for individuals of African ancestry, we are ensuring those solutions can become a reality in the future,” said Marcus Schindler, PhD, Prof., EVP Research & Early Development and Chief Scientific Officer of Novo Nordisk. “Roche is fully committed to increasing health equity globally and reducing inequalities caused by insufficient global populations in trial and research data, especially as it relates to African populations. As part of our contribution to the consortium and as a component of our ongoing African Genomics Program, Roche will be leading efforts to collect up to 20,000 samples and related phenotype data from diverse regions of Africa,” said James Sabry, Global Head of Pharma Partnering, Roche. “We are very excited to join this initiative with the goal of understanding genetic diversity within Africa and African-descent populations, and thereby increasing the opportunities to discover new human biology and better diagnose, prevent and treat human disease.” More information can be found at TheDHGI.org. About the Together for CHANGE InitiativeThe Together for CHANGE Initiative seeks to address inequities in STEM careers and research with a two-pronged approach. First, the DHGI will establish a grant program to support research and educational capacity in genomics and related fields at HBCUs, as well as broader STEM programs in minority communities for grade school-aged children. Providing opportunities throughout an individual’s educational journey is key, as African Americans are more likely to attend a high-poverty school where mathematics and sciences scores are up to 90 points worse than low-poverty schools.3 By the time students are in undergraduate school, 40 percent of Black students switch out of STEM majors, compared with 29 percent of White students,4 and another study found that 54 percent of young African Americans would be a lot more likely to pursue STEM college degrees if there were more examples of high achievers in those fields who were Black.5 Second, in close consultation with the local Black community through listening sessions and ongoing input, the DHGI will help facilitate the building of the largest African ancestry genomics research database, composed of de-identified genomic and phenotypic data from up to 500,000 volunteer participants. People of African ancestry represent the most genetically diverse population in the world, and there is a massive underrepresentation of this group in available genomic data. The focus on increasing information around African ancestry strives to improve health outcomes for this community through deeper understanding of their genetics. About Meharry Medical CollegeLocated in Nashville, Tennessee, Meharry Medical College is the nation’s largest private, independent historically Black academic health sciences center dedicated to educating physicians, dentists, researchers, and health policy experts. Founded in 1876 as the Medical Department of Central Tennessee College, Meharry was the first medical school in the South for African Americans. It was chartered separately in 1915. Today, Meharry includes schools of medicine, dentistry, graduate studies and applied computational sciences and is home to The Institute for Global Public Health and Center for Health Policy. Degrees include Doctor of Medicine (M.D.), Doctor of Dental Surgery (D.D.S.), Master of Public Health (M.P.H.), Master of Health Science (M.H.S.), and Doctor of Philosophy (Ph.D.). Meharry is a United Methodist Church related institution. A 2010 study published in the Annals of Internal Medicine ranked Meharry as one of the nation’s top five producers of primary care physicians. Meharry is also a leading producer of African Americans with Ph.Ds. in biomedical sciences. In addition to providing quality professional health care education, exemplary patient care, and compassionate community outreach, Meharry Medical College produces the Journal of Health Care for the Poor and Underserved, a public health journal. About the Regeneron Genetics CenterThe Regeneron Genetics Center LLC (RGC) is a wholly owned subsidiary of Regeneron Pharmaceuticals, Inc. that focuses on early gene discovery and functional genomics. The primary goal of RGC is to improve patient outcomes by identifying novel drug targets, clinical indications for development programs, and genomic biomarkers for pharmacogenomic applications. RGC is tackling large-scale sequencing and analytical approaches and has established numerous collaborations with leading human genetics researchers. To enable this large-scale sequencing and analysis program, RGC utilizes fully automated sample preparation and data processing, as well as cutting-edge cloud-based informatics. At RGC, scientists around the globe with diverse skills and backgrounds work together to uncover the genetic basis of human disease. Their efforts have culminated in landmark discoveries like CIDEB in NASH and have led to multiple new therapeutic development programs at Regeneron across a range of therapeutic modalities. Since its inception in 2013 and through a network of over 120 collaborators globally, RGC has developed one of the largest and richest human genetics datasets in the world by sequencing more than 2 million exomes. For more information, please visit www.Regeneron.com or follow Regeneron on LinkedIn. About AstraZenecaAstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company founded in 1999 that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca. About Novo NordiskNovo Nordisk is a leading global healthcare company, founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases, built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 59,000 people in 80 countries and markets its products in around 170 countries. For more information, visit novonordisk.com, Facebook, Instagram, X, LinkedIn and YouTube. About Roche Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For more information, please visit www.roche.com and LinkedIn. Regeneron Contacts: Media RelationsElla CampbellElla.campbell@regeneron.comInvestor RelationsVesna TosicVesna.Tosic@regeneron.com References Zhang C, Hansen MEB, Tishkoff SA. Advances in integrative African genomics. Trends in Genetics. 2022;38(2):152-168. doi:https://doi.org/10.1016/j.tig.2021.09.013“The Impact of HBCUs on Diversity in STEM Fields.” United Negro College Fund, Inc. https://uncf.org/the-latest/the-impact-of-hbcus-on-diversity-in-stem-fields. Last accessed June 16, 2023.King S N et al. “Determinants of Black families’ access to a community-based STEM program: A latent class análisis.” Science Education. Nov 2021;105:6.Suran M. “Keeping Black students in STEM.” PNAS. 12 June 2021;18(23).Funk C. “Black Americans’ Views of and Engagement With Science.” Pew Research Center. 7 April 2022.

Target knockdown and safety results support continued clinical development Regeneron and Alnylam intend to initiate a Phase 2 study in late 2022 Detailed results to be presented at an upcoming medical congress TARRYTOWN, N.Y and CAMBRIDGE, Mass., Sept. 15, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals ( Nasdaq: REGN) and Alnylam Pharmaceuticals, Inc. ( Nasdaq: ALNY) announced today preliminary Phase 1 data supporting the clinical advancement of ALN-HSD, an investigational RNAi therapeutic targeting HSD17B13 in development for the treatment of nonalcoholic steatohepatitis (NASH). After single-dose evaluation in healthy adult volunteers (Part A), multiple doses of ALN-HSD are being studied in adult patients with NASH (Part B). Patients in the first two Part B cohorts (200 and 400 mg quarterly) have completed at least 6 months on the study; remaining cohorts are exploring a lower dose or a later biopsy time point. In the first two Part B cohorts, ALN-HSD was associated with robust target knockdown and numerically lower liver enzymes and biopsy-derived nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS)* over six months in patients receiving ALN-HSD (N=20) relative to placebo (N=4). The study was not powered to achieve statistical significance on these endpoints, and the primary outcome measure is frequency of adverse events. ALN-HSD has exhibited an encouraging safety and tolerability profile to date; the most common treatment-emergent adverse event in healthy subjects treated with ALN-HSD (N=44) was injection site reaction in five patients; all injection site reactions were mild in severity. No treatment-related serious adverse events have been reported in either healthy volunteers or patients with NASH to date. Based on these results, the companies plan to initiate a Phase 2 study in adult patients with NASH in late 2022. "We are excited to share these initial results, indicating what we believe to be a favorable profile for ALN-HSD and supporting continued clinical development of this investigational medicine, particularly given the significant prevalence and unmet need in NASH – a progressive liver disease and a leading cause of liver transplant," said Kevin Sloan, Ph.D., Vice President, Development Programs and Program Leader for the ALN-HSD program at Alnylam. "Our RNAi platform is ideally suited for this genetic target. We look forward to reporting detailed results from this study at an upcoming medical congress and to share details of the Phase 2 study design in partnership with our colleagues at Regeneron." "The Regeneron and Alnylam collaboration continues to produce compelling clinical and pre-clinical stage therapeutic candidates targeting notoriously hard-to-treat diseases such as NASH and Alzheimer's," said Aris Baras, M.D., Senior Vice President and Head of the Regeneron Genetics Center. "By building on each company's deep expertise in human genetics as well as drug technology and development capabilities, we are progressing ALN-HSD to Phase 2 assessment and are rapidly moving PNPLA3- and CIDEB-targeting therapeutics towards first-in-human studies, resulting in an exciting portfolio of potential future genetic medicines for NASH." * The NAFLD Activity Score (NAS) is a widely accepted scoring system developed by the NASH Clinical Research Network for use in clinical trials. The score is based on histological assessment of liver biopsies and is comprised of a sum of steatosis, ballooning, and lobular inflammation component scores. About the Phase 1 Study Design The Phase 1 trial is a randomized, double-blind, placebo-controlled, multi-center, single-ascending dose (SAD) and multiple-dose (MD) study designed to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ALN-HSD in healthy adult subjects and adult patients with NASH. The primary endpoint of the study is the frequency of adverse events. The study was conducted in two parts. Part A enrolled 58 healthy adult subjects randomized 3:1 to receive a single ascending dose of 25, 100, 200, 400, or 800 mg of ALN-HSD or placebo; Part A of the study is complete. Part B enrolled 45 patients with NASH randomized 4:1 to receive two doses of 25, 200, or 400 mg of ALN-HSD or placebo, quarterly. Patients in the first two cohorts (200 and 400 mg) have completed at least 6 months on the study; remaining cohorts are exploring a lower dose or a later biopsy time point. Secondary and exploratory endpoints of the study include the characterization of plasma and urine PK of ALN-HSD and the evaluation of the drug PD effect. About ALN-HSD ALN-HSD is an investigational, subcutaneously administered RNAi therapeutic targeting HSD17B13 for the treatment of NASH. It is being developed in collaboration with Regeneron following their identification of a loss-of-function variant in HSD17B13 that is associated with a reduced risk of chronic liver disease and progression from steatosis to steatohepatitis1. ALN-HSD utilizes Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables subcutaneous dosing with increased selectivity and a wide therapeutic index. The safety and efficacy of ALN-HSD have not been evaluated by the FDA, EMA or any other health authority. About NASH Nonalcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease in which inflammation and liver cell injury are caused by accumulation of hepatic fat. NASH is a subset of a group of conditions called nonalcoholic fatty liver disease (NAFLD) that can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. Comorbidities include obesity, metabolic syndrome, and type 2 diabetes. Approximately 16 million people in the US live with NASH, with prevalence of the disease increasing due to rising rates of obesity. NASH is projected to be the leading indication for liver transplants in developed countries within the next 10 years. There are currently no approved medical therapies for NASH. About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today's medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam ( Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding 20 years ago, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam's commercial RNAi therapeutic products are ONPATTRO® (patisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and AMVUTTRA® (vutrisiran), as well as Leqvio® (inclisiran) which is being developed and commercialized by Alnylam's partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its "Alnylam P5x25" strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram. About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for nearly 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases. Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world. For more information, please visit or follow @Regeneron on Twitter. Alnylam Forward Looking Statements Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam's views with respect to the initial results of the Phase 1 study of ALN-HSD in patients with NASH, the potential timing to report detailed results, Regeneron's involvement in the research, development and commercialization of ALN-HSD, Alnylam's aspiration to become a leading biotech company, and the planned achievement of its "Alnylam P5x25" strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam's business, results of operations and financial condition and the effectiveness or timeliness of Alnylam's efforts to mitigate the impact of the pandemic; the potential impact of the recent leadership transition on Alnylam's ability to attract and retain talent and to successfully execute on its "Alnylam P5x25" strategy; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates, including ALN-HSD; the pre-clinical and clinical results for its product candidates, including ALN-HSD; actions or advice of regulatory agencies and Alnylam's ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam's ability to successfully expand the indication for ONPATTRO, AMVUTTRA or OXLUMO in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile in the future without the need for future equity financing; Alnylam's ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential impact of current and the risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the "Risk Factors" filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements. Regeneron Forward-Looking Statements and Use of Digital Media This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the impact of SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on Regeneron's business and its employees, collaborators, and suppliers and other third parties on which Regeneron relies, Regeneron's and its collaborators' ability to continue to conduct research and clinical programs, Regeneron's ability to manage its supply chain, net product sales of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products"), and the global economy; the nature, timing, and possible success and therapeutic applications of Regeneron's Products and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, such as ALN-HSD (an investigational RNAi therapeutic targeting HSD17B13 in development for the treatment of nonalcoholic steatohepatitis (NASH)) as well as any PNPLA3- and CIDEB-targeting therapeutics for NASH referenced in this press release; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees (including the studies evaluating ALN-HSD discussed in this press release) may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; the potential of the RNAi technology discussed in this press release for therapeutic development; uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron's Products and Regeneron's Product Candidates (such as ALN-HSD); the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates (such as ALN-HSD) and new indications for Regeneron's Products; the ability of Regeneron's collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron and/or its collaborators to manufacture and manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron's Products and Regeneron's Product Candidates in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates (such as ALN-HSD) in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron's Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron's agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), as well as Regeneron's collaboration with Alnylam Pharmaceuticals, Inc. discussed in this press release, to be cancelled or terminated; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA® (aflibercept) Injection, Dupixent® (dupilumab), Praluent® (alirocumab), and REGEN-COV® (casirivimab and imdevimab)), other litigation and other proceedings and government investigations relating to the Company and/or its operations, the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron's filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2021 and its Form 10-Q for the quarterly period ended June 30, 2022. Any forward-looking statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website () and its Twitter feed (). References Abul-Husn NS., et al., 2018, The New England Journal of Medicine, "A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease", 378:1096-1106. Alnylam Contacts: Investors and Media: Christine Regan Lindenboom +1-617-682-4340 Investors: Josh Brodsky +1-617-551-8276 Regeneron Contacts Media: Alexandra Bowie +1-914-847-3407 [email protected] Investors: Vesna Tosic +1-914-847-5443 [email protected] SOURCE Regeneron Pharmaceuticals, Inc.

Sept. 15, 2022 11:00 UTC Target knockdown and safety results support continued clinical development Alnylam and Regeneron intend to initiate a Phase 2 study in late 2022 Detailed results to be presented at an upcoming medical congress CAMBRIDGE, Mass. & TARRYTOWN, N.Y.--(BUSINESS WIRE)-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY) and Regeneron Pharmaceuticals, Inc. (Nasdaq: REGN) announced today preliminary Phase 1 data supporting the clinical advancement of ALN-HSD, an investigational RNAi therapeutic targeting HSD17B13 in development for the treatment of nonalcoholic steatohepatitis (NASH). After single-dose evaluation in healthy adult volunteers (Part A), multiple doses of ALN-HSD are being studied in adult patients with NASH (Part B). Patients in the first two Part B cohorts (200 and 400 mg quarterly) have completed at least 6 months on the study; remaining cohorts are exploring a lower dose or a later biopsy time point. In the first two Part B cohorts, ALN-HSD was associated with robust target knockdown and numerically lower liver enzymes and biopsy-derived nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS)* over six months in patients receiving ALN-HSD (N=20) relative to placebo (N=4). The study was not powered to achieve statistical significance on these endpoints, and the primary outcome measure is frequency of adverse events. ALN-HSD has exhibited an encouraging safety and tolerability pro date; the most common treatment-emergent adverse event in healthy subjects treated with ALN-HSD (N=44) was injection site reaction in five patients; all injection site reactions were mild in severity. No treatment-related serious adverse events have been reported in either healthy volunteers or patients with NASH to date. Based on these results, the companies plan to initiate a Phase 2 study in adult patients with NASH in late 2022. “We are excited to share these initial results, indicating what we believe to be a favorable pro ALN-HSD and supporting continued clinical development of this investigational medicine, particularly given the significant prevalence and unmet need in NASH – a progressive liver disease and a leading cause of liver transplant,” said Kevin Sloan, Ph.D., Vice President, Development Programs and Program Leader for the ALN-HSD program at Alnylam. “Our RNAi platform is ideally suited for this genetic target. We look forward to reporting detailed results from this study at an upcoming medical congress and to share details of the Phase 2 study design in partnership with our colleagues at Regeneron.” “The Regeneron and Alnylam collaboration continues to produce compelling clinical and pre-clinical stage therapeutic candidates targeting notoriously hard-to-treat diseases such as NASH and Alzheimer’s,” said Aris Baras, M.D., Senior Vice President and Head of the Regeneron Genetics Center. “By building on each company’s deep expertise in human genetics as well as drug technology and development capabilities, we are progressing ALN-HSD to Phase 2 assessment and are rapidly moving PNPLA3- and CIDEB-targeting therapeutics towards first-in-human studies, resulting in an exciting portfolio of potential future genetic medicines for NASH.” * The NAFLD Activity Score (NAS) is a widely accepted scoring system developed by the NASH Clinical Research Network for use in clinical trials. The score is based on histological assessment of liver biopsies and is comprised of a sum of steatosis, ballooning, and lobular inflammation component scores. About the Phase 1 Study Design The Phase 1 trial is a randomized, double-blind, placebo-controlled, multi-center, single-ascending dose (SAD) and multiple-dose (MD) study designed to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) effects of ALN-HSD in healthy adult subjects and adult patients with NASH. The primary endpoint of the study is the frequency of adverse events. The study was conducted in two parts. Part A enrolled 58 healthy adult subjects randomized 3:1 to receive a single ascending dose of 25, 100, 200, 400, or 800 mg of ALN-HSD or placebo; Part A of the study is complete. Part B enrolled 45 patients with NASH randomized 4:1 to receive two doses of 25, 200, or 400 mg of ALN-HSD or placebo, quarterly. Patients in the first two cohorts (200 and 400 mg) have completed at least 6 months on the study; remaining cohorts are exploring a lower dose or a later biopsy time point. Secondary and exploratory endpoints of the study include the characterization of plasma and urine PK of ALN-HSD and the evaluation of the drug PD effect. About ALN-HSD ALN-HSD is an investigational, subcutaneously administered RNAi therapeutic targeting HSD17B13 for the treatment of NASH. It is being developed in collaboration with Regeneron following their identification of a loss-of-function variant in HSD17B13 that is associated with a reduced risk of chronic liver disease and progression from steatosis to steatohepatitis1. ALN-HSD utilizes Alnylam's Enhanced Stabilization Chemistry Plus (ESC+) GalNAc-conjugate technology, which enables subcutaneous dosing with increased selectivity and a wide therapeutic index. The safety and efficacy of ALN-HSD have not been evaluated by the FDA, EMA or any other health authority. About NASH Nonalcoholic steatohepatitis (NASH) is a highly prevalent chronic liver disease in which inflammation and liver cell injury are caused by accumulation of hepatic fat. NASH is a subset of a group of conditions called nonalcoholic fatty liver disease (NAFLD) that can lead to progressive fibrosis, cirrhosis, and hepatocellular carcinoma. Comorbidities include obesity, metabolic syndrome, and type 2 diabetes. Approximately 16 million people in the US live with NASH, with prevalence of the disease increasing due to rising rates of obesity. NASH is projected to be the leading indication for liver transplants in developed countries within the next 10 years. There are currently no approved medical therapies for NASH. About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam's RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines with the potential to transform the lives of people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding 20 years ago, Alnylam has led the RNAi Revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO® (patisiran), GIVLAARI® (givosiran), OXLUMO® (lumasiran), and AMVUTTRA® (vutrisiran), as well as Leqvio® (inclisiran) which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “Alnylam P5x25” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit and engage with us on Twitter at @Alnylam, on LinkedIn, or on Instagram. About Regeneron Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents, develops and commercializes life-transforming medicines for people with serious diseases. Founded and led for nearly 35 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases. Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite® technologies, such as VelocImmune®, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world. For more information, please visit or follow @Regeneron on Twitter. Alnylam Forward Looking Statements Various statements in this release concerning Alnylam's future expectations, plans and prospects, including, without limitation, Alnylam’s views with respect to the initial results of the Phase 1 study of ALN-HSD in patients with NASH, the potential timing to report detailed results, Regeneron’s involvement in the research, development and commercialization of ALN-HSD, Alnylam’s aspiration to become a leading biotech company, and the planned achievement of its “Alnylam P5x25” strategy, constitute forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation: the direct or indirect impact of the COVID-19 global pandemic or any future pandemic on Alnylam’s business, results of operations and financial condition and the effectiveness or timeliness of Alnylam’s efforts to mitigate the impact of the pandemic; the potential impact of the recent leadership transition on Alnylam’s ability to attract and retain talent and to successfully execute on its “Alnylam P5x25” strategy; Alnylam's ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates, including ALN-HSD; the pre-clinical and clinical results for its product candidates, including ALN-HSD; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, as well as favorable pricing and reimbursement; successfully launching, marketing and selling its approved products globally; delays, interruptions or failures in the manufacture and supply of its product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the indication for ONPATTRO, AMVUTTRA or OXLUMO in the future; Alnylam's ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial pro the future without the need for future equity financing; Alnylam’s ability to maintain strategic business collaborations; Alnylam's dependence on third parties for the development and commercialization of certain products, including Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the potential impact of current and the risk of future government investigations; and unexpected expenditures; as well as those risks more fully discussed in the “Risk Factors” filed with Alnylam's most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) and in its other SEC filings. In addition, any forward-looking statements represent Alnylam's views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements. Regeneron Forward-Looking Statements and Use of Digital Media This press release includes forward-looking statements that involve risks and uncertainties relating to future events and the future performance of Regeneron Pharmaceuticals, Inc. ("Regeneron" or the "Company"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the impact of SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on Regeneron's business and its employees, collaborators, and suppliers and other third parties on which Regeneron relies, Regeneron's and its collaborators' ability to continue to conduct research and clinical programs, Regeneron's ability to manage its supply chain, net product sales of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products"), and the global economy; the nature, timing, and possible success and therapeutic applications of Regeneron's Products and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, such as ALN-HSD (an investigational RNAi therapeutic targeting HSD17B13 in development for the treatment of nonalcoholic steatohepatitis (NASH)) as well as any PNPLA3- and CIDEB-targeting therapeutics for NASH referenced in this press release; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators or licensees (including the studies evaluating ALN-HSD discussed in this press release) may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; the potential of the RNAi technology discussed in this press release for therapeutic development; uncertainty of the utilization, market acceptance, and commercial success of Regeneron's Products and Regeneron's Product Candidates and the impact of studies (whether conducted by Regeneron or others and whether mandated or voluntary), including the studies discussed or referenced in this press release, on any of the foregoing or any potential regulatory approval of Regeneron's Products and Regeneron's Product Candidates (such as ALN-HSD); the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates (such as ALN-HSD) and new indications for Regeneron's Products; the ability of Regeneron's collaborators, licensees, suppliers, or other third parties (as applicable) to perform manufacturing, filling, finishing, packaging, labeling, distribution, and other steps related to Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron and/or its collaborators to manufacture and manage supply chains for multiple products and product candidates; safety issues resulting from the administration of Regeneron's Products and Regeneron's Product Candidates in patients, including serious complications or side effects in connection with the use of Regeneron's Products and Regeneron's Product Candidates (such as ALN-HSD) in clinical trials; determinations by regulatory and administrative governmental authorities which may delay or restrict Regeneron's ability to continue to develop or commercialize Regeneron's Products and Regeneron's Product Candidates; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; the availability and extent of reimbursement of Regeneron's Products from third-party payers, including private payer healthcare and insurance programs, health maintenance organizations, pharmacy benefit management companies, and government programs such as Medicare and Medicaid; coverage and reimbursement determinations by such payers and new policies and procedures adopted by such payers; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; unanticipated expenses; the costs of developing, producing, and selling products; the ability of Regeneron to meet any of its financial projections or guidance and changes to the assumptions underlying those projections or guidance; the potential for any license, collaboration, or supply agreement, including Regeneron's agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), as well as Regeneron's collaboration with Alnylam Pharmaceuticals, Inc. discussed in this press release, to be cancelled or terminated; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA® (aflibercept) Injection, Dupixent® (dupilumab), Praluent® (alirocumab), and REGEN-COV® (casirivimab and imdevimab)), other litigation and other proceedings and government investigations relating to the Company and/or its operations, the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on Regeneron's business, prospects, operating results, and financial condition. A more complete description of these and other material risks can be found in Regeneron's filings with the U.S. Securities and Exchange Commission, including its Form 10-K for the year ended December 31, 2021 and its Form 10-Q for the quarterly period ended June 30, 2022. Any forward-looking statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any forward-looking statements made by Regeneron. Regeneron does not undertake any obligation to update (publicly or otherwise) any forward-looking statement, including without limitation any financial projection or guidance, whether as a result of new information, future events, or otherwise. Regeneron uses its media and investor relations website and social media outlets to publish important information about the Company, including information that may be deemed material to investors. Financial and other information about Regeneron is routinely posted and is accessible on Regeneron's media and investor relations website ( ) and its Twitter feed ( ). References Abul-Husn NS., et al., 2018, The New England Journal of Medicine, “A Protein-Truncating HSD17B13 Variant and Protection from Chronic Liver Disease”, 378:1096-1106.