A2M

*仅供医学专业人士阅读参考帕金森病（PD）是一种高度异质性疾病，可按照运动症状将患者分成不同的临床亚型，如震颤为主型PD（TD）、姿势不稳定和步态困难为主型PD（PIGD），以及混合型PD（Mix）。但截至目前，由于我们对不同PD亚型的病理生理机制了解的还不够透彻，因此，也没有开发出针对这些亚型的治疗方案。为了填补这一治疗领域的空白，近期，中国医学科学院杜冠华/方莲花团队、首都医科大学附属北京天坛医院赵志刚团队联合发表了一项研究成果。他们在成功构建了与PD患者临床表现一致的PD亚型大鼠模型后，利用转录组学分析阐明，不同PD亚型的发展与神经递质、中枢神经系统或外周神经系统神经元损伤及脂质代谢相关的基因表达改变有关。基于这些基因表达差异，研究人员进一步筛选出了25种潜在候选药物（包括治疗TD的2种，治疗PIGD的7种，以及治疗Mix的16种），其中Alox15抑制剂黄芩素（baicalein）在治疗Mix大鼠，尤其是在缓解运动和震颤症状方面，效果最好。研究发表在Signal Transduction and Targeted Therapy上[1]。论文首页截图鉴于以前还没有可用的能模拟不同PD亚型的动物模型，研究人员先是通过向大鼠大脑注射6-羟基多巴胺（6-OHDA），构建了PD大鼠模型，随后对大鼠旋转测试和其他行为学测试数据进行聚类分析，并根据大鼠是否出现现运动障碍和震颤，将其分为TD亚型、PIGD亚型，以及同时具有运动障碍和震颤症状的混合型Mix亚型。PD亚型大鼠的建立接下来，为了评估这些不同PD亚型的大鼠能否具备临床实用性，研究人员比较了它们和不同PD亚型患者在临床表现上的差异。结果发现，无论在血清生物标志物（血清神经丝轻链和尿酸水平）、神经活性和代谢物的变化上，这些不同PD亚型的大鼠均与临床PD患者之间存在很高的相似性（其中，不同亚型PD大鼠和临床患者的血清中有超过70%的代谢物呈现一致改变）。这也意味着，研究人员构建的不同PD亚型大鼠确实具备临床实用性。PD亚型大鼠与PD患者临床表现相似进一步，为了探索不同PD亚型的异质性，研究人员对不同PD亚型大鼠的RNA样本进行了基因组测序，并分析了对照组和不同PD亚型之间的差异表达基因（DEGs）。结果发现，与对照组相比，Mix亚型有36个DEGs、TD亚型有10个DEGs、PIGD亚型有7个DEGs与PD有关，这些基因可能是不同PD亚型的关键靶点。对照组和不同PD亚型之间的差异表达基因随后的KEGG通路富集、GO富集等一系列分析也显示，不同PD亚型的DEGs主要集中在神经递质、中枢神经系统或外周神经系统神经元损伤及脂质代谢方面。比如，在神经递质差异上，TD大鼠大脑5-羟色胺浓度显著低于PIGD大鼠，而Mix大鼠则表现出γ-氨基丁酸浓度的降低。在神经递质差异在中枢神经系统或外周神经系统神经元损伤方面，TD亚型主要与外周神经系统（PNS）损伤有关，涉及PNS的髓鞘形成、发育和轴突包裹等过程；PIGD亚型则与中枢神经系统（CNS）的神经元分化和发育异常有关。Mix大鼠的PNS和CNS会同时发生病理改变。在脂质代谢方面，Mix和TD亚型在脂质合成、脂质转运和脂质代谢调节上存在明显异常，而PIGD亚型则不存在任何脂质或脂肪酸代谢异常。PNS和CNS损伤和脂质代谢差异以上结果提示，不同PD亚型的发展与神经递质、中枢神经系统或外周神经系统神经元损伤及脂质代谢相关的基因表达差异有关，而这些差异可能是导致不同PD亚型出现不同运动症状的原因。最后，基于以上DEGs，研究人员与药物基因交互数据库（DGIdb）进行比对，最终筛选出25种治疗PD的潜在候选药物，包括治疗TD的2种（可定位的靶点为SLC18A2），治疗PIGD的7种（可定位的靶点为Kcnj6、Nfkbia和Nr4a1），以及治疗Mix的16种（可定位的靶点有A2m、Alox15、Grm2、Rgs4、Slc7a11和VDR）。不同亚型对应的关键治疗靶点鉴于以往研究发现，Alox15抑制剂黄芩素(baicalein) 具有抗炎、抗凋亡等神经保护作用，或可用于改善PD的行为特征。于是本研究要主要观察了Alox15抑制剂baicalein（200 mg/kg/天，灌胃，持续4周）对不同PD亚型的治疗效果。结果与预想的一样，虽然不同PD亚型大鼠大脑黑质中均存在Alox15表达升高的现象，但Alox15作为Mix亚型的关键治疗靶点，相比其他亚型，Alox15抑制剂baicalein治疗Mix大鼠效果最好。具体来说，baicalein治疗后，Mix亚型大鼠的运动迟滞时间显著增加，震颤和运动症状也得到了显著缓解。综上，该研究通过构建不同PD亚型大鼠模型，深入探讨了PD亚型的差异，并找到了不同亚型的关键治疗靶点和相关候选药物，其中Alox15抑制剂baicalein在Mix亚型大鼠表现出的显著疗效也为PD的个性化治疗提供了方案。参考文献：[1]Kong, D., Li, C., Ma, L. et al. Identifying genetic targets in clinical subtypes of Parkinson’s disease for optimizing pharmacological treatment strategies. Sig Transduct Target Ther 9, 320 (2024).本文作者｜张金旭

July 26, 2021 13:05 UTC Cortexyme Presents Data Linking P. Gingivalis to Elevated Levels of Phospho-tau217 Reinforcing Evidence of Pathogen as Causative Agent of Alzheimer’s Disease at AAIC 2021 New GAIN Trial baseline data demonstrates majority of patients have elevated Von Willebrand factor and alpha-2-macroglobulin Cortexyme to host AAIC symposium titled “Getting to the Root Cause of Alzheimer’s Disease: An Innovative, Upstream Approach for Disease Modification” on Tuesday, July 27 Join KOL webinar on atuzaginstat titled “Innovation in Alzheimer's Disease – Getting to the Root Cause of Neurodegeneration” on Friday, July 30 at 10 a.m. ET SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Cortexyme, Inc. (Nasdaq: CRTX), a company advancing a pivotal trial in Alzheimer’s disease with top-line data expected in the fourth quarter of 2021 and a growing pipeline of therapeutics for degenerative diseases, announced the presentation of new preclinical data linking P. gingivalis to increased levels of phospho-tau217, an emerging biomarker for Alzheimer’s disease. This research, along with new baseline data from its pivotal GAIN Trial, is being presented by the company at the Alzheimer's Association International Conference® 2021 (AAIC®) taking place July 26-30, 2021, in Denver, Colorado, as well as virtually. In addition to its presentations, Cortexyme will host a corporate sponsored symposium held in conjunction with the conference titled “Getting to the Root Cause of Alzheimer’s Disease: An Innovative, Upstream Approach for Disease Modification” on Tuesday, July 27, 2021, from 5:30 p.m. to 7:30 p.m. MT. “Cortexyme continues to conduct research that validates and reinforces the gingipain hypothesis and P. gingivalis’ role as a causative agent of Alzheimer’s disease,” said Casey Lynch, Cortexyme’s chief executive officer, co-founder, and chair. “The GAIN Trial, which is designed to be 90% powered to show a 50% slowing of disease, will read out on the gold standard measures of disease modification as Cortexyme looks to shift the paradigm in effective Alzheimer’s treatment.” Cortexyme is pioneering an innovative, upstream, and disease-modifying therapeutic approach to Alzheimer's disease. The Phase 2/3 GAIN Trial is a potentially pivotal study in 643 patients with mild to moderate Alzheimer’s Disease. Cortexyme’s seminal discovery, along with confirmatory clinical and preclinical studies, demonstrate that the intracellular pathogen, P. gingivalis, is found in the brain of more than 90% of Alzheimer’s patients and that a simple oral infection with P. gingivalis in animals results in brain infiltration and downstream hallmark Alzheimer’s pathologies, including Aβ42 production, tau hyperphosphorylation, microglial activation, and neurodegeneration. The company’s lead drug candidate, atuzaginstat (COR388), is a first-in-class, orally administered, brain penetrant small molecule targeting P. gingivalis, which is upstream of neuronal death and Alzheimer’s disease pathology. Atuzaginstat blocks gingipains, protease virulence factors secreted by P. gingivalis, which are required for its survival and responsible for its toxicity. The GAIN Trial also includes a REPAIR sub-study of 233 patients targeting P. gingivalis – most commonly known as a keystone bacterium associated with periodontal disease – and measuring the efficacy of atuzaginstat on clinical endpoints of periodontal disease. Cortexyme’s innovative therapeutic approach continues to be supported by research from laboratories around the world published in peer-reviewed scientific journals. Cortexyme’s work will be featured in two poster presentations at AAIC 2021: Increased Levels of Phospho-tau217 Linked to P. gingivalis Reduced by Atuzaginstat: In its poster “Increased levels of phospho-tau217 in neuron cultures and CVN mice infected with Porphyromonas gingivalis” (Poster #52438), Cortexyme demonstrates P. gingivalis infected neuronal cell cultures and chronically infected CVN mice display elevated tau phosphorylation at T217 (phospho-tau217). Using IPSC-derived neuron cultures, neuron-astrocyte-microglia co-cultures, and CVN mice (APPSwDI/NOS2 bigenic) as model systems for P. gingivalis-induced Alzheimer’s disease, the company demonstrated that phospho-tau217 was susceptible to P. gingivalis-induced and gingipain dependent digestion in a dose-dependent manner. At lower infection levels, tau protein persisted and an elevated phospho-tau217/total tau ratio was observed in a manner that might reflect the physiological level of gingipain exposure. In CVN mice chronically infected with P. gingivalis, the phospho-tau217/total tau ratio was elevated in the brain in infected compared to uninfected mice. Furthermore, after five weeks of treatment with atuzaginstat, the level of phospho-tau217 was similar to that seen in uninfected controls, while tau degradation was completely inhibited by treatment with atuzaginstat. New Baseline Data from GAIN Trial: In its poster titled “An update and baseline data from the Phase 2/3 GAIN trial of COR388 (atuzaginstat) a novel bacterial virulence factor inhibitor for the treatment of Alzheimer’s Disease” (Poster #50624), Cortexyme shares updated and new baseline biomarker data from the full set of patients in the study that supports that this is an appropriate population for testing atuzaginstat for Alzheimer’s disease. In addition to demonstrating that 100% of patients have evidence of systemic P. gingivalis exposure, GAIN baseline biomarker highlights include traditional CSF biomarkers Aβ, total tau, and phospho-tau 181. New data shows that a majority of patients have elevated Von Willebrand factor (vWF), a vascular injury marker, and alpha-2-macroglobulin (A2M), an endogenous protease inhibitor, in serum. GAIN baseline demographics also demonstrate that 90% of its periodontal disease REPAIR sub-study patients have moderate to severe periodontitis without requiring it as a criterion for study participation. Cortexyme AAIC Symposium – Getting to the Root Cause of Alzheimer’s Disease Cortexyme will host a corporate sponsored symposium and dinner held in conjunction with AAIC 2021 titled “Getting to the Root Cause of Alzheimer’s Disease: An Innovative, Upstream Approach for Disease Modification” on Tuesday, July 27, 2021, from 5:30 p.m. to 7:30 p.m. MT at the Hilton Denver City Center. Led by Cortexyme’s chief executive officer and co-founder Casey Lynch and chief medical officer Michael Detke, M.D., Ph.D., the symposium will provide an informative presentation on how Cortexyme is moving beyond the prevailing targets to deliver a game-changing shift in Alzheimer’s disease treatment. For AAIC 2021 registered participants wishing to attend Cortexyme’s symposium in person, please email info@cortexyme.com to sign up. The symposium also may be accessed online by registering to attend AAIC 2021 through its virtual conference experience here. KOL Webinar: Innovation in Alzheimer's Disease – Getting to the Root Cause of Neurodegeneration In conjunction with its participation at AAIC 2021, Cortexyme is hosting a key opinion leader (KOL) webinar titled “Innovation in Alzheimer's Disease – Getting to the Root Cause of Neurodegeneration” on Friday, July 30, 2021, at 10:00 a.m. ET. The webinar will feature KOL Marwan Noel Sabbagh, M.D., (Cleveland Clinic) who will discuss the current treatment landscape of Alzheimer’s disease and dementia, the unmet medical need, as well as recent activity and evidence to support the role of P. gingivalis as an important upstream driver of Alzheimer’s disease pathology. Dr. Sabbagh will also address new baseline data from Cortexyme’s pivotal Phase 2/3 GAIN Trial of atuzaginstat for the treatment of Alzheimer’s disease being presented at AAIC 2021. Cortexyme's management team will provide an update on its ongoing pivotal Phase 2/3 GAIN Trial, which builds on Phase 1 data demonstrating atuzaginstat was well tolerated in both healthy subjects and in patients with Alzheimer’s disease. Dr. Sabbagh and Cortexyme’s management will be available to answer questions following the formal presentations. To register for this webinar, please click here. Marwan Noel Sabbagh, M.D., board certified neurologist and geriatric neurologist, hopes to work himself out of a job. Considered one of the leading experts in Alzheimer’s and dementia, he is the Camille and Larry Ruvo Endowed Chair for Brain Health and Director of Translational Research at Cleveland Clinic Lou Ruvo Center for Brain Health in Las Vegas. Dr. Sabbagh has dedicated his career to finding a cure for Alzheimer’s and other age-related neurodegenerative diseases. Dr. Sabbagh is a leading investigator for many prominent national Alzheimer’s prevention and treatment trials. Dr. Sabbagh is on the editorial board for Journal of Alzheimer's Disease and BMC Neurology. He is now editor in chief of Neurology and Therapy. He has authored and co-authored almost 370 medical and scientific articles on Alzheimer’s research. Dr. Sabbagh is the author of The Alzheimer’s Answer: Reduce Your Risk and Keep Your Brain Healthy, with foreword by Justice Sandra Day O’Connor, and The Alzheimer’s Prevention Cookbook: 100 Recipes to Boost Brain Health. He has edited Palliative Care for Advanced Alzheimer’s and Dementia: Guidelines and Standards for Evidence Based Care and Geriatric Neurology published in 2014 and Fighting for my Life: living in the shadow of Alzheimer’s disease published in 2019. He has been recognized with numerous awards, including WestMarc Innovator Award, 2015; Fellow of the American Academy of Neurology, 2004. Dr. Sabbagh earned his undergraduate degree from the University of California, Berkeley and his medical degree from the University of Arizona in Tucson. He received his residency training in neurology at Baylor College of Medicine, Houston, Texas, and completed his fellowship in geriatric neurology and dementia at the University of California, San Diego School of Medicine, where he served on the faculty as assistant professor. Before joining the faculty of the Cleveland Clinic, he was at the Barrow Neurological Institute where he served for three years, and prior to that he was the director of the Banner Sun Health Research Institute for 15 years. About Cortexyme Cortexyme, Inc. (Nasdaq: CRTX) is a clinical stage biopharmaceutical company pioneering upstream therapeutic approaches designed to improve the lives of patients diagnosed with Alzheimer’s and other degenerative diseases. The company is advancing its disease-modifying pivotal GAIN Trial in mild to moderate Alzheimer's disease with top-line data expected in the fourth quarter of 2021, in addition to growing a proprietary pipeline of first-in-class small molecule therapeutics for Parkinson’s disease, periodontitis, and other diseases with high unmet clinical need. Cortexyme’s lead program targets a specific, infectious pathogen called P. gingivalis found in the brain and other organs and tied to degeneration and inflammation in humans and animal models. The company’s causation evidence for Alzheimer’s disease and the mechanism of its novel therapeutic has been independently replicated and confirmed by multiple laboratories around the world, as well as published in peer-reviewed scientific journals. To learn more about Cortexyme, visit or follow @Cortexyme on Twitter. Forward-Looking Statements Statements in this news release contain “forward-looking statements” that are subject to substantial risks and uncertainties. Forward-looking statements contained in this news release may be identified by the use of words such as “anticipate,” “expect,” “believe,” “will,” “may,” “should,” “estimate,” “project,” “outlook,” “forecast,” or other similar words. Examples of forward-looking statements include, among others, statements we make regarding our business plans, strategy, timeline, prospects, and milestone expectations; the timing and success of the company’s clinical trials and related data, including with respect to the GAIN and REPAIR Trials; the potential of atuzaginstat to treat Alzheimer’s disease, periodontal disease, and other potential indications; the timing of announcements and updates relating to its clinical trials and related data; the potential therapeutic benefits, safety and efficacy of the company’s product candidate or library of compounds and statements about its ability to obtain, and the timing relating to, regulatory submissions and approvals with respect to the company’s drug product candidate. Forward-looking statements are based on Cortexyme’s current expectations and are subject to inherent uncertainties, risks, and assumptions that are difficult to predict and could cause actual results to differ materially from what the company expects. Further, certain forward-looking statements are based on assumptions as to future events that may not prove to be accurate. Factors that could cause actual results to differ include, but are not limited to, the risks and uncertainties described in the section titled “Risk Factors” in Cortexyme’s Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 1, 2021, its Quarterly Report on Form 10-Q filed with the SEC on May 6, 2021, and other reports as filed with the SEC. Forward-looking statements contained in this news release are made as of this date, and Cortexyme undertakes no duty to update such information except as required under applicable law.

Innovative multi-biomarker blood test based on GENFIT’S NIS4™ technology is specifically designed to identify patients with at-risk non-alcoholic steatohepatitis (NASH) LabCorp to commercialize the test for clinical care use in U.S. and Canada to help identify the approximately 10 million individuals at risk of progressing to late stage complications due to NASH among the tens of millions of people with metabolic risk factors and suspected disease The test is expected to be available from LabCorp by early 2021 Lille, France; Cambridge, MA; [AND Burlington, N.C.,] September 28, 2020 GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with metabolic and liver diseases, and LabCorp® (NYSE:LH), a leading global life sciences company that is focused on advancing health and guiding patient care decisions, have agreed to a five-year exclusive licensing agreement for GENFIT’s NIS4™ technology to help identify patients with at-risk non-alcoholic steatohepatitis (NASH). As part of the agreement, LabCorp will develop and commercialize a blood-based molecular diagnostic test powered by NIS4™ technology throughout the U.S. and Canada enabling widespread access to healthcare providers. NASH remains a highly underdiagnosed disease due to its asymptomatic nature and the limitations of existing diagnostic approaches. Liver biopsy, a highly invasive procedure, is the current clinical standard to formally diagnose NASH and to determine the stage of fibrosis. NIS4™ technology, as recently published in The Lancet Gastroenterology & Hepatology (available here ), is a novel, multi-biomarker-based algorithm specifically developed to identify at-risk NASH, defined as the presence of NASH based on a non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) ≥4 and significant to advanced fibrosis (F≥2). Patients with at-risk NASH have an advanced form of the disease and face a greater likelihood of progression to severe complications including liver cancer, cirrhosis and the need for liver transplant, if left untreated. A single test score generated from the integration of four independent biomarkers – miR-34a-5p, alpha-2-macroglobulin, YKL-40, and HbA1c – can be used by a healthcare provider to help inform the best course of intervention. This agreement with LabCorp will provide broad clinical availability of the test to specialty and primary care physicians across the U.S. and Canada. LabCorp will leverage its deep experience in commercializing innovative diagnostics to educate providers on NASH and the importance of non-invasive testing. The collaboration between the organizations began in early 2019, when LabCorp began offering NIS4™ technology to biopharmaceutical customers for use in clinical studies through Covance, its drug development business. Marcia Eisenberg, Ph.D., Chief Scientific Officer of LabCorp Diagnostics, stated: “LabCorp is committed to developing and distributing novel diagnostics to support the diagnosis of patients with NASH, which is one of the fastest growing serious medical conditions in the U.S. GENFIT’s NIS4™ is a non-invasive technology specifically designed to identify patients with both NASH and significant to advanced fibrosis, and is an important advance in the ability to identify patients with NASH. We have gained valuable experience with this test since we began performing it in 2019 for clinical studies with biopharmaceutical clients, which will provide insights as we develop and prepare to make it available for use in patient care.” Suneil Hosmane, Ph.D., Head of Global Diagnostics at GENFIT added: “We are pleased to expand our collaboration with LabCorp and are very enthusiastic about the potential impact of this agreement. We strongly believe that this test will help healthcare providers identify the approximately 10 million patients with at-risk NASH and higher risk of progression among the tens of millions with metabolic risk factors, such as type 2 diabetes and obesity, and suspected disease.” Pascal Prigent, CEO of GENFIT, continued, “This partnership supports GENFIT’s pioneering research efforts in the field of NASH diagnostics that were recently recognized by experts in our most recent Lancet publication. The commercialization of NIS4™ technology by LabCorp is a defining opportunity whereby millions of NASH patients can become aware of, and then begin to take control of their disease.” GENFIT is a pioneer in NASH diagnostics and is committed to the development of additional diagnostics and therapeutics in chronic liver disease. LabCorp has been involved in the development of drugs and diagnostics for more than 50 years and is a recognized global leader in NASH clinical trials. Specific financial terms for this agreement have not been disclosed. ABOUT NIS4™ NIS4™ is GENFIT’s non-invasive, blood-based diagnostic technology, which was developed to identify patients with non-alcoholic steatohepatitis (NASH) and significant to advanced fibrosis (F > 2), also referred to as at-risk NASH. In January 2019, GENFIT signed a licensing agreement with LabCorp® to make NIS4™ technology available for use in clinical research through their drug development subsidiary, Covance. GENFIT also continues to explore opportunities to obtain formal marketing authorization of an in vitro diagnostic (IVD) version of NIS4™ in both the U.S. and European markets. For more information, please visit: . ABOUT GENFIT GENFIT is a late-stage biopharmaceutical company dedicated to improving the lives of patients with metabolic and liver diseases. GENFIT is a pioneer in the field of nuclear receptor-based drug discovery, with a rich history and strong scientific heritage spanning more than two decades. GENFIT initiated a Phase 3 clinical trial of elafibranor in patients with primary biliary cholangitis (PBC). As part of GENFIT’s comprehensive approach to clinical management of patients with liver disease, the Company is also developing NIS4™, a new, non-invasive blood-based diagnostic technology which, if approved, could enable easier identification of patients with at-risk NASH. With facilities in Lille and Paris, France, and Cambridge, MA, USA, the Company has approximately 200 employees. GENFIT is a publicly traded company listed on the Nasdaq Global Select Market and on compartment B of Euronext’s regulated market in Paris (Nasdaq and Euronext: GNFT). FORWARD LOOKING STATEMENTS This press release contains certain forward-looking statements, including those within the meaning of the Private Securities Litigation Reform Act of 1995, with respect to GENFIT, including statements about NIS4™’s performance in identifying patients with at-risk NASH, the performance of NIS4™ relative to other technologies, the potential for diagnostic tests powered by NIS4™ technology to play a critical role in the diagnosis and management of patients with NASH, the potential for non-invasive testing to gain importance, its capability to identify patients who may require medical intervention, the development plans for NIS4™ in the U.S. and in Europe and timing of such development plans, and the potential to obtain formal marketing authorization of an IVD version of NIS4™ in the U.S. and/or European markets. The use of certain words, including “believe,” “potential,” “expect” and “will” and similar expressions, is intended to identify forward-looking statements. Although the Company believes its expectations are based on the current expectations and reasonable assumptions of the Company’s management, these forward-looking statements are subject to numerous known and unknown risks and uncertainties, which could cause actual results to differ materially from those expressed in, or implied or projected by, the forward-looking statements. These risks and uncertainties include, among other things, the uncertainties inherent in research and development, including related to safety, biomarkers, progression of, and results from, its ongoing and planned clinical trials, review and approvals by regulatory authorities of its drug and diagnostic candidates and the Company’s continued ability to raise capital to fund its development, as well as those risks and uncertainties discussed or identified in the Company’s public filings with the French Autorité des marchés financiers (“AMF”), including those listed in Section 2.1 “Main Risks and Uncertainties” of the Company’s 2019 Universal Registration Document filed with the AMF on May 27, 2020 under n° D.20-0503, which is available on GENFIT’s website ( ) and on the website of the AMF ( ) and public filings and reports filed with the U.S. Securities and Exchange Commission (“SEC”), including the Company’s 20-F dated May 27, 2020. In addition, even if the Company’s results, performance, financial condition and liquidity, and the development of the industry in which it operates are consistent with such forward-looking statements, they may not be predictive of results or developments in future periods. These forward-looking statements speak only as of the date of publication of this document. Other than as required by applicable law, the Company does not undertake any obligation to update or revise any forward-looking information or statements, whether as a result of new information, future events or otherwise. ABOUT LABCORP LabCorp (NYSE: LH), an S&P 500 company, is a leading global life sciences company that is deeply integrated in guiding patient care, providing comprehensive clinical laboratory and end-to-end drug development services. With a mission to improve health and improve lives, LabCorp delivers world-class diagnostics solutions, brings innovative medicines to patients faster, and uses technology to improve the delivery of care. LabCorp reported revenue of more than $11.5 billion in 2019. To learn more about LabCorp, visit , and to learn more about LabCorp’s Covance Drug Development business, visit . LABCORP FORWARD-LOOKING STATEMENTS This press release contains forward-looking statements, including but not limited to statements with respect to clinical laboratory testing, including a testing in development based on GENFIT’s NIS4™ technology, the impact of various factors on operating and financial results, and the opportunities for future growth. Each of the forward-looking statements is subject to change based on various important factors, many of which are beyond the Company’s control, including without limitation, competitive actions and other unforeseen changes and general uncertainties in the marketplace, changes in government regulations, including healthcare reform, customer purchasing decisions, including changes in payer regulations or policies, other adverse actions of governmental and third-party payers, the Company’s satisfaction of regulatory and other requirements, patient safety issues, changes in testing guidelines or recommendations, adverse results in material litigation matters, failure to maintain or develop customer relationships, our ability to develop or acquire new products and adapt to technological changes, failure in information technology, systems or data security, and employee relations. These factors, in some cases, have affected and in the future (together with other factors) could affect the Company’s ability to implement the Company’s business strategy and actual results could differ materially from those suggested by these forward-looking statements. As a result, readers are cautioned not to place undue reliance on any of our forward-looking statements. The Company has no obligation to provide any updates to these forward-looking statements even if its expectations change. All forward-looking statements are expressly qualified in their entirety by this cautionary statement. Further information on potential factors, risks and uncertainties that could affect operating and financial results is included in the Company’s most recent Annual Report on Form 10-K and subsequent Forms 10-Q, including in each case under the heading RISK FACTORS, and in the Company’s other filings with the SEC. GENFIT CONTACT GENFIT | Investors Naomi EICHENBAUM – Investor Relations | Tel: +1 (617) 714 5252 | investors@genfit.com PRESS RELATIONS | Media Hélène LAVIN – Press Relations | Tel: +3 33 2016 4000 | Helene.lavin@genfit.com LABCORP CONTACTS Clarissa Willett – Investors | Tel: +1 (336) 436 5076 | Investor@LabCorp.com Donald Von Hagen – Media | Tel: +1 (336) 436 8263 | Media@LabCorp.com GENFIT | 885 Avenue Eugène Avinée, 59120 Loos - FRANCE | +333 2016 4000 | Attachment