NPRA

Researchers have pinpointed a particular peptide's role in activating atopic dermatitis, or eczema. The work could lead to more effective treatments for the condition. Researchers from North Carolina State University have pinpointed a particular peptide's role in activating atopic dermatitis, or eczema. The work could lead to more effective treatments for the condition. Atopic dermatitis (AD) is a skin condition characterized by itching, irritated and thickened skin at the site of the irritation. The brain natriuretic peptide (BNP) is a peptide, or short chain of amino acids, that is elevated in patients with AD. "BNP is expressed in sensory neurons, the neurons responsible for conveying sensation to the brain via the spinal cord," says Santosh Mishra, associate professor of molecular biomedical sciences at NC State and corresponding author of the work. "We know from previous work that BNP helps translate the sensation of itch from the skin to the brain. In this work we wanted to see if BNP was involved in activating AD." In a chemically induced mouse model of AD, the researchers saw that mice without BNP did not exhibit the thickened or irritated skin commonly associated with AD, and their itching was reduced compared with control mice who did have BNP. "The results show that BNP likely plays a role in itch activation," Mishra says. "We next looked at BNP's relationship to periostin, to see if we could determine how that activation takes place." Periostin is a protein that can interact with sensory neurons in skin to activate itch response. It is produced in skin cells called keratinocytes and fibroblasts. Keratinocytes in turn, have receptors for BNP, which are called NPR1 receptors. When the BNP receptors are activated, periostin is produced and itch can be turned on. "But the interesting thing here is that the sensory neurons are the activator," Mishra says. The neuron releases BNP, which activates keratinocytes with the NPR1 receptor, which then release the periostin. "This work shows that peripheral neurons, not just central neurons, are playing a role in AD -- it begins in the sensory neurons, and cascades from there," Mishra adds. "It also points to some potential therapeutic strategies, such as blocking BNP's ability to bind to NPR1 receptors in the skin." The research appears as a letter to the editor in the Oct. 11 issue of the Journal of Investigative Dermatology. The work was supported by the National Institutes of Health under grant number 1R56AR077692-01. NC State undergraduate student Junho Yu, former NC State undergraduate student Nidha Williams, and NC State postdoctoral research scholar Joshua Wheeler, also contributed to the work.

Akosua Mireku @AkosuaMireku1 Under Section 505 of the Cures Act, the FDA was mandated to create a framework on how real-world evidence and data could be used in the drug evaluation process. Credit: Bet_Noire via Getty Images. The US Food and Drug Administration (FDA) has released a final draft guidance detailing how pharmaceutical companies should use real-world evidence to support the regulatory review process for new therapies. The FDA defines real-world data as “data relating to patient health status and/or the delivery of healthcare routinely collected from a variety of sources” and real-world evidence as “the clinical evidence about the usage and potential benefits or risks of a medical product derived from analysis of real-world data ”. Recommended Reports Reports Atrial Natriuretic Peptide Receptor 1 (Atrial Natriuretic Peptide Receptor Type A or Guanylate Cy... GlobalData Reports Platelet Derived Growth Factor Receptor (PDGFR or EC 2.7.10.1) Drugs in Development by Therapy Ar... GlobalData View all The new draft guidance is designed as per stipulations in the 21st Century Cures Act (Cures Act). Enacted in 2016, the legislation is meant to boost medical product development and give patients quicker access to health innovations. Under Section 505 of the Cures Act, the FDA was mandated to create a framework on how real-world evidence and data could be used in the drug evaluation process. Since the Act’s conception, the FDA has increasingly accepted the use of real-world evidence and data for the approvals of different drugs . In addition, real-world data has become a more popular way for sponsors to conduct Phase IV studies, above other phases, according to GlobalData . GlobalData is the parent company of Pharmaceutical Technology. The FDA stated that it would be open to receiving evidence from “non-interventional studies, including registries, electronic health records (EHRs), and medical claims”, without the need for an investigational new drug (IND) application. However, the guidance highlighted that drug manufacturers using non-interventional studies to support a marketing application should engage with the agency early in the drug development process. This would be through an appropriate regulatory pathway such as arranging a type C meeting through an IND. In the document, the agency also acknowledged the benefits of the potential use of real-world data to support the safety and/or effectiveness of a drug. However, they asserted that if this data is obtained in non-interventional studies, it is important for sponsors to take responsibility for maintaining study records and allow FDA access to the records amongst other things. The guidance also recommended that sponsors come to an agreement with any external sources of real-world data to ensure that relevant patient-level data can be provided to the FDA. If this is not possible for a justifiable reason, the FDA would allow third parties to submit the data through a separate regulatory pathway. The recommendations made in the guidance are non-binding but represent the agency’s current thinking on the topic.

Second quarter 2022 revenues decreased 44% to $2.86 billion versus second quarter 2021; excluding REGEN-COV ®(a)(b), revenues increased 20% Second quarter 2022 EYLEA® U.S. net sales increased 14% versus second quarter 2021 to a record $1.62 billion Second quarter 2022 Dupixent® global net sales(c)(recorded by Sanofi) increased 40% to $2.09 billion versus second quarter 2021 Second quarter 2022 GAAP diluted EPS of $7.47; non-GAAP diluted EPS(a) of $9.77 including unfavorable $1.71 impact from acquired IPR&D charges FDA approved Dupixent for atopic dermatitis in children aged 6 months to 5 years and eosinophilic esophagitis in adults and adolescents; FDA priority review granted for prurigo nodularis Encouraging preliminary anti-tumor activity observed for novel investigational PSMAxCD28 costimulatory bispecific antibody in combination with Libtayo® in advanced metastatic castration-resistant prostate cancer Strengthened commitment to oncology through purchase of Sanofi's stake in Libtayo and acquisition of Checkmate Pharmaceuticals TARRYTOWN, N.Y., Aug. 3, 2022 /PRNewswire/ -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced financial results for the second quarter of 2022 and provided a business update. "The second quarter of 2022 was distinguished by record net product sales of EYLEA, Dupixent, and Libtayo, as well as multiple regulatory achievements for Dupixent, including U.S. approvals for atopic dermatitis among very young patients and for eosinophilic esophagitis in adults and adolescents, as well as European approval for pediatric asthma," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "In addition, we have continued to strengthen our oncology franchise, including through the purchase of worldwide rights to Libtayo as well as encouraging but preliminary anti-tumor activity observed at higher doses of our novel PSMAxCD28 costimulatory bispecific in combination with Libtayo for advanced metastatic castration-resistant prostate cancer." Financial Highlights "We are pleased with our second quarter 2022 financial performance, including 20% revenue growth when excluding contributions from REGEN-COV. This demonstrates the continued strength of our core business," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "Additionally, we updated our full-year 2022 financial guidance primarily to reflect the recently completed acquisition of Libtayo global rights from Sanofi, a transaction that we believe will deliver significant shareholder value over time. In the second half of 2022, we look forward to advancing our pipeline with important clinical data readouts in oncology and ophthalmology as well as continued commercial execution and prudent capital allocation to drive value creation for shareholders." Business Highlights Key Pipeline Progress Regeneron has approximately 35 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include: Dupixent® (dupilumab) In June 2022, the U.S. Food and Drug Administration (FDA) approved Dupixent as the first biologic medicine for children aged 6 months to 5 years with moderate-to-severe atopic dermatitis. In May 2022, the FDA approved Dupixent for adults and adolescents aged 12 years and older with eosinophilic esophagitis (EoE). In April 2022, the European Commission (EC) approved Dupixent for the treatment of severe asthma in children aged 6 to 11 years. The Company and Sanofi announced positive results from a Phase 3 trial in children aged 1 to 11 years with EoE. The trial met its primary endpoint of histological disease remission at 16 weeks with both higher and lower dose weight-tiered regimens. The FDA accepted for priority review the supplemental Biologics License Application (sBLA) for Dupixent for adults with prurigo nodularis, with a target action date of September 30, 2022. Regulatory applications have also been submitted in the European Union (EU) and Japan. EYLEA® (aflibercept) Injection The FDA accepted for review the sBLA for EYLEA for an every-16-weeks dosing regimen in patients with diabetic retinopathy (DR), with a target action date of February 28, 2023. REGN5678, a PSMAxCD28 costimulatory bispecific antibody Reported preliminary, first-in-human data in combination with Libtayo® in patients with advanced metastatic castration-resistant prostate cancer. Antibodies to SARS-CoV-2 virus The Company is continuing to progress investigational "next generation" antibodies that are active against multiple variants including those of Omicron-lineage. REGN5381, an agonist antibody to NPR1 A Phase 2 study in heart failure was initiated. Corporate and Business Development Updates In May 2022, the Company completed its acquisition of Checkmate Pharmaceuticals, Inc. for a total equity value of approximately $250 million. In connection with the acquisition, the Company obtained the rights to vidutolimod (immune activator targeting TLR9), which is in clinical development for oncology. Effective July 1, 2022, the Company obtained the exclusive right to develop, commercialize, and manufacture Libtayo worldwide under an Amended and Restated Immuno-oncology License and Collaboration Agreement with Sanofi. Under the terms of the agreement, the Company made a $900 million up-front payment, and Sanofi is eligible to receive a $100 million regulatory milestone and up to an aggregate of $100 million in sales-based milestones upon achieving certain amounts of worldwide net product sales of Libtayo through 2023. The Company will also pay Sanofi a royalty on net product sales of Libtayo. Also effective July 1, 2022, the Company will increase from 10% to 20% the share of its profits that are paid to Sanofi in connection with the development balance reimbursement under the antibody collaboration. Second Quarter 2022 Financial Results Revenues Total revenues decreased by 44% to $2.857 billion in the second quarter of 2022, compared to $5.139 billion in the second quarter of 2021. Total revenues excluding REGEN-COV and Ronapreve(b) revenues for both periods increased by 20% to $2.849 billion in the second quarter of 2022, compared to the second quarter of 2021(a). There have been no sales of REGEN-COV in the United States during 2022 as the Company had completed its final deliveries of drug product under its agreements with the U.S. government as of December 31, 2021. Sanofi collaboration revenue increased by 55% to $678 million in the second quarter of 2022, compared to the second quarter of 2021. This increase was primarily due to the Company's share of profits from commercialization of antibodies, which were $497 million in the second quarter of 2022, compared to $328 million in the second quarter of 2021. The change in the Company's share of profits from commercialization of antibodies was driven by higher Dupixent profits. Roche collaboration revenue decreased in the second quarter of 2022, compared to the second quarter of 2021, due to lower sales of Ronapreve. Refer to Table 4 for a summary of collaboration revenue. Operating Expenses GAAP and non-GAAP R&D expenses increased in the second quarter of 2022, compared to the second quarter of 2021, primarily due to higher headcount and headcount-related costs and an increase in clinical manufacturing activities, partly offset by lower costs incurred in connection with REGEN-COV development activities. Acquired IPR&D in the second quarter of 2022 included a $195 million charge related to the Company's acquisition of Checkmate Pharmaceuticals. The increase in GAAP and non-GAAP SG&A expenses in the second quarter of 2022, compared to the second quarter of 2021, was primarily due to higher headcount and headcount-related costs and an increase in commercialization-related expenses for EYLEA, partly offset by costs in 2021 for educational campaigns related to COVID-19 that did not recur in 2022. GAAP and non-GAAP COGS decreased in the second quarter of 2022, compared to the second quarter of 2021, primarily due to the Company not recognizing any REGEN-COV net product sales in the United States during 2022. Other Financial Information GAAP other income (expense) included the recognition of net unrealized losses on equity securities of $164 million in the second quarter of 2022, compared to $409 million of net unrealized gains in the second quarter of 2021. In the second quarter of 2022, the Company's GAAP effective tax rate (ETR) was 11.5%, compared to 17.4% in the second quarter of 2021. The decrease in the GAAP ETR was primarily driven by the proportion of income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate, the impact of income earned in the United States during 2021 related to REGEN-COV, and, to a lesser extent, stock-based compensation. In the second quarter of 2022, the non-GAAP ETR was 13.6%, compared to 17.0% in the second quarter of 2021. GAAP net income per diluted share was $7.47 in the second quarter of 2022, compared to $27.97 in the second quarter of 2021. Non-GAAP net income per diluted share was $9.77 in the second quarter of 2022, compared to $25.80 in the second quarter of 2021. A reconciliation of the Company's GAAP to non-GAAP results is included in Table 3 of this press release. During the second quarter of 2022, the Company repurchased shares of common stock under its share repurchase program, and recorded the cost of the shares received, or $394 million, as Treasury Stock. As of June 30, 2022, $2.099 billion remained available for share repurchases under the program. 2022 Financial Guidance (d) The Company's full year 2022 financial guidance consists of the following components (inclusive of updates made in connection with the Company's purchase of Sanofi's stake in Libtayo and acquisition of Checkmate Pharmaceuticals): A reconciliation of full year 2022 GAAP to non-GAAP financial guidance is included below: Conference Call Information Regeneron will host a conference call and simultaneous webcast to discuss its second quarter 2022 financial and operating results on Wednesday, August 3, 2022, at 8:30 AM Eastern Time. Participants may access the conference call live via webcast, or register in advance and participate via telephone, on the "Investors and Media" page of Regeneron's website at . Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the Company's website for at least 30 days. About Regeneron Pharmaceuticals, Inc. Regeneron 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, Regeneron's unique ability to repeatedly and consistently translate science into medicine has led to numerous FDA-approved treatments and product candidates in development, almost all of which were homegrown in Regeneron's laboratories. Regeneron's 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 its 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 additional information about Regeneron, please visit or follow @Regeneron on Twitter. 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, including without limitation EYLEA ® (aflibercept) Injection, Dupixent ® (dupilumab), Libtayo ® (cemiplimab), Praluent ® (alirocumab), Kevzara ® (sarilumab), Evkeeza ® (evinacumab), fasinumab, REGEN-COV ® (casirivimab and imdevimab), aflibercept 8 mg, pozelimab, odronextamab, itepekimab, fianlimab, REGN5458, REGN5713-5714-5715, REGN1908-1909, Regeneron's other oncology programs (including its costimulatory bispecific portfolio), Regeneron's and its collaborators' earlier-stage programs, and the use of human genetics in Regeneron's research programs; the likelihood and timing of achieving any of the anticipated milestones described in this press release; 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 in clinical trials; the likelihood, timing, and scope of possible regulatory approval and commercial launch of Regeneron's Product Candidates and new indications for Regeneron's Products, including those listed above and/or otherwise discussed in this press release; the extent to which the results from the research and development programs conducted by Regeneron and/or its collaborators may be replicated in other studies and/or lead to advancement of product candidates to clinical trials, therapeutic applications, or regulatory approval; ongoing regulatory obligations and oversight impacting Regeneron's Products, research and clinical programs, and business, including those relating to patient privacy; 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; competing drugs and product candidates that may be superior to, or more cost effective than, Regeneron's Products and Regeneron's Product Candidates; 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) or recommendations and guidelines from governmental authorities and other third parties on the commercial success of Regeneron's Products and Regeneron's Product Candidates; the ability of Regeneron to manufacture and manage supply chains for multiple products and product candidates; the ability of Regeneron's collaborators, 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 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; 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, including GAAP and non-GAAP R&D, GAAP and non-GAAP SG&A, GAAP and non-GAAP gross margin on net product sales, COCM, other operating (income) expense, net, capital expenditures, and GAAP and non-GAAP ETR; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), 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, Dupixent, Praluent, and REGEN-COV), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil litigation initiated by the U.S. Attorney's Office for the District of Massachusetts), 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 fiscal 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 (). Non-GAAP Financial Measures This press release and/or the financial results attached to this press release include amounts that are considered "non-GAAP financial measures" under SEC rules. As required, Regeneron has provided reconciliations of such non-GAAP financial measures. SOURCE Regeneron Pharmaceuticals, Inc.