Fasinumab

Fourth quarter 2022 revenues decreased 31% to $3.41 billion versus fourth quarter 2021; excluding REGEN-COV® and RonapreveTM(a)(b), revenues increased 14%Full year 2022 revenues decreased 24% to $12.17 billion versus full year 2021; excluding REGEN-COV and Ronapreve(a)(b), revenues increased 17%Fourth quarter 2022 EYLEA® U.S. net sales decreased 3% to $1.50 billion versus fourth quarter 2021; full year 2022 EYLEA U.S. net sales increased 8% to $6.26 billion versus 2021Fourth quarter 2022 Dupixent® global net sales (recorded by Sanofi) increased 38% to $2.45 billion versus fourth quarter 2021; full year 2022 Dupixent global net sales increased 40% to $8.68 billion versus 2021Fourth quarter 2022 GAAP diluted EPS of $10.50 and non-GAAP diluted EPS(a) of $12.56; includes unfavorable $0.21 impact from acquired IPR&D chargeAflibercept 8 mg BLA for neovascular age-related macular degeneration (wet AMD) and diabetic macular edema (DME) submitted to FDA in December 2022FDA approved Libtayo® in combination with chemotherapy as first-line treatment for advanced non-small cell lung cancer (NSCLC)European Commission approved Dupixent for adults with prurigo nodularis and adults and adolescents with eosinophilic esophagitis (EoE)Allocated $3.4 billion to business development and share repurchases in 2022; new $3.0 billion share repurchase program authorized in January 2023 TARRYTOWN, N.Y., Feb. 03, 2023 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced financial results for the fourth quarter and full year 2022 and provided a business update. "In 2022, Regeneron reported record revenue for EYLEA, Dupixent and Libtayo and made exciting progress across the entire pipeline," said Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. "In the fourth quarter of 2022, we submitted our Biologics License Application for neovascular age-related macular degeneration and diabetic macular edema for aflibercept 8 mg, which could potentially reach patients in the third quarter of 2023. We also continued to expand the use of our commercial products with the U.S. FDA approval of Libtayo in combination with chemotherapy for non-small cell lung cancer and the European Commission approval of Dupixent for prurigo nodularis. In 2023, we remain committed to achieving the full potential of our diverse commercial- and clinical-stage portfolio, with a particular focus on aflibercept 8 mg, Dupixent in a variety of type 2 allergic diseases, and our promising oncology and hematology assets." Financial Highlights Three Months EndedDecember 31, Year Ended December 31, ($ in millions, except per share data) 2022 2021 % Change 2022 2021 % ChangeTotal revenues $3,414 $4,952 (31%) $12,173 $16,072 (24%)Total revenues excluding REGEN-COV and Ronapreve(a)(b) $3,018 $2,654 14% $11,546 $9,882 17%GAAP net income $1,197 $2,229 (46%) $4,338 $8,075 (46%)GAAP net income per share - diluted $10.50 $19.69 (47%) $38.22 $71.97 (47%)Non-GAAP net income(a) $1,449 $2,677 (46%) $5,164 $8,454 (39%)Non-GAAP net income per share - diluted(a) $12.56 $23.42 (46%) $44.98 $74.35 (40%) "We were pleased with our fourth-quarter and full-year 2022 financial performance, highlighted by revenue growth of 14% and 17%, respectively, when excluding contributions from REGEN-COV and Ronapreve, demonstrating the commercial strength and increasing diversity of our business," said Robert E. Landry, Executive Vice President, Finance and Chief Financial Officer of Regeneron. "In January 2023, our Board of Directors authorized a new $3.0 billion share repurchase program, enabling us to continue returning capital directly to shareholders. This year, we look forward to driving long-term shareholder value through continued investment in R&D, excellent commercial execution and strategic business development." Business Highlights Key Pipeline ProgressRegeneron 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: Aflibercept 8 mg A Biologics License Application (BLA) for the treatment of wet AMD and DME was submitted to the U.S. Food and Drug Administration (FDA) in December 2022. The Company is utilizing a priority review voucher in connection with the submission. EYLEA (aflibercept) Injection In December 2022, the European Commission (EC) approved EYLEA for the treatment of retinopathy of prematurity (ROP) in preterm infants. The supplemental BLA (sBLA) for EYLEA to treat ROP in preterm infants is currently under review by the FDA, with a target action date of February 11, 2023. Dupixent (dupilumab) In December 2022, the EC approved Dupixent for the treatment of adult patients with moderate-to-severe prurigo nodularis who are candidates for systemic therapy, making Dupixent the first and only targeted medicine specifically indicated to treat prurigo nodularis in Europe.In January 2023, the EC also approved Dupixent for the treatment of adults and adolescents with EoE, making Dupixent the first and only targeted medicine specifically indicated to treat EoE in Europe.The European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for Dupixent to treat children aged 6 months to 5 years with severe atopic dermatitis. The EC decision is expected in the coming months.An sBLA for the treatment of adult and adolescent patients with chronic spontaneous urticaria (CSU) was submitted. Oncology ProgramsLibtayo (cemiplimab) In November 2022, the FDA approved Libtayo in combination with platinum-based chemotherapy for the first-line treatment of adult patients with advanced NSCLC.In November 2022, the EC approved Libtayo as a monotherapy for the treatment of adult patients with recurrent or metastatic cervical cancer and disease progression on or after platinum-based chemotherapy. In December 2022, the Ministry of Health, Labour and Welfare (MHLW) in Japan also approved Libtayo in advanced or recurrent cervical cancer. Fianlimab, an antibody to LAG-3 A Phase 3 study in first-line adjuvant melanoma was initiated. Linvoseltamab, a bispecific antibody targeting BCMA and CD3 The Company announced positive initial data from a pivotal Phase 2 expansion cohort evaluating linvoseltamab at the 200 mg dose in patients with heavily pre-treated, relapsed/refractory multiple myeloma. The results were presented at the American Society of Hematology (ASH) Annual Meeting and Exposition. Odronextamab, a bispecific antibody targeting CD20 and CD3 Positive data were also presented at ASH from two cohorts of a pivotal Phase 2 trial studying odronextamab in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Other Programs A BLA for pozelimab, an antibody to C5, for the treatment of CD55-deficient protein-losing enteropathy (CHAPLE) was submitted.The FDA accepted for priority review the sBLA for Kevzara® (sarilumab) to treat polymyalgia rheumatica (PMR), with a target action date of February 28, 2023.The FDA accepted for priority review the sBLA for Evkeeza® (evinacumab) as an adjunct to other lipid-lowering therapies to treat children aged 5 to 11 years with homozygous familial hypercholesterolemia (HoFH), with a target action date of March 30, 2023. Corporate and Business Development Updates In November 2022, the Company and CytomX Therapeutics, Inc. entered into a license and collaboration agreement to create conditionally-activated investigational bispecific cancer therapies utilizing CytomX's Probody® therapeutic platform and Regeneron's Veloci-Bi® bispecific antibody development platform. Under the terms of the agreement, the Company made an upfront payment of $30 million and will be responsible for funding development and commercial activities, and CytomX will be eligible to receive future target nomination payments and preclinical, clinical, and commercial milestone payments as well as royalties on global net sales.The Company was included on the Dow Jones Sustainability World Index (DJSI World) for the fourth consecutive year and on the Dow Jones Sustainability North America Index (DJSI North America) for the third year. Select 2023 Milestones Programs MilestonesAflibercept 8 mg - FDA decision on BLA for wet AMD and DME (third quarter 2023) - Report two-year data from PULSAR (wet AMD) and PHOTON (DME) Phase 3 studies (third quarter 2023)EYLEA (aflibercept) - FDA decision on sBLA for ROP (target action date of February 11, 2023)Dupixent (dupilumab) - EC decision on regulatory submission for atopic dermatitis in pediatrics (6 months–5 years of age) (first half 2023) - Submit sBLA for EoE in pediatrics (mid-2023) - FDA decision on sBLA for CSU in adults and adolescents (second half 2023) - Report results from first Phase 3 study in COPD and Phase 3 study in chronic inducible urticaria - cold (first half 2023)Solid Organ Oncology - Initiate Phase 3 study for fianlimab (in combination with Libtayo) in perioperative melanoma (mid-2023) - Initiate Phase 2/3 studies for fianlimab (in combination with Libtayo) in first-line advanced NSCLC (first half 2023) and Phase 2 study in perioperative NSCLC (second half 2023) - Report additional results from Phase 1/2 study of REGN5678 (PSMA and CD28 bispecific antibody) in combination with Libtayo in prostate cancer (2023) - Report initial data across solid organ oncology, including for CD3 bispecifics and CD28 costimulatory bispecifics (2023) - EC decision on regulatory submission for Libtayo (in combination with chemotherapy) in advanced NSCLC (first half 2023)Odronextamab (CD20 and CD3 Bispecific Antibody) - Initiate Phase 3 studies in FL and DLBCL, including earlier lines of therapy (first half 2023) - Submit BLA for relapsed/refractory FL and DLBCL (second half 2023)Linvoseltamab (BCMA and CD3 Bispecific Antibody) - Initiate Phase 3 study in multiple myeloma, including earlier lines of therapy (first half 2023) - Submit BLA for relapsed/refractory multiple myeloma (second half 2023)Pozelimab (C5 Antibody) - FDA decision on BLA for CHAPLE (second half 2023) Fourth Quarter 2022 Financial Results Revenues ($ in millions) Q4 2022 Q4 2021 % Change FY 2022 FY 2021 % ChangeNet product sales: EYLEA - U.S. $1,496 $1,547 (3%) $6,265 $5,792 8% Libtayo - U.S. 110 81 36% 375 306 23% Libtayo - ROW** 42 — * 73 — * Praluent® - U.S. 36 40 (10%) 130 170 (24%)REGEN-COV - U.S. — 2,298 (100%) — 5,828 (100%)Evkeeza - U.S. 15 9 67% 48 19 153% Inmazeb® - U.S. — — —% 3 — * ARCALYST® - U.S.*** — — * — 2 * Total net product sales 1,699 3,975 (57%) 6,894 12,117 (43%) Collaboration revenue: Sanofi 836 518 61% 2,856 1,902 50% Bayer 355 372 (5%) 1,431 1,409 2% Roche 396 — * 627 362 73% Other revenue 128 87 47% 365 282 29% Total revenues $3,414 $4,952 (31%) $12,173 $16,072 (24%) Total revenues excluding REGEN-COV and Ronapreve(a) $3,018 $2,654 14% $11,546 $9,882 17% * Percentage not meaningful.** Rest of world (ROW). Effective July 1, 2022, the Company began recording net product sales of Libtayo outside the United States. Excluded from this line item is approximately $17 million and $34 million of net product sales recorded by Sanofi in the fourth quarter and second half of 2022, respectively, in connection with sales in certain markets (Sanofi will record net product sales in such markets during a transition period until inventory on hand as of July 1, 2022 is sold through to the end customers).*** Effective April 1, 2021, Kiniksa records net product sales of ARCALYST in the United States. Previously, the Company recorded net product sales of ARCALYST in the United States. Net product sales of EYLEA in the U.S. in the fourth quarter of 2022 were negatively impacted by (i) a short-term shift to off-label use of compounded bevacizumab, (ii) a temporary closing in the fourth quarter of 2022 of a not-for-profit fund that provides patient co-pay assistance, and (iii) an increase in sales-related deductions. Volumes of U.S. EYLEA in the fourth quarter of 2022 increased compared to the fourth quarter of 2021. There were no sales of REGEN-COV in the U.S. 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 61% to $836 million in the fourth quarter of 2022, compared to the fourth quarter of 2021, and increased 50% to $2.856 billion for the full year 2022, compared to the full year 2021. This increase was primarily due to the Company's share of profits from commercialization of antibodies, which were $619 million and $388 million in the fourth quarter of 2022 and 2021, respectively, and $2.082 billion and $1.363 billion for full year 2022 and 2021, respectively. The change in the Company's share of profits from commercialization of antibodies was driven by profits associated with higher Dupixent sales. In addition, during 2022 the Company earned two $50 million sales-based milestones (including one in the fourth quarter of 2022) from Sanofi based upon sales of antibodies outside the U.S. on a rolling twelve-month basis, compared to earning one $50 million sales-based milestone in 2021 (in the third quarter of 2021). Sanofi and Bayer collaboration revenue (and specifically, the share of profits the Company earned in connection with commercialization of products) was adversely impacted in 2022 by the U.S. dollar strengthening against foreign currencies, including the Japanese yen and the euro. The Company recorded Roche collaboration revenue during full year 2022 and 2021 in connection with payments from Roche attributable to global gross profits from sales of Ronapreve. Roche collaboration revenue increased in the fourth quarter of 2022, compared to the fourth quarter of 2021, as no Roche collaboration revenue was recorded during the fourth quarter of 2021 since the Company owed a payment to Roche (which was recorded to Cost of goods sold) in connection with global gross profits of REGEN-COV and Ronapreve. Refer to Table 4 for a summary of collaboration revenue. Operating Expenses GAAP %Change Non-GAAP(a) %Change($ in millions) Q4 2022 Q4 2021 Q4 2022 Q4 2021 Research and development (R&D)** $1,043 $738 41% $911 $635 43% Acquired in-process research and development (IPR&D)** $30 $48 (38%) * * n/a Selling, general, and administrative (SG&A) $661 $560 18% $579 $495 17% Cost of goods sold (COGS) $302 $812 (63%) $126 $559 (77%)Cost of collaboration and contract manufacturing (COCM) $238 $171 39% * * n/a Other operating (income) expense, net $(7) $(16) (56%) * * n/a GAAP %Change Non-GAAP(a) %Change FY 2022 FY 2021 FY 2022 FY 2021 Research and development** $3,593 $2,860 26% $3,169 $2,544 25% Acquired in-process research and development** $255 $48 431% * * n/a Selling, general, and administrative $2,116 $1,825 16% $1,853 $1,606 15% Cost of goods sold $800 $1,773 (55%) $507 $1,470 (66%)Cost of collaboration and contract manufacturing $760 $664 14% * * n/a Other operating (income) expense, net $(90) $(46) 96% * * n/a * GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been recorded.** Certain reclassifications have been made to prior period amounts to conform with the current period's presentation. See note (f) below for additional information. GAAP and non-GAAP R&D expenses increased in the fourth quarter and full year of 2022, compared to the same periods in the prior year, driven by the impact of the 2022 amendments to the Sanofi collaboration agreements, additional costs incurred in connection with the Company's late-stage pipeline, an increase in clinical manufacturing activities, and higher headcount and headcount-related costs. The increase for the full year of 2022, compared to full year 2021, was partly offset by lower costs incurred in connection with development activities for REGEN-COV and fasinumab.Acquired IPR&D for full year 2022 included a $195 million charge related to the Company's acquisition of Checkmate Pharmaceuticals, Inc., a $30 million up-front payment in connection with the Company's collaboration agreement with CytomX (fourth quarter 2022), and a $20 million opt-in payment in connection with a product candidate under the Company's collaboration agreement with Adicet Bio, Inc. Acquired IPR&D for the fourth quarter and full year of 2021 included $34 million in aggregate up-front payments in connection with the Company's collaboration agreement with Nykode Therapeutics.GAAP and non-GAAP SG&A expenses increased in the fourth quarter and full year of 2022, compared to the same periods in the prior year, primarily due to an increase in commercialization-related expenses for Libtayo (as effective July 1, 2022, the Company became solely responsible for the commercialization of Libtayo worldwide), higher contributions to an independent not-for-profit patient assistance organization, and higher headcount and headcount-related costs, partly offset by educational campaigns related to COVID-19 that did not recur during 2022.GAAP and non-GAAP COGS decreased in the fourth quarter and full year of 2022, compared to the same periods in the prior year, primarily due to the Company recognizing U.S. REGEN-COV net product sales (and corresponding cost of goods sold) during 2021 and a 2021 payment of $260 million owed by the Company in connection with global gross profits under its Roche collaboration agreement; such transactions did not recur in 2022. GAAP and non-GAAP COGS also decreased in 2022 since effective July 1, 2022, following the acquisition of Libtayo worldwide rights, the Company is no longer obligated to pay Sanofi for their share of U.S. Libtayo gross profits.GAAP COGS also decreased in the fourth quarter and full year of 2022 due to lower inventory write-offs and reserves. Non-GAAP COGS excluded certain charges related to REGEN-COV (primarily inventory write-offs and reserves) of $134 million and $197 million in the fourth quarter and full year of 2022, respectively, and $232 million in each of the fourth quarter and full year of 2021.Other operating (income) expense, net, for full year 2022 included the recognition of $44 million (an increase to other operating income) as a result of discontinuing further clinical development of fasinumab related to the Company's Teva and Mitsubishi Tanabe Pharma collaborative arrangements. Other Financial Information GAAP other income (expense) included the recognition of net unrealized gains on equity securities of $81 million in the fourth quarter of 2022, compared to $138 million of net unrealized losses in the fourth quarter of 2021. GAAP other income (expense) included the recognition of net unrealized losses on equity securities of $40 million for full year 2022, compared to net unrealized gains of $386 million for full year 2021. In the fourth quarter and full year 2022, the Company's GAAP effective tax rate (ETR) was 9.6% and 10.7%, respectively, compared to 11.0% and 13.4% in the fourth quarter and full year 2021, respectively. The GAAP ETR in the fourth quarter and full year 2022, compared to the same periods in the prior year, included a higher benefit from the proportion of income earned in foreign jurisdictions with tax rates lower than the U.S. federal statutory rate (including the impact from REGEN-COV income earned in the U.S. during 2021). In the fourth quarter and full year 2022, the non-GAAP ETR was 11.3% and 12.1%, respectively, compared to 12.6% and 13.5% in the fourth quarter and full year 2021, respectively. GAAP net income per diluted share was $10.50 in the fourth quarter of 2022, compared to $19.69 in the fourth quarter of 2021. GAAP net income per diluted share was $38.22 for the full year 2022, compared to $71.97 for full year 2021. Non-GAAP net income per diluted share was $12.56 in the fourth quarter of 2022, compared to $23.42 in the fourth quarter of 2021. Non-GAAP net income per diluted share was $44.98 for the full year 2022, compared to $74.35 for the full year 2021. A reconciliation of the Company's GAAP to non-GAAP results is included in Table 3 of this press release. During the full year 2022, the Company repurchased shares of common stock under its share repurchase program, and recorded the cost of the shares, or $2.100 billion, as Treasury Stock. As of December 31, 2022, $745 million remained available for share repurchases under the program. In January 2023, the Company's board of directors authorized a new share repurchase program to repurchase up to an additional $3.0 billion of the Company's common stock. Repurchases may be made from time to time at management's discretion through a variety of methods. The program has no time limit and can be discontinued at any time. 2023 Financial Guidance(c) The Company's full year 2023 financial guidance consists of the following components: 2023 GuidanceGAAP R&D $4.200–$4.435 billionNon-GAAP R&D(a) $3.725–$3.925 billionGAAP SG&A $2.460–$2.650 billionNon-GAAP SG&A(a) $2.130–$2.280 billionGAAP gross margin on net product sales(d) 88%–90%Non-GAAP gross margin on net product sales(a)(d) 90%–92%COCM(e)* $720–$800 millionCapital expenditures* $825–$950 millionGAAP effective tax rate 10%–12%Non-GAAP effective tax rate(a) 11%–13% * GAAP and non-GAAP amounts are equivalent as no non-GAAP adjustments have been or are expected to be recorded. A reconciliation of full year 2023 GAAP to non-GAAP financial guidance is included below: Projected Range($ in millions) Low HighGAAP R&D $4,200 $4,435 Stock-based compensation expense 470 500 Acquisition-related integration costs 5 10 Non-GAAP R&D $3,725 $3,925 GAAP SG&A $2,460 $2,650 Stock-based compensation expense 310 330 Acquisition-related integration costs 20 40 Non-GAAP SG&A $2,130 $2,280 GAAP gross margin on net product sales 88% 90% Stock-based compensation expense 1% 1% Intangible asset amortization expense 1% 1% Non-GAAP gross margin on net product sales 90% 92% GAAP ETR 10% 12% Income tax effect of GAAP to non-GAAP reconciling items 1% 1% Non-GAAP ETR 11% 13% (a)This press release uses non-GAAP R&D, non-GAAP SG&A, non-GAAP COGS, non-GAAP gross margin on net product sales, non-GAAP other income (expense), net, non-GAAP ETR, non-GAAP net income, non-GAAP net income per share, total revenues excluding REGEN-COV and Ronapreve, and free cash flow, which are financial measures that are not calculated in accordance with U.S. Generally Accepted Accounting Principles (GAAP). These non-GAAP financial measures are computed by excluding certain non-cash and/or other items from the related GAAP financial measure. The Company also includes a non-GAAP adjustment for the estimated income tax effect of reconciling items. A reconciliation of the Company's GAAP to non-GAAP results is included in Table 3 of this press release.The Company makes such adjustments for items the Company does not view as useful in evaluating its operating performance. For example, adjustments may be made for items that fluctuate from period to period based on factors that are not within the Company's control (such as the Company's stock price on the dates share-based grants are issued or changes in the fair value of the Company's investments in equity securities) or items that are not associated with normal, recurring operations (such as restructuring- or integration-related expenses). Management uses these non-GAAP measures for planning, budgeting, forecasting, assessing historical performance, and making financial and operational decisions, and also provides forecasts to investors on this basis. With respect to free cash flows, the Company believes that this non-GAAP measure provides a further measure of the Company’s operations' ability to generate cash flows. Additionally, such non-GAAP measures provide investors with an enhanced understanding of the financial performance of the Company's core business operations. However, there are limitations in the use of these and other non-GAAP financial measures as they exclude certain expenses that are recurring in nature. Furthermore, the Company's non-GAAP financial measures may not be comparable with non-GAAP information provided by other companies. Any non-GAAP financial measure presented by Regeneron should be considered supplemental to, and not a substitute for, measures of financial performance prepared in accordance with GAAP. (b)The casirivimab and imdevimab antibody cocktail for COVID-19 is known as REGEN-COV in the United States and Ronapreve in other countries. The Company records net product sales of REGEN-COV in the United States and Roche records net product sales of Ronapreve outside the United States. (c)The Company's 2023 financial guidance does not assume the completion of any significant business development transactions not completed as of the date of this press release. (d)Gross margin on net product sales represents gross profit expressed as a percentage of total net product sales recorded by the Company. Gross profit is calculated as net product sales less cost of goods sold. (e)Corresponding reimbursements from collaborators and others for manufacturing of commercial supplies is recorded within revenues. (f)Beginning with the first quarter of 2022, the Company added Acquired in-process research and development as a new line item to its Statements of Operations, which includes IPR&D acquired in connection with asset acquisitions as well as up-front/opt-in payments related to license and collaboration agreements. Amounts recorded in this line would have historically been recorded to Research and development expenses. Prior period amounts have been reclassified to conform with the current period's presentation. Beginning with the first quarter of 2022, IPR&D expenses are no longer excluded in the determination of non-GAAP financial results. Prior period non-GAAP results have also been updated to reflect these changes. Conference Call Information Regeneron will host a conference call and simultaneous webcast to discuss its fourth quarter and full year 2022 financial and operating results on Friday, February 3, 2023, 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 www.regeneron.com. 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 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 www.regeneron.com 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), aflibercept 8 mg, pozelimab, odronextamab, itepekimab, fianlimab, garetosmab, linvoseltamab, REGN5713-5714-5715, 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, capital expenditures, and GAAP and non-GAAP ETR; the potential for any license or collaboration agreement, including Regeneron's agreements with Sanofi and Bayer (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, Praluent, and REGEN-COV® (casirivimab and imdevimab)), 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. 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 (http://newsroom.regeneron.com) and its Twitter feed (http://twitter.com/regeneron). 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. Contact Information: Ryan Crowe Christina ChanInvestor Relations Corporate Communications914-847-8790 914-847-8827ryan.crowe@regeneron.com christina.chan@regeneron.com TABLE 1 REGENERON PHARMACEUTICALS, INC.CONDENSED CONSOLIDATED BALANCE SHEETS (Unaudited)(In millions) December 31, 2022 2021 Assets: Cash and marketable securities $14,334.1 $12,532.7 Accounts receivable, net 5,328.7 6,036.5 Inventories 2,401.9 1,951.3 Property, plant, and equipment, net 3,763.0 3,482.2 Intangible assets, net 915.5 6.7 Deferred tax assets 1,723.7 876.9 Other assets 747.6 548.5 Total assets $29,214.5 $25,434.8 Liabilities and stockholders' equity: Accounts payable, accrued expenses, and other liabilities $3,301.4 $3,451.0 Finance lease liabilities 720.0 719.7 Deferred revenue 547.7 515.3 Long-term debt 1,981.4 1,980.0 Stockholders' equity 22,664.0 18,768.8 Total liabilities and stockholders' equity $29,214.5 $25,434.8 TABLE 2 REGENERON PHARMACEUTICALS, INC.CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS (Unaudited)(In millions, except per share data) Three Months Ended December 31, Year EndedDecember 31, 2022 2021* 2022 2021*Revenues: Net product sales $1,699.3 $3,975.2 $6,893.7 $12,117.2 Collaboration revenue 1,587.4 890.3 4,914.1 3,673.3 Other revenue 127.7 86.2 365.1 281.2 3,414.4 4,951.7 12,172.9 16,071.7 Expenses: Research and development 1,043.1 737.6 3,592.5 2,860.1 Acquired in-process research and development 30.0 48.0 255.1 48.0 Selling, general, and administrative 660.5 559.6 2,115.9 1,824.9 Cost of goods sold 302.2 811.7 800.0 1,773.1 Cost of collaboration and contract manufacturing 238.4 170.9 760.4 664.4 Other operating (income) expense, net (6.6) (15.8) (89.9) (45.6) 2,267.6 2,312.0 7,434.0 7,124.9 Income from operations 1,146.8 2,639.7 4,738.9 8,946.8 Other income (expense): Other income (expense), net 195.3 (122.2) 179.3 436.3 Interest expense (17.4) (14.1) (59.4) (57.3) 177.9 (136.3) 119.9 379.0 Income before income taxes 1,324.7 2,503.4 4,858.8 9,325.8 Income tax expense 127.6 274.4 520.4 1,250.5 Net income $1,197.1 $2,229.0 $4,338.4 $8,075.3 Net income per share - basic $11.19 $20.99 $40.51 $76.40 Net income per share - diluted $10.50 $19.69 $38.22 $71.97 Weighted average shares outstanding - basic 107.0 106.2 107.1 105.7 Weighted average shares outstanding - diluted 114.0 113.2 113.5 112.2 * Certain reclassifications have been made to prior period amounts to conform with the current period's presentation. See note (f) above for additional information. TABLE 3 REGENERON PHARMACEUTICALS, INC.RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL INFORMATION (Unaudited)(In millions, except per share data) Three Months Ended December 31, Year EndedDecember 31, 2022 2021* 2022 2021*GAAP R&D $1,043.1 $737.6 $3,592.5 $2,860.1 R&D: Stock-based compensation expense 131.0 102.9 406.8 316.6 R&D: Acquisition-related integration costs 1.4 — 17.0 — Non-GAAP R&D $910.7 $634.7 $3,168.7 $2,543.5 GAAP SG&A $660.5 $559.6 $2,115.9 $1,824.9 SG&A: Stock-based compensation expense 78.4 64.2 256.4 213.3 SG&A: Acquisition-related integration costs and other 3.5 — 6.6 5.6 Non-GAAP SG&A $578.6 $495.4 $1,852.9 $1,606.0 GAAP COGS $302.2 $811.7 $800.0 $1,773.1 COGS: Stock-based compensation expense 22.6 21.3 61.8 71.8 COGS: Intangible asset amortization expense 19.7 — 34.8 — COGS: Charges related to REGEN-COV 133.7 231.7 196.6 231.7 Non-GAAP COGS $126.2 $558.7 $506.8 $1,469.6 GAAP other income (expense), net $177.9 $(136.3) $119.9 $379.0 Other income/expense: (Gains) losses on investments (80.5) 137.6 36.8 (387.0)Non-GAAP other income (expense), net $97.4 $1.3 $156.7 $(8.0) GAAP net income $1,197.1 $2,229.0 $4,338.4 $8,075.3 Total of GAAP to non-GAAP reconciling items above 309.8 557.7 1,016.8 452.0 Income tax effect of GAAP to non-GAAP reconciling items (57.9) (110.0) (191.3) (73.7)Non-GAAP net income $1,449.0 $2,676.7 $5,163.9 $8,453.6 Non-GAAP net income per share - basic $13.54 $25.20 $48.22 $79.98 Non-GAAP net income per share - diluted $12.56 $23.42 $44.98 $74.35 Shares used in calculating: Non-GAAP net income per share - basic 107.0 106.2 107.1 105.7 Non-GAAP net income per share - diluted 115.4 114.3 114.8 113.7 * Prior period results have been revised to reflect certain changes to amounts excluded from non-GAAP results. See note (f) above for additional information. RECONCILIATION OF GAAP TO NON-GAAP FINANCIAL INFORMATION (Unaudited) (continued) Three Months Ended December 31, Year EndedDecember 31, 2022 2021 2022 2021Revenue reconciliation: Total revenues $3,414.4 $4,951.7 $12,172.9 $16,071.7 REGEN-COV net product sales in the United States — 2,297.9 — 5,828.0 Global gross profit payment from Roche in connection with sales of Ronapreve 396.4 — 627.3 361.8 Total revenues excluding REGEN-COV and Ronapreve $3,018.0 $2,653.8 $11,545.6 $9,881.9 Effective tax rate reconciliation: GAAP ETR 9.6% 11.0% 10.7% 13.4% Income tax effect of GAAP to non-GAAP reconciling items 1.7% 1.6% 1.4% 0.1% Non-GAAP ETR 11.3% 12.6% 12.1% 13.5% Year EndedDecember 31, 2022 2021 Free cash flow reconciliation: Net cash provided by operating activities $5,014.9 $7,081.3 Capital expenditures (590.1) (551.9) Free cash flow $4,424.8 $6,529.4 TABLE 4 REGENERON PHARMACEUTICALS, INC.COLLABORATION REVENUE (Unaudited)(In millions) Three Months Ended December 31, Year EndedDecember 31, 2022 2021 2022 2021 Sanofi collaboration revenue: Antibody: Regeneron's share of profits in connection with commercialization of antibodies $619.0 $387.8 $2,082.0 $1,363.0 Sales-based milestones earned 50.0 — 100.0 50.0 Reimbursement for manufacturing of commercial supplies 166.9 127.6 633.7 488.8 Other — — 28.7 — Immuno-oncology: Regeneron's share of profits (losses) in connection with commercialization of Libtayo outside the United States — (1.0) 6.7 (13.6)Reimbursement for manufacturing of ex-U.S. commercial supplies — 3.5 4.6 14.0 Total Sanofi collaboration revenue 835.9 517.9 2,855.7 1,902.2 Bayer collaboration revenue: Regeneron's share of profits in connection with commercialization of EYLEA outside the United States 324.0 353.9 1,317.4 1,349.2 Reimbursement for manufacturing of ex-U.S. commercial supplies 31.1 18.5 91.4 60.1 One-time payment in connection with change in Japan arrangement — — 21.9 — Total Bayer collaboration revenue 355.1 372.4 1,430.7 1,409.3 Other collaboration revenue: Global gross profit payment from Roche in connection with sales of REGEN-COV and Ronapreve 396.4 — 627.3 361.8 Other — — 0.4 — Total collaboration revenue $1,587.4 $890.3 $4,914.1 $3,673.3 TABLE 5 REGENERON PHARMACEUTICALS, INC.NET PRODUCT SALES OF REGENERON-DISCOVERED PRODUCTS (Unaudited)(In millions) Three Months Ended December 31, 2022 2021 % Change U.S. ROW Total U.S. ROW Total (Total Sales)EYLEA(a) $1,496.4 $838.6 $2,335.0 $1,547.2 $883.2* $2,430.4 (4%)Dupixent(b) $1,936.3 $512.6 $2,448.9 $1,348.2 $425.6 $1,773.8 38% Libtayo(c) $110.0 $58.8 $168.8 $80.8 $40.2 $121.0 40% Praluent(d) $35.5 $97.9 $133.4 $40.0 $62.6 $102.6 30% REGEN-COV(e) $— $1,088.4 $1,088.4 $2,297.9 $572.7 $2,870.6 (62%)Kevzara(b) $46.6 $34.6 $81.2 $42.0 $61.9 $103.9 (22%)Other products(f) $16.6 $15.0 $31.6 $10.7 $20.3 $31.0 2% Year Ended December 31, 2022 2021 % Change U.S. ROW Total U.S. ROW Total (Total Sales)EYLEA(a) $6,264.6 $3,382.8 $9,647.4 $5,792.3 $3,450.9* $9,243.2 4% Dupixent(b) $6,668.0 $2,013.2 $8,681.2 $4,713.0 $1,485.3 $6,198.3 40% Libtayo(c) $374.5 $203.5 $578.0 $306.3 $151.9 $458.2 26% Praluent(d) $130.0 $337.4 $467.4 $170.0 $251.1 $421.1 11% REGEN-COV(e) $— $1,769.6 $1,769.6 $5,828.0 $1,745.9 $7,573.9 (77%)Kevzara(b) $199.7 $158.3 $358.0 $161.9 $176.1 $338.0 6% Other products(f) $56.1 $69.1 $125.2 $25.9 $86.4 $112.3 11% * Effective January 1, 2022, the Company and Bayer commenced sharing equally in profits and losses based on sales from Bayer to its distributor in Japan. Previously, the Company received from Bayer a tiered percentage of sales based on sales by Bayer's distributor in Japan. Consequently, the prior year net product sales amount has been revised for comparability purposes.(a) Regeneron records net product sales of EYLEA in the United States. Bayer records net product sales of EYLEA outside the United States. The Company records its share of profits/losses in connection with sales of EYLEA outside the United States.(b) Sanofi records global net product sales of Dupixent and Kevzara. The Company records its share of profits/losses in connection with global sales of Dupixent and Kevzara.(c) Prior to July 1, 2022, Regeneron recorded net product sales of Libtayo in the United States and Sanofi recorded net product sales of Libtayo outside the United States. The parties equally shared profits/losses in connection with global sales of Libtayo. Effective July 1, 2022, the Company began recording net product sales of Libtayo outside the United States and pays Sanofi a royalty on global sales. Included in this line item is approximately $17 million and $34 million of net product sales recorded by Sanofi in the fourth quarter and second half of 2022, respectively, in connection with sales in certain markets (Sanofi will record net product sales in such markets during a transition period until inventory on hand as of July 1, 2022 is sold through to the end customers).(d) Regeneron records net product sales of Praluent in the United States. Sanofi records net product sales of Praluent outside the United States and pays the Company a royalty on such sales.(e) Regeneron records net product sales of REGEN-COV in the United States and Roche records net product sales of Ronapreve outside the United States. The parties share gross profits from global sales of REGEN-COV and Ronapreve based on a pre-specified formula.(f) Included in this line item are products which are sold by the Company and others. Refer to "Fourth Quarter 2022 Financial Results" section above for a complete listing of net product sales recorded by the Company. Not included in this line item are net product sales of ARCALYST subsequent to the first quarter of 2021, which are recorded by Kiniksa.

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here . This is the rare week where Endpoints News is making news. If you haven’t heard, Drew Armstrong will be joining us from Bloomberg to become our new executive editor. We are thrilled to have him on board. Read founder and editor John Carroll’s note about our big announcement — and what that means for Endpoints. Patient death in n-of-1 CRISPR trial Almost two months after the nonprofit Cure Rare Disease received FDA clearance to administer its first-in-human CRISPR therapeutic for Duchenne muscular dystrophy, the nonprofit announced that the one patient in the trial, Terry Horgan , the brother of the nonprofit’s founder and CEO, Rich Horgan , passed away . Researchers are still trying to figure out what exactly happened with the single shot CRISPR therapy, the nonprofit said in a statement, and that process may take up to four months. Good news for RSV After years of efforts, companies working on the prevention of respiratory syncytial virus infections had a streak of good news to report. In a first, Pfizer said Phase III results show it can protect infants from RSV by vaccinating their mothers during pregnancy. GSK , on the other hand, scored priority review for the use of its vaccine among older adults. Then to close out the week, the EU officially approved nirsevimab , the antibody jointly developed by Sanofi and AstraZeneca , to prevent RSV disease in a broad group of infants. Vaccine R&D revolution The historic campaign to vaccinate the world against Covid-19 produced its first shot in 326 days. But can we do even better next time around? As the world attempts to strengthen vaccine R&D infrastructure to go even faster and more equitably distribute vaccines, with many congregating around CEPI’s moonshot goal of delivering a vaccine within 100 days, scientific, regulatory and manufacturing challenges persist. Here’s my deep dive and accompanying panel . IRA weighs on pharma hivemind President Joe Biden’s Inflation Reduction Act, which will open the door to Medicare drug price negotiation, is continuing to shape decision-making across the industry. Eli Lilly laid blame on the new law as the reason it scrapped a $40 million cancer drug — a BCL2 inhibitor — licensed from Fosun Pharma . Specifically, the company cited how the law changes the dynamics of small molecule R&D. Days later, Alkermes announced it would siphon off its burgeoning oncology business , in order to capitalize on biologics research. And while Amgen didn’t shift any directions yet, it warned of “material adverse effect” on sales. Rubius implodes Just weeks after Rubius , a one-time Flagship star, looked to restructure around a second try at making red blood cells a drug tech of the future, the biotech put out word that it’s axing the bulk of the remaining staff and looking for a sale or merger. With shares trading slightly north of 30 cents apiece, it won’t take much to take over the crumbling structure that once commanded a market valuation in the billions. Up for grabs: preclinical primate data and a drug — dubbed RTX-250 — marketed as an avenue to activate dendritic cells. New mRNA player enters the fray Australian pharma giant CSL is making a late bid for mRNA glory, and it lined up one of the also-ran US Covid-19 biotechs touting its own particular tech twist to partner with. CSL Seqirus , the big vaccines arm of the global player, shelled out $200 million in cash and put up another $4.3 billion in milestones — including a hefty $1.3 billion for development goals — to ally itself with Arcturus Therapeutics . Together they’ll work on Covid-19, flu, pandemic prep and three unnamed respiratory infectious diseases. PREMIUM From private equity to venture Just how much has private equity come to love biopharma during these stressful post-boom times and battered valuations? JP Morgan made a lavish entry into life sciences venture investing, tapping Alexion co-founder and ex- OrbiMed investor Stephen Squinto to lead a new group that promises to play advisor as well as financier to the companies they back. Life Sciences Private Capital is taking the field to go after “early and growth stage healthcare companies” with a special focus on drugs and tech . Forget about IPO, let’s go for Series C Elicio Therapeutics , an oncology and Covid-19 biotech led by a former Flagship Pioneering venture partner, is close to wrapping up its $40 million Series C after a bear market shut the doors to a planned IPO, Kyle LaHucik reports. The Boston biotech had sought to list on Nasdaq as $ELTX, with a draft registration statement filed in April 2021. More backers for tRNA play Leslie Williams’ plans to climb Mount Everest almost got in the way of her new tRNA biotech, but after Covid-19 disrupted those trips, she had time to go full throttle on securing the IP from the University of Iowa, hiring a core team and putting hC Bioscience together. Already backed by Takeda and ARCH, hC got more investors on board in a Series A extension that’s giving it another $16 million. EARNINGS While Novo Nordisk plots a comeback for the obesity drug Wegovy , two early-stage programs in obesity and cardiovascular disease are on the chopping block . Due to portfolio considerations, the Danish drugmaker will be scrapping a Phase I obesity program dubbed LA-GDF15 and a PCSK9 inhibitor that just completed a Phase II trial in patients with or at risk of developing atherosclerotic cardiovascular disease. Thanks to higher-than-expected sales of Mounjaro ( tirzepatide ), Eli Lilly reported better-than-expected Q3 sales of $6.94 billion. As it pushes forward with plans to make the drug a megablockbuster, the company also discussed plans to double manufacturing capacity by the end of 2023 to meet “unprecedented” demand. It is, however, trimming its year-end guidance. Regeneron revealed a 15% drop in revenue compared to Q3 last year, pulling in $2.94 billion after its Covid-19 antibody cocktail got pulled from the market. It also quietly disclosed that it’s cutting two drugs from its pipeline: a multi-antibody therapy, known as REGN1908-1909 , to treat allergies in cats — and the Teva and Mitsubishi Tanabe -partnered NGF antibody fasinumab . Pfizer suffered its first quarterly revenue dip since its BioNTech -partnered Covid vaccine was authorized in 2020 — and expects patent expiries to cost the company around $17 billion between 2025 and 2030. But CEO Albert Bourla emphasized “It’s all about what’s next,” as it outlined plans for bringing new drugs to the market as well as scoping out deals. A decade after the crew that would become AbbVie teamed up with the French biotech Inventiva to find small molecule drugs that target RORγ for autoimmune diseases, AbbVie is winding down the resulting program , which is in Phase IIb for psoriasis, due to new findings observed in a preclinical chronic toxicology study. Moderna’s stock plunged in premarket trading as CEO Stéphane Bancel r eported a drop in Covid sales and lowered his full-year sales expectations due to delivery delays, short-term supply shortages and a “very complex third quarter from a manufacturing standpoint.” But the mRNA player reassured investors that it’s in a much better place now. GSK touted record sales of shingles vaccine Shingrix , which contributed to total revenue of $8.9 billion. CEO Emma Walmsley made it “categorically clear” her team will be prioritizing dealmaking going forward. At the same time, tens of thousands of Zantac cases — with accusations that the heartburn drug caused cancer — are still waiting to be heard. New approved indications and massive year-over-year sales growth have Daiichi Sankyo eyeing a year-end pop in sales for its AstraZeneca -partnered cancer drug Enhertu . The Japanese pharma upped its forecast for Enhertu this year by more than $400 million, projecting it could haul in about $1.3 billion. R&D J&J hit the brakes on one of its partner’s early-stage programs, halting enrollment in ESSA Pharma’s Phase I trial combining ESSA’s experimental drug with approved prostate cancer drugs from J&J. The biotech chalked the decision up to “operational recruitment challenges” and, in a follow-up, said it will explore testing the combo in a different population. GSK is wrapping up two large clinical trials on a new antibiotic for uncomplicated urinary tract infections early, setting it up for an FDA filing next year. An independent review group determined that the non-inferiority trials testing GSK’s gepotidacin versus nitrofurantoin already met their primary endpoints in an interim analysis, a major win for the antibiotic space. Senescent cells have been at the heart of Unity Biotechnology for years, and after previous stumbles, the anti-aging biotech says it likely found a light at the end of the tunnel : a pivotal study of its only clinical-stage drug is now on tap for September 2023 after a Phase II trial in diabetic macular edema proved a single injection to be durable out to 24 weeks. Almost exactly three years after a data update at SITC underwhelmed, NextCure is calling it. The Yale spinout will stop working on its lead program , known as NC318 , after observing no responses in a Phase II monotherapy portion. However, it will still support Yale’s investigator-initiated trial testing the drug in combo with Merck’s Keytruda in patients with lung cancer. Radiotherapy maker Actinium made headway on a pivotal readout for CD45-targeting lead candidate Iomab-B , which beat placebo when given to patients with relapsed or refractory acute myeloid leukemia before they undergo bone marrow transplants. The endpoint of the study was durable, complete remission of at least six months after initial remission. Abeona Therapeutics is trumpeting a data drop for the rare “butterfly skin” disease, with Phase III results showing its EB-101 healed wounds by at least 50% at a significantly greater margin than a placebo over six months, and significantly reduced patients’ pain associated with the wounds. Simultaneously, Abeona announced it had secured a $35 million private placement. Not even two weeks after watching its stock nosedive, Tricida is looking at all of its strategic alternatives and options to reduce its operating expenses — usually a precursor to layoffs, a sale, or both. Ever since the FDA rejected its kidney drug, the biotech has banked its hopes on a comeback trial. But the high-stakes wager proved disappointing. Exscientia is looking at breaking out of small molecule R&D. The UK AI player announced it will make a foray into biologics , more specifically antibodies, looking to implement precision engineering and utilize in silico screening. To that end, it will be adding new building space to its headquarters to house the new laboratory. #CPHI22 The time is upon us as the manufacturing world descends on Frankfurt for CPHI. This year’s conference plans to be filled to the brim with the top companies and experts from around the world of pharmaceutical manufacturing. Reporting live on the ground, my colleague Tyler Patchen sat down with a conference exec ahead of the meeting to find out what was in store . Samsung Biologics , the CDMO arm of the South Korean conglomerate, is committed to boosting its presence both at home and abroad. Just as it kicks off operations at its latest manufacturing plant, the company spoke at CPHI about a new campus in the works , for which the company had already dropped $324 million to purchase the land. What challenges do companies that transport biopharma material encounter on the ground when they talk about supply chain issues? UPS Healthcare execs weighed in on how the pandemic woke the logistics world up to gaps in cold chain delivery, and what they are most concerned about as deliveries at ultra-low temperatures are becoming the norm. CPHI’s annual report, which polled 400 industry execs from around the world, suggests that a majority sees a moderate outlook for manufacturers and biotechs. However, executives are extremely bullish on mRNA technologies, with it getting well north of 60% of the vote as a tech that will see the most preclinical investment next year. Another area that execs seem to be excited about is psychedelic-based therapeutics. Tyler also previewed several top themes that were likely to shape conversations at the confab, from supply chain woes (exacerbated by rising energy costs and inflation) to growth and potential bottleneck of cell and gene therapies to the specific challenges faced by contract manufacturers . He also took a look back at the biggest manufacturing projects so far in 2022. CELL/GENE TX As million-plus-dollar gene therapies appear set to become the norm rather than the exception, the Boston-based drug pricing watchdog ICER is coming on board — in some cases. Its latest report finds that CSL Behring’s potential gene therapy etranacogene dezaparvovec for hemophilia B could be considered fairly priced at around $3 million. As cell therapy player Allogene launched a study for its candidate targeting large B-cell lymphoma, its joint venture, Allogene Overland Biopharm put the finishing touches on a new CAR-T manufacturing facility in Shanghai just under a year after starting construction — a feat the company calls “truly remarkable” considering Shanghai was in lockdown for a big part of it. Texas’ Instil Bio hit pause on enrollment in clinical trials because “a recent decrease in the rate of successful manufacturing” meant it was unable to dose some patients with its lead tumor infiltrating lymphocyte (TIL) therapy. The biotech is looking into the issues and reviewing its manufacturing processes before resuming the trials in melanoma and other solid tumors. CHINA For F-star , the once high-flying UK biotech helmed by Eliot Forster , the $161 million all-cash acquisition by China’s Sino Biopharm was a last resort as it grappled with a brutal public market and dwindling cash reserves. But even that deal is running into a snag . Nasdaq-listed F-star and its buyer are once again extending the deal to allow CFIUS more time to review. Following an inspection of GSK’s contract manufacturer in Poland that identified questionable practices, China decided to ban the company from participating in its centralized drug procurement program through April 29, 2024. GSK noted that it only supplies one drug, the urinary retention drug Avodart ( dutasteride ), through this program. STARTUPS In late July, Sangamo’s former R&D chief Adrian Woolfson launched his own gene therapy outfit. Replay’s primary platform was an HSV vector which, as a hub-and-spoke biotech, it said it was building four different companies around. Now, the first of those four companies is out of the bag . Named Eudora and led by a quartet of academics, it will go after three eye diseases. A year and a half after diving headfirst into the psychedelic colloquially known as “toad venom,” RA Capital is back for more. The VC firm is leading a $60 million into Lusaris Therapeutics , whose main focus is looking at the psychedelic 5-MeO-DMT , a compound naturally derived from plants and the Colorado river toad, to go after treatment-resistant depression. The latest startup to enter the microbiome world is keen to serve more than just drug R&D. Concerto Biosciences , which came out with a $23 million Series A , hopes that with the “rulebook of microbial ecology” it’s building with a screening platform, it can treat atopic dermatitis, protect crops and get rid of bad odor in those sweaty armpits. A new biotech incubated at Samsara BioCapital just dropped with a basket of assets , including two clinical-stage ones, from Gilead , Shionogi , Phenex Pharmaceuticals , Astellas’ Mitobridge and Yale. With a Gilead vet at the helm, OrsoBio was originally branded The Liver Company and is looking to treat severe metabolic disorders, such as NASH and type 2 diabetes. Remember that secretive ARCH biotech that licensed two antibodies from MorphoSys in June? HI-Bio , short for Human Immunology Biosciences , is now back with a $120 million financing round , as well as more details about itself. Capitalizing on new science, the biotech has a focus on autoimmune and immune-mediated diseases. PEOPLE New Galapagos CEO Paul Stoffels — best known for his turn as the longtime CSO at J&J — has come up with a three-pronged strategy to dig a way out of the big hole the biotech finds itself in. And it calls for taking out the budget axe and chopping 200 jobs so they can put more money into deals. The biotech will also shutter work in fibrosis and kidney diseases. California-based Avanir Pharmaceuticals filed a WARN notice in late October detailing 109 layoffs in California at its headquarters in Aliso Viejo, on the south side of Los Angeles. This comes after Otsuka’s American subsidiary announced that it would be integrating Avanir into its business, effective starting 2023. Otsuka acquired Avanir back in 2015 for $3.5 billion. Surface Oncology is letting go of 20% of its workforce as the biotech prunes its pipeline and narrows the scope of its lead drug. The cancer drug developer is looking for external partners on its CD39 asset, dubbed SRF617, after a strategic review, which the company said would extend the runway into the second quarter of 2024. In September, iBio paid a very affordable price to gain access to an AI-based platform and new therapeutic candidates from the startup RubrYc as the Texas CDMO looks to dive further into drug discoveries. In its latest move, iBio is now jumping headfirst into drug discovery and the AI approach — while getting rid of its CDMO arm and cutting 60% of its workforce . DEALS As it turned out, the main reason Artiva chose to withdraw its IPO had to do with a different big plan it wanted to share — one that couldn’t be done under the constraints of having an S-1 on file with the SEC: a joint development, manufacturing and commercialization pact with Affimed to combine the biotechs’ therapies into a treatment for CD30-positive lymphoma patients. Bayer is punting an Ionis Pharmaceuticals -partnered drug back to the biotech, giving up on a program on which it had spent $240 million. It had grabbed Ionis-developed fesomersen , an antisense designed to prevent blood clots, as part of a 2015 licensing deal, but it decided to focus on an in-house blood thinner, asundexian , instead. Now that its cabozantinib franchise has nestled its way into blockbuster status, Exelixis is replenishing the pipeline with some early-stage bets. The 28-year-old out biotech shelled a total of $100 million in cash to grab a preclinical antibody targeting SIRPα and a Phase I peptide-drug conjugate from Sairopa and Cybrexa , respectively. Always on the lookout for the next thing to buy, Thermo Fisher Scientific settled on an oncology diagnostic player for its latest acquisition. The life sciences conglomerate is shelling out $2.6 billion to acquire The Binding Site Group from a group of private equity investors, integrating a suite of diagnostic assays and instruments for blood cancers and immune system disorders into its specialty diagnostics business. FINANCING Skipping an IPO, Emalex Biosciences instead secured $250 million in Series D funds to bankroll a Phase III clinical trial in children, adolescents and adults who have Tourette syndrome. The Chicago biotech plans to kick off the trial this quarter and will target 90 sites across the US, Canada and Europe with a 220-patient trial. After touting some first-in-human data late last week, Nuvalent is attempting to capitalize on the momentum with a $200 million public offering . With its next-gen ROS1 inhibitor, Nuvalent is attempting to challenge Big Pharma rivals — specifically, Pfizer’s Xalkori and Roche’s Rozlytrek . Artiva Biotherapeutics quietly withdrew its IPO a year and a half after first filing its paperwork, with a pitch centered on its NK cell therapies. Boasting a collaboration with Merck , Artiva got an IND clearance for its second oncology asset just recently. Two other companies have similarly backed out of plans to go public just this week. In January, Alterome launched from stealth — but remained quite stealthy. Armed with an additional $35 million , it is now shedding just a little of that secrecy. The biotech said it raised the Series A extension to fund a third program arising from its strategy to go after “undruggable 3.0” with targeted therapies. Seeking money to get its first microbiome-based candidate into a clinical trial in Australia, Intrinsic Medicine couldn’t succeed down the IPO route during a rough sweeping of the biotech market this year, so the Seattle upstart is instead going with a blank check. The Seattle company will combine with Phoenix Biotech Acquisition , a SPAC vehicle that looked at more than 90 companies before signing on the dotted line with Intrinsic. Despite setbacks on its own candidate as well as cooling enthusiasm across the field, ALX Oncology is still keen to push forward its CD47 drug. And it’s getting a loan of up to $100 million from Oxford Finance and Silicon Valley Bank to fund multiple trials, from gastric and head and neck cancer to urothelial and breast cancers. CORONAVIRUS In the fight against Covid-19, AbbVie’s approved products and investigational assets have run into multiple hurdles. The latest is a Phase I axe, quietly revealed on the federal clinical trials database in recent days. The Chicago-area Big Pharma cited “re-evaluation of risk vs benefit (based on animal data)” in an update to the Phase I trial of an oral drug dubbed ABBV-990 . Penny stock biotech Rigel Pharmaceuticals reported a close miss for its sole approved drug in a Phase III Covid-19 trial. Its tyrosine kinase inhibitor, fostamatinib , failed to meaningfully reduce days on oxygen for patients without respiratory failure and who had certain “high-risk prognostic” factors. Nonetheless, the biotech said it’s encouraged by the results and plans to talk them through with its partner at the Department of Defense. “Where’s Juan?” a soccer player asks while nervously eyeing the goal. “Covid, again,” a teammate responds while holding up a text message. The referee blows the whistle. That’s the introduction to one of HHS’ latest Covid-19 ads designed to convince those who are disproportionately affected by the pandemic to get the updated vaccine boosters. LAW AbbVie is putting up a fight against generic versions of its endometriosis drug Orilissa . It filed suit against more than a dozen competitors, including Sandoz and Teva , asserting patents — the latest of which expires in 2036 — and claiming that abbreviated NDAs filed by the rival drugmakers have caused or will lead to “foreseeable harm and injury” to AbbVie. Teva execs confirmed that a settlement was reached in New York resolving claims about its role in the US opioid epidemic. By signing on to the national agreement, the state will get $523 million from the generics giant, ending years of litigation against opioid manufacturers and distributors. “And it’s done in the way that New York basically signs on to the national agreement, which has a certain value. And then they also get what you call a trial bump because they have a verdict against us,” CEO Kåre Schultz told investors and analysts. Top pharmacy chains are looking to bundle the bulk of their opioid-related litigation into a major settlement. All told, CVS Health said it agreed to pay more than $5 billion to states, tribes and other groups over the next decade to resolve claims, Walgreens would pay $4.8 billion in remediation payments over 15 years and Walmart will likely pay another $3 billion. PHARMA Since at least mid-August, President Joe Biden’s rallying cry around beating Big Pharma on the issue of drug pricing has been the highlight of stump speeches, serving as the centerpiece of more than a dozen speeches, according to an Endpoints News tally of the transcripts. It is, however, unclear to what extent this accomplishment will translate into votes in the midterms. Bristol Myers Squibb unveiled a surprise victory for its potential $4 billion-per-year drug Reblozyl . In a Phase III trial, the drug spurred a “statistically significant and clinically meaningful improvement” in red blood cell transfusion independence, or how long a patient with anemia goes without a transfusion. With drug price negotiations in the books, Rep. Katie Porter (D-CA) is onto the next challenge. Her office released a new report on skyrocketing drug launch prices , particularly in oncology, which she calls for Congress to address with the momentum from the passage of the Inflation Reduction Act. MARKETINGRX Almost half of all adults with type 1 diabetes say they felt like quitting sports as a kid because of their health condition – and one in five ended up doing so. Now Dexcom wants to encourage the next generation to stick with sports, so it’s lined up a first-ever name, image, likeness (NIL) college athlete program to showcase 14 players living with type 1 diabetes. The athletes all use Dexcom’s continuous glucose monitoring devices. Through the campaign, Dexcom is also breaking ground in the pharma and medtech industries for national NIL sponsorship deals. Novo Nordisk expects the supply of its obesity med Wegovy to finally stabilize by the end of this year — and with that, a “broad commercial re-launch is expected to commence next year.” The company had halted promotional efforts in the US after high demand, compounded by manufacturing issues, led to a shortage of the drug. Despite years of public health messaging and awareness advertising, people over the age of 50 still aren’t getting the shingles shots — or even widely understanding the risks. So GSK is doubling down on advertising , this time with a direct message about the dormant virus that causes shingles, with two new TV ads, one in English and another in Spanish, warning this group to “wake up” to their shingles risk. Astellas’ fezolinetant isn’t due for an FDA decision until February in vasomotor symptoms associated with menopause — but the pharma company isn’t waiting until then to educate women about what’s causing their hot flashes. Its latest TV ad spots seek to spread the word about VMS and offer more educational resources. As Merck looks to expand its cash cow Keytruda into earlier lines of cancer, the company’s marketing team is encouraging patients to meet scientists halfway. Its campaign, “Focus on Your Lungs,” debuted to help spread the word about annual lung cancer screening. The new campaign focuses on who should be getting tested — and on addressing the stigma often associated with lung cancer. East coast biotech and pharma companies once again took the top four spots on Science’s list of top 20 industry employers this year, headed by Insmed for the second year in a row. Alnylam , Regeneron and Incyte followed, with the Swiss Syngenta Group ranking fifth, according to Science. The companies were chosen by more than 6,200 survey respondents. Merz Aesthetics is going even younger with its anti-wrinkle campaign. The Raleigh, NC-based company tapped 31-year-old singer-songwriter, actress and choreographer Teyana Taylor as the latest brand partner for its Botox rival Xeomin . The partnership is part of Merz’s broader “Beauty on Your Terms” campaign, which enlisted 33-year-old Joe Jonas back in August. We got a relatively brief MarketingRx roundup this week , but it’s no less interesting: Moderna created a custom clue for “Jeopardy” last week in a new TV ad; Bristol Myers Squibb Foundation and Gilead Sciences posted its next class of awardees in a training program to increase diversity across clinical trials; AIDS advocacy group wrapped a campaign against Gilead with local Sunday print ad; and more. FDA+ Amicus added to its series of painful pratfalls as the biotech repeatedly trips its way toward what executive chairman John Crowley still sees as a sure layup at the FDA. The agency yet again delayed an approval decision needed for AT-GAA — Amicus’ treatment for Pompe disease — after regulators were unable to complete a manufacturing inspection in China. The number of pharma sponsors taking advantage of the FDA’s expedited programs has skyrocketed in recent years, including the use of multiple designations to hurry a new compound along. Those increases are only expected to continue , according to FDA-authored research published in JAMA that reviewed 581 novel drug indication approvals from 2008 to 2021. Since the Covid pandemic began in 2020, the FDA has shuttered its White Oak, MD, doors to outside companies not only seeking input on their developing assets, but for adcomm meetings too. And the agency is still not ready to go back , although it did update how it defines in-person meetings to include Zoom meetings with cameras on. Slowly but surely the FDA is cracking down on the vast, illegal online sale of drugs made possible by behemoths like Amazon . In a warning letter, the FDA told Amazon CEO Andy Jassy that the company sold and distributed drugs with undeclared active ingredients — including those of an NSAID pain drug — that were marketed as dietary supplements. Apellis had secured a priority review for its geographic atrophy program, but it turns out the FDA wants to wait a little bit longer before making a decision. Regulators pushed back their decision date for pegcetacoplan from Nov. 26 to sometime next February, to consider newly submitted two-year efficacy data from a pair of Phase III studies — which qualify as a major amendment. As the FDA pushes to more broadly standardize the way it collects safety data to better detect concerning signals with pharmaceuticals, biopharma companies are pushing back on why there isn’t a more international approach given the global nature of the industry. The comments follow a one-day public meeting in September focused on two new FDA documents. After a rapid rise in the use of expanded access during the pandemic, the FDA released an updated Q&A on the program. This latest revision comes as the agency says it’s received fresh questions on how to implement some of the new regulatory requirements. In the document, the agency clarifies when sponsors’ expanded access policies need to be made public and when (on the rare occasion) it might reject an expanded access request. MANUFACTURING The FDA is ready for participants to apply to a pilot program that will kick off on April 1, 2023, around chemistry, manufacturing and controls (CMC) readiness. The pilot project will help expedite the CMC development of products that may have faster development timelines, through increased communication between the FDA and sponsors. New warning letters from the FDA outline quality issues for Fort Worth, TX-based Sovereign Pharmaceuticals and India-based generics giant Lupin . For Sovereign, regulators said it “failed to validate the manufacturing process” for an undisclosed tablet, while Lupin’s problem was it had not established written procedures for cleaning equipment for manufacturing APIs. This week in Manufacturing roundup : The CDMO arm of the Terumo Corporation is looking to branch out of Japan and offer its services in other nations; Sanofi’s API spinoff, EUROAPI , will augment a production site in Frankfurt, Germany, with an €18 million investment; The AAV manufacturer Avirmax CMC put the finishing touches on a new facility in the San Francisco Bay Area city of Hayward, CA; and more. DON’T MISS In a difficult year for biotechs, a startup out of Jeff Aronin’s incubator Paragon Biosciences had a midnight burial , Endpoints News has learned. Skyline Biosciences was built around an attempt to treat oral pre-cancerous lesions, but it “did not meet the milestones necessary to warrant additional development resources,” according to Paragon, which characterized Skyline as a “pre-proof of concept stage company.” AstraZeneca is still trying to figure out how some of its confidential patient data ended up on GitHub , a software developer’s platform, but the company said the data have now been taken down . The incident seemingly happened due to a user error. Some of the data were related to AstraZeneca’s prescription assistance program, which offers discounts to those in need. With a record number of biotechs now trading below cash amid a brutal public market downturn, many have sought ways to extend the cash runway. In the case of Sensei Biotherapeutics , though, a billionaire investor believes the right thing to do would be to reduce the cash runway. Writing in an open letter, he called on the company to return money to shareholders . Treatment-resistant depression may have finally met its match (for some) as new Phase II results published in the New England Journal of Medicine showed the feasibility of a single dose of psilocybin in helping patients with treatment-resistant major depression for up to 12 weeks. An accompanying editorial called the findings “both intriguing and sobering.”