Cemdisiran

CAMBRIDGE, Mass.--( BUSINESS WIRE )-- Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, today reported its consolidated financial results for the fourth quarter and full year ended December 31, 2024 and reviewed recent business highlights. “ 2024 was another year of impressive execution for Alnylam, generating product revenues of over $1.6 billion, reflecting growth of 33% compared to 2023, and highlighting the strength of our base business in hATTR-PN and Rare in both the U.S. and international markets. We look forward to potential global launches of vutrisiran in ATTR-CM this year, which will mark an inflection point for our TTR franchise and put us on a path to achieve the financial guidance we’ve provided,” said Yvonne Greenstreet, MBChB, Chief Executive Officer of Alnylam. “ Furthermore, driven by our proven RNAi platform, we anticipate 2025 will bring major advancements in our pipeline and expect to have over 25 high-value programs in the clinic across diverse indications by the end of the year. We’ve seen a remarkable pace of progress toward our Alnylam P 5 x25 goals and believe we are well positioned for the next half of the decade to continue delivering sustainable innovation to patients.” Fourth Quarter 2024 and Recent Significant Business Highlights Commercial Performance Total TTR: ONPATTRO ® (patisiran) & AMVUTTRA ® (vutrisiran) Achieved global net product revenues for ONPATTRO and AMVUTTRA for the fourth quarter of $56 million and $287 million, respectively, and $343 million combined, representing 35% total TTR growth compared to Q4 2023, and full year 2024 revenues of $253 million and $970 million, respectively, and $1,223 million combined, representing 34% total TTR growth compared to full year 2023. Total Rare: GIVLAARI ® (givosiran) & OXLUMO ® (lumasiran) Achieved global net product revenues for GIVLAARI and OXLUMO for the fourth quarter of $65 million and $44 million, respectively, and $108 million combined, representing 18% total Rare growth compared to Q4 2023, and full year 2024 revenues of $256 million and $167 million, respectively, and $423 million combined, representing 29% total Rare growth compared to full year 2023. R&D Highlights Submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) using a Priority Review Voucher for vutrisiran for the treatment of ATTR amyloidosis with cardiomyopathy. Parallel filings for regulatory approval have also been submitted in all major regions, including Europe and Japan. The FDA has accepted the sNDA and set an action goal date of March 23, 2025, under the Prescription Drug User Fee Act (PDUFA). Received United States Food & Drug Administration (FDA) Orphan Drug Designation for nucresiran (ALN-TTRsc04) and announced positive interim Phase 1 data in patients with ATTR amyloidosis. Announced positive initial results from the multiple dose portion of the Phase 1 study of mivelsiran in patients with Alzheimer’s disease. Initiated a Phase 1 study of ALN-HTT02 in adult patients with Huntington’s disease. Completed enrollment in the KARDIA-3 Phase 2 study of zilebesiran , and initiated a Phase 1 study of zilebesiran + REVERSIR for hypertension. Initiated Phase 1 studies of ALN-6400 for a bleeding disorder, and ALN-4324 for type 2 diabetes mellitus. Alnylam's partner, Regeneron Pharmaceuticals, reported positive updated Phase 3 data from an exploratory cohort in the ACCESS-1 trial investigating its first-in-class pozelimab and cemdisiran combination treatment compared to standard-of-care ravulizumab in patients with paroxysmal nocturnal hemoglobinuria (PNH) at the American Society of Hematology 2024 Annual Meeting. Upcoming Events Alnylam will host an R&D Day on February 25, 2025 at 9:00 am ET in New York City. This event, which will be webcast live on the Investors section of the Company’s website, www.alnylam.com , will showcase Alnylam’s robust pipeline comprising numerous multi-billion-dollar opportunities and highlight RNAi platform innovation driving the next era of growth. A replay will be available on the Company's website within 48 hours after the event. The PDUFA target action date for the sNDA for vutrisiran is March 23, 2025. Alnylam intends to initiate a Phase 3 study of nucresiran in patients with ATTR amyloidosis with cardiomyopathy in the first half of 2025. The PDUFA target action date for fitusiran , an investigational RNAi therapeutic in development for the treatment of hemophilia A and B, with or without inhibitors, is March 28, 2025. Fitusiran is being advanced by Alnylam’s partner Sanofi. Assuming approval, Alnylam is eligible to receive tiered royalties of between 15 and 30 percent on global net sales of fitusiran. Alnylam’s partner, Vir Biotechnology, expects to initiate a Phase 3 chronic hepatitis delta registrational study of elebsiran and to report functional cure results from a Phase 2 chronic hepatitis B study of elebsiran in 2025. Financial Highlights for the Fourth Quarter and Year End 2024 Three Months Ended December 31, Twelve Months Ended December 31, (In thousands) 2024 2023 2024 2023 Net product revenues $ 450,831 $ 346,288 $ 1,646,228 $ 1,241,474 Net revenues from collaborations 106,948 76,407 510,221 546,185 Royalty revenue 35,387 17,023 91,794 40,633 Total revenues 593,166 439,718 2,248,243 1,828,292 Total operating costs and expenses 698,325 556,122 2,425,128 2,110,467 Loss from operations (105,159 ) (116,404 ) (176,885 ) (282,175 ) Total other expense, net (88,799 ) (21,283 ) (200,490 ) (151,342 ) Benefit from (provision for) income taxes 110,195 (183 ) 99,218 (6,725 ) Net loss $ (83,763 ) $ (137,870 ) $ (278,157 ) $ (440,242 ) Non-GAAP Operating (loss) income* $ (13,514 ) $ (74,410 ) $ 95,199 $ (60,495 ) Non-GAAP Net income (loss)* $ 8,048 $ (96,643 ) $ (3,051 ) $ (201,618 ) *For an explanation of our use of non-GAAP financial measures refer to the "Use of Non-GAAP Financial Measures" section later in this press release and for a reconciliation of each non-GAAP financial measure to the most comparable GAAP measures, see the table at the end of this press release. Net Product Revenues Three Months Ended December 31, Twelve Months Ended December 31, (In thousands) 2024 2023 2024 2023 ONPATTRO net product revenues $ 56,103 $ 79,006 $ 252,857 $ 354,546 AMVUTTRA net product revenues 286,510 175,254 970,450 557,838 Total TTR net product revenues 342,613 254,260 1,223,307 912,384 GIVLAARI net product revenues 64,645 59,298 255,871 219,251 OXLUMO net product revenues 43,573 32,730 167,050 109,839 Total Rare net product revenues 108,218 92,028 422,921 329,090 Total net product revenues $ 450,831 $ 346,288 $ 1,646,228 $ 1,241,474 Year over Year % Growth Three Months Ended December 31, 2024 Twelve Months Ended December 31, 2024 As Reported At CER* As Reported At CER* Total TTR net product revenues 35 % 34 % 34 % 34 % Total Rare net product revenues 18 % 17 % 29 % 28 % Total net product revenues 30 % 29 % 33 % 33 % * CER = Constant Exchange Rate, representing growth calculated as if the exchange rates had remained unchanged from those used in 2023. CER is a non-GAAP measure. For an explanation of our use of non-GAAP financial measures refer to the "Use of Non-GAAP Financial Measures" section later in this press release and for a reconciliation of each non-GAAP financial measure to the most comparable GAAP measures, see the table at the end of this press release. Net product revenues increased 30% and 33% at actual currency during the three and twelve months ended December 31, 2024, respectively, compared to the same periods in 2023, and 29% and 33% at CER, respectively. The increases are primarily due to growth from sales of AMVUTTRA driven by increased patient demand, partially offset by a decrease in sales of ONPATTRO due to patient switches to AMVUTTRA, as well as increased patients on GIVLAARI and OXLUMO therapies. Net Revenues from Collaborations Net revenues from collaborations increased $30.5 million during the three months ended December 31, 2024, as compared to the same period in 2023, primarily due to the timing of manufacturing activities under our collaboration with Regeneron, as well as revenue recognized under our license agreement with Novartis associated with the achievement of specified commercialization milestones. Net revenues from collaborations decreased by $36.0 million during the twelve months ended December 31, 2024, as compared to the same period in 2023, primarily due to differences in certain revenue items between 2023 and 2024. During 2023, we recognized $310.0 million of revenue from the upfront payment received from Roche in connection with execution of our zilebesiran collaboration. In comparison, during 2024, we recognized $185.0 million in revenues under our collaboration with Regeneron as we modified the collaboration in June 2024 and provided Regeneron with an exclusive license to develop, manufacture and commercialize cemdisiran as a monotherapy. Operating Expenses Three Months Ended December 31, Twelve Months Ended December 31, (In thousands) 2024 2023 2024 2023 Cost of goods sold $ 102,649 $ 71,975 $ 306,513 $ 268,216 Cost of goods sold as a percentage of net product revenues 22.8 % 20.8 % 18.6 % 21.6 % Cost of collaborations and royalties $ 168 $ 13,883 $ 16,857 $ 42,190 GAAP Research and development expenses $ 300,169 $ 272,141 $ 1,126,232 $ 1,004,415 Non-GAAP Research and development expenses $ 259,544 $ 253,056 $ 998,483 $ 907,142 GAAP Selling, general and administrative expenses $ 295,339 $ 198,123 $ 975,526 $ 795,646 Non-GAAP Selling, general and administrative expenses $ 244,319 $ 175,214 $ 831,191 $ 671,239 Cost of Goods Sold Cost of goods sold as a percentage of net product revenues increased during the three months ended December 31, 2024, as compared to the same period in the prior year, primarily due to higher royalty rates payable on net sales of AMVUTTRA. Cost of goods sold as a percentage of net product revenues decreased during the twelve months ended December 31, 2024, as compared to the same period in the prior year. Approximately 5.0% of the 21.6% of cost of goods sold as a percentage of net product revenues for the year ended December 31, 2023 was attributable to cancelled manufacturing commitments and the impairment of ONPATTRO inventory that had been manufactured for future demand associated with the use of ONPATTRO for the treatment of patients with ATTR amyloidosis with cardiomyopathy, for which we did not receive regulatory approval in the U.S. These one-time charges in 2023 did not recur in 2024, resulting in the decrease in cost of goods sold as a percentage of net product revenues in 2024, which was partially offset by higher volume and royalty rates payable on net sales of AMVUTTRA in 2024. Research & Development (R&D) Expenses GAAP and non-GAAP R&D expenses increased during the three and twelve months ended December 31, 2024, compared to the same periods in 2023, primarily due to increased costs associated with our preclinical activities as we develop our clinical pipeline of RNAi therapeutics targeting multiple tissues, increased clinical trial expenses associated with increased Phase 2 activities for the zilebesiran KARDIA-3 and mivelsiran cAPPRicorn-1 clinical trials, and increased employee compensation expenses. GAAP R&D expenses further increased during the three and twelve months ended December 31, 2024, compared to the same periods in 2023, due to higher stock-based compensation expense in 2024. Selling, General & Administrative (SG&A) Expenses GAAP and non-GAAP SG&A expenses increased during the three and twelve months ended December 31, 2024, compared to the same periods in 2023, primarily due to higher costs associated with marketing investments to promote our TTR therapies and prepare for the potential launch of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy and increased employee compensation expenses. Benefit from (provision for) income taxes During the year ended December 31, 2024, we recorded a net benefit from income taxes of $99.2 million. This is primarily comprised of $106.8 million of foreign deferred benefit, partially offset by $1.6 million of domestic state current provision and $5.9 million of foreign current provision. Other Financial Highlights Cash, cash equivalents and marketable securities were $2.69 billion as of December 31, 2024, as compared to $2.44 billion as of December 31, 2023, with the increase primarily due to improved operating performance and increased net proceeds from the issuance of common stock in connection with stock option exercises. A reconciliation of our GAAP to non-GAAP results for the three and twelve months ended December 31, 2024 and 2023, is included in the tables of this press release. 2025 Financial Guidance Our full-year 2025 financial guidance is summarized below: Total TTR net product revenues (ONPATTRO, AMVUTTRA) 1 $1,600 million - $1,725 million Total Rare net product revenues (GIVLAARI, OXLUMO) $450 million - $525 million Total net product revenues $2,050 million - $2,250 million Net product revenues growth vs. 2024 at currency exchange rates as of December 31, 2024 2 25% - 37% Net product revenues growth vs. 2024 at constant exchange rates 3 26% - 39% Net revenues from collaborations and royalties 4 $650 million - $750 million Non-GAAP R&D and SG&A expenses 5 $2,100 million - $2,200 million Non-GAAP Operating income 5 Achieve profitability 1 Assumes U.S. sNDA approval of AMVUTTRA for ATTR-CM by the March 23, 2025 PDUFA action date and approvals and launches in Germany and Japan in the second half of 2025 2 Full-year 2025 guidance utilizing currency exchange rates as of December 31, 2024: 1 EUR = 1.04 USD and 1 USD = 157 JPY 3 Representing growth calculated as if the exchange rates had remained unchanged from those used in 2024, which is a non-GAAP financial measure 4 Collaboration revenues assume achievement of $300 million milestone from Roche for initiation of a Phase 3 cardiovascular outcomes trial for zilebesiran. Royalty revenues assume approval of fitusiran by Sanofi by the March 28, 2025 PDUFA action date 5 Primarily excludes $270-$330 million of stock-based compensation expense from estimated GAAP R&D and SG&A expenses Use of Non-GAAP Financial Measures This press release contains non-GAAP financial measures, including adjustments to exclude certain non-cash items and non-recurring transactions or events outside the ordinary course of the Company’s business. These measures are not in accordance with, or an alternative to, GAAP, and may be different from non-GAAP financial measures used by other companies. The items included in GAAP presentations but excluded for purposes of determining non-GAAP financial measures for the periods presented in this press release are stock-based compensation expenses and realized and unrealized gains and losses on marketable equity securities. The Company has excluded the impact of stock-based compensation expense, which may fluctuate from period to period based on factors including the variability associated with performance-based grants for stock options and restricted stock units and changes in the Company’s stock price, which impacts the fair value of these awards. The Company has excluded the impact of the realized and unrealized gains and losses on marketable equity securities because the Company does not believe these adjustments accurately reflect the performance of the Company’s ongoing operations for the period in which such gains or losses are reported, as their sole purpose is to adjust amounts on the balance sheet. Percentage changes in revenue growth at CER are presented excluding the impact of changes in foreign currency exchange rates for investors to understand the underlying business performance. The current period’s foreign currency revenue values are converted into U.S. dollars using the average exchange rates from the prior period. The Company believes the presentation of non-GAAP financial measures provides useful information to management and investors regarding the Company’s financial condition and results of operations. When GAAP financial measures are viewed in conjunction with non-GAAP financial measures, investors are provided with a more meaningful understanding of the Company’s ongoing operating performance and are better able to compare the Company’s performance between periods. Non-GAAP financial measures are not intended to be considered in isolation or as a substitute for GAAP financial measures. A reconciliation between GAAP and non-GAAP measures is provided later in this press release. Conference Call Information Management will provide an update on the Company and discuss fourth quarter and full year 2024 results as well as expectations for the future via conference call on Thursday, February 13, 2025 at 8:30 am ET. A live audio webcast of the call will be available on the Investors section of the Company’s website at www.alnylam.com/events . An archived webcast will be available on the Alnylam website approximately two hours after the event. About ONPATTRO ® (patisiran) ONPATTRO is an RNAi therapeutic that is approved in the United States and Canada for the treatment of adults with hATTR amyloidosis with polyneuropathy. ONPATTRO is also approved in the European Union, Switzerland and Brazil for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. ONPATTRO is an intravenously administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby reducing the production of TTR protein before it is made. Reducing the pathogenic protein leads to a reduction in amyloid deposits in tissues. For more information about ONPATTRO, including full Prescribing Information , visit ONPATTRO.com . About AMVUTTRA ® (vutrisiran) AMVUTTRA ® (vutrisiran) is an RNAi therapeutic that delivers rapid knockdown of mutant and wild-type transthyretin (TTR), addressing the underlying cause of transthyretin (ATTR) amyloidosis. Administered quarterly via subcutaneous injection, AMVUTTRA is approved and marketed in more than 15 countries for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR-PN) in adults. Vutrisiran is also in development for the treatment of ATTR amyloidosis with cardiomyopathy (ATTR-CM), which encompasses both wild-type and hereditary forms of the disease. For more information about AMVUTTRA, including the full U.S. Prescribing Information , visit AMVUTTRA.com . About GIVLAARI ® (givosiran) GIVLAARI (givosiran) is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) approved in the United States and Brazil for the treatment of adults with acute hepatic porphyria (AHP). GIVLAARI is also approved in the European Union for the treatment of AHP in adults and adolescents aged 12 years and older. In the pivotal study, GIVLAARI was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or intravenous hemin administration at home compared to placebo. GIVLAARI is Alnylam’s first commercially available therapeutic based on its Enhanced Stabilization Chemistry ESC-GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of ALAS1 messenger RNA (mRNA), leading to reduction of toxins associated with attacks and other disease manifestations of AHP. For more information about GIVLAARI, including the full U.S. Prescribing Information , visit GIVLAARI.com . About OXLUMO ® (lumasiran) OXLUMO (lumasiran) is an RNAi therapeutic targeting hydroxyacid oxidase 1 (HAO1). HAO1 encodes glycolate oxidase (GO). Thus, by silencing HAO1 and depleting the GO enzyme, OXLUMO inhibits production of oxalate – the metabolite that directly contributes to the pathophysiology of PH1. OXLUMO utilizes Alnylam’s Enhanced Stabilization Chemistry (ESC)-GalNAc-conjugate technology, which enables subcutaneous dosing with increased potency and durability and a wide therapeutic index. OXLUMO has received regulatory approvals from the U.S. Food and Drug Administration (FDA) for the treatment of primary hyperoxaluria type 1 (PH1) to lower urinary and plasma oxalate levels in pediatric and adult patients and from the European Medicines Agency (EMA) for the treatment of PH1 in all age groups. In the pivotal ILLUMINATE-A study, OXLUMO was shown to significantly reduce levels of urinary oxalate relative to placebo, with the majority of patients reaching normal or near-normal levels. In the ILLUMINATE-B pediatric Phase 3 study, OXLUMO demonstrated an efficacy and safety profile consistent to that observed in ILLUMINATE-A. In the ILLUMINATE-C study, OXLUMO resulted in substantial reductions in plasma oxalate in patients with advanced PH1. Across all three studies, injection site reactions (ISRs) were the most common drug-related adverse reaction. OXLUMO is administered via subcutaneous injection once monthly for three months, then once quarterly beginning one month after the last loading dose at a dose based on actual body weight. For patients who weigh less than 10 kg, ongoing dosing remains monthly. OXLUMO should be administered by a healthcare professional. For more information about OXLUMO, including the full U.S. Prescribing Information , visit OXLUMO.com . About LNP Technology Alnylam has licenses to Arbutus Biopharma lipid nanoparticle (LNP) intellectual property for use in RNAi therapeutic products using LNP technology. About RNAi RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as “ a major scientific breakthrough that happens once every decade or so,” and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines known as RNAi therapeutics is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing or disease pathway proteins, thus preventing them from being made. This revolutionary approach has transformed the care of patients with genetic and other diseases. About Alnylam Pharmaceuticals Alnylam Pharmaceuticals (Nasdaq: ALNY) has led the translation of RNA interference (RNAi) into a whole new class of innovative medicines for people afflicted with rare and prevalent diseases with unmet need. Based on Nobel Prize-winning science, RNAi therapeutics represent a powerful, clinically validated approach yielding transformative medicines. Since its founding in 2002, Alnylam has led the RNAi revolution and continues to deliver on a bold vision to turn scientific possibility into reality. Alnylam’s commercial RNAi therapeutic products are ONPATTRO ® (patisiran), AMVUTTRA ® (vutrisiran), GIVLAARI ® (givosiran), OXLUMO ® (lumasiran), and Leqvio ® (inclisiran), which is being developed and commercialized by Alnylam’s partner, Novartis. Alnylam has a deep pipeline of investigational medicines, including multiple product candidates that are in late-stage development. Alnylam is executing on its “ Alnylam P 5 x25 ” strategy to deliver transformative medicines in both rare and common diseases benefiting patients around the world through sustainable innovation and exceptional financial performance, resulting in a leading biotech profile. Alnylam is headquartered in Cambridge, MA. For more information about our people, science and pipeline, please visit www.alnylam.com and engage with us on X (formerly Twitter) at @Alnylam , or on LinkedIn , Facebook , or Instagram . Alnylam Forward Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Alnylam’s expectations, beliefs, goals, plans or prospects including, without limitation, statements regarding Alnylam’s expectations regarding the potential approval and launch of AMVUTTRA for the treatment of ATTR amyloidosis with cardiomyopathy in the U.S. in early 2025 and in other countries later in 2025; Alnylam’s advancement towards its “Alnylam P 5 x25” goals and positioning to deliver sustainable innovation to patients for the next half of the decade; the potential for Alnylam to advance its research and development programs, including the number of high-value programs Alnylam will have in the clinic by the end of 2025 and the timing of Alnylam’s initiation of a Phase 3 clinical trial of nucresiran in ATTR-CM; the advancement of fitusiran through regulatory review and approval and Alnylam’s receipt of any royalties on sales of fitusiran; and Alnylam’s projected commercial and financial performance, including the expected range of net product revenues and net revenues from collaborations and royalties for 2025 and the expected range of aggregate annual GAAP and non-GAAP R&D and SG&A expenses for 2025, should be considered forward-looking statements. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: Alnylam’s ability to successfully execute on its “ Alnylam P 5 x25 ” strategy; Alnylam’s ability to discover and develop novel drug candidates and delivery approaches and successfully demonstrate the efficacy and safety of its product candidates; the pre-clinical and clinical results for Alnylam’s product candidates, including vutrisiran, zilebesiran, nucresiran and mivelsiran; actions or advice of regulatory agencies and Alnylam’s ability to obtain and maintain regulatory approval for its product candidates, including vutrisiran, as well as favorable pricing and reimbursement; successfully launching, marketing and selling Alnylam’s approved products globally; delays, interruptions or failures in the manufacture and supply of Alnylam’s product candidates or its marketed products; obtaining, maintaining and protecting intellectual property; Alnylam’s ability to successfully expand the approved indications for AMVUTTRA in the future; Alnylam’s ability to manage its growth and operating expenses through disciplined investment in operations and its ability to achieve a self-sustainable financial profile; Alnylam’s ability to maintain strategic business collaborations; Alnylam’s dependence on third parties for the development and commercialization of certain products, including Roche, Novartis, Sanofi, Regeneron and Vir; the outcome of litigation; the risk of future government investigations; and unexpected expenditures; as well as those risks and uncertainties more fully discussed in the “Risk Factors” filed with Alnylam’s most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC), as may be updated from time to time in other filings that Alnylam makes with the SEC. In addition, any forward-looking statements represent Alnylam’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Alnylam explicitly disclaims any obligation, except to the extent required by law, to update any forward-looking statements. This release discusses investigational RNAi therapeutics and uses of previously approved RNAi therapeutics in development and is not intended to convey conclusions about efficacy or safety as to those investigational therapeutics or uses. Vutrisiran has not been approved by any regulatory agency for the treatment of ATTR amyloidosis with cardiomyopathy. No conclusions can or should be drawn regarding its safety or effectiveness in treating cardiomyopathy in this population. There is no guarantee that any investigational therapeutics or expanded uses of commercial products will successfully complete clinical development or gain health authority approval. ALNYLAM PHARMACEUTICALS, INC. CONSOLIDATED BALANCE SHEETS (In thousands, except per share amounts) December 31, 2024 December 31, 2023 ASSETS Current assets: Cash and cash equivalents $ 966,428 $ 812,688 Marketable debt securities 1,719,920 1,615,516 Marketable equity securities 8,156 11,178 Accounts receivable, net 405,308 327,787 Inventory 78,509 89,146 Prepaid expenses and other current assets 116,964 126,382 Total current assets 3,295,285 2,982,697 Property, plant and equipment, net 502,784 526,057 Operating lease right-of-use assets 191,148 199,732 Deferred tax assets 116,863 10,101 Restricted investments 68,593 49,391 Other assets 65,310 61,902 Total assets $ 4,239,983 $ 3,829,880 LIABILITIES AND STOCKHOLDERS’ EQUITY (DEFICIT) Current liabilities: Accounts payable $ 88,415 $ 55,519 Accrued expenses 887,472 713,013 Operating lease liabilities 41,886 41,510 Deferred revenue 55,481 102,753 Liability related to the sale of future royalties 113,018 54,991 Total current liabilities 1,186,272 967,786 Operating lease liabilities, net of current portion 229,541 243,101 Deferred revenue, net of current portion — 188,175 Convertible debt 1,024,621 1,020,776 Liability related to the sale of future royalties, net of current portion 1,334,353 1,322,248 Other liabilities 398,108 308,438 Total liabilities 4,172,895 4,050,524 Stockholders’ equity (deficit): Preferred stock, $0.01 par value per share, 5,000 shares authorized and no shares issued and outstanding as of December 31, 2024 and December 31, 2023 — — Common stock, $0.01 par value per share, 250,000 shares authorized as of December 31, 2024 and December 31, 2023, respectively; 129,294 shares issued and outstanding as of December 31, 2024; 125,794 shares issued and outstanding as of December 31, 2023 1,293 1,259 Additional paid-in capital 7,388,061 6,811,063 Accumulated other comprehensive loss (34,518 ) (23,375 ) Accumulated deficit (7,287,748 ) (7,009,591 ) Total stockholders’ equity (deficit) 67,088 (220,644 ) Total liabilities and stockholders’ equity (deficit) $ 4,239,983 $ 3,829,880 This selected financial information should be read in conjunction with the consolidated financial statements and notes thereto included in Alnylam’s Annual Report on Form 10-K which includes the audited financial statements for the year ended December 31, 2024. ALNYLAM PHARMACEUTICALS, INC. CONSOLIDATED STATEMENTS OF OPERATIONS (In thousands, except per share amounts) Three Months Ended December 31, Twelve Months Ended December 31, 2024 2023 2024 2023 (Unaudited) (Unaudited) Revenues: Net product revenues $ 450,831 $ 346,288 $ 1,646,228 $ 1,241,474 Net revenues from collaborations 106,948 76,407 510,221 546,185 Royalty revenue 35,387 17,023 91,794 40,633 Total revenues 593,166 439,718 2,248,243 1,828,292 Operating costs and expenses: Cost of goods sold 102,649 71,975 306,513 268,216 Cost of collaborations and royalties 168 13,883 16,857 42,190 Research and development 300,169 272,141 1,126,232 1,004,415 Selling, general and administrative 295,339 198,123 975,526 795,646 Total operating costs and expenses 698,325 556,122 2,425,128 2,110,467 Loss from operations (105,159 ) (116,404 ) (176,885 ) (282,175 ) Other (expense) income: Interest expense (38,971 ) (31,338 ) (141,858 ) (121,221 ) Interest income 31,019 30,406 121,992 95,561 Other expense, net (80,847 ) (20,351 ) (180,624 ) (125,682 ) Total other expense, net (88,799 ) (21,283 ) (200,490 ) (151,342 ) Loss before income taxes (193,958 ) (137,687 ) (377,375 ) (433,517 ) Benefit from (provision for) income taxes 110,195 (183 ) 99,218 (6,725 ) Net loss $ (83,763 ) $ (137,870 ) $ (278,157 ) $ (440,242 ) Net loss per common share — basic and diluted $ (0.65 ) $ (1.10 ) $ (2.18 ) $ (3.52 ) Weighted-average common shares used to compute basic and diluted net loss per common share 129,116 125,613 127,651 124,906 ALNYLAM PHARMACEUTICALS, INC. RECONCILIATION OF SELECTED GAAP MEASURES TO NON-GAAP MEASURES (In thousands, except per share amounts) (Unaudited) Three Months Ended December 31, Twelve Months Ended December 31, 2024 2023 2024 2023 Reconciliation of GAAP to Non-GAAP research and development: GAAP Research and development expenses $ 300,169 $ 272,141 $ 1,126,232 $ 1,004,415 Less: Stock-based compensation expenses (40,625 ) (19,085 ) (127,749 ) (97,273 ) Non-GAAP Research and development expenses $ 259,544 $ 253,056 $ 998,483 $ 907,142 Reconciliation of GAAP to Non-GAAP selling, general and administrative: GAAP Selling, general and administrative expenses $ 295,339 $ 198,123 $ 975,526 $ 795,646 Less: Stock-based compensation expenses (51,020 ) (22,909 ) (144,335 ) (124,407 ) Non-GAAP Selling, general and administrative expenses $ 244,319 $ 175,214 $ 831,191 $ 671,239 Reconciliation of GAAP to Non-GAAP operating (loss) income: GAAP Loss from operations $ (105,159 ) $ (116,404 ) $ (176,885 ) $ (282,175 ) Add: Stock-based compensation expenses 91,645 41,994 272,084 221,680 Non-GAAP Operating (loss) income $ (13,514 ) $ (74,410 ) $ 95,199 $ (60,495 ) Reconciliation of GAAP to Non-GAAP other expense, net: GAAP Total other expense, net $ (88,799 ) $ (21,283 ) $ (200,490 ) $ (151,342 ) Add (Less): Realized and unrealized losses (gains) on marketable equity securities 166 (767 ) 3,022 16,944 Non-GAAP Other expense, net $ (88,633 ) $ (22,050 ) $ (197,468 ) $ (134,398 ) Reconciliation of GAAP to Non-GAAP net income (loss): GAAP Net loss $ (83,763 ) $ (137,870 ) $ (278,157 ) $ (440,242 ) Add: Stock-based compensation expenses 91,645 41,994 272,084 221,680 Add (Less): Realized and unrealized losses (gains) on marketable equity securities 166 (767 ) 3,022 16,944 Non-GAAP Net income (loss) $ 8,048 $ (96,643 ) $ (3,051 ) $ (201,618 ) Reconciliation of GAAP to Non-GAAP net loss per common share-basic and diluted: GAAP Net loss per common share - basic and diluted $ (0.65 ) $ (1.10 ) $ (2.18 ) $ (3.52 ) Add: Stock-based compensation expenses 0.71 0.33 2.13 1.77 Add (Less): Realized and unrealized losses (gains) on marketable equity securities — (0.01 ) 0.02 0.14 Non-GAAP Net loss per common share - basic and diluted $ 0.06 $ (0.77 ) $ (0.02 ) $ (1.61 ) Please note that the figures presented above may not sum exactly due to rounding ALNYLAM PHARMACEUTICALS, INC. RECONCILIATION OF GAAP TO NON-GAAP PRODUCT REVENUE GROWTH AT CONSTANT EXCHANGE RATE December 31, 2024 Three Months Ended Twelve Months Ended Total TTR net product revenue growth*, as reported 35 % 34 % Add: Impact of foreign currency translation (1 ) — Total TTR net product revenue growth at constant exchange rate 34 % 34 % Total Rare net product revenue growth*, as reported 18 % 29 % Add: Impact of foreign currency translation (1 ) (1 ) Total Rare net product revenue growth at constant exchange rate 17 % 28 % Total net product revenue growth*, as reported 30 % 33 % Add: Impact of foreign currency translation (1 ) — Total net product revenue growth at constant exchange rate 29 % 33 % Total revenue growth*, as reported 35 % 23 % Add: Impact of foreign currency translation (1 ) — Total revenue growth at constant exchange rate 34 % 23 % *As compared to the three and twelve months ended December 31, 2023, respectively.

Fourth quarter 2024 revenues increased 10% to $3 .79 billion versus fourth quarter 2023 Full year 2024 revenues increased 8% to $14 .20 billion versus 2023; excluding RonapreveTM(a)(b), revenues increased 10% Fourth quarter 2024 Dupixent® global net sales (recorded by Sanofi) increased 15% to $3 .70 billion versus fourth quarter 2023; full year 2024 Dupixent global net sales increased 22% to $14 .15 billion versus 2023 Fourth quarter 2024 U.S. net sales for EYLEA HD® and EYLEA® increased 2% versus fourth quarter 2023 to $1 .50 billion, including $305 million from EYLEA HD; full year 2024 U.S. net sales for EYLEA HD and EYLEA increased 1% versus 2023 to $5 .97 billion versus 2023, including $1.20 billion from EYLEA HD Fourth quarter 2024 Libtayo® global net sales increased 50% to $367 million versus fourth quarter 2023; full year 2024 Libtayo global net sales increased 40% to $1.22 billion versus 2023 Fourth quarter 2024 GAAP diluted EPS of $8.06 and non-GAAP diluted EPS(a) of $12.07 ; fourth quarter 2024 includes unfavorable $0.11 impact from acquired IPR&D charge Initiation of quarterly cash dividend program, $0.88 dividend declared; additional $3 .0 billion share repurchase program authorized, bringing current repurchase capacity to ~$4.5 billion Regulatory applications submitted to FDA for EYLEA HD pre-filled syringe, Dupixent in bullous pemphigoid, odronextamab in follicular lymphoma, and linvoseltamab in multiple myeloma Positive Phase 3 results reported for EYLEA HD in retinal vein occlusion (RVO) and Libtayo in high-risk adjuvant cutaneous squamous cell carcinoma (CSCC) TARRYTOWN, N.Y. , Feb. 04, 2025 (GLOBE NEWSWIRE) -- Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced financial results for the fourth quarter and full year 2024 and provided a business update. " Regeneron 's financial and commercial strength allows for continued investment in our industry-leading R&D pipeline, while simultaneously returning capital to our shareholders through our newly initiated dividend program and increased share repurchase capacity," said Leonard S. Schleifer , M.D., Ph.D., Board co-Chair, President and Chief Executive Officer of Regeneron . "In 2025, we will continue to focus on our four blockbuster medicines as we progress our approximately 40 investigational candidates covering dozens of disease states with expansive market potential." Financial Highlights "2024 was another year of top- and bottom-line growth for Regeneron . This strong financial performance, coupled with the strength of our balance sheet, allows us to initiate a quarterly cash dividend program as well as increase our current share repurchase capacity to approximately $4.5 billion ," said Christopher Fenimore , Executive Vice President, Finance and Chief Financial Officer of Regeneron . Business Highlights Key Pipeline Progress Regeneron has approximately 40 product candidates in clinical development, including a number of marketed products for which it is investigating additional indications. Updates from the clinical pipeline include: EYLEA HD (aflibercept) 8 mg The Company announced that the primary endpoint was met in the Phase 3 QUASAR trial investigating EYLEA HD for the treatment of patients with macular edema following RVO, including those with central, branch, and hemiretinal vein occlusions. In the trial, patients treated with EYLEA HD every 8 weeks (after initial monthly doses) experienced non-inferior vision gains compared to those treated with the approved monthly dosing regimen of EYLEA, the current standard of care. The Company plans to submit a supplemental Biologics License Application (sBLA) to the U.S. Food and Drug Administration (FDA) in the first quarter of 2025. A regulatory application for a pre-filled syringe was submitted to the FDA, with an FDA decision expected by mid-2025. Dupixent (dupilumab) In November 2024 , the European Commission (EC) approved Dupixent to treat eosinophilic esophagitis (EoE) in children aged 1 to 11 years, making Dupixent the first and only medicine indicated to treat these young patients. The FDA accepted for review the resubmission of an sBLA for Dupixent to treat adults and adolescents aged 12 years and older with chronic spontaneous urticaria (CSU) whose disease is not adequately controlled with H1 antihistamine treatment, with a target action date of April 18, 2025 . An sBLA for Dupixent in bullous pemphigoid was submitted to the FDA. A Phase 3 study in lichen simplex chronicus was initiated. Libtayo (cemiplimab) The Company announced positive results from a Phase 3 trial of Libtayo, which demonstrated that adjuvant treatment with Libtayo was the first and only immunotherapy that led to a statistically significant and clinically meaningful improvement in the primary endpoint of disease-free survival (DFS) in patients with high-risk CSCC after surgery. A Phase 3 study of Libtayo administered intralesionally in patients with early-stage CSCC was initiated. Hematology Programs In January 2025 , the Company resubmitted to the FDA the BLA for linvoseltamab, a bispecific antibody targeting BCMA and CD3, in relapsed/refractory (R/R) multiple myeloma following resolution of third-party manufacturing issues. In January 2025 , the Company resubmitted to the FDA the BLA for odronextamab, a bispecific antibody targeting CD20 and CD3, in R/R follicular lymphoma. The Company presented new and updated data for odronextamab spanning several B-cell non-Hodgkin lymphoma (B-NHL) subtypes across earlier lines of treatment at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition. The Company announced positive Phase 2 results for two antibodies targeting distinct domains of Factor XI. REGN7508 (catalytic domain) is designed to maximize anticoagulant activity while minimizing bleeding risk, and REGN9933 (A2 domain) is designed to provide an additional option for patients with the highest bleeding risk who would otherwise not be candidates for currently available anticoagulants. Per the Phase 2 results, there was a robust antithrombotic effect for each antibody, and no clinically relevant bleeding was observed. The Company announced positive updated data from a Phase 3 study of pozelimab (C5 antibody), in combination with cemdisiran (siRNA therapy), against ravulizumab, a standard-of-care C5 inhibitor, in patients with paroxysmal nocturnal hemoglobinuria (PNH). The study showed that the combination treatment helped patients achieve and maintain greater disease control, compared to ravulizumab. These results were presented at the 66th ASH Annual Meeting and Exposition. Other Programs The EC approved Kevzara® (sarilumab) for the treatment of polymyalgia rheumatica (PMR) and polyarticular juvenile idiopathic arthritis (pJIA). A Phase 3 study for mibavademab, an agonist antibody to leptin receptor (LEPR), in generalized lipodystrophy was initiated. Enrollment was completed in a Phase 2 study in obesity for trevogrumab, an antibody to myostatin (GDF8), in combination with semaglutide with and without garetosmab, an antibody to Activin A. A Phase 2 study for itepekimab, an antibody to IL-33, in chronic rhinosinusitis without nasal polyposis (CRSsNP) was initiated. A Phase 2 study for REGN7544, an antagonist antibody to NPR1 , in postural orthostatic tachycardia syndrome (POTS) was initiated. The Company shared initial data from the first patient in a Phase 1 study of linvoseltamab, in combination with Dupixent, in severe food allergy at the 43rd Annual J.P. Morgan Healthcare Conference . Corporate and Business Development Updates In February 2025 , the Company's board of directors approved the initiation of a quarterly cash dividend program and declared a cash dividend of $0.88 per share on the Company's common stock and Class A stock, payable on March 20, 2025 to shareholders of record as of February 20, 2025 . The Company intends to pay a cash dividend on a quarterly basis going forward, subject to market conditions and approval by the Company's board of directors in its sole discretion. In February 2025 , the Company's board of directors also authorized an additional $3 .0 billion share repurchase program, bringing the total current capacity to approximately $4.5 billion . 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. In January 2025 , the Company entered into an agreement with Truveta Inc. pursuant to which the Company will sequence exomes and conduct genotyping and imputation of up to ten million de-identified consented volunteers using biospecimens provided by Truveta health system members across the United States . The Company announced its inclusion on the Dow Jones Sustainability World Index ( DJSI World ) for the sixth consecutive year, as well as its fifth consecutive inclusion on the Dow Jones Sustainability North America Index ( DJSI North America ). Select Upcoming 2025 Milestones Fourth Quarter and Full Year 2024 Financial Results Revenues EYLEA HD was approved by the FDA in August 2023 and net product sales in 2024 were driven by the transition of patients from other anti-VEGF products, including EYLEA, as well as new patients naïve to anti-VEGF therapy. Net product sales of EYLEA HD and EYLEA in the fourth quarter and full year 2024 were adversely impacted by a lower net selling price compared to the same periods of 2023. In addition, fourth quarter 2024 total EYLEA HD and EYLEA net product sales were favorably impacted by approximately $85 million as a result of higher wholesaler inventory levels for EYLEA, partially offset by lower wholesaler inventory levels for EYLEA HD, at the end of the fourth quarter 2024 compared to the end of the third quarter 2024. Sanofi collaboration revenue increased in the fourth quarter and full year 2024, compared to the same periods of 2023, due to an increase in the Company's share of profits from the commercialization of antibodies, which were $1 .043 billion and $886 million in the fourth quarter of 2024 and 2023, respectively, and $3 .924 billion and $3 .137 billion for full year 2024 and 2023, respectively. The change in the Company's share of profits from commercialization of antibodies was driven by higher profits associated with an increase in Dupixent sales. Sanofi collaboration revenue in 2023 was positively impacted by the recognition of a $50 million sales-based milestone. Collaboration revenue for full year 2023 included $224 million in connection with the Company's share of global gross profits from sales of Ronapreve by Roche. Refer to Table 4 for a summary of collaboration revenue. Operating Expenses GAAP and non-GAAP R&D expenses increased in the fourth quarter and full year 2024, compared to the same periods in the prior year, driven by the advancement of the Company's mid- and late-stage clinical pipeline and higher headcount-related costs. Acquired IPR&D expense for full year 2024 included a $45 million development milestone in connection with the Company's collaboration agreement with Sonoma Biotherapeutics, Inc. Acquired IPR&D expense for full year 2023 included a $100 million development milestone in connection with the Company's collaboration with Alnylam Pharmaceuticals, Inc. GAAP and non-GAAP SG&A expenses increased for full year 2024, compared to full year 2023, due to higher commercialization-related expenses to support the Company's launch of EYLEA HD and higher headcount and headcount-related costs partly related to the Company's international commercial expansion. GAAP and non-GAAP COGS increased for full year 2024, compared to full year 2023, primarily due to higher start-up costs for the Company's Rensselaer, New York fill/finish facility. GAAP other operating expense (income), net, for the fourth quarter and full year 2024 reflects charges related to the increase in the estimated fair value of the contingent consideration liability recognized in connection with the Company's 2023 acquisition of Decibel Therapeutics, Inc. Other Financial Information GAAP other income (expense), net included the recognition of net unrealized losses on equity securities of $213 million in the fourth quarter of 2024, compared to $58 million of net unrealized gains in the fourth quarter of 2023. GAAP other income (expense), net included the recognition of net unrealized gains on equity securities of $118 million for full year 2024, compared to net unrealized losses of $238 million for full year 2023. GAAP and non-GAAP other income (expense), net also included interest income of $711 million for full year 2024, compared to $496 million for full year 2023. In the fourth quarter and full year 2024, the Company's GAAP effective tax rate (ETR) was 4.2% and 7.7%, respectively, compared to (1.0%) and 5.9% in the fourth quarter and full year 2023, respectively. The GAAP ETR increased in the fourth quarter of 2024, compared to the same period in the prior year, due to a lower benefit from stock-based compensation. In the fourth quarter and full year 2024, the non-GAAP ETR was 9.9% and 9.6%, respectively, compared to 2.4% and 9.1% in the fourth quarter and full year 2023, respectively. GAAP net income per diluted share was $8.06 in the fourth quarter of 2024, compared to $10.19 in the fourth quarter of 2023. GAAP net income per diluted share was $38.34 for the full year 2024, compared to $34.77 for the full year 2023. Non-GAAP net income per diluted share was $12.07 in the fourth quarter of 2024, compared to $11.86 in the fourth quarter of 2023. Non-GAAP net income per diluted share was $45.62 for the full year 2024, compared to $43.79 for the full year 2023. A reconciliation of the Company's GAAP to non-GAAP results is included in Table 3 of this press release. The Company repurchased $976 million and $2.6 billion of shares of its common stock during the fourth quarter and full year 2024, respectively, and recorded the cost of the shares as Treasury Stock. 2025 Financial Guidance(c) The Company's full year 2025 financial guidance consists of the following components: A reconciliation of full year 2025 GAAP to non-GAAP financial guidance is included below: Conference Call Information Regeneron will host a conference call and simultaneous webcast to discuss its fourth quarter and full year 2024 financial and operating results on Tuesday, February 4, 2025 , 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 by physician-scientists, Regeneron 's unique ability to repeatedly and consistently translate science into medicine has led to numerous approved treatments and product candidates in development, most 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, neurological diseases, hematologic conditions, infectious diseases, and rare diseases. Regeneron pushes the boundaries of scientific discovery and accelerates drug development using its proprietary technologies, such as VelociSuite®, which produces optimized fully human antibodies and new classes of bispecific antibodies. Regeneron is shaping the next frontier of medicine with data-powered insights from the Regeneron Genetics Center® and pioneering genetic medicine platforms, enabling Regeneron to identify innovative targets and complementary approaches to potentially treat or cure diseases. For more information, please visit www.regeneron.com or follow Regeneron on LinkedIn, Instagram, Facebook, or X. 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 nature, timing, and possible success and therapeutic applications of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, " 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 HD® (aflibercept) Injection 8 mg, EYLEA® (aflibercept) Injection, Dupixent® (dupilumab), Libtayo® (cemiplimab), Praluent® (alirocumab), Kevzara® (sarilumab), Evkeeza® (evinacumab), Veopoz® (pozelimab), Ordspono™ (odronextamab), itepekimab, fianlimab, garetosmab, linvoseltamab, Regeneron 's other oncology programs (including its costimulatory bispecific portfolio), REGN5713-5715, nexiguran ziclumeran (nex-z, NTLA-2001), REGN1908-1909, mibavademab, 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 (including biosimilar versions of Regeneron 's Products); 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; changes in laws, regulations, and policies affecting the healthcare industry; 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; the impact of public health outbreaks, epidemics, or pandemics on Regeneron 's business; and risks associated with litigation and other proceedings and government investigations relating to the Company and/or its operations (including the pending civil proceedings initiated or joined by the U.S. Department of Justice and the U.S. Attorney's Office for the District of Massachusetts ), 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), 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 (https://investor.regeneron.com) and its LinkedIn page (https://www.linkedin.com/company/regeneron-pharmaceuticals). 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. TABLE 1 TABLE 2 TABLE 3 TABLE 4 TABLE 5 Source: Regeneron Pharmaceuticals, Inc.