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What changed in Regeneron Pharmaceuticals's 10-K — 2022 vs 2023

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Paragraph-level year-over-year comparison of Regeneron Pharmaceuticals's 2022 and 2023 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2023 report.

+602 added−712 removedSource: 10-K (2024-02-05) vs 10-K (2023-02-06)

Top changes in Regeneron Pharmaceuticals's 2023 10-K

602 paragraphs added · 712 removed · 479 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

164 edited+45 added−75 removed183 unchanged
Biggest changeFood and Drug Administration ("FDA") in connection with ROP study, extending period of EYLEA U.S. market exclusivity by six months through May 17, 2024 –Approved by European Commission ("EC") for ROP –Approved by Ministry of Health, Labour and Welfare ("MHLW") for ROP in Japan –Withdrew supplemental Biologics License Application ("sBLA") for every-16-weeks dosing regimen in patients with DR –FDA decision on sBLA for ROP (target action date of February 11, 2023) Aflibercept 8 mg (a) –Wet AMD –DME –Wet AMD and DME (U.S.) –Reported that Phase 3 trials in wet AMD and DME met their primary endpoints –FDA decision on BLA for wet AMD and DME (third quarter 2023) –Submit regulatory application in the EU for wet AMD and DME (first quarter 2023) –Report two-year data from Phase 3 studies in wet AMD and DME (third quarter 2023) 6 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2022 and 2023 Events to Date Select Upcoming Milestones Immunology & Inflammation Dupixent (dupilumab) (b) Antibody to IL-4R alpha subunit –EoE in pediatrics (c) –Chronic obstructive pulmonary disease ("COPD") –Bullous pemphigoid (Phase 2/3) (c) –Chronic spontaneous urticaria ("CSU") –Chronic inducible urticaria - cold –Chronic rhinosinusitis without nasal polyposis –Allergic fungal rhinosinusitis –Chronic pruritus of unknown origin –Atopic dermatitis in pediatrics (6 months–5 years of age) (EU) and in pediatrics and adolescents (6 months–14 years of age (Japan) –Prurigo nodularis (Japan) –CSU in adults and adolescents (U.S.) –Approved by FDA for atopic dermatitis in pediatrics (6 months–5 years of age) –European Medicines Agency's ("EMA") Committee for Medicinal Products for Human Use ("CHMP") adopted positive opinion for atopic dermatitis in pediatrics (6 months–5 years of age) –Approved by EC for severe asthma in pediatrics (6–11 years of age) –Approved by FDA and EC for EoE in adults and adolescents –Reported that Phase 3 trial in EoE in pediatrics (1–11 years of age) met its primary endpoint –Approved by FDA and EC for prurigo nodularis –Stopped one of the Phase 3 trials in CSU (in patients refractory to omalizumab) due to futility, based on pre-specified interim analysis –Initiated additional Phase 3 trial in CSU (in biologic-naïve patients) –Discontinued further clinical development in peanut allergy –EC decision on regulatory submission for atopic dermatitis in pediatrics (6 months–5 years of age) (first half 2023) –MHLW decision on regulatory submission for atopic dermatitis in pediatrics and adolescents (6 months–14 years of age) in Japan (second half 2023) –Submit sBLA for EoE in pediatrics (mid-2023) –Report results from first Phase 3 study in COPD (first half 2023) –FDA decision on sBLA for CSU in adults and adolescents (second half 2023) –Report results from Phase 3 study in chronic inducible urticaria - cold (first half 2023) 7 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2022 and 2023 Events to Date Select Upcoming Milestones Kevzara (sarilumab) (b) Antibody to IL-6R –Polyarticular-course juvenile idiopathic arthritis ("pcJIA") –Systemic juvenile idiopathic arthritis ("sJIA") –Polymyalgia rheumatica ("PMR") (U.S.) –FDA decision on sBLA for PMR (target action date of February 28, 2023) Itepekimab (b) (REGN3500) Antibody to IL-33 –COPD –Report results from Phase 3 study in COPD (2024) REGN5713-5714-5715 Multi-antibody therapy to Bet v 1 –Birch allergy Solid Organ Oncology Libtayo (cemiplimab) (n)(g) Antibody to PD-1 –Neoadjuvant CSCC –Second-line cervical cancer, ISA101b combination –Adjuvant CSCC –First-line NSCLC, chemotherapy combination (EU) –Approved by FDA in combination with chemotherapy for NSCLC –Approved by EC and MHLW for cervical cancer –Voluntarily withdrew sBLA for cervical cancer due to inability to align with FDA on certain post-marketing studies –Positive data from Phase 2 trial in neoadjuvant CSCC presented at European Society for Medical Oncology ("ESMO") Congress 2022 and published in New England Journal of Medicine –EC decision on regulatory submission for NSCLC, chemotherapy combination (first half 2023) Fianlimab (f) (REGN3767) Antibody to LAG-3 –Solid tumors and advanced hematologic malignancies –First-line metastatic melanoma –First-line adjuvant melanoma –Presented positive data from Phase 1 trial (in combination with Libtayo) in advanced melanoma at ESMO Congress 2022 –Initiate Phase 3 study (in combination with Libtayo) in perioperative melanoma (mid-2023) 8 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2022 and 2023 Events to Date Select Upcoming Milestones Fianlimab (f) (continued) –Positive initial data from Phase 1 trial (in combination with Libtayo) in NSCLC presented at ESMO Immuno-Oncology Congress 2022 –Initiate Phase 2/3 studies (in combination with Libtayo) in first-line advanced NSCLC (first half 2023) –Initiate Phase 2 study (in combination with Libtayo) in perioperative NSCLC (second half 2023) Vidutolimod Immune activator targeting TLR9 –Solid tumors –Initiate Phase 2 study in melanoma Ubamatamab (f) (REGN4018) Bispecific antibody targeting MUC16 and CD3 –Platinum-resistant ovarian cancer –Presented positive initial data from monotherapy dose escalation portion of Phase 1/2 study in platinum-resistant ovarian cancer at ESMO Congress 2022 –Report results from Phase 1/2 study (in combination with Libtayo) in platinum-resistant ovarian cancer (2023) REGN5668 (o) Bispecific antibody targeting MUC16 and CD28 –Platinum-resistant ovarian cancer REGN5678 Bispecific antibody targeting PSMA and CD28 –Prostate cancer –Reported preliminary data from dose escalation portion of Phase 1/2 study (in combination with Libtayo) in prostate cancer –Report additional results from Phase 1/2 study (in combination with Libtayo) in prostate cancer (2023) REGN4336 Bispecific antibody targeting PSMA and CD3 –Prostate cancer REGN5093 Bispecific antibody targeting two distinct MET epitopes –MET-altered advanced NSCLC –Presented positive initial data from dose escalation portion of Phase 1/2 study in MET-altered advanced NSCLC at ESMO Congress 2022 REGN5093-M114 Bispecific antibody-drug conjugate targeting two distinct MET epitopes –MET overexpressing advanced cancer REGN6569 Antibody to GITR –Solid tumors 9 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2022 and 2023 Events to Date Select Upcoming Milestones REGN7075 Bispecific antibody targeting EGFR and CD28 –Solid tumors Hematology Odronextamab (i) (REGN1979) Bispecific antibody targeting CD20 and CD3 –Certain B-cell malignancies (c)(m) –B-cell non-Hodgkin lymphoma ("B-NHL") (m) (pivotal study) –Presented positive data from two cohorts of pivotal Phase 2 study in patients with diffuse large B-cell lymphoma ("DLBCL") and follicular lymphoma ("FL") at American Society of Hematology ("ASH") Annual Meeting –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 (f) (REGN5458) Bispecific antibody targeting BCMA and CD3 –Multiple myeloma (c) –Multiple myeloma (pivotal study) (c) –Completed enrollment in pivotal Phase 2 study in multiple myeloma –Presented positive data from pivotal Phase 2 study in multiple myeloma at ASH Annual Meeting –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) REGN5459 (f) Bispecific antibody targeting BCMA and CD3 –Transplant desensitization in patients with chronic kidney disease Pozelimab (f) (REGN3918) Antibody to C5; studied as monotherapy and in combination with cemdisiran –CD55-deficient protein-losing enteropathy ("CHAPLE"), monotherapy (c)(e) (potentially pivotal study) –Myasthenia gravis, cemdisiran combination (k) –Paroxysmal nocturnal hemoglobinuria ("PNH"), cemdisiran combination (c)(k) –CHAPLE, monotherapy (U.S.) –FDA decision on BLA for CHAPLE, monotherapy (second half 2023) REGN7257 Antibody to IL2Rg –Aplastic anemia NTLA-2001 (j) TTR gene knockout using CRISPR/Cas9 –Transthyretin ("ATTR") amyloidosis (c) –Reported positive interim data from Phase 1 trial in ATTR REGN9933 Antibody to Factor XI –Thrombosis 10 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2022 and 2023 Events to Date Select Upcoming Milestones REGN7508 Antibody to Factor XI –Thrombosis REGN7999 Antibody to TMPRSS6 –Transfusion dependent iron overload General Medicine "Next Generation" Covid Antibodies Antibodies to SARS-CoV-2 variants –Initiate clinical development of "next generation" antibody Praluent (alirocumab) Antibody to PCSK9 –HeFH in pediatrics –Submit sBLA for HeFH in pediatrics (mid-2023) Evkeeza (evinacumab) (f)(l) Antibody to ANGPTL3 –HoFH in pediatrics (5–11 years of age) (U.S.) –Reported that Phase 3 trial for HoFH in pediatrics (5–11 years of age) met its primary endpoint –FDA decision on sBLA for HoFH in pediatrics (5–11 years of age) (target action date of March 30, 2023) Garetosmab (f) (REGN2477) Antibody to Activin A –Fibrodysplasia ossificans progressiva ("FOP") (c)(d)(e) Mibavademab (f) (REGN4461) Agonist antibody to leptin receptor ("LEPR") –Generalized lipodystrophy (e) –Partial lipodystrophy REGN5381/REGN9035 Agonist antibody to NPR1/reversal agent to REGN5381 –Reversal agent in healthy volunteers –Heart failure –Report initial data in healthy volunteers (2023) ALN-HSD (p) RNAi therapeutic targeting HSD17B13 –Nonalcoholic steatohepatitis ("NASH") –Reported preliminary data from Phase 1 study in NASH –Initiate Phase 2 study in NASH (first quarter 2023) ALN-PNP (k) RNAi therapeutic targeting PNPLA3 –NASH ALN-APP (k) RNAi therapeutic targeting APP –Early-onset Alzheimer’s disease –Report results from Phase 1 study in early-onset Alzheimer’s disease (mid-2023) 11 Table of Contents Note 1: For purposes of the table above, a program is classified in Phase 1, 2, or 3 clinical development after recruitment for the corresponding study or studies has commenced.
Biggest changeFood and Drug Administration ("FDA") for wAMD, DME, and DR –Approved by European Commission ("EC") and Japan's Ministry of Health, Labour and Welfare ("MHLW") for wAMD and DME –Reported positive two-year data from Phase 3 studies in wAMD and DME –Initiate Phase 3 study in RVO (mid-2024) to enable FDA submission EYLEA (aflibercept) (a) –Approved by FDA for ROP Pozelimab (f) (REGN3918) Antibody to C5 –Initiate Phase 3 study in combination with cemdisiran in geographic atrophy (second half 2024) Immunology & Inflammation Dupixent (dupilumab) (b) Antibody to IL-4R alpha subunit –Ulcerative colitis –Eosinophilic gastroenteritis (Phase 2/3) –Chronic obstructive pulmonary disease ("COPD") (d) –Bullous pemphigoid (c) –Chronic spontaneous urticaria ("CSU") –Chronic pruritus of unknown origin –EoE in pediatrics (1–11 years of age) (EU) –COPD with type 2 inflammatory phenotype (U.S. and EU) –CSU in adults and adolescents (Japan) –Approved by EC for atopic dermatitis in pediatrics (6 months–5 years of age) –Approved by MHLW for atopic dermatitis in pediatrics and adolescents (6 months–14 years of age) –Approved by FDA for EoE in pediatrics (1–11 years of age) –Approved by EC for EoE in adults and adolescents –Approved by MHLW for prurigo nodularis –EC decision on regulatory submission for EoE in pediatrics (second half 2024) –FDA decision on supplemental Biologics License Application ("sBLA") (mid/second half 2024) and EC decision on regulatory submission (second half 2024) for COPD with type 2 inflammatory phenotype 7 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2023 and 2024 Events to Date Select Upcoming Milestones Dupixent (dupilumab) (b) (continued) –Reported that Phase 3 BOREAS trial in COPD with evidence of type 2 inflammation met its primary and all key secondary endpoints; presented at 2023 American Thoracic Society International Conference and published in New England Journal of Medicine –Reported that results from interim analysis of replicate Phase 3 NOTUS trial in COPD with evidence of type 2 inflammation met its primary endpoint –FDA issued Complete Response Letter ("CRL") for sBLA for CSU due to requirement for additional efficacy data –Phase 3 trial in chronic cold induced urticaria did not meet its required efficacy endpoints –Discontinued further clinical development in allergic fungal rhinosinusitis and chronic rhinosinusitis without nasal polyposis –MHLW decision on regulatory submission for CSU in adults and adolescents (first half 2024) –Report results from ongoing Phase 3 trial in CSU (in biologic-naïve patients) (fourth quarter 2024) –Report results from Phase 3 trial in bullous pemphigoid (second half 2024) –Initiate Phase 1 study in severe food allergy following transient linvoseltamab treatment (2024) Kevzara (sarilumab) (b) Antibody to IL-6R –Polyarticular-course juvenile idiopathic arthritis ("pcJIA") (pivotal study) –Systemic juvenile idiopathic arthritis ("sJIA") (pivotal study) –PMR (EU) –pcJIA (U.S. and EU) –Approved by FDA for PMR –EC decision on regulatory submission for PMR (second half 2024) –FDA decision on sBLA (target action date of June 10, 2024) and EC decision (second half 2024) on regulatory submission for pcJIA 8 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2023 and 2024 Events to Date Select Upcoming Milestones Itepekimab (b) (REGN3500) Antibody to IL-33 –COPD (e) –Phase 3 COPD program passed interim futility analysis conducted by Independent Data Monitoring Committee ("IDMC") –Report results from Phase 3 study in COPD (2025) REGN5713-5714-5715 Multi-antibody therapy to Bet v 1 –Birch allergy Solid Organ Oncology Libtayo (cemiplimab) (g) Antibody to PD-1 –Neoadjuvant CSCC –First-line NSCLC, BNT116 (r) combination –Adjuvant CSCC –Approved by EC for first-line NSCLC, chemotherapy combination –Conduct interim analysis from Phase 3 study in adjuvant CSCC (second half 2024) Fianlimab (f) (REGN3767) Antibody to LAG-3 –Solid tumors and advanced hematologic malignancies –First-line advanced NSCLC (Phase 2/3) (pivotal study) –First-line metastatic melanoma (e) –First-line adjuvant melanoma –Presented positive data from Phase 1 trial (in combination with Libtayo) in advanced melanoma at 2023 American Society of Clinical Oncology ("ASCO") Annual Meeting –Initiate potentially pivotal Phase 2 study (in combination with Libtayo) in perioperative melanoma (first half 2024) –Initiate Phase 2 study (in combination with Libtayo) in perioperative NSCLC (first half 2024) –Initiate Phase 2 study (in combination with Libtayo) in perioperative head and neck squamous cell carcinoma (2024) –Report potentially pivotal initial results from Phase 2/3 study in first-line metastatic melanoma (second half 2024) –Report initial data from Phase 2/3 study in first-line advanced NSCLC (second half 2024) Vidutolimod Immune activator targeting TLR9 –Solid tumors 9 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2023 and 2024 Events to Date Select Upcoming Milestones Ubamatamab (f) (REGN4018) Bispecific antibody targeting MUC16 and CD3 –Platinum-resistant ovarian cancer –Presented results from Phase 1/2 study (in combination with Libtayo) in platinum-resistant ovarian cancer at European Society for Medical Oncology ("ESMO") Congress REGN5668 (n) Bispecific antibody targeting MUC16 and CD28 –Platinum-resistant ovarian cancer REGN5678 Bispecific antibody targeting PSMA and CD28 –Prostate cancer –Discontinued enrollment in cohorts in combination with full-dose Libtayo (cemiplimab) –Expanded enrollment in monotherapy cohort –Initiate cohorts in combination with REGN4336 in metastatic castration-resistant prostate cancer (first half 2024) REGN4336 Bispecific antibody targeting PSMA and CD3 –Prostate cancer Davutamig (REGN5093) Bispecific antibody targeting two distinct MET epitopes –MET-altered advanced NSCLC REGN5093-M114 Bispecific antibody-drug conjugate targeting two distinct MET epitopes –MET overexpressing advanced cancer REGN6569 Antibody to GITR –Solid tumors REGN7075 Bispecific antibody targeting EGFR and CD28 –Solid tumors –Initiate dose-expansion cohorts (in combination with Libtayo) in EGFR-high tumors (first half 2024) 10 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2023 and 2024 Events to Date Select Upcoming Milestones Hematology Pozelimab (f) (REGN3918) Antibody to C5 –Myasthenia gravis, cemdisiran combination (c)(s) –Paroxysmal nocturnal hemoglobinuria ("PNH"), cemdisiran combination (c)(s) –Veopoz (pozelimab) approved by FDA for CHAPLE in adults and children aged 1 year and older, monotherapy Odronextamab (m) (REGN1979) Bispecific antibody targeting CD20 and CD3 –Certain B-cell malignancies (c) –B-cell non-Hodgkin lymphoma ("B-NHL") (pivotal study) –Follicular lymphoma ("FL") –Diffuse large B-cell lymphoma ("DLBCL") –Relapsed/refractory FL and DLBCL (U.S. and EU) –Presented updated data from trials in patients with relapsed/refractory FL and DLBCL at American Society of Hematology ("ASH") Annual Meeting –FDA decision on BLA (target action date of March 31, 2024) and EC decision on regulatory submission (second half 2024) for relapsed/refractory FL and DLBCL REGN5837 (p) Bispecific antibody targeting CD22 and CD28 –B-NHL Linvoseltamab (f) (REGN5458) Bispecific antibody targeting BCMA and CD3 –Multiple myeloma (c)(e) –Multiple myeloma (pivotal study) (c)(e) –Earlier (pre-malignant) multiple myeloma –Multiple myeloma (c)(e) –Relapsed/refractory multiple myeloma (U.S. and EU) –Presented updated positive data from pivotal trial in multiple myeloma at ASCO and ASH Annual Meetings –FDA decision on BLA (second half 2024) and EC decision on regulatory submission (first half 2025) for relapsed/refractory multiple myeloma REGN5459 (f) Bispecific antibody targeting BCMA and CD3 –Transplant desensitization in patients with chronic kidney disease REGN7257 Antibody to IL2Rg –Aplastic anemia NTLA-2001 (j) TTR gene knockout using CRISPR/Cas9 –Transthyretin ("ATTR") amyloidosis (c) –ATTR amyloidosis with cardiomyopathy ("ATTR-CM") REGN9933 Antibody to Factor XI –Thrombosis –Report results from Phase 2 study in thrombosis (second half 2024) REGN7508 Antibody to Factor XI –Thrombosis 11 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2023 and 2024 Events to Date Select Upcoming Milestones REGN7999 Antibody to TMPRSS6 –Transfusion dependent iron overload Internal Medicine/Genetic Medicines Praluent (alirocumab) Antibody to PCSK9 –HeFH in pediatrics and adolescents –HeFH in pediatrics and adolescents (8–17 years of age) (U.S.) –Approved by EC for HeFH in pediatrics and adolescents (8–17 years of age) –FDA decision on sBLA for HeFH in pediatrics and adolescents (target action date of March 10, 2024) Evkeeza (f)(l) (evinacumab) Antibody to ANGPTL3 –Approved by FDA and EC for HoFH in pediatrics (5–11 years of age) and MHLW for HoFH in adults, adolescents, and pediatrics Garetosmab (f) (REGN2477) Antibody to Activin A –Fibrodysplasia ossificans progressiva ("FOP") (c)(d)(e) Trevogrumab (f) (REGN1033) Antibody to myostatin (GDF8) –Initiate Phase 2 study in combination with semaglutide with and without garetosmab (mid-2024) Mibavademab (f) (REGN4461) Agonist antibody to leptin receptor ("LEPR") –Generalized lipodystrophy (d)(e) –Presented results from Phase 2 study in generalized lipodystrophy at ENDO 2023 REGN5381/REGN9035 Agonist antibody to NPR1/reversal agent to REGN5381 –Reversal agent in healthy volunteers –Heart failure –Resumed enrollment in previously paused Phase 1 and Phase 2 studies following protocol amendments –Reported positive initial data from Phase 1 trial in healthy volunteers REGN7544 Antagonist antibody to NPR1 –Healthy volunteers ALN-HSD (o) RNAi therapeutic targeting HSD17B13 –Nonalcoholic steatohepatitis ("NASH") 12 Table of Contents Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2023 and 2024 Events to Date Select Upcoming Milestones ALN-PNP (k) RNAi therapeutic targeting PNPLA3 –NASH ALN-APP (k) RNAi therapeutic targeting APP –Early-onset Alzheimer’s disease (q) –Reported positive interim data from single dose part of Phase 1 trial in early-onset Alzheimer’s disease DB-OTO AAV-based gene therapy –Hearing loss in pediatrics (c) (Phase 1/2) –Reported preliminary, positive safety and efficacy results from first patient dosed in Phase 1/2 trial in pediatrics with hearing loss "Next Generation" Covid Antibody (i) Antibody to SARS-CoV-2 variants –Healthy volunteers REGN13335 Antagonist antibody to PDGF-B –Healthy volunteers 13 Table of Contents Note: For purposes of the table above, a program is classified in Phase 1, 2, or 3 clinical development after recruitment for the corresponding study or studies has commenced.
Marketed Products The table below provides an overview of the current competitive landscape for the key products marketed by us and/or our collaborators in such products' currently approved indications. The table below is provided for illustrative purposes only and is not exhaustive.
Marketed Products The table below provides an overview of the current competitive landscape for key products marketed by us and/or our collaborators in such products' currently approved indications. The table below is provided for illustrative purposes only and is not exhaustive.
If we become aware that our reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data for up to three years after those data originally were due, which revisions could affect our rebate liability for prior quarters.
If we become aware that our Medicaid reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data for up to three years after those data originally were due, which revisions could affect our rebate liability for prior quarters.
Different EU member states, as well as the United Kingdom and Switzerland, have promulgated national privacy laws that impose additional requirements, which add to the complexity of processing and transferring EU personal data. In October 2022, the United States issued an executive order to implement EU-U.S. data privacy safeguards.
Different EU member states, as well as the United Kingdom and Switzerland, have promulgated national privacy laws that impose additional requirements, which add to the complexity of processing and transferring EU personal data. In October 2022, the United States issued an executive order to implement the EU-U.S.
The results of these studies must be submitted to the FDA or the relevant regulatory authority outside the United States as part of an IND or clinical trial application (as applicable), which must be reviewed by the FDA or the relevant government authority before proposed clinical testing can begin in the applicable country or jurisdiction.
The results of these studies must be submitted to the FDA or the relevant regulatory authority outside the United States as part of an IND or other clinical trial application (as applicable), which must be reviewed by the FDA or the relevant government authority before proposed clinical testing can begin in the applicable country or jurisdiction.
For example, as part of our $100 million, 10-year commitment to support the Regeneron Science Talent Search, we allocate $3.1 million annually to fund the Society for Science’s science, technology, engineering, and math ("STEM") outreach and equity programs.
For example, as part of our $100 million, 10-year commitment to support the Regeneron Science Talent Search ("STS"), we allocate $3.1 million annually to fund the Society for Science’s science, technology, engineering, and math ("STEM") outreach and equity programs.
Mild-to-moderate atopic dermatitis United States, EU Opzelura ® (ruxolitinib) Incyte Corporation Mild-to-moderate atopic dermatitis United States Olumiant ® (baricitinib) Eli Lilly and Company/Incyte Corporation Moderate-to-severe atopic dermatitis EU, Japan Cibinqo ® (abrocitinib) Pfizer Moderate-to-severe atopic dermatitis Worldwide Rinvoq ® (upadacitinib) AbbVie Moderate-to-severe atopic dermatitis Worldwide Adbry ™ /Adtralza ® (tralokinumab) LEO Pharma Inc.
Mild-to-moderate atopic dermatitis United States, EU Opzelura ® (ruxolitinib) Incyte Corporation Mild-to-moderate atopic dermatitis United States Olumiant ® (baricitinib) Eli Lilly and Company/Incyte Corporation Moderate-to-severe atopic dermatitis EU, Japan Cibinqo ® (abrocitinib) Pfizer Moderate-to-severe atopic dermatitis United States, EU, Japan Rinvoq ® (upadacitinib) AbbVie Moderate-to-severe atopic dermatitis United States, EU, Japan Adbry ™ /Adtralza ® (tralokinumab) LEO Pharma Inc.
Investors and other interested parties should note that we use our media and investor relations website ( http://newsroom.regeneron.com ) and our social media channels to publish important information about Regeneron, including information that may be deemed material to investors.
Investors and other interested parties should note that we use our media and investor relations website ( http://investor.regeneron.com ) and our social media channels to publish important information about Regeneron, including information that may be deemed material to investors.
Some countries outside of the EU have reacted to the GDPR by promulgating and enacting new privacy legislation that reflects similar principles and obligations on companies that operate and process their citizens' personal data.
Some countries outside the EU have reacted to the GDPR by promulgating and enacting new privacy legislation that reflects similar principles and obligations on companies that operate and process their citizens' personal data.
RGC is undertaking multiple collaborative approaches to study design and implementation, including large population-based efforts that engage study participants to more discrete disease specific and founder populations with data on strategic phenotypes of interest. RGC utilizes laboratory automation and innovative approaches to cloud computing to achieve high-quality throughput, attaining approximately 2 million samples sequenced to date.
RGC is undertaking multiple collaborative approaches to study design and implementation, including large population-based efforts that engage study participants to more discrete disease specific and founder populations with data on strategic phenotypes of interest. RGC utilizes laboratory automation and innovative approaches to cloud computing to achieve high-quality throughput, attaining more than 2 million samples sequenced to date.
We co-commercialize Dupixent in the United States and in certain countries outside the United States. We supply certain commercial bulk product to Sanofi. We and Sanofi equally share profits and losses from sales within the United States.
We co-commercialize Dupixent in the United States and in certain countries outside the United States. We supply certain commercial bulk product to Sanofi. We and Sanofi equally share profits from sales within the United States.
We and Sanofi share profits outside the United States on a sliding scale based on sales starting at 65% (Sanofi)/35% (us) and ending at 55% (Sanofi)/45% (us), and share losses outside the United States at 55% (Sanofi)/45% (us).
We and Sanofi share profits outside the United States on a sliding scale based on sales starting at 65% (Sanofi)/35% (us) and ending at 55% (Sanofi)/45% (us).
Dupixent (dupilumab) Dupixent is a fully human monoclonal antibody that inhibits signaling of the IL-4 and IL-13 pathways, and is not an immunosuppressant. IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma, CRSwNP, EoE, prurigo nodularis, and potentially other chronic allergic and inflammatory diseases.
Dupixent (dupilumab) Dupixent is a fully human monoclonal antibody that inhibits signaling of the IL-4 and IL-13 pathways, and is not an immunosuppressant. IL-4 and IL-13 are key and central drivers of the type 2 inflammation that plays a major role in atopic dermatitis, asthma, CRSwNP, EoE, prurigo nodularis, and potentially other chronic allergic and inflammatory diseases, including COPD.
Under the agreement, we pay royalties of 8.0% on worldwide sales of Libtayo through December 31, 2023, and royalties of 2.5% from January 1, 2024 through December 31, 2026. Patent law relating to the patentability and scope of claims in the biotechnology field is evolving and our patent rights are subject to this additional uncertainty.
Under the agreement, we paid royalties of 8.0% on worldwide sales of Libtayo through December 31, 2023, and are obligated to pay royalties of 2.5% from January 1, 2024 through December 31, 2026. Patent law relating to the patentability and scope of claims in the biotechnology field is evolving and our patent rights are subject to this additional uncertainty.
In addition, we hold an ownership interest in thousands of patent applications in the United States and foreign countries. Our patent portfolio includes granted patents and pending patent applications covering our VelociSuite technologies, including our VelocImmune mouse platform which produces fully human antibodies. Our issued patents covering these technologies generally expire between 2022 and 2032.
In addition, we hold an ownership interest in thousands of patent applications in the United States and other countries. Our patent portfolio includes granted patents and pending patent applications covering our VelociSuite technologies, including our VelocImmune mouse platform which produces fully human antibodies. Our issued patents covering these technologies generally expire between 2022 and 2032.
Through genetic humanizations, VelociHum mice have been optimized to allow for better development of human immune cells in vivo , as well as to allow for engraftment of primary patient-derived tumors that do not take in other commercially available mice. 15 Table of Contents Regeneron Genetics Center ® Regeneron Genetics Center LLC (RGC ™ ), a wholly owned subsidiary of Regeneron Pharmaceuticals, Inc., leverages de-identified clinical, genomic, and other types of molecular data from properly consented human volunteers from around the world to identify medically relevant associations in a blinded fashion designed to preserve a patients' privacy while uncovering the unique characteristics of their health and wellness.
Through genetic humanizations, VelociHum mice have been optimized to allow for better development of human immune cells in vivo , as well as to allow for engraftment of primary patient-derived tumors that do not take in other commercially available mice. 18 Table of Contents Regeneron Genetics Center ® Regeneron Genetics Center LLC (RGC ® ), a wholly owned subsidiary of Regeneron Pharmaceuticals, Inc., leverages de-identified clinical, genomic, and other types of molecular data from properly consented human volunteers from around the world to identify medically relevant associations in a blinded fashion designed to preserve a patient's privacy while uncovering the unique characteristics of their health and wellness.
In 2019, we and Alnylam entered into a global, strategic collaboration to discover, develop, and commercialize RNAi therapeutics for a broad range of diseases by addressing therapeutic disease targets expressed in the eye and central nervous system ("CNS"), in addition to a select number of targets expressed in the liver.
Alnylam In 2019, we and Alnylam Pharmaceuticals, Inc. entered into a global, strategic collaboration to discover, develop, and commercialize RNAi therapeutics for a broad range of diseases by addressing therapeutic disease targets expressed in the eye and central nervous system ("CNS"), in addition to a select number of targets expressed in the liver.
Starting in 2023, manufacturers must pay refunds to Medicare for single-source drugs or biological products, or biosimilar biological products, reimbursed under Medicare Part B and packaged in single-dose containers or single-use packages for units of discarded drug reimbursed by Medicare Part B in excess of 10 percent of total allowed charges under Medicare Part B for that drug.
Manufacturers must pay refunds to Medicare for single-source drugs or biological products, or biosimilar biological products, reimbursed under Medicare Part B and packaged in single-dose containers or single-use packages for units of discarded drug reimbursed by Medicare Part B in excess of 10 percent of total allowed charges under Medicare Part B for that drug.
Our policy is to file patent applications to protect technology, inventions, and improvements that we consider important to our business and operations. We hold an ownership interest in a number of issued patents in the United States and foreign countries with respect to our products and technologies.
Our policy is to file patent applications to protect technology, inventions, and improvements that we consider important to our business and operations. We hold an ownership interest in a number of issued patents in the United States and other countries with respect to our products and technologies.
Additionally, we have placed in the top five for the past 12 years in Science magazine’s annual "Top Employers Survey" of the global biotechnology and pharmaceutical industry. Compensation and Benefits We are committed to rewarding and supporting our employees in order to continue to attract and retain top talent.
Additionally, we have placed in the top five for the past 13 years in Science magazine’s annual "Top Employers Survey" of the global biotechnology and pharmaceutical industry. Compensation and Benefits We are committed to rewarding and supporting our employees in order to continue to attract and retain top talent.
Government Regulation Regulation by government authorities in the United States and foreign countries is a significant factor in the research, development, manufacture, and marketing of our products and our product candidates. A summary of the primary areas of government regulation that are relevant to our business is provided below.
Government Regulation Regulation by government authorities in the United States and other countries is a significant factor in the research, development, manufacture, and marketing of our products and our product candidates. A summary of the primary areas of government regulation that are relevant to our business is provided below.
"Risk Factors - Other Regulatory and Litigation Risks - Our business activities have been, and may in the future be, challenged under U.S. federal or state and foreign healthcare laws, which may subject us to civil or criminal proceedings, investigations, or penalties ." 30 Table of Contents Adverse-event reporting and submission of periodic reports are required following marketing approval.
"Risk Factors - Other Regulatory and Litigation Risks - Our business activities have been, and may in the future be, challenged under U.S. federal or state and foreign healthcare laws, which may subject us to civil or criminal proceedings, investigations, or penalties ." Adverse-event reporting and submission of periodic reports are required following marketing approval.
The RGC continues to publish results from its research efforts in journals and publications in partnership with its collaborators to advance the field of genomics. These efforts at the RGC have led to the identification of more than 20 novel genetic targets.
The RGC continues to publish results from its research efforts in journals and publications in partnership with its collaborators to advance the field of genomics. These efforts at the RGC have led to the identification of more than 30 novel genetic targets.
Our core business strategy is to maintain a strong foundation in basic scientific research and discovery-enabling technologies, and to build on that foundation with our clinical development, manufacturing, and commercial capabilities. Our objective is to continue to be an integrated, multi-product biotechnology company that provides patients and medical professionals with important medicines for preventing and treating human diseases.
Our core business strategy is to maintain a strong foundation in basic scientific research and discovery-enabling technologies, and to build on that foundation with our clinical development, manufacturing, and commercial capabilities. Our objective is to continue to advance as an integrated, multi-product biotechnology company that provides patients and medical professionals with important medicines for preventing and treating human diseases.
We also compete with others in acquiring technology from these institutions, agencies, and organizations. 23 Table of Contents Patents, Trademarks, and Trade Secrets We rely on a combination of intellectual property laws, including patent, trademark, copyright, trade secret, and domain name protection laws, as well as confidentiality and license agreements, to protect our intellectual property and proprietary rights.
We also compete with others in acquiring technology from these institutions, agencies, and organizations. Patents, Trademarks, and Trade Secrets We rely on a combination of intellectual property laws, including patent, trademark, copyright, trade secret, and domain name protection laws, as well as confidentiality and license agreements, to protect our intellectual property and proprietary rights.
"Risk Factors - Risks Related to Intellectual Property 27 Table of Contents and Market Exclusivity - We may be restricted in our development, manufacturing, and/or commercialization activities by patents or other proprietary rights of others, and could be subject to awards of damages if we are found to have infringed such patents or rights "; and Note 16 to our Consolidated Financial Statements).
"Risk Factors - Risks Related to Intellectual Property and Market Exclusivity - We may be restricted in our development, manufacturing, and/or commercialization activities by patents or other proprietary rights of others, and could be subject to awards of damages if we are found to have infringed such patents or rights "; and Note 16 to our Consolidated Financial Statements).
Prescription drug manufacturers in the U.S. must comply with applicable provisions of the Drug Supply Chain Security Act and provide and receive product tracing information, maintain appropriate licenses, ensure they only work with other properly licensed entities, and have procedures in place to identify and properly handle suspect and illegitimate products.
Prescription drug manufacturers in the U.S. must comply with applicable provisions of the Drug Supply Chain Security Act and provide and receive product tracing information, maintain appropriate licenses, ensure they only work with other properly licensed entities, and have procedures in place to identify and 31 Table of Contents properly handle suspect and illegitimate products.
We are also aware of several companies developing or marketing small molecules that may compete with our antibody product candidates in various indications, if such product candidates obtain regulatory approval in those indications.
We are also aware of other companies developing or marketing small molecules that may compete with our antibody product candidates in various indications, if such product candidates obtain regulatory approval in those indications.
Before approving a new drug or biologic product, the FDA also requires that the facilities at which the product will be manufactured or advanced through the supply chain be in compliance with current Good Manufacturing Practices, or cGMP, requirements and regulations governing, among other things, the manufacture, shipment, and storage of the product.
Before approving a new drug or biologic product, the FDA 29 Table of Contents also requires that the facilities at which the product will be manufactured or advanced through the supply chain be in compliance with current Good Manufacturing Practices, or cGMP, requirements and regulations governing, among other things, the manufacture, shipment, and storage of the product.
In the United States, under the Pediatric Research Equity Act ("PREA"), certain applications for approval must include an assessment, generally based on clinical study data, of the safety and effectiveness of the subject product in relevant pediatric populations, unless a waiver or 29 Table of Contents deferral is granted.
In the United States, under the Pediatric Research Equity Act ("PREA"), certain applications for approval must include an assessment, generally based on clinical study data, of the safety and effectiveness of the subject product in relevant pediatric populations, unless a waiver or deferral is granted.
Kevzara (sarilumab) Kevzara is a fully human monoclonal antibody that binds specifically to the IL-6 receptor and inhibits IL-6-mediated signaling. IL-6 is a signaling protein produced in increased quantities in patients with RA and has been associated with disease activity, joint destruction, and other systemic problems.
Kevzara (sarilumab) Kevzara is a fully human monoclonal antibody that binds specifically to the IL-6 receptor and inhibits IL-6-mediated signaling. IL-6 is an immune system protein produced in increased quantities in patients with RA and has been associated with disease activity, joint destruction, and other systemic problems.
These institutions are becoming more active in seeking patent and other intellectual property protection and licensing arrangements to collect royalties or other consideration for use of the technology they have developed. Products developed in this manner may compete directly with products we develop.
These institutions are becoming more active in seeking patent and other intellectual property protection and licensing arrangements to 24 Table of Contents collect royalties or other consideration for use of the technology they have developed. Products developed in this manner may compete directly with products we develop.
Under the Medicaid Drug Rebate program, we are required to pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state 31 Table of Contents Medicaid program as a condition of having federal funds being made available for our drugs under Medicaid and Part B of the Medicare program.
Under the Medicaid Drug Rebate program, we are required to pay a rebate to each state Medicaid program for our covered outpatient drugs that are dispensed to Medicaid beneficiaries and paid for by a state Medicaid program as a condition of having federal funds being made available for our drugs under Medicaid and Part B of the Medicare program.
If concerns arise about the safety of the product candidate, the FDA or other regulatory authorities can stop clinical trials by placing them on a "clinical hold" pending receipt of additional data, which can result in a delay or termination of a clinical development 28 Table of Contents program.
If concerns arise about the safety of the product candidate, the FDA or other regulatory authorities can stop clinical trials by placing them on a "clinical hold" pending receipt of additional data, which can result in a delay or termination of a clinical development program.
Intellia In 2016, we entered into a license and collaboration agreement with Intellia Therapeutics, Inc. to advance CRISPR/Cas9 gene-editing technology for in vivo therapeutic development.
Intellia In 2016, we entered into a license and collaboration agreement with Intellia to advance CRISPR/Cas9 gene-editing technology for in vivo therapeutic development.
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.
The Company records its share of profits in connection with sales outside the United States. (b) Sanofi records global net product sales of Dupixent and Kevzara. The Company records its share of profits in connection with global sales of Dupixent and Kevzara.
The PPACA expanded the list of covered entities to include certain free-standing cancer hospitals, critical access hospitals, rural referral centers, and sole community hospitals, but exempts "orphan drugs" from 32 Table of Contents the ceiling price requirements for these covered entities.
The PPACA expanded the list of covered entities to include certain free-standing cancer hospitals, critical access hospitals, rural referral centers, and sole community hospitals, but exempts "orphan drugs" from the ceiling price requirements for these covered entities.
On a combined basis, our product sales to these customers accounted for 83% of our total gross product revenue for the year ended December 31, 2022. We promote approved medicines to healthcare professionals via our team of field employees, as well as medical journals, medical exhibitions, distribution of literature and samples, and online channels.
On a combined basis, our product sales to these customers accounted for 76% of our total gross product revenue for the year ended December 31, 2023. We promote approved medicines to healthcare professionals via our team of field employees, as well as medical journals, medical exhibitions, distribution of literature and samples, and online channels.
Approval of a product candidate by comparable regulatory authorities in foreign countries is generally required prior to commencement of marketing of the product in those countries. The approval procedure varies among countries and may involve different or additional testing, and the time required to obtain such approval may differ from that required for FDA approval.
Approval of a product candidate by comparable regulatory authorities in countries outside the United States is generally required prior to commencement of marketing of the product in those countries. The approval procedure varies among countries and may involve different or additional testing, and the time required to obtain such approval may differ from that required for FDA approval.
Similarly, there are a number of legislative proposals in the United States, at both the federal and state level, that could impose new obligations or limitations in 34 Table of Contents the area of consumer protection.
Similarly, there are a number of legislative proposals in the United States, at both the federal and state level, that could impose new obligations or limitations in the area of consumer protection.
These statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any such statements. In evaluating such statements, shareholders and potential investors should specifically consider the various factors identified under Part I, Item 1A.
These statements are made based on management's current beliefs and judgment, and the reader is cautioned not to rely on any such statements. In evaluating such statements, shareholders and potential investors should specifically consider the various 2 Table of Contents factors identified under Part I, Item 1A.
Post-approval modifications to the drug, such as changes in indications, labeling, or manufacturing processes or facilities, may require a sponsor to develop additional data or conduct additional preclinical studies or clinical trials, to be submitted in a new or supplemental BLA, which would require FDA approval.
Post-approval modifications to 30 Table of Contents the drug, such as changes in indications, labeling, or manufacturing processes or facilities, may require a sponsor to develop additional data or conduct additional preclinical studies or clinical trials, to be submitted in a new or supplemental BLA, which would require FDA approval.
We may be subject to audits by the FDA and other regulatory authorities to ensure that we are complying with the applicable requirements. Rules that are equivalent in scope but which vary in application apply in foreign countries in which we conduct clinical trials.
We may be subject to audits by the FDA and other regulatory authorities to ensure that we are complying with the applicable requirements. Rules that are equivalent in scope but which vary in application apply in countries outside the United States in which we conduct clinical trials.
Under the terms of our agreement, Sanofi is entitled to receive royalties on sales of the product, if any.
Under the terms of our agreement, Alnylam is entitled to receive royalties on sales of the product, if any.
VelocImmune was generated by leveraging our VelociGene technology (see below), in a process in which six megabases of mouse immunoglobulin gene loci were replaced, or "humanized," with corresponding human immunoglobulin gene loci. VelocImmune mice can be used efficiently to generate fully human antibodies to targets of therapeutic interest.
The VelocImmune mouse platform is utilized to produce fully human antibodies. VelocImmune was generated by leveraging our VelociGene technology (see below), in a process in which six megabases of mouse immunoglobulin gene loci were replaced, or "humanized," with corresponding human immunoglobulin gene loci. VelocImmune mice can be used efficiently to generate fully human antibodies to targets of therapeutic interest.
We encourage investors and other interested parties to review the 37 Table of Contents information we may publish through our media and investor relations website and the social media channels listed on our media and investor relations website, in addition to our SEC filings, press releases, conference calls, and webcasts.
We encourage investors and other interested parties to review the information we may publish through our media and investor relations website and the social media channels listed on our media and investor relations website, in addition to our SEC filings, press releases, conference calls, and webcasts.
Excluding those that did not disclose such information, the percentage shown in this table would be 33.6%. Externally, we support DEI efforts in our community, including by supporting young scientific talent in underrepresented communities.
Excluding those that did not disclose such information, the percentage shown in this table would be 34.9%. Externally, we support DEI efforts in our community, including by supporting young scientific talent in underrepresented communities.
In each of 2020 and 2021, we earned a $50.0 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $1.0 billion and $1.5 billion, respectively, on a rolling twelve-month basis.
In each of 2020 and 2021, we earned a $50.0 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outside the United States (including Praluent, which was previously included in the LCA) exceeding $1.0 billion and $1.5 billion, respectively, on a rolling twelve-month basis.
Net product sales of Regeneron-discovered products consist of the following: Year Ended December 31, 2022 2021 2020 (In millions) U.S. ROW Total U.S. ROW Total U.S.
Net product sales of Regeneron-discovered products consist of the following: Year Ended December 31, 2023 2022 2021 (In millions) U.S. ROW (g) Total U.S. ROW Total U.S.
CMS recently modified Medicaid Drug Rebate program regulations to, among other things, permit reporting multiple best price figures with regard to value‑based purchasing arrangements and provide definitions for "line extension," "new formulation," and related terms with the practical effect of expanding the scope of drugs considered to be line extensions (beginning in 2022).
CMS has since modified Medicaid Drug Rebate program regulations to, among other things, permit reporting multiple best price figures with regard to value‑based purchasing arrangements and provide definitions for "line extension," "new formulation," and related terms with the practical effect of expanding the scope of drugs considered to be line extensions.
Only) ** 28.7% * Based on full-time employees as of December 31, 2022 ** Represents the percentage of our full-time employees in the United States that self-identified as belonging to a racial or ethnic minority group. The denominator used in this calculation includes employees who did not disclose information related to their race or ethnicity.
Only) ** 30.5% * Based on full-time employees as of December 31, 2023 ** Represents the percentage of our full-time employees in the United States that self-identified as belonging to a racial or ethnic minority group. The denominator used in this calculation includes employees who did not disclose information related to their race or ethnicity.
In particular, human therapeutic products are subject to rigorous preclinical and clinical trials and other pre-market approval requirements by the FDA, EMA, and other foreign regulatory authorities. The structure and substance of the FDA and foreign pharmaceutical regulatory practices may evolve over time. The ultimate outcome and impact of such developments cannot be predicted.
In particular, human therapeutic products are subject to rigorous preclinical and clinical trials and other pre-market approval requirements by the FDA, European Medicines Agency ("EMA"), and regulatory authorities of other countries. The structure and substance of the FDA and other countries' pharmaceutical regulatory practices may evolve over time. The ultimate outcome and impact of such developments cannot be predicted.
In 2021, the European Commission published new standard contractual clauses required to be incorporated into new and existing agreements within prescribed timeframes in order to continue to lawfully transfer personal data outside of the EU.
In 2021, the European Commission published new standard contractual clauses required to be incorporated into new and existing agreements in order to continue to lawfully transfer personal data outside the EU.
The prescription drug plans negotiate pricing with manufacturers and pharmacies, and may condition formulary placement on the availability of manufacturer discounts.
The prescription drug plans negotiate pricing with manufacturers and pharmacies, and may condition formulary placement on the availability of manufacturer 33 Table of Contents discounts.
We had sales to two customers (Besse Medical, a subsidiary of AmerisourceBergen Corporation, and McKesson Corporation) that each accounted for more than 10% of total gross product revenue for the year ended December 31, 2022.
We had sales to two customers (Besse Medical, a subsidiary of Cencora, Inc., and McKesson Corporation) that each accounted for more than 10% of total gross product revenue for the year ended December 31, 2023.
In 2022, we earned two additional $50.0 million sales-based milestones, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $2.0 billion and $2.5 billion, respectively, on a rolling twelve-month basis.
In 2022, we earned two additional $50.0 million sales-based milestones, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $2.0 billion and $2.5 billion, respectively, on a rolling twelve-month basis, and in 2023, we earned the final $50.0 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $3.0 billion on a rolling twelve-month basis.
Rules that are equivalent in scope but which vary in application apply in foreign countries. Product Approval All of our product candidates require regulatory approval by relevant government authorities before they can be commercialized.
Rules that are equivalent in scope but which vary in application apply in other countries. 28 Table of Contents Product Approval All of our product candidates require regulatory approval by relevant government authorities before they can be commercialized.
Selected financial information is summarized as follows: Year Ended December 31, (In millions, except per share data) 2022 2021 2020 Revenues $ 12,172.9 $ 16,071.7 $ 8,497.1 Net income $ 4,338.4 $ 8,075.3 $ 3,513.2 Net income per share - diluted $ 38.22 $ 71.97 $ 30.52 For purposes of this report, references to our products encompass products marketed or otherwise commercialized by us and/or our collaborators or licensees and references to our product candidates encompass product candidates in development by us and/or our collaborators or licensees (in the case of collaborated or licensed products or product candidates under the terms of the applicable collaboration or license agreements), unless otherwise stated or required by the context.
Selected financial information is summarized as follows: Year Ended December 31, (In millions, except per share data) 2023 2022 2021 Revenues $ 13,117.2 $ 12,172.9 $ 16,071.7 Net income $ 3,953.6 $ 4,338.4 $ 8,075.3 Net income per share - diluted $ 34.77 $ 38.22 $ 71.97 For purposes of this report, references to our products encompass products marketed or otherwise commercialized by us and/or our collaborators or licensees and references to our product candidates encompass product candidates in development by us and/or our collaborators or licensees (in the case of collaborated or licensed products or product candidates under the terms of the applicable collaboration or license agreements), unless otherwise stated or required by the context.
Manufacturers that fail to pay refunds could be subject to civil monetary penalties. Further, starting in 2023, the Inflation Reduction Act ("IRA") establishes a Medicare Part B inflation rebate scheme under which, generally speaking, manufacturers will owe rebates if the average sales price of a Part B drug increases faster than the pace of inflation.
Manufacturers that fail to pay refunds could be subject to civil monetary penalties. Further, the Inflation Reduction Act ("IRA") has established a Medicare Part B inflation rebate scheme under which, generally speaking, manufacturers owe rebates if the average sales price of a Part B drug increases faster than the pace of inflation.
Through our Regeneron Genetics Medicines initiative, we are currently advancing these targets using either our VelociSuite technologies or other technologies, such as siRNA gene silencing, genome editing, and targeted viral-based gene delivery and expression. See the "Collaboration, License, and Other Agreements" section below for descriptions of our collaborations with Alnylam and Intellia. Agreements Related to COVID-19 U.S.
Through our Regeneron Genetics Medicines initiative, we are currently advancing these targets using either our VelociSuite technologies or other technologies, such as siRNA gene silencing, genome editing, and targeted viral-based gene delivery and expression. See the "Collaboration, License, and Other Agreements" section below for descriptions of our collaborations with Alnylam and Intellia Therapeutics, Inc.
One or more patents with the same or earlier expiry date may fall under the same "general subject matter class" for certain products and may not be separately listed. Product Molecule Territory Patent No.
One or more patents with the same or earlier expiry date may fall under the same "general subject matter class" for certain products and may not be separately listed.
Other Programs Our preclinical research programs include the areas of oncology/immuno-oncology, angiogenesis, ophthalmology, metabolic and related diseases, muscle diseases and disorders, inflammation and immune diseases, bone and cartilage, pain and neurobiology, auditory conditions, enzyme replacement therapy, cardiovascular diseases, infectious diseases, and diseases related to aging.
Other Programs Our preclinical research programs include the areas of oncology/immuno-oncology, angiogenesis, ophthalmology, metabolic and related diseases, muscle diseases and disorders, inflammation and immune diseases, bone and cartilage, pain and neurobiology, auditory conditions, enzyme replacement therapy, cardiovascular diseases, infectious diseases, and diseases related to aging. These preclinical research programs include both rare diseases and those involving broader populations.
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) Injection, Libtayo ® (cemiplimab) Injection, Praluent ® (alirocumab) Injection, Kevzara ® (sarilumab) Injection, 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 our anticipated development milestones referenced in this report; 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 our late-stage product candidates and new indications for Regeneron's Products, including without limitation those listed above; the extent to which the results from the research and development programs conducted by us and/or our 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 our 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; our ability to manufacture and manage supply chains for multiple products and product candidates; the ability of our 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 payors, including private payor 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 payors and new policies and procedures adopted by such payors; unanticipated expenses; the costs of developing, producing, and selling products; our ability to meet any of our financial projections or guidance, including without limitation capital expenditures, and changes to the assumptions underlying those projections or guidance; the potential for any license or collaboration agreement, including our 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 described further in Note 16 to our Consolidated Financial Statements included in this report), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including without limitation those described in Note 16 to our Consolidated Financial Statements included in this report), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on our business, prospects, operating results, and financial condition.
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 those discussed or referenced in this report, 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 our anticipated development milestones referenced in this report; • 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 our late-stage product candidates and new indications for Regeneron's Products, including without limitation those discussed or referenced in this report; • the extent to which the results from the research and development programs conducted by us and/or our 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 our 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; • our ability to manufacture and manage supply chains for multiple products and product candidates; • the ability of our 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 payors, including private payor 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 payors and new policies and procedures adopted by such payors; • unanticipated expenses; • the costs of developing, producing, and selling products; our ability to meet any of our financial projections or guidance, including without limitation capital expenditures, and changes to the assumptions underlying those projections or guidance; • the potential for any license or collaboration agreement, including our 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 (such as the COVID-19 pandemic) on our business; 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 described further in Note 16 to our Consolidated Financial Statements included in this report), other litigation and other proceedings and government investigations relating to the Company and/or its operations (including without limitation those described in Note 16 to our Consolidated Financial Statements included in this report), the ultimate outcome of any such proceedings and investigations, and the impact any of the foregoing may have on our business, prospects, operating results, and financial condition.
In 2022, we were named to the Civic 50 of most community-minded companies in the United States for the sixth consecutive year.
In 2023, we were named to the Civic 50 of most community-minded companies in the United States for the seventh consecutive year.
Our board of directors receives a detailed update on our DEI efforts at least once a year and continues to monitor our progress. 2022 Workforce Diversity Representation * Female Representation (Global) 49.8% People of Color Representation (U.S.
Our board of directors receives a detailed update on our DEI efforts at least once a year and continues to monitor our progress. 36 Table of Contents 2023 Workforce Diversity Representation * Female Representation (Global) 49.9% People of Color Representation (U.S.
The success of our employee engagement efforts is demonstrated by our employee retention rate of 91% in 2022, as well as the fact that 87% of our employees who responded to our annual engagement survey said Regeneron is a great place to work.
The success of our employee engagement efforts is demonstrated by our employee retention rate of 93.6% in 2023, as well as the fact that 88% of our employees who responded to our annual engagement survey said Regeneron is a great place to work.
EU Japan ROW (e) Dupixent (dupilumab) Injection (b) (continued) Eosinophilic esophagitis ("EoE") (in adults and adolescents) a a a Prurigo nodularis a a a Libtayo (cemiplimab) Injection (c) Metastatic or locally advanced first-line non-small cell lung cancer ("NSCLC") a a a Metastatic or locally advanced first-line NSCLC (in combination with chemotherapy) a Metastatic or locally advanced basal cell carcinoma ("BCC") a a a Metastatic or locally advanced cutaneous squamous cell carcinoma ("CSCC") a a a Metastatic or recurrent second-line cervical cancer a a a Praluent (alirocumab) Injection (d) LDL-lowering in heterozygous familial hypercholesterolemia ("HeFH") or clinical atherosclerotic cardiovascular disease ("ASCVD") a a a Cardiovascular risk reduction in patients with established cardiovascular disease a a a Homozygous familial hypercholesterolemia ("HoFH") a REGEN-COV ®(f) COVID-19 a a a Kevzara (sarilumab) Solution for Subcutaneous Injection (b) Rheumatoid arthritis ("RA") a a a a Evkeeza (evinacumab) Injection (g) HoFH (in adults and adolescents) a a a Inmazeb ® (atoltivimab, maftivimab, and odesivimab-ebgn) Injection Infection caused by Zaire ebolavirus a ARCALYST ® (rilonacept) Injection for Subcutaneous Use (h) Cryopyrin-associated periodic syndromes ("CAPS"), including familial cold auto-inflammatory syndrome ("FCAS") and Muckle-Wells syndrome ("MWS") (in adults and adolescents) a Deficiency of interleukin-1 receptor antagonist ("DIRA") (in adults and pediatrics) a Recurrent pericarditis (in adults and adolescents) a ZALTRAP ® (ziv-aflibercept) Injection for Intravenous Infusion (i) Metastatic colorectal cancer ("mCRC") a a a a Note: Refer to table below (net product sales of Regeneron-discovered products) for information regarding whether net product sales for a particular product are recorded by us or others.
EU Japan Dupixent (dupilumab) Injection (b) (continued) Asthma (in pediatrics 6–11 years of age) a a Chronic rhinosinusitis with nasal polyposis ("CRSwNP") a a a Eosinophilic esophagitis ("EoE") (in adults and adolescents) a a EoE (in pediatrics 1–11 years of age) a Prurigo nodularis a a a Libtayo ® (cemiplimab) Injection (c) Metastatic or locally advanced first-line non-small cell lung cancer ("NSCLC") a a Metastatic or locally advanced first-line NSCLC (in combination with chemotherapy) a a Metastatic or locally advanced basal cell carcinoma ("BCC") a a Metastatic or locally advanced cutaneous squamous cell carcinoma ("CSCC") a a Metastatic or recurrent second-line cervical cancer a a Praluent ® (alirocumab) Injection (d) LDL-lowering in heterozygous familial hypercholesterolemia ("HeFH") or clinical atherosclerotic cardiovascular disease ("ASCVD") a a HeFH in pediatrics and adolescents (8–17 years of age) a Cardiovascular risk reduction in patients with established cardiovascular disease a a Homozygous familial hypercholesterolemia ("HoFH") a REGEN-COV ®(e) COVID-19 a a Kevzara (sarilumab) Injection (b) Rheumatoid arthritis ("RA") a a a Polymyalgia rheumatica ("PMR") a Evkeeza ® (evinacumab) Injection (f) HoFH (in adults, adolescents, and pediatrics aged 5 years and older) a a a Inmazeb ® (atoltivimab, maftivimab, and odesivimab) Injection Infection caused by Zaire ebolavirus a Veopoz ™ (pozelimab) Injection CD55-deficient protein-losing enteropathy ("CHAPLE") (in adults, adolescents, and pediatrics aged 1 year and older) a ARCALYST ® (rilonacept) Injection (g) Cryopyrin-associated periodic syndromes ("CAPS"), including familial cold auto-inflammatory syndrome ("FCAS") and Muckle-Wells syndrome ("MWS") (in adults and adolescents) a Deficiency of interleukin-1 receptor antagonist ("DIRA") (in adults, adolescents, and pediatrics) a Recurrent pericarditis (in adults and adolescents) a ZALTRAP ® (ziv-aflibercept) Injection for Intravenous Infusion (h) Metastatic colorectal cancer ("mCRC") a a a 4 Table of Contents Note: Refer to table below (net product sales of Regeneron-discovered products) for information regarding whether net product sales for a particular product are recorded by us or others.
Among the conditions for regulatory marketing approval of a medicine is the requirement that the prospective manufacturer's quality control and manufacturing procedures conform to the good manufacturing practice ("GMP") regulations of the health authority.
"Risk Factors - Risks Related to Manufacturing and Supply" for further information. Among the conditions for regulatory marketing approval of a medicine is the requirement that the prospective manufacturer's quality control and manufacturing procedures conform to the good manufacturing practice ("GMP") regulations of the health authority.
In addition, we rely on our collaborators or third parties to perform packaging, filling, finishing, labeling, distribution, laboratory testing, and other services related to the manufacture of our products and product candidates, and to supply various raw materials and other products. See Part I, Item 1A. "Risk Factors - Risks Related to Manufacturing and Supply" for further information.
In addition, we rely on our collaborators or third parties to perform packaging, filling, finishing, labeling, distribution, laboratory testing, and other services related to the manufacture of our products and product candidates, and to 21 Table of Contents supply various raw materials and other products. See Part I, Item 1A.
A key component of our culture is our commitment to diversity, equity, and inclusion ("DEI"). We believe this commitment allows us to better drive innovation and achieve our mission to repeatedly bring important new medicines to patients with serious diseases.
A key component of our culture is our commitment to diversity, equity, and inclusion ("DEI"). We believe this commitment allows us to better drive innovation and achieve our mission to repeatedly bring important new medicines to patients with serious diseases. Our strategy is rooted in the understanding that DEI drives better science and that better science drives a better world.
Under the Amended and Restated Immuno-oncology Discovery and Development Agreement, we were obligated to reimburse Sanofi for half of the development costs it funded that were attributable to clinical development of product candidates from our share of profits from commercialized IO Collaboration products.
Under the terms of the IO Collaboration, we were obligated to reimburse Sanofi for half of the development costs it funded that were attributable to clinical development of product candidates from our share of profits from commercialized IO Collaboration products.
(c) Supplementary protection certificates ("SPCs") are pending and/or have been granted in various European countries, extending the original patent terms in those countries, where granted, to the applicable dates indicated in parentheses.
Patent and Trademark Office and patent infringement proceedings relating to EYLEA. (b) Supplementary protection certificates ("SPCs") are pending or have been granted in various European countries, extending the original patent terms in those countries, where granted, to the applicable dates indicated in parentheses.
EU Japan ROW (e) EYLEA (aflibercept) Injection (a) Neovascular age-related macular degeneration ("wet AMD") a a a a Diabetic macular edema ("DME") a a a a Macular edema following retinal vein occlusion ("RVO"), which includes macular edema following central retinal vein occlusion ("CRVO") and macular edema following branch retinal vein occlusion ("BRVO") a a a a Myopic choroidal neovascularization ("mCNV") a a a Diabetic retinopathy ("DR") a Neovascular glaucoma ("NVG") a Retinopathy of prematurity ("ROP") a a Dupixent (dupilumab) Injection (b) Atopic dermatitis (in adults and adolescents) a a a a Atopic dermatitis (in pediatrics 6–11 years of age) a a a Atopic dermatitis (in pediatrics 6 months–5 years of age) a a Asthma (in adults and adolescents) a a a a Asthma (in pediatrics 6–11 years of age) a a a Chronic rhinosinusitis with nasal polyposis ("CRSwNP") a a a a 3 Table of Contents Product (continued) Disease Territory U.S.
EU Japan EYLEA ® HD (aflibercept) Injection 8 mg (a) Wet age-related macular degeneration ("wAMD") a a a Diabetic macular edema ("DME") a a a Diabetic retinopathy ("DR") a EYLEA ® (aflibercept) Injection (a) wAMD a a a DME a a a DR a Macular edema following retinal vein occlusion ("RVO"), which includes macular edema following central retinal vein occlusion ("CRVO") and macular edema following branch retinal vein occlusion ("BRVO") a a a Myopic choroidal neovascularization ("mCNV") a a Neovascular glaucoma ("NVG") a Retinopathy of prematurity ("ROP") a a a Dupixent ® (dupilumab) Injection (b) Atopic dermatitis (in adults, adolescents, and pediatrics aged 6 months and older) a a a Asthma (in adults and adolescents) a a a 3 Table of Contents Product (continued) Disease Territory U.S.
Any of such risks and uncertainties may, among other matters, negatively impact the development timelines set forth in the table below. 5 Table of Contents Clinical Program Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2022 and 2023 Events to Date Select Upcoming Milestones Ophthalmology EYLEA (aflibercept) (a) –ROP (c) –ROP (U.S.) –Granted pediatric exclusivity by U.S.
Any of such risks and uncertainties may, among other matters, negatively impact the development timelines set forth in the table below. 6 Table of Contents Clinical Program Phase 1 Phase 2 Phase 3 Regulatory Review (h) 2023 and 2024 Events to Date Select Upcoming Milestones Ophthalmology EYLEA HD (aflibercept) 8 mg (a) –RVO –Approved by U.S.
Bayer We and Bayer are parties to a license and collaboration agreement for the global development and commercialization of EYLEA and aflibercept 8 mg outside the United States. Agreed-upon development expenses incurred by the Company and Bayer are generally shared equally. Bayer markets EYLEA outside the United States, and the companies share equally in profits and losses from such sales.
Bayer We and Bayer are parties to a license and collaboration agreement for the global development and commercialization of EYLEA 8 mg and EYLEA outside the United States. Agreed-upon development expenses incurred by the Company and Bayer are generally shared equally.
In addition, we are in process of building additional commercial capabilities outside the United States as a result of us obtaining the rights, in 2022, to commercialize Libtayo outside the United States. Refer to "Collaboration, License, and Other Agreements" section above for additional information related to these agreements. Competition We face substantial competition from pharmaceutical, biotechnology, and chemical companies.
In addition, we are in process of building additional commercial capabilities outside the United States as a result of us obtaining the rights, in 2022, to commercialize Libtayo outside the United States. Competition We face substantial competition from pharmaceutical, biotechnology, and chemical companies.
The federal Patient Protection and Affordable Care Act (the "PPACA") made significant changes to the Medicaid Drug Rebate program, and CMS issued a final regulation, which became effective on April 1, 2016, to implement the changes to the Medicaid Drug Rebate program under the PPACA.
The federal Patient Protection and Affordable Care Act (the "PPACA") made significant changes to the Medicaid Drug Rebate program, and thereafter CMS issued a final regulation to implement the changes to the Medicaid Drug Rebate program under the PPACA.
"Risk Factors - Other Regulatory and Litigation Risks - We face risks related to the personal data we collect, process, and share ." In addition to the foregoing, our present business is, and our future business may be, subject to regulation under the United States Atomic Energy Act, the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation and Liability Act, the National Environmental Policy Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, national restrictions, and other current and potential future local, state, federal, and foreign regulations.
"Risk Factors - Other Regulatory and Litigation Risks - We face risks related to the personal data we collect, process, and share ." In addition to the foregoing, our present business is, and our future business may be, subject to regulation under the United States Atomic Energy Act, the Clean Air Act, the Clean Water Act, the Comprehensive Environmental Response, Compensation and Liability Act, the National Environmental Policy Act, the Toxic Substances Control Act, the Resource Conservation and Recovery Act, national restrictions, and other current and potential future local, state, federal, and foreign regulations. 35 Table of Contents Business Segments We manage our business as one segment which includes all activities related to the discovery, development, and commercialization of medicines for serious diseases.
The parties shared equally, on an ongoing basis, development and commercialization expenses for Libtayo. We had principal control over the development of Libtayo and led commercialization activities in the United States, while Sanofi led commercialization activities outside of the United States. The parties shared equally in profits and losses in connection with the commercialization of Libtayo.
We had principal control over the development of Libtayo and led commercialization activities in the United States, while Sanofi led 19 Table of Contents commercialization activities outside the United States. The parties shared equally in profits and losses in connection with the commercialization of Libtayo.
Programs in Clinical Development Product candidates in clinical development, which are being developed by us and/or our collaborators, are summarized in the table below.
(g) Rest of world ("ROW") 5 Table of Contents Programs in Clinical Development Product candidates in clinical development, which are being developed by us and/or our collaborators, are summarized in the table below.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeRisks Related to Our Reliance on or Transactions with Third Parties • If our collaborations with Sanofi or Bayer or other third parties are terminated or breached, our ability to develop, manufacture, and commercialize certain of our products and product candidates in the time expected, or at all, would be materially harmed. • Our collaborators and service providers may fail to perform adequately in their efforts to support the development, manufacture, and commercialization of our drug candidates and current and future products. • We have undertaken and may in the future undertake strategic acquisitions, and any difficulties from integrating such acquisitions could adversely affect our business, operating results, and financial condition. 39 Table of Contents Other Risks Factors – Risks Related to Employees, Information Technology, Financial Results and Liquidity, and Our Common Stock • Our business is dependent on our key personnel and will be harmed if we cannot recruit and retain leaders in our research, development, manufacturing, and commercial organizations. • Significant disruptions of information technology systems or breaches of data security could adversely affect our business. • We may need additional funding in the future, which may not be available to us, and which may force us to delay, reduce, or eliminate our product development programs or commercialization efforts. • Our indebtedness could adversely impact our business. • Our stock price is extremely volatile. • Our existing shareholders may be able to exert substantial influence over matters requiring shareholder approval and over our management. * * * Risks Related to the COVID-19 Pandemic Our business may be further adversely affected by the effects of the COVID-19 pandemic.
Biggest changeRisks Related to Our Reliance on or Transactions with Third Parties • If our collaborations with Sanofi or Bayer or other third parties are terminated or breached, our ability to develop, manufacture, and commercialize certain of our products and product candidates in the time expected, or at all, may be materially harmed. • Our collaborators and service providers may fail to perform adequately in their efforts to support the development, manufacture, and commercialization of our drug candidates and current and future products. • We have undertaken and may in the future undertake strategic acquisitions, and any difficulties from integrating such acquisitions or failure to realize the expected benefits from such acquisitions could adversely affect our business, operating results, and financial condition.
Bribery Act. • Our operations are subject to environmental, health, and safety laws and regulations, including those governing the use of hazardous materials. • Changes in laws and regulations affecting the healthcare industry could adversely affect our business. • Tax liabilities and risks associated with our operations outside of the United States could adversely affect our business. • We face risks related to the personal data we collect, process, and share.
Bribery Act. • Our operations are subject to environmental, health, and safety laws and regulations, including those governing the use of hazardous materials. • Changes in laws and regulations affecting the healthcare industry could adversely affect our business. • Tax liabilities and risks associated with our operations outside the United States could adversely affect our business. • We face risks related to the personal data we collect, process, and share.
In addition, we are aware of several companies developing biosimilar versions of EYLEA and other approved anti-VEGF treatments. Other potentially competitive products in development include products for use in combination with EYLEA and/or other anti-VEGF treatments, small-molecule tyrosine kinase inhibitors, gene therapies, and other eye-drop formulations, devices, and oral therapies.
In addition, we are aware of several other companies developing biosimilar versions of EYLEA and other approved anti-VEGF treatments. Other potentially competitive products in development include products for use in combination with EYLEA and/or other anti-VEGF treatments, small-molecule tyrosine kinase inhibitors, gene therapies, and other eye-drop formulations, devices, and oral therapies.
However, the term of regulatory exclusivity may not remain at 12 years in the United States and could be shortened if, for example, the PPACA is amended. A number of jurisdictions outside of the United States have also established abbreviated pathways for regulatory approval of biological products that are biosimilar to earlier versions of biological products.
However, the term of regulatory exclusivity may not remain at 12 years in the United States and could be shortened if, for example, the PPACA is amended. A number of jurisdictions outside the United States have also established abbreviated pathways for regulatory approval of biological products that are biosimilar to earlier versions of biological products.
Also, the complexity of our manufacturing process may make it difficult, time-consuming, and expensive to transfer our technology to our collaborators or contract manufacturers. Also, certain raw materials or other products necessary for the manufacture and formulation of our marketed products and product candidates, some of which are difficult to source, are provided by single-source unaffiliated third-party suppliers.
Also, the complexity of our manufacturing process may make it difficult, time-consuming, and expensive to transfer our technology to our collaborators or contract manufacturers. Certain raw materials or other products necessary for the manufacture and formulation of our marketed products and product candidates, some of which are difficult to source, are provided by single-source unaffiliated third-party suppliers.
If Bayer were to terminate its collaboration agreement with us, we may not have the resources or skills to replace those of our collaborator, which could require us to seek another collaboration that might not be available on favorable terms or at all, and could cause significant issues for the commercialization of EYLEA outside the United States and result in substantial additional costs and/or lower revenues to us.
If Bayer were to terminate its collaboration agreement with us, we may not have the resources or skills to replace those of our collaborator, which could require us to seek another collaboration that might not be available on favorable terms or at all, and could cause significant issues for the commercialization of EYLEA HD and EYLEA outside the United States and result in substantial additional costs and/or lower revenues to us.
A reduction in the availability or extent of reimbursement from U.S. government programs (including as a result of the legislation, proposals, initiatives, and developments described above) could have a material adverse effect on the sales of EYLEA or our other marketed products. Economic pressure on state budgets may also have a similar impact.
A reduction in the availability or extent of reimbursement from U.S. government programs (including as a result of the legislation, proposals, initiatives, and developments described above) could have a material adverse effect on the sales of EYLEA, EYLEA HD, or our other marketed products. Economic pressure on state budgets may also have a similar impact.
As we increase our production in response to higher product demand or in anticipation of a potential regulatory approval, our current manufacturing capacity will likely not be sufficient, and our dependence on our collaborators and/or contract manufacturers may increase, to produce adequate quantities of drug material for both commercial and clinical purposes. • Expanding our manufacturing capacity and establishing fill/finish capabilities will be costly and we may be unsuccessful in doing so in a timely manner, which could delay or prevent the launch and successful commercialization of our products approved for marketing and could jeopardize our clinical development programs. • Our ability to manufacture products may be impaired if any of our or our collaborators' manufacturing activities, or the activities of other third parties involved in our manufacture and supply chain, are found to infringe patents of others. • If sales of our marketed products do not meet the levels currently expected, or if the launch of any of our product candidates is delayed or unsuccessful, we may face costs related to excess inventory or unused capacity at our manufacturing facilities and at the facilities of third parties or our collaborators. • Third-party service or supply failures, failures at our manufacturing facilities in Rensselaer, New York and Limerick, Ireland, or failures at the facilities of any other party participating in the supply chain would adversely affect our ability to supply our products. • Our or our collaborators' failure to meet the stringent requirements of governmental regulation in the manufacture of drug products or product candidates could result in incurring substantial remedial costs, delays in the development or approval of our product candidates or new indications for our marketed products and/or in their commercial launch if regulatory approval is obtained, and a reduction in sales.
As we increase our production in response to higher product demand or in anticipation of a potential regulatory approval, our current manufacturing capacity will likely not be sufficient, and our dependence on our collaborators and/or contract manufacturers may increase, to produce adequate quantities of drug material for both commercial and clinical purposes. • Expanding our manufacturing capacity and establishing fill/finish capabilities will be costly and we may be unsuccessful in doing so in a timely manner, which could delay or prevent the launch and successful commercialization of our products approved for marketing and could jeopardize our clinical development programs. • Our ability to manufacture products may be impaired if any of our or our collaborators' manufacturing activities, or the activities of other third parties involved in our manufacture and supply chain, are found to infringe patents of others. • If sales of our marketed products do not meet the levels currently expected, or if the launch of any of our product candidates is delayed or unsuccessful, we may face costs related to excess inventory or unused capacity at our manufacturing facilities and at the facilities of third parties or our collaborators. • Third-party service or supply failures, failures at our manufacturing facilities in Rensselaer, New York and Limerick, Ireland, or failures at the facilities of any other party participating in the supply chain would adversely affect our ability to supply our products. 39 Table of Contents • Our or our collaborators' failure to meet the stringent requirements of governmental regulation in the manufacture of drug products or product candidates could result in incurring substantial remedial costs, delays in the development or approval of our product candidates or new indications for our marketed products and/or in their commercial launch if regulatory approval is obtained, and a reduction in sales.
There may be other circumstances in which we need to establish commercial capabilities outside the United States, including because we decide to commercialize a particular product independently; we are unable to find an appropriate collaborator; or an existing collaborator decides to opt out or breaches its obligations to us with respect to a particular product.
There may be other circumstances in which we need to establish further commercial capabilities outside the United States, including because we decide to commercialize a particular product independently; we are unable to find an appropriate collaborator; or an existing collaborator decides to opt out or breaches its obligations to us with respect to a particular product.
The GDPR has a wide range of compliance obligations, including increased transparency requirements and data subject rights. Violations of the GDPR carry significant financial penalties for noncompliance (including possible fines of up to 4% of global annual turnover for the preceding financial year or €20 million (whichever is higher)).
The GDPR has a wide range of compliance obligations, including increased consent and transparency requirements and data subject rights. Violations of the GDPR carry significant financial penalties for noncompliance (including possible fines of up to 4% of global annual turnover for the preceding financial year or €20 million (whichever is higher)).
In the case of our Medicaid pricing data, if we become aware that our reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data for up to three years after those data originally were due.
For example, in the case of our Medicaid pricing data, if we become aware that our reporting for a prior quarter was incorrect, or has changed as a result of recalculation of the pricing data, we are obligated to resubmit the corrected data for up to three years after those data originally were due.
Although we believe we can find additional distributors, if necessary, our revenue during any period of disruption could suffer and we might incur additional costs. In addition, these customers are responsible for a significant portion of our net trade accounts receivable balances.
Although we believe we can find additional distributors, if necessary, our revenue during any period of disruption could suffer and we might incur additional costs. In addition, these distributor customers are responsible for a significant portion of our net trade accounts receivable balances.
A judicial or regulatory decision in favor of one or more parties making such allegations could directly or indirectly preclude the manufacture of our products to which those intellectual property rights apply on a temporary or permanent basis, which could materially harm our business, prospects, operating results, and financial condition. 57 Table of Contents If sales of our marketed products do not meet the levels currently expected, or if the launch of any of our product candidates is delayed or unsuccessful, we may face costs related to excess inventory or unused capacity at our manufacturing facilities and at the facilities of third parties or our collaborators.
A judicial or regulatory decision in favor of one or more parties making such allegations could directly or indirectly preclude the manufacture of our products to which those intellectual property rights apply on a temporary or permanent basis, which could materially harm our business, prospects, operating results, and financial condition. 56 Table of Contents If sales of our marketed products do not meet the levels currently expected, or if the launch of any of our product candidates is delayed or unsuccessful, we may face costs related to excess inventory or unused capacity at our manufacturing facilities and at the facilities of third parties or our collaborators.
If we or Sanofi were to experience any difficulty with the commercialization of Dupixent or if we or Sanofi are unable to maintain current marketing approvals of Dupixent, we may experience a reduction in revenue and our business, prospects, operating results, and financial condition would be materially harmed.
If we or Sanofi were to experience any difficulty with the commercialization of Dupixent or if we or Sanofi are unable to maintain current marketing approvals of Dupixent, we may experience a reduction in revenue and our business, prospects, operating results, and financial condition may be materially harmed.
Department of the Treasury), and other trade barriers; • difficulties in attracting and retaining qualified personnel; and • cultural differences in the conduct of business. We have large-scale manufacturing operations in Limerick, Ireland and have also established offices in the United Kingdom, Germany, and other countries outside the United States.
Department of the Treasury), and other trade barriers; • difficulties in attracting and retaining qualified personnel; and • cultural differences in the conduct of business. We have large-scale manufacturing operations in Limerick, Ireland and have also established offices in the United Kingdom, Germany, Japan, and other countries outside the United States.
The loss of any large customer, a significant reduction in sales we make to them, any cancellation of orders they have made with us, or any failure to pay for the products we have shipped to them could adversely affect our results of operations.
The loss of any large distributor customer, a significant reduction in sales we make to them, any cancellation of orders they have made with us, or any failure to pay for the products we have shipped to them could adversely affect our results of operations.
If our collaboration with Bayer for EYLEA is terminated, or Bayer materially breaches its obligations thereunder, our business, prospects, operating results, and financial condition, and our ability to continue to commercialize EYLEA outside the United States would be materially harmed.
If our collaboration with Bayer for EYLEA HD and EYLEA is terminated, or Bayer materially breaches its obligations thereunder, our business, prospects, operating results, and financial condition, and our ability to continue to commercialize EYLEA HD and EYLEA outside the United States would be materially harmed.
We and our collaborators are subject to significant ongoing regulatory obligations and oversight with respect to the products we or they commercialize for the products' currently approved indications in the United States, EU, and other countries where such products are approved.
We and our collaborators are subject to significant ongoing regulatory obligations and oversight with respect to the products we or they commercialize for the products' currently approved indications in the United States, EU, Japan, and other countries where such products are approved.
Additionally, access to such data by fraud-and-abuse investigators and industry critics may draw scrutiny to our collaborations with reported entities. 60 Table of Contents If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations, and future prospects.
Additionally, access to such data by fraud-and-abuse investigators and industry critics may draw scrutiny to our collaborations with reported entities. 59 Table of Contents If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate program or other governmental pricing programs, we could be subject to additional reimbursement requirements, penalties, sanctions and fines, which could have a material adverse effect on our business, financial condition, results of operations, and future prospects.
In particular, Bayer has responsibility for selling EYLEA outside the United States using its sales force and, in Japan, in cooperation with Santen pursuant to a Co-Promotion and Distribution Agreement with Bayer's Japanese affiliate.
In particular, Bayer has responsibility for selling EYLEA HD and EYLEA outside the United States using its sales force and, in Japan, in cooperation with Santen pursuant to a Co-Promotion and Distribution Agreement with Bayer's Japanese affiliate.
If Bayer and, in Japan, Santen do not perform their obligations in a timely manner, or at all, our ability to commercialize EYLEA outside the United States will be significantly adversely affected.
If Bayer and, in Japan, Santen do not perform their obligations in a timely manner, or at all, our ability to commercialize EYLEA HD and EYLEA outside the United States will be significantly adversely affected.
These tests and trials may not achieve favorable results for many reasons, including, among others, failure of the product candidate to demonstrate safety or efficacy, the development of serious or life-threatening adverse events (or side effects) caused by or connected with exposure to the product candidate (or prior or concurrent exposure to other products or product candidates), difficulty in enrolling and maintaining subjects in a clinical trial, clinical trial design that may not make it possible to enroll or retain a sufficient number of 50 Table of Contents patients to achieve a statistically significant result or the desired level of statistical significance for the endpoint in question, lack of sufficient supplies of the product candidate or comparator drug, and the failure of clinical investigators, trial monitors, contractors, consultants, or trial subjects to comply with the trial plan, protocol, or applicable regulations related to the FDA's GLPs or GCPs.
These tests and trials may not achieve favorable results for many reasons, including, among others, failure of the product candidate to demonstrate safety or efficacy, the development of serious or life-threatening adverse events (or side effects) caused by or connected with exposure to the product candidate (or prior or concurrent exposure to other products or product candidates), difficulty in enrolling and maintaining subjects in a clinical trial, clinical trial design that may not make it possible to enroll or retain a sufficient number of patients to achieve a statistically significant result or the desired level of statistical significance for the endpoint in question, lack of sufficient supplies of the product candidate or comparator drug, and the failure of clinical investigators, trial monitors, contractors, consultants, or trial subjects to comply with the trial plan, protocol, or applicable regulations related to the FDA's GLPs or GCPs.
Under our arrangement with Bayer, pricing and reimbursement for EYLEA outside the United States is the responsibility of Bayer. Similarly, under our Antibody Collaboration with Sanofi, pricing and reimbursement for the products commercialized or co-commercialized thereunder outside the United States are the responsibility of Sanofi.
Under our arrangement with Bayer, pricing and reimbursement for EYLEA HD and EYLEA outside the United States is the responsibility of Bayer. Similarly, under our Antibody Collaboration with Sanofi, pricing and reimbursement for the products commercialized or co-commercialized thereunder outside the United States are the responsibility of Sanofi.
While we have established our own sales and marketing organization for EYLEA in the United States for its currently approved indications, we have no sales, marketing, commercial, or distribution capabilities for EYLEA outside the United States.
While we have established our own sales and marketing organization for EYLEA HD and EYLEA in the United States for its currently approved indications, we have no sales, marketing, commercial, or distribution capabilities for EYLEA HD or EYLEA outside the United States.
The applicable regulations in countries outside the U.S. grant similar powers to the competent authorities and impose similar obligations on companies. 59 Table of Contents In addition to FDA and related regulatory requirements, we are subject to health care "fraud and abuse" laws, such as the federal civil False Claims Act, the anti-kickback provisions of the federal Social Security Act, and other state and federal laws and regulations.
The applicable regulations in countries outside the U.S. grant similar powers to the competent authorities and impose similar obligations on companies. 58 Table of Contents In addition to FDA and related regulatory requirements, we are subject to health care "fraud and abuse" laws, such as the federal civil False Claims Act, the anti-kickback provisions of the federal Social Security Act, and other state and federal laws and regulations.
Risks Related to Our Reliance on or Transactions with Third Parties If our Antibody Collaboration with Sanofi is terminated, or Sanofi materially breaches its obligations thereunder, our business, prospects, operating results, and financial condition, and our ability to develop, manufacture, and commercialize certain of our products and product candidates in the time expected, or at all, would be materially harmed.
Risks Related to Our Reliance on or Transactions with Third Parties If our Antibody Collaboration with Sanofi is terminated, or Sanofi materially breaches its obligations thereunder, our business, prospects, operating results, and financial condition, and our ability to develop, manufacture, and commercialize certain of our products and product candidates in the time expected, or at all, may be materially harmed.
In addition, our employees may knowingly or inadvertently make use of social media in ways that may not comply with our social media policy or other legal or contractual requirements, which may give rise to liability, lead to the loss of trade secrets or other intellectual property, or result in public exposure of personal data of our employees, clinical trial patients, customers, and others.
In addition, our employees may knowingly or inadvertently make use of social media in ways that may not comply with our social media policy or other legal or contractual requirements, which may give rise to liability, lead to the loss of trade secrets or other intellectual property, or result in public exposure of personal data of our employees, clinical trial participants, customers, and others.
Although we do not believe that any of our products or our late-stage antibody-based product candidates infringe any valid claim in these patents or patent applications, these other parties could initiate lawsuits for patent infringement and assert that their patents are valid and cover our products or our late-stage antibody-based product candidates, similar to the patent infringement proceedings referred to above.
Although we do not believe that any of our products or our late-stage product candidates infringe any valid claim in these patents or patent applications, these other parties could initiate lawsuits for patent infringement and assert that their patents are valid and cover our products or our late-stage product candidates, similar to the patent infringement proceedings referred to above.
Future sales of our Common Stock by our significant shareholders or us may depress our stock price and impair our ability to raise funds in new share offerings. A small number of our shareholders beneficially own a substantial amount of our Common Stock. As of December 31, 2022, our five largest shareholders plus Dr.
Future sales of our Common Stock by our significant shareholders or us may depress our stock price and impair our ability to raise funds in new share offerings. A small number of our shareholders beneficially own a substantial amount of our Common Stock. As of December 31, 2023, our five largest shareholders plus Dr.
Starting in 2023, manufacturers must pay refunds to Medicare for single-source drugs or biological products, or biosimilar biological products, reimbursed under Medicare Part B and packaged in single-dose containers or single-use packages for units of discarded drug reimbursed by Medicare Part B in excess of 10 percent of total allowed charges under Medicare Part B for that drug.
Manufacturers must pay refunds to Medicare for single-source drugs or biological products, or biosimilar biological products, reimbursed under Medicare Part B and packaged in single-dose containers or single-use packages for units of discarded drug reimbursed by Medicare Part B in excess of 10 percent of total allowed charges under Medicare Part B for that drug.
We also rely on Sanofi for sales, marketing, and distribution of Dupixent in countries outside the United States. While we exercised our option under the Antibody Collaboration to co-commercialize Dupixent in certain jurisdictions outside the United States, we will continue to rely in part on Sanofi's sales and marketing organization in such jurisdictions.
We also rely on Sanofi for sales, marketing, and distribution of Dupixent in many countries outside the United States. While we exercised our option under the Antibody Collaboration to co-commercialize Dupixent in certain jurisdictions outside the United States, we will continue to rely in considerable part on Sanofi's sales and marketing organization in such jurisdictions.
There are several other potentially competitive products in development that may compete with Dupixent in asthma, as well as potential future indications, including antibodies against the IL-33 ligand or receptor. Dupixent also faces competition from inhaled products in asthma and potential future indications. Libtayo. Libtayo also faces significant competition.
There are several other potentially competitive products in development that may compete with Dupixent in asthma, as well as potential future indications, including antibodies against the IL-33 ligand. Dupixent also faces competition from inhaled products in asthma and potential future indications. Libtayo. Libtayo also faces significant competition.
All aspects of our business, including research and development, manufacturing, marketing, pricing, sales, intellectual property rights, and the framework for dispute resolution and asserting our rights against others, are subject to extensive legislation and regulation. Changes in applicable federal and state laws and agency regulations could have a materially negative impact on our business.
All aspects of our business, including research and development, manufacturing, marketing, pricing, sales, intellectual property rights, and the framework for dispute resolution and asserting our rights against others, are subject to extensive legislation and regulation. Changes in applicable U.S. federal, state, and foreign laws and agency regulations could have a materially negative impact on our business.
These risks include: • unfamiliar foreign laws or regulatory requirements or unexpected changes to those laws or requirements, including those with which we and/or our collaborators must comply in order to maintain our marketing authorizations outside the United States; • other laws and regulatory and industry trade association requirements to which our business activities abroad are subject, such as the FCPA and the U.K.
These risks include: • unfamiliar foreign laws or regulatory requirements or unexpected changes to those laws or requirements, including those with which we and/or our collaborators must comply in order to maintain our marketing authorizations outside the United States, and the cost of compliance with such foreign laws and regulatory requirements; • other laws and regulatory and industry trade association requirements to which our business activities abroad are subject, such as the FCPA and the U.K.
Parallel traders (who may repackage or otherwise alter the original product or sell it through alternative channels such as mail order or the Internet) take advantage of 46 Table of Contents the price differentials between markets arising from factors including sales costs, market conditions (such as intermediate trading stages), tax rates, or national regulation of prices.
Parallel traders (who may repackage or otherwise alter the original product or sell it through alternative channels such as mail order or the Internet) take advantage of the price differentials between markets arising from factors including sales costs, market conditions (such as intermediate trading stages), tax rates, or national regulation of prices.
In addition, there are risks inherent in intravenous administration (which are used for some of our antibody-based products and product candidates), such as infusion-related reactions (including nausea, pyrexia, rash, and dyspnea). These and other 52 Table of Contents complications or side effects could harm further development and/or commercialization of our antibody-based products and product candidates utilizing this method of administration.
In addition, there are risks inherent in intravenous administration (which are used for some of our antibody-based products and product candidates), such as infusion-related reactions (including nausea, pyrexia, rash, and dyspnea). These and other complications or side effects could harm further development and/or commercialization of our antibody-based products and product candidates utilizing this method of administration.
The FDA may also require us to conduct additional clinical trials after granting approval of a product. The FDA has the explicit authority to require post-marketing studies (also referred to as post-approval or Phase 4 studies), labeling changes based on new 48 Table of Contents safety information, and compliance with FDA-approved risk evaluation and mitigation strategies.
The FDA may also require us to conduct additional clinical trials after granting approval of a product. The FDA has the explicit authority to require post-marketing studies (also referred to as post-approval or Phase 4 studies), labeling changes based on new safety information, and compliance with FDA-approved risk evaluation and mitigation strategies.
This could significantly increase the resources and time required to bring a particular combination product to market. 53 Table of Contents Risks Related to Intellectual Property and Market Exclusivity For purposes of this subsection, references to our intellectual property (including patents, trademarks, copyrights, and trade secrets) include that of our collaborators and licensees, unless otherwise stated or required by the context.
This could significantly increase the resources and time required to bring a particular combination product to market. Risks Related to Intellectual Property and Market Exclusivity For purposes of this subsection, references to our intellectual property (including patents, trademarks, copyrights, and trade secrets) include that of our collaborators and licensees, unless otherwise stated or required by the context.
In addition to the GDPR, certain EU Member States have issued or will be issuing their own implementation legislation. In June 2021, the European Commission introduced new standard contractual clauses required to be incorporated into certain new and existing agreements within prescribed timeframes in order to continue to lawfully transfer personal data outside the EU.
In addition to the GDPR, certain EU Member States have issued or will be issuing their own implementation legislation. In June 2021, the EC introduced new standard contractual clauses required to be incorporated into certain new and existing agreements within prescribed timeframes in order to continue to lawfully transfer personal data outside the EU.
In addition, in order for private insurance and governmental payors (such as Medicare and Medicaid in the United States) to reimburse the cost of our marketed products, we must maintain, among other things, our FDA registration and our National Drug Code, formulary approval by PBMs, and recognition by insurance companies and CMS.
In addition, in order for private insurance and governmental payors (such as Medicare and Medicaid in the United States) to reimburse the cost of our marketed products, we must maintain, among other things, our FDA registration and our National Drug 42 Table of Contents Code, formulary approval by PBMs, and recognition by insurance companies and CMS.
We are also aware of a number of companies working on the development of product candidates and extended delivery devices for the potential treatment of one or more of EYLEA's indications, including those that act by blocking VEGF and VEGF receptors (including therapies designed to extend the treatment interval) and/or other targets.
We are also aware of a number of companies working on the development of product candidates and extended delivery devices for the potential treatment of one or more of EYLEA's and EYLEA HD's respective indications, including those that act by blocking VEGF and VEGF receptors (including therapies designed to extend the treatment interval) and/or other targets.
Loss of regulatory approval or clearance of a device that is used with our product may also result in the removal of our product from the market. Further, failure to successfully develop or supply and manufacture these devices, or to gain or maintain their approval, could adversely affect sales of the related products.
Loss of regulatory approval or clearance of a device that is used with our product may also result in the removal of our product from the 52 Table of Contents market. Further, failure to successfully develop or supply and manufacture these devices, or to gain or maintain their approval, could adversely affect sales of the related products.
If these service providers do not perform their services adequately, sales of our marketed products will suffer. We have undertaken and may in the future undertake strategic acquisitions, and any difficulties from integrating such acquisitions could adversely affect our business, operating results, and financial condition.
If these service providers do not perform their services adequately, sales of our marketed products will suffer. 65 Table of Contents We have undertaken and may in the future undertake strategic acquisitions, and any difficulties from integrating such acquisitions could adversely affect our business, operating results, and financial condition.
See the risk factor above captioned " Our existing shareholders may be able to exert substantial influence over matters requiring shareholder approval and over our management. " Further, certain of our collaborators are currently bound by "standstill" provisions under their respective agreements with us.
See the risk factor above captioned " Our existing shareholders may be able to exert substantial influence over matters requiring shareholder approval and over our management. " Further, certain of our current or former collaborators are currently bound by "standstill" provisions under their respective agreements with us.
In asthma, competitors to Dupixent include antibodies against the IL-5 ligand or the IL-5 receptor, immunoglobulin E, or thymic stromal lymphopoietin ("TSLP"); and some of these antibodies are either approved or in development for indications that also compete or may compete in the future with Dupixent in CRSwNP and EoE.
In asthma, competitors to Dupixent include antibodies against the IL-5 ligand or the IL-5 receptor, immunoglobulin E, or thymic stromal lymphopoietin 44 Table of Contents ("TSLP"); and some of these antibodies are either approved or in development for indications that also compete or may compete in the future with Dupixent in CRSwNP and EoE.
Moreover, other parties may allege that they have blocking patents to antibody-based products 54 Table of Contents made using our VelocImmune technology, or any other of our technologies, either because of the way the antibodies are discovered or produced or because of a proprietary composition covering an antibody or the antibody's target.
Moreover, other parties may allege that they have blocking patents to antibody-based products made using our VelocImmune technology, or any other of our technologies, either because of the way the antibodies are discovered or produced or because of a proprietary composition covering an antibody or the antibody's target.
In addition, these five shareholders plus our Chief Executive Officer held approximately 46.6% of the combined voting power of our outstanding shares of Common Stock and Class A Stock, assuming the exercise of all options held by our Chief Executive Officer which are exercisable within 60 days of December 31, 2022. 72 Table of Contents The anti-takeover effects of provisions of our charter, by-laws, and of New York corporate law, as well as the contractual provisions in our investor and collaboration agreements and certain provisions of our compensation plans and agreements, could deter, delay, or prevent an acquisition or other "change of control" of us and could adversely affect the price of our Common Stock.
In addition, these five shareholders plus our Chief Executive Officer held approximately 46.5% of the combined voting power of our outstanding shares of Common Stock and Class A Stock, assuming the exercise of all options held by our Chief Executive Officer which are exercisable within 60 days of December 31, 2023. 69 Table of Contents The anti-takeover effects of provisions of our charter, by-laws, and of New York corporate law, as well as the contractual provisions in our investor and collaboration agreements and certain provisions of our compensation plans and agreements, could deter, delay, or prevent an acquisition or other "change of control" of us and could adversely affect the price of our Common Stock.
For additional information regarding our collaborations with Bayer and Sanofi, see "Risks Related to Our Reliance on or Transactions with Third Parties - If our collaboration with Bayer for EYLEA is terminated, or Bayer materially breaches its obligations thereunder, our business, prospects, operating results, and financial condition, and our ability to continue to commercialize EYLEA outside the United States would be materially harmed " below and "Risks Related to Our Reliance on or Transactions with Third Parties - If our Antibody Collaboration with Sanofi is terminated, or Sanofi materially breaches its obligations thereunder, our business, prospects, operating results, and financial condition, and our ability to develop, manufacture, and commercialize certain of our products and product candidates in the time expected, or at all, would be materially harmed " below.
For additional information regarding our collaborations with Bayer and Sanofi, see "Risks Related to Our Reliance on or Transactions with Third Parties - If our collaboration with Bayer for EYLEA HD and EYLEA is terminated, or Bayer materially breaches its obligations thereunder, 45 Table of Contents our business, prospects, operating results, and financial condition, and our ability to continue to commercialize EYLEA HD and EYLEA outside the United States would be materially harmed " below and "Risks Related to Our Reliance on or Transactions with Third Parties - If our Antibody Collaboration with Sanofi is terminated, or Sanofi materially breaches its obligations thereunder, our business, prospects, operating results, and financial condition, and our ability to develop, manufacture, and commercialize certain of our products and product candidates in the time expected, or at all, may be materially harmed " below.
These developments may also result in our inability to access sites for monitoring or to obtain data from affected sites or patients going forward. We could also experience disruptions in our supply chain or limits to our ability to provide sufficient investigational materials in Ukraine and surrounding regions.
These developments may also result in our inability to access sites for monitoring or to obtain data from affected sites or patients going forward. We could also experience disruptions in our supply chain or limits to our ability to provide sufficient investigational materials in such countries and surrounding regions.
Data security breaches could lead to the loss of trade secrets or other intellectual property, result in demands for ransom or other forms of blackmail, or lead to the public exposure of personal information (including sensitive personal information) of our employees, clinical trial patients, customers, and others.
Data security breaches could lead to the loss of trade secrets or other intellectual property, 66 Table of Contents result in demands for ransom or other forms of blackmail, or lead to the public exposure of personal information (including sensitive personal information) of our employees, clinical trial patients, customers, and others.
Civil monetary penalties can be applied if we are found to have knowingly submitted any false price or product information to the government, if we are found to have made a misrepresentation in the reporting of our average sales price, if we fail to submit the required price data on a timely basis, or if we are found to have charged 340B covered entities more than the statutorily mandated ceiling price.
Civil monetary penalties can be applied if we fail to pay the required rebate, if we are found to have knowingly submitted any false price or product information to the government, if we are found to have made a misrepresentation in the reporting of our average sales price, if we fail to submit the required price data on a timely basis, or if we are found to have knowingly and intentionally charged 340B covered entities more than the statutorily mandated ceiling price.
Obtaining FDA approval for a new drug or indication is typically a lengthy and expensive process, and approval is highly uncertain. We cannot predict with certainty if or when we might submit for regulatory approval for any of our product candidates currently under development.
Obtaining FDA or comparable foreign regulatory authority approval for a new drug or indication is typically a lengthy and expensive process, and approval is highly uncertain. We cannot predict with certainty if or when we might submit for regulatory approval for any of our product candidates currently under development.
Congressional inquiries and recently approved or proposed federal and state legislation and policies (in addition to those already in effect) designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the out-of-pocket cost of prescription drugs, and reform government program reimbursement methodologies for drugs. Notably, the U.S.
Congressional inquiries and recently approved or proposed federal and state legislation, regulations, and policies (in addition to those already in effect) designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the out-of-pocket cost of prescription drugs, and reform government program reimbursement methodologies for drugs.
Commercialization Risks • We are substantially dependent on the success of EYLEA and Dupixent. • Sales of our products are dependent on the availability and extent of reimbursement from third-party payors, including private payors and government programs such as Medicare and Medicaid, which could change due to various factors such as drug price control measures that have been or may be enacted or introduced in the United States by various federal and state authorities. • The commercial success of our products is subject to significant competition from products or product candidates that may be superior to, or more cost effective than, our products or product candidates. • We and our collaborators on which we rely to commercialize some of our marketed products may be unable to continue to successfully commercialize or co-commercialize our products, both in the United States and abroad.
Commercialization Risks • We are substantially dependent on the success of EYLEA, EYLEA HD, and Dupixent. • Sales of our products are dependent on the availability and extent of coverage and reimbursement from third-party payors, including private payors and government programs such as Medicare and Medicaid. • Product reimbursement and coverage policies and practices could change due to various factors such as drug price control measures that have been or may be enacted or introduced in the United States by various federal and state authorities. • The commercial success of our products is subject to significant competition from products or product candidates that may be superior to, or more established or cost effective than, our products or product candidates. • We and our collaborators on which we rely to commercialize some of our marketed products may be unable to continue to successfully commercialize or co-commercialize our products, both in and outside the United States.
If any of our existing collaborators or service providers breaches or terminates its agreement with us or does not perform its development or manufacturing services under an agreement in a timely manner (including as a result of its inability to perform due to financial or other relevant constraints, such as due to Russia's invasion of Ukraine) or in compliance with applicable GMPs, GLPs, or GCP standards, we could experience additional costs, delays, and difficulties in the manufacture or development of, or in obtaining approval by regulatory authorities for, or successfully commercializing our product candidates.
If any of our existing collaborators or service providers breaches or terminates its agreement with us or does not perform its development or manufacturing services under an agreement in a timely manner (including as a result of its inability to perform due to financial or other relevant constraints, such as due to the armed conflict between Russia and Ukraine) or in compliance with applicable GMPs, GLPs, or GCP standards, we could experience additional costs, delays, and difficulties in the manufacture or development of, or in obtaining approval by regulatory authorities for, or successfully commercializing our product candidates.
If these entities do not provide coverage and reimbursement with respect to 43 Table of Contents our marketed products or provide an insufficient level of coverage and reimbursement, such products may be too costly for many patients to afford them, and physicians may not prescribe them.
If these entities do not provide coverage and reimbursement with respect to our marketed products or provide an insufficient level of coverage and reimbursement, such products may be too costly for many patients to afford them, and physicians may not prescribe them.
Our indebtedness could adversely impact our business. We have certain indebtedness and contingent liabilities, including milestone and royalty payment obligations. As of December 31, 2022, we had an aggregate of $2.701 billion of outstanding indebtedness under our senior unsecured notes and the lease financing facility. We may also incur additional debt in the future.
Our indebtedness could adversely impact our business. We have certain indebtedness and contingent liabilities, including milestone and royalty payment obligations. As of December 31, 2023, we had an aggregate of $2.703 billion of outstanding indebtedness under our senior unsecured notes and the lease financing facility. We may also incur additional debt in the future.
A REMS may include various elements, ranging from a medication guide or patient package insert to limitations on who may prescribe or dispense the drug, depending on what the FDA considers necessary for the safe use of the drug.
A REMS may include various elements, ranging from a medication guide or patient package 47 Table of Contents insert to limitations on who may prescribe or dispense the drug, depending on what the FDA considers necessary for the safe use of the drug.
Furthermore, health privacy laws, data breach notification laws, consumer protection laws, data localization laws, and genetic privacy laws may apply directly to our operations and/or those of our collaborators and may impose restrictions on our collection, use, and dissemination of individuals' health and other personal data.
Furthermore, health privacy laws, data breach notification laws, consumer protection laws, data localization laws, biometric privacy laws, and genetic privacy laws may apply directly to our operations and/or those of our collaborators and business partners and may impose restrictions on our collection, use, and dissemination of individuals' health and other personal data.
Sales of our marketed products in other countries are dependent, in large part, on similar reimbursement mechanisms and programs in those countries. Our future revenues and profitability will be adversely affected in a material manner if such third-party payors do not adequately defray or reimburse the cost of our marketed products.
Sales of our marketed products in other countries are also dependent, in large part, on complex coverage and reimbursement mechanisms and programs in those countries. Our future revenues and profitability will be adversely affected in a material manner if such third-party payors do not adequately defray or reimburse the cost of our marketed products.
There are several competitors that are marketing and/or developing antibodies against PD-1 and/or PDL-1 (some of which were approved in the relevant indications and commercialized before Libtayo), including Merck's Keytruda, Bristol-Myers Squibb's Opdivo, Roche's Tecentriq, and AstraZeneca's Imfinzi. Other marketed products.
There are several competitors that are marketing and/or developing antibodies against PD-1 and/or PDL-1 (some of which were approved in the relevant indications and commercialized before Libtayo), including Merck's Keytruda ® (pembrolizumab), Bristol-Myers Squibb's Opdivo ® (nivolumab), Roche's Tecentriq ® (atezolizumab), and AstraZeneca's Imfinzi ® (durvalumab). Other marketed products.
We sell our marketed products for which we record net product sales in the United States to several distributors and specialty pharmacies, as applicable, which generally sell the product directly to healthcare providers or other pharmacies (as applicable).
We sell our marketed products for which we record net product sales in the United States to several distributors and specialty pharmacies, as applicable (collectively, "distributor customers"), which generally sell the product directly to healthcare providers or other pharmacies (as applicable).
Broad market fluctuations may also adversely affect the market price of our Common Stock. In the past, securities class action litigation has often been initiated against companies following periods of volatility in their stock 71 Table of Contents price.
Broad market fluctuations may also adversely affect the market price of our Common Stock. In the past, securities class action litigation has often been initiated against companies following periods of volatility in their stock price.
Schleifer, our Chief Executive Officer, beneficially owned approximately 39.4% of our outstanding shares of Common Stock, assuming, in the case of our Chief Executive Officer, the conversion of his Class A Stock into Common Stock and the exercise of all options held by him which are exercisable within 60 days of December 31, 2022.
Schleifer, our Chief Executive Officer, beneficially owned approximately 39.3% of our outstanding shares of Common Stock, assuming, in the case of our Chief Executive Officer, the conversion of his Class A Stock into Common Stock and the exercise of all options held by him which are exercisable within 60 days of December 31, 2023.
Schleifer, our Chief Executive Officer, beneficially owned approximately 39.4% of our outstanding shares of Common Stock, assuming, in the case of our Chief Executive Officer, the conversion of his Class A Stock into Common Stock and the exercise of all options held by him which are exercisable within 60 days of December 31, 2022.
Schleifer, our Chief Executive Officer, beneficially owned approximately 39.3% of our outstanding shares of Common Stock, assuming, in the case of our Chief Executive Officer, the conversion of his Class A Stock into Common Stock and the exercise of all options held by him which are exercisable within 60 days December 31, 2023.
Any of our ongoing clinical trials may be discontinued or amended in response to 51 Table of Contents recommendations made by responsible IDMCs based on their review of such interim trial results.
Any of our ongoing clinical trials may be discontinued or amended in response to recommendations made by responsible IDMCs based on their review of such interim trial results.
Changes of suppliers or modifications of methods of manufacturing may require amending our application(s) to the FDA or such comparable foreign agencies and acceptance of the change by the FDA or such comparable foreign agencies prior to release of product(s).
Changes of suppliers or 57 Table of Contents modifications of methods of manufacturing may require amending our application(s) to the FDA or such comparable foreign agencies and acceptance of the change by the FDA or such comparable foreign agencies prior to release of product(s).
We also have similar reporting obligations in other countries based on laws, regulations, and/or industry trade association requirements. We continue to dedicate significant resources to comply with these requirements and need to be prepared to comply with additional reporting obligations outside the United States that may apply in the future.
We also have similar reporting obligations in other countries based on laws, regulations, and/or industry trade association requirements. We continue to dedicate significant resources to comply with these requirements and need to be prepared to comply with additional reporting obligations outside the United States.
Obligations equivalent in scope, but which can vary widely in application, apply in foreign countries. According to the FDA policies under the Prescription Drug User Fee Act, the FDA system of review times for new drugs includes standard review and priority review.
Obligations equivalent in scope, but which can vary widely in application, apply in countries outside the United States. According to the FDA policies under the Prescription Drug User Fee Act, the FDA system of review times for new drugs includes standard review and priority review.
There is the potential that our systems may be directly or indirectly affected as nation-states conduct global cyberwarfare, including in connection with the current Russia-Ukraine hostilities. Due to the nature of some of these attacks, there is a risk that an attack may remain undetected for a period of time.
There is the potential that our systems may be directly or indirectly affected as nation-states conduct global cyberwarfare, including in connection with the current Russia-Ukraine or Hamas-Israel armed conflict. Due to the nature of some of these attacks, there is a risk that an attack may remain undetected for a period of time.
In order to commercialize or co-commercialize any products outside the United States, we must build our sales, marketing, distribution, regulatory, managerial, and other capabilities in the relevant markets or make arrangements with third parties to perform these services, any of which will likely be expensive and time consuming and could delay product launch or the co-commercialization of a product in one or more markets outside the United States.
In order to commercialize or co-commercialize any products outside the United States beyond what we have done so far, we must build our sales, marketing, distribution, regulatory, managerial, and other capabilities in the relevant markets or make arrangements with third parties to perform these services, any of which will likely be expensive and time consuming and could delay product launch or the co-commercialization of a product in one or more markets outside the United States.
In addition, commercialization of EYLEA or our other products and potential future commercialization of aflibercept 8 mg or our other product candidates may be impacted by actions of third parties on which we rely, such as manufacturers of syringes or other devices used in the administration of our products.
In addition, commercialization of EYLEA and EYLEA HD or our other products and potential future commercialization of our product candidates may be impacted by actions of third parties on which we rely, such as manufacturers of syringes or other devices used in the administration of our products.
In some foreign countries, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements 44 Table of Contents governing drug pricing and reimbursement vary widely from country to country, and may take into account the clinical effectiveness, cost, and service impact of existing, new, and emerging drugs and treatments.
In some of these countries, the proposed pricing for a drug must be approved before it may be lawfully marketed. The requirements governing drug pricing and reimbursement vary widely from country to country, and may take into account the clinical effectiveness, cost, and service impact of existing, new, and emerging drugs and treatments.
Additionally, the FDA may determine that a REMS is necessary to ensure that the benefits of a new product outweigh its risks, and the product can therefore be approved.
Additionally, in the United States, the FDA may determine that a REMS is necessary to ensure that the benefits of a new product outweigh its risks, and the product can therefore be approved.
The foreign regulatory approval process is similarly a lengthy and expensive process, the result of which is highly uncertain, and foreign regulatory requirements include all of the risks associated with FDA approval as well as country specific regulations. We and our collaborators must maintain regulatory compliance for the products we or they commercialize in foreign jurisdictions.
The foreign regulatory approval process is similarly a lengthy and expensive process, the result of which is highly uncertain, and foreign regulatory requirements include all of the risks associated with FDA approval as well as country specific regulations. We and our collaborators must maintain regulatory compliance for the products we or they commercialize in countries outside the United States.
Conversely, if the U.S. dollar strengthens against a specific foreign currency, our revenues will decrease, having a negative impact on net income, but our overall expenses will decrease, having a positive impact. Therefore, significant changes in foreign exchange rates can impact our operating results and the financial condition of our Company. See Part II, Item 7.
Conversely, if the U.S. dollar strengthens against a specific foreign currency, our revenues will decrease, having a negative impact on net income, but our overall expenses will decrease, having a positive impact. Therefore, significant changes in foreign exchange rates can impact our operating results and the financial condition of our Company.
For example, we previously discontinued actively treating patients with fasinumab following a recommendation from the responsible IDMC that the program be terminated based on available evidence to date; and we later discontinued further clinical development of fasinumab.
For example, we previously discontinued actively treating patients with fasinumab following a recommendation from the responsible IDMC that the program be terminated based on available evidence at that time; and we later discontinued further clinical development of fasinumab.
As of December 31, 2022: • our current executive officers and directors beneficially owned 7.1% of our outstanding shares of Common Stock, assuming conversion of their Class A Stock into Common Stock and the exercise of all options held by such persons which are exercisable within 60 days of December 31, 2022, and 18.5% of the combined voting power of our outstanding shares of Common Stock and Class A Stock, assuming the exercise of all options held by such persons which are exercisable within 60 days of December 31, 2022; and • our five largest shareholders plus Dr.
As of December 31, 2023: • our current executive officers and directors beneficially owned 6.1% of our outstanding shares of Common Stock, assuming conversion of their Class A Stock into Common Stock and the exercise of all options held by such persons which are exercisable within 60 days of December 31, 2023, and 17.7% of the combined voting power of our outstanding shares of Common Stock and Class A Stock, assuming the exercise of all options held by such persons which are exercisable within 60 days of December 31, 2023; and • our five largest shareholders plus Dr.
If we are unable to establish commercial capabilities outside the United States for products we intend to commercialize or co-commercialize outside the United States, our business, prospects, operating results, and financial condition may be adversely affected.
If we are unable to establish commercial capabilities outside the United States for Libtayo, Dupixent, and any other products we intend to commercialize or co-commercialize outside the United States, our business, prospects, operating results, and financial condition may be adversely affected.
Some states are also considering legislation that would control the prices and reimbursement of prescription drugs, and state Medicaid programs are increasingly requesting manufacturers to pay supplemental rebates and requiring prior authorization by the state program for use of any prescription drug for which supplemental rebates are not being paid.
Some states have also enacted or are considering legislation to control the prices and reimbursement of prescription drugs, and state Medicaid programs are increasingly requesting manufacturers to pay supplemental rebates and requiring prior authorization by the state program for use of any prescription drug for which supplemental rebates are not being paid.

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Item 2. Properties

Properties — owned and leased real estate

2 edited+1 added−1 removed2 unchanged
Biggest changeLimerick, Ireland We own a facility in Limerick, Ireland totaling approximately 555,000 square feet of manufacturing, warehouse, laboratory, and office space. Item 3. Legal Proceedings The information called for by this item is incorporated herein by reference to the information set forth in Note 16 to our Consolidated Financial Statements included in this report. Item 4.
Biggest changeLegal Proceedings The information called for by this item is incorporated herein by reference to the information set forth in Note 16 to our Consolidated Financial Statements included in this report. Item 4. Mine Safety Disclosures Not applicable. 71 Table of Contents PART II
We also own an approximate 100-acre parcel of land adjacent to our Tarrytown, New York location, which we are in the process of developing, primarily in connection with expanding our research and support facilities to accommodate our growth. Rensselaer, New York We own facilities in Rensselaer, New York totaling approximately 1,189,000 square feet of manufacturing, research, office, and warehouse space.
We also own an approximate 100-acre parcel of land adjacent to our Tarrytown, New York location, which we are in the process of developing, primarily in connection with expanding our research and support facilities to accommodate our growth. Rensselaer, New York We own facilities in Rensselaer, New York totaling approximately 1,260,000 square feet of manufacturing, research, office, and warehouse space.
Removed
This includes approximately 452,000 square feet of warehouse, laboratory, and office space which we 73 Table of Contents constructed on a 130-acre parcel of land near our Rensselaer facility. We are in the process of further developing this property, primarily in connection with constructing a fill/finish facility.
Added
In addition, we have constructed an approximately 341,000 square foot fill/finish facility in Rensselaer, New York that is undergoing process validation as required by regulatory authorities. Limerick, Ireland We own a facility in Limerick, Ireland totaling approximately 555,000 square feet of manufacturing, warehouse, laboratory, and office space. Item 3.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

5 edited+0 added−1 removed2 unchanged
Biggest changeThe historical stock price performance of our Common Stock shown in the graph below is not necessarily indicative of future stock price performance. 74 Table of Contents 12/31/2017 12/31/2018 12/31/2019 12/31/2020 12/31/2021 12/31/2022 Regeneron $ 100.00 $ 99.35 $ 99.87 $ 128.50 $ 167.98 $ 191.91 S&P 500 $ 100.00 $ 93.76 $ 120.84 $ 140.49 $ 178.27 $ 143.61 NQ US Pharma TR Index $ 100.00 $ 106.80 $ 122.30 $ 135.17 $ 168.13 $ 187.21 This performance graph shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or incorporated by reference into any filing of ours under the Securities Act of 1933, as amended, or the Securities Exchange Act, except as shall be expressly set forth by specific reference to such filing. 75 Table of Contents Issuer Purchases of Equity Securities The table below reflects shares of Common Stock we repurchased under our share repurchase programs, as well as Common Stock withheld by us for employees to satisfy their tax withholding obligations arising upon the vesting of restricted stock granted under one of our long-term incentive plans, during the three months ended December 31, 2022.
Biggest changeThe historical stock price performance of our Common Stock shown in the graph below is not necessarily indicative of future stock price performance. 12/31/2018 12/31/2019 12/31/2020 12/31/2021 12/31/2022 12/31/2023 Regeneron $ 100.00 $ 100.53 $ 129.35 $ 169.08 $ 193.17 $ 235.15 S&P 500 $ 100.00 $ 128.88 $ 149.83 $ 190.13 $ 153.16 $ 190.27 NQ US Pharma TR Index $ 100.00 $ 114.51 $ 126.56 $ 157.42 $ 175.29 $ 182.08 This performance graph shall not be deemed "filed" for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or incorporated by reference into any filing of ours under the Securities Act of 1933, as amended, or the Securities Exchange Act, except as shall be expressly set forth by specific reference to such filing. 72 Table of Contents Issuer Purchases of Equity Securities The table below reflects shares of Common Stock we repurchased under our share repurchase programs, as well as Common Stock withheld by us for employees to satisfy their tax withholding obligations arising upon the vesting of restricted stock granted under one of our long-term incentive plans, during the three months ended December 31, 2023.
The comparison assumes that $100 was invested on December 31, 2017 in our Common Stock and in both of the foregoing indices. All values assume reinvestment of the pre-tax value of dividends paid by companies included in these indices.
The comparison assumes that $100 was invested on December 31, 2018 in our Common Stock and in both of the foregoing indices. All values assume reinvestment of the pre-tax value of dividends paid by companies included in these indices.
STOCK PERFORMANCE GRAPH Set forth below is a line graph comparing the cumulative total shareholder return on Regeneron's Common Stock with the cumulative total return of (i) the NASDAQ US Benchmark Pharmaceuticals Total Return Index ("NQ US Pharma TR Index"), and (ii) Standard & Poor's 500 Stock Index ("S&P 500") for the period from December 31, 2017 through December 31, 2022.
STOCK PERFORMANCE GRAPH Set forth below is a line graph comparing the cumulative total shareholder return on Regeneron's Common Stock with the cumulative total return of (i) the NASDAQ US Benchmark Pharmaceuticals Total Return Index ("NQ US Pharma TR Index"), and (ii) Standard & Poor's 500 Stock Index ("S&P 500") for the period from December 31, 2018 through December 31, 2023.
As of January 26, 2023, there were 161 shareholders of record of our Common Stock and 14 shareholders of record of our Class A Stock. We have never paid cash dividends on our Common Stock or Class A Stock and do not anticipate paying any in the foreseeable future.
As of January 25, 2024, there were 153 shareholders of record of our Common Stock and 14 shareholders of record of our Class A Stock. We have never paid cash dividends on our Common Stock or Class A Stock and do not currently have plans to do so.
Period Total Number of Shares Purchased Average Price Paid per Share Total Number of Shares Purchased as Part of Publicly Announced Programs Approximate Dollar Value of Shares that May Yet Be Purchased Under the Programs (b) (in millions) 10/1/2022–10/31/2022 48,078 $ 719.10 48,078 $ 1,151.7 11/1/2022–11/30/2022 236,526 $ 737.86 234,834 $ 978.4 12/1/2022–12/31/2022 418,427 $ 737.15 317,470 $ 745.2 Total 703,031 (a) 600,382 (a) (a) The difference between the total number of shares purchased and the total number of shares purchased as part of publicly announced programs relates to Common Stock withheld by us for employees to satisfy their tax withholding obligations arising upon the vesting of restricted stock granted under one of our long-term incentive plans.
Period Total Number of Shares Purchased Average Price Paid per Share Total Number of Shares Purchased as Part of Publicly Announced Programs Approximate Dollar Value of Shares that May Yet Be Purchased Under the Programs (In millions) 11/1/2023–11/30/2023 272,952 $ 802.55 269,976 $ 1,609.1 12/1/2023–12/31/2023 558,642 $ 849.22 93,108 $ 1,530.6 Total 831,594 (a) 363,084 (a) (a) The difference between the total number of shares purchased and the total number of shares purchased as part of publicly announced programs relates to Common Stock withheld by us for employees to satisfy their tax withholding obligations arising upon the vesting of restricted stock granted under one of our long-term incentive plans.
Removed
(b) In January 2023, our board of directors authorized a new share repurchase program to repurchase up to an additional $3.0 billion of our Common Stock. See Item 7. "Liquidity and Capital Resources - Share Repurchase Programs" for further details. 76 Table of Contents Item 6. [Reserved]

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

86 edited+23 added−59 removed35 unchanged
Biggest changeResults of Operations Net Income Year Ended December 31, (In millions, except per share data) 2022 2021 2020 Revenues $ 12,172.9 $ 16,071.7 $ 8,497.1 Operating expenses 7,434.0 7,124.9 4,920.5 Income from operations 4,738.9 8,946.8 3,576.6 Other income (expense) 119.9 379.0 233.8 Income before income taxes 4,858.8 9,325.8 3,810.4 Income tax expense 520.4 1,250.5 297.2 Net income $ 4,338.4 $ 8,075.3 $ 3,513.2 Net income per share - diluted $ 38.22 $ 71.97 $ 30.52 80 Table of Contents Revenues Year Ended December 31, $ Change (In millions) 2022 2021 2020 2022 vs. 2021 2021 vs. 2020 Net product sales: EYLEA - U.S. $ 6,264.6 $ 5,792.3 $ 4,947.2 $ 472.3 $ 845.1 Libtayo - U.S. 374.5 306.3 270.7 68.2 35.6 Libtayo - ROW 73.0 — — * * Praluent - U.S. ** 130.0 170.0 150.9 (40.0) * REGEN-COV - U.S. — 5,828.0 185.7 (5,828.0) 5,642.3 Evkeeza - U.S. 48.6 18.4 — 30.2 18.4 Inmazeb - U.S. 3.0 — — 3.0 — ARCALYST - U.S. *** — 2.2 13.1 * * Total net product sales $ 6,893.7 $ 12,117.2 $ 5,567.6 $ (5,294.3) $ 6,541.4 Collaboration revenue: Sanofi $ 2,855.7 $ 1,902.2 $ 1,186.4 $ 953.5 $ 715.8 Bayer 1,430.7 1,409.3 1,186.1 21.4 223.2 Roche 627.3 361.8 — 265.5 361.8 Other 0.4 — — 0.4 — Other revenue 365.1 281.2 557.0 83.9 (275.8) Total revenues $ 12,172.9 $ 16,071.7 $ 8,497.1 $ (3,969.6) $ 7,566.4 * Not meaningful ** Net product sales of Praluent in the United States were recorded by Sanofi prior to April 1, 2020. *** Effective April 1, 2021, Kiniksa records net product sales of ARCALYST in the United States.
Biggest changeResults of Operations Net Income Year Ended December 31, (In millions, except per share data) 2023 2022 2021 Revenues $ 13,117.2 $ 12,172.9 $ 16,071.7 Operating expenses 9,070.1 7,434.0 7,124.9 Income from operations 4,047.1 4,738.9 8,946.8 Other income (expense) 152.2 119.9 379.0 Income before income taxes 4,199.3 4,858.8 9,325.8 Income tax expense 245.7 520.4 1,250.5 Net income $ 3,953.6 $ 4,338.4 $ 8,075.3 Net income per share - diluted $ 34.77 $ 38.22 $ 71.97 77 Table of Contents Revenues Year Ended December 31, $ Change (In millions) 2023 2022 2021 2023 vs. 2022 2022 vs. 2021 Net product sales: EYLEA HD - U.S. $ 165.8 $ — $ — $ 165.8 $ — EYLEA - U.S. 5,719.6 6,264.6 5,792.3 (545.0) 472.3 Total EYLEA HD and EYLEA - U.S. 5,885.4 6,264.6 5,792.3 (379.2) 472.3 Libtayo - U.S. 538.8 374.5 306.3 164.3 68.2 Libtayo - ROW * 324.3 73.0 — 251.3 73.0 Total Libtayo - Global 863.1 447.5 306.3 415.6 141.2 Praluent - U.S. 182.4 130.0 170.0 52.4 (40.0) REGEN-COV - U.S. — — 5,828.0 — (5,828.0) Evkeeza - U.S. 77.3 48.6 18.4 28.7 30.2 Inmazeb - U.S. 69.8 3.0 — 66.8 3.0 ARCALYST - U.S. ** — — 2.2 — (2.2) Total net product sales $ 7,078.0 $ 6,893.7 $ 12,117.2 $ 184.3 $ (5,223.5) Collaboration revenue: Sanofi $ 3,799.5 $ 2,855.7 $ 1,902.2 $ 943.8 $ 953.5 Bayer 1,487.5 1,430.7 1,409.3 56.8 21.4 Roche 211.0 627.3 361.8 (416.3) 265.5 Other 5.1 0.4 — 4.7 0.4 Other revenue 536.1 365.1 281.2 171.0 83.9 Total revenues $ 13,117.2 $ 12,172.9 $ 16,071.7 $ 944.3 $ (3,898.8) * Effective July 1, 2022, the Company became solely responsible for the research, development, and commercialization of Libtayo worldwide and began recording net product sales of Libtayo outside the United States. ** Effective April 1, 2021, Kiniksa records net product sales of ARCALYST in the United States.
Our intangible assets are reviewed for recoverability whenever events or changes in circumstances (e.g., changes in economic, regulatory, or legal conditions) indicate that the carrying amount of the asset may not be recoverable. If an indicator of impairment exists, we compare the projected undiscounted cash flows to be generated by the asset to the intangible asset's carrying amount.
Intangible assets are reviewed for recoverability whenever events or changes in circumstances (e.g., changes in economic, regulatory, or legal conditions) indicate that the carrying amount of the asset may not be recoverable. If an indicator of impairment exists, we compare the projected undiscounted cash flows to be generated by the asset to the intangible asset's carrying amount.
Clinical manufacturing costs primarily consist of costs to manufacture bulk drug product for clinical development purposes as well as related external drug filling, packaging, and labeling costs. Clinical manufacturing costs also includes pre-launch commercial supplies which did not meet the criteria to be capitalized as inventory (see "Critical Accounting Policies and Use of Estimates - Inventories" above).
Clinical manufacturing costs primarily consist of costs to manufacture bulk drug product for clinical development purposes as well as related drug filling, packaging, and labeling costs. Clinical manufacturing costs also includes pre-launch commercial supplies which did not meet the criteria to be capitalized as inventory (see "Critical Accounting Policies and Use of Estimates - Inventories" above).
The critical accounting estimates that impact our Consolidated Financial Statements are described below. Revenue Recognition - Product Revenue We recognize revenue from product sales at a point in time when our customer is deemed to have obtained control of the product, which generally occurs upon receipt or acceptance by our customer.
The critical accounting estimates that impact our Consolidated Financial Statements are described below. Product Revenue We recognize revenue from product sales at a point in time when our customer is deemed to have obtained control of the product, which generally occurs upon receipt or acceptance by our customer.
Amounts borrowed under the 2022 Credit Facility may be prepaid, and the commitments under the 2022 Credit Facility may be terminated, at any time without premium or penalty. We had no borrowings outstanding under the 2022 Credit Facility as of December 31, 2022. The 2022 Credit Agreement contains operating covenants and a maximum total leverage ratio financial covenant.
Amounts borrowed under the 2022 Credit Facility may be prepaid, and the commitments under the 2022 Credit Facility may be terminated, at any time without premium or penalty. We had no borrowings outstanding under the 2022 Credit Facility as of December 31, 2023. The 2022 Credit Agreement contains operating covenants and a maximum total leverage ratio financial covenant.
In agreements involving multiple goods or services promised to be transferred to our collaborator, we must assess, at the inception of the contract, whether each promise represents a separate obligation (i.e., is "distinct"), or whether such promises should be combined as a single unit of account.
In agreements involving multiple goods or services promised to be transferred to our collaborator, we assess, at the inception of the contract, whether each promise represents a separate obligation (i.e., is "distinct"), or whether such promises should be combined as a single unit of account.
There are numerous uncertainties associated with drug development, including uncertainties related to safety and efficacy data from each phase of drug development, uncertainties related to the enrollment and performance of clinical trials, changes in regulatory requirements, changes in the competitive landscape affecting a product candidate, and other risks and uncertainties described in Part I, Item 1A. "Risk Factors".
There are numerous uncertainties associated with drug development, including uncertainties related to safety and efficacy data from each phase of drug development, uncertainties related to the enrollment and performance of clinical trials, changes in regulatory requirements, changes in the competitive landscape affecting a product candidate, and other risks and uncertainties described in Part I, Item 1A.
During the year ended December 31, 2022, we earned two $50.0 million sales-based milestones from Sanofi, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $2.0 billion and $2.5 billion, respectively, on a rolling twelve-month basis.
During the year ended December 31, 2022, the Company earned two $50.0 million sales-based milestones from Sanofi, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $2.0 billion and $2.5 billion, respectively, on a rolling twelve-month basis.
The Restated Lease is classified as a finance lease as we have the option to purchase the Facility under terms that make it reasonably certain to be exercised. The agreements governing the Restated Lease financing contain financial and operating covenants.
The Third Amended and Restated Lease is classified as a finance lease as we have the option to purchase the Facility under terms that make it reasonably certain to be exercised. The agreements governing the Third Amended and Restated Lease financing contain financial and operating covenants.
These reimbursements are deducted each quarter, in accordance with a formula, from our share of the collaboration profits otherwise payable to us, unless, in the case of EYLEA, we elect to reimburse these expenses at a faster rate.
These reimbursements are deducted each quarter, in accordance with a formula, from our share of the collaboration profits otherwise payable to us, unless, in the case of Bayer, we elect to reimburse these expenses at a faster rate.
The Restated Participation Agreement and Restated Lease include an option for us to elect to further extend the maturity date of the Restated Participation Agreement and the term of the Restated Lease for an additional five-year period, subject to the consent of all the Participants and certain other conditions.
The Third Amended and Restated Participation Agreement and Third Amended and Restated Lease include an option for us to elect to further extend the maturity date of the Third Amended and Restated Participation Agreement and the term of the Third Amended and Restated Lease for an additional five-year period, subject to the consent of all the Participants and certain other conditions.
We also have the option prior to the end of the term of the Restated Lease to (a) purchase the Facility by paying an amount equal to the outstanding principal amount of the Participants' advances under the Restated Participation Agreement, all accrued and unpaid yield thereon, and all other outstanding amounts under the Restated Participation Agreement, Restated Lease, and certain related documents or (b) sell the Facility to a third party on behalf of the Lessor.
We also have the option prior to the end of the term of the Third Amended and Restated Lease to (a) purchase the Facility by paying an amount equal to the outstanding principal amount of the Participants' advances under the Third Amended and Restated Participation Agreement, all accrued and unpaid yield thereon, and all other outstanding amounts under the Third Amended and Restated Participation Agreement, Third Amended and Restated Lease, and certain related documents or (b) sell the Facility to a third party on behalf of BAL.
Treasury rates for 78 Table of Contents securities with maturities approximating the options' expected lives. Expected volatility is estimated based on actual movements in our stock price over the most recent historical periods equivalent to the options' expected lives. Expected lives are principally based on our historical exercise experience with previously issued employee and board of director option grants.
Treasury rates for securities with maturities approximating the options' expected lives. Expected volatility is estimated based on actual movements in our stock price over the most recent historical periods equivalent to the options' expected lives. Expected lives are principally based on our historical exercise experience with previously issued employee and board of director option grants.
Such financial covenants and certain of the operating covenants are substantially similar to the covenants set forth in our 2018 Credit Agreement. The Company was in compliance with all such covenants as of December 31, 2022.
Such financial covenants and certain of the operating covenants are substantially similar to the covenants set forth in our 2022 Credit Agreement. The Company was in compliance with all such covenants as of December 31, 2023.
We 77 Table of Contents review our estimates of rebates, chargebacks, and other applicable provisions each period and record any necessary adjustments in the current period's net product sales. Refer to the "Results of Operations - Revenues - Net Product Sales" section below for further details regarding our provisions, and credits/payments, for sales-related deductions.
We review our estimates of rebates, chargebacks, and other applicable provisions each period and record any necessary adjustments in the current period's net product sales. Refer to the "Results of Operations - Revenues - Net Product Sales" section below for further details regarding our provisions, and credits/payments, for sales-related deductions.
Refer to Part II, Item 7 in our Annual Report on Form 10-K for the fiscal year ended December 31, 2021 (filed with the SEC on February 7, 2022) for additional discussion of our financial condition and results of operations for the year ended December 31, 2020, as well as our financial condition and results of operations for the year ended December 31, 2021 compared to the year ended December 31, 2020.
Refer to Part II, Item 7 in our Annual Report on Form 10-K for the fiscal year ended December 31, 2022 (filed with the SEC on February 6, 2023) for additional discussion of our financial condition and results of operations for the year ended December 31, 2021, as well as our financial condition and results of operations for the year ended December 31, 2022 compared to the year ended December 31, 2021.
If contingent consideration is recognized subsequent to the acquisition date in an asset acquisition, the amount of such consideration is recorded as an addition to the cost basis of the 79 Table of Contents intangible asset with a cumulative catch-up adjustment for amortization expense as if the additional amount of consideration had been accrued from the outset of the acquisition.
If contingent consideration is recognized subsequent to the acquisition date in an asset acquisition, the amount of such consideration is recorded as an addition to the cost basis of the intangible asset with a cumulative catch-up adjustment for amortization expense as if the additional amount of consideration had been accrued from the outset of the acquisition.
Acquired In-process Research and Development ("IPR&D") Acquired IPR&D in 2022 included a $195.0 million charge related to our acquisition of Checkmate, a $30.0 million up-front payment in connection with our collaboration agreement with CytomX Therapeutics, Inc., and a $20.0 million opt-in payment in connection with a product candidate under our collaboration agreement with Adicet Bio, Inc.
Acquired IPR&D in 2022 included: • $195.0 million charge related to our acquisition of Checkmate Pharmaceuticals, Inc.; • $30.0 million up-front payment in connection with our collaboration agreement with CytomX Therapeutics, Inc.; and • $20.0 million opt-in payment in connection with a product candidate under our collaboration agreement with Adicet Bio, Inc.
As of December 31, 2020, the Company had repurchased the entire $1.0 billion of its Common Stock that it was authorized to repurchase under the program. In January 2021, our board of directors authorized a share repurchase program to repurchase up to $1.5 billion of our Common Stock.
As of December 31, 2021, the Company had repurchased the entire $1.5 billion of its Common Stock that it was authorized to repurchase under the program. In November 2021, our board of directors authorized a share repurchase program to repurchase up to $3.0 billion of our Common Stock.
The share repurchase program permitted the Company to make repurchases through a variety of methods, including open- 89 Table of Contents market transactions (including pursuant to a trading plan adopted in accordance with Rule 10b5-1 of the Exchange Act), privately negotiated transactions, accelerated share repurchases, block trades, and other transactions in compliance with Rule 10b-18 of the Exchange Act.
The share repurchase program permits the Company to make repurchases through a variety of methods, including open-market transactions (including pursuant to a trading plan adopted in accordance with Rule 10b5-1 of the Exchange Act), privately negotiated transactions, accelerated share repurchases, block trades, and other transactions in compliance with Rule 10b-18 of the Exchange Act.
See Note 15 to our Consolidated Financial Statements. We enter into collaboration and licensing agreements that may require us to pay (i) amounts contingent upon the occurrence of various future events (e.g., upon the achievement of various development and commercial milestones), which, in the aggregate, could be significant, and/or (ii) royalties calculated based on a percentage of net product sales.
We enter into collaboration and licensing agreements that may require us to pay (i) amounts contingent upon the occurrence of various future events (e.g., upon the achievement of various development and commercial milestones), which, in the aggregate, could be significant, and/or (ii) royalties calculated based on a percentage of net product sales.
The Company recognizes the financial statement effects of a tax position when management's assessment is that there is more than a 50% probability that the position will be sustained upon examination by a taxing authority based upon its technical merits. Uncertain tax positions are recorded based upon certain recognition and measurement criteria.
We recognize the financial statement effects of a tax position when our assessment is that there is more than a 50% probability that the position will be sustained upon examination by a taxing authority based upon its technical merits. Uncertain tax positions are recorded based upon certain recognition and measurement criteria.
In December 2022, we entered into an agreement with a syndicate of lenders (the "2022 Credit Agreement") which provides for a $750.0 million senior unsecured five-year revolving credit facility (the "2022 Credit Facility") and replaces the 2018 Credit Agreement, which was contemporaneously terminated.
Credit Facility In December 2022, we entered into an agreement with a syndicate of lenders (the "2022 Credit Agreement") which provides for a $750.0 million senior unsecured five-year revolving credit facility (the "2022 Credit Facility") and replaced the then-existing credit agreement, which was contemporaneously terminated.
In arrangements where we: • supply commercial product to our collaborator, we may be reimbursed for our manufacturing costs as commercial product is shipped to the collaborator (however, recognition of such cost reimbursements may be deferred until the product is sold by our collaborator to third-party customers); • share in any profits or losses arising from the commercialization of such products, we record our share of the variable consideration, representing net product sales less cost of goods sold and shared commercialization and other expenses, in the period in which such underlying sales occur and costs are incurred by the collaborator; and • receive royalties and/or sales-based milestone payments from our collaborator, we recognize such amounts in the period earned.
In arrangements where we: • supply commercial product to our collaborator, we may be reimbursed for our manufacturing costs as commercial product is shipped to the collaborator (however, recognition of such cost reimbursements may be deferred until the product is sold by our collaborator to third-party customers); • share in any profits or losses arising from the commercialization of such products, we record our share of the variable consideration, representing net product sales less cost of goods sold and shared commercialization and other expenses, in the period in which such underlying sales occur and costs are incurred by the collaborator; • receive royalties and/or sales-based milestone payments from our collaborator, we recognize such amounts in the period earned. 74 Table of Contents Our collaborators provide us with estimates of product sales and our share of profits or losses, as applicable, for each quarter.
Cash Flows from Investing Activities Capital expenditures in 2022 included costs associated with the expansion of our manufacturing facilities in Rensselaer, New York (including the ongoing construction of a fill/finish facility and related equipment) and Limerick, Ireland, as well as costs incurred in connection with the expansion of the Tarrytown, New York campus.
Cash Flows from Investing Activities Capital expenditures in 2023 included costs incurred in connection with the expansion of our Tarrytown, New York location, as well as costs associated with the expansion of our manufacturing facilities in Rensselaer, New York (including the ongoing construction of a fill/finish facility and related equipment).
The expected dividend yield is zero as we have never paid dividends and do not currently anticipate paying any in the foreseeable future. We use a Monte Carlo simulation to compute the estimated fair value of performance-based restricted stock units that are subject to vesting based on the Company's attainment of pre-established performance criteria that include a market condition.
The expected dividend yield is zero as we have never paid dividends and do not currently have plans to do so. We use a Monte Carlo simulation to compute the estimated fair value of performance-based restricted stock units that are subject to vesting based on the Company's attainment of pre-established criteria that include a market condition.
The amount of funding that will be required for our clinical programs depends upon the results of our research and preclinical programs and early-stage clinical trials, regulatory requirements, the duration and results of clinical trials underway and of additional clinical trials that we decide to initiate, and the various factors that affect the cost of 91 Table of Contents each trial, including the size of trials, fees charged for services provided by clinical trial investigators and other third parties, the costs for manufacturing the product candidate for use in the trials, and other expenses.
The amount of funding that will be required for our clinical programs depends upon the results of our research and preclinical programs and early-stage clinical trials, regulatory requirements, the duration and results of clinical trials underway and of additional clinical trials that we decide to initiate, and the various factors that affect the cost of each trial, including the size of trials, fees charged for services provided by clinical trial investigators and other third parties, the costs for manufacturing the product candidate for use in the trials, and other expenses. 88 Table of Contents We also anticipate continuing to incur substantial commercialization costs for our marketed products.
In accordance with the terms of the Restated Lease, we continue to pay all maintenance, insurance, taxes, and other costs arising out of the use of the Facility.
In accordance with the terms of the Third Amended and Restated Lease, we pay all maintenance, insurance, taxes, and other costs arising out of the use of the Facility.
We expect to incur capital expenditures of $825 million to $950 million in 2023 primarily in connection with the continued expansion of our research, preclinical manufacturing, and support facilities at our Tarrytown, New York campus and our manufacturing facilities (including the fill/finish facility).
We expect to incur capital expenditures of $825 million to $950 million in 2024 primarily in connection with the continued expansion of our research, preclinical manufacturing, and support facilities at our Tarrytown, New York campus and our manufacturing facilities.
The payment of these amounts, however, is contingent upon the occurrence of various future events, which have a high degree of uncertainty of occurring and for which the specific timing cannot be predicted. See Note 3 and Note 11 to our Consolidated Financial Statements.
The payment of these amounts, however, is contingent upon the occurrence of various future events, which have a high degree of uncertainty of occurring and for which the specific timing cannot be predicted. See Note 3 to our Consolidated Financial Statements. As described in Part I, Item 1.
We were in compliance with all covenants of the 2022 Credit Agreement as of December 31, 2022. Share Repurchase Programs In November 2019, our board of directors authorized a share repurchase program to repurchase up to $1.0 billion of our Common Stock.
We were in compliance with all covenants of the 2022 Credit Agreement as of December 31, 2023. Share Repurchase Programs In January 2021, our board of directors authorized a share repurchase program to repurchase up to $1.5 billion of our Common Stock.
During the year ended December 31, 2021, we earned a $50.0 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $1.5 billion on a rolling twelve-month basis.
During the year ended December 31, 2023, the Company earned the final $50.0 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outside the United States (including Praluent) exceeding $3.0 billion on a rolling twelve-month basis.
Significant judgment is required in making this assessment, and, therefore, we re-evaluate uncertain tax positions and consider various factors, including, but not limited to, changes in tax law, the measurement of tax positions taken or expected to be taken in tax returns, and changes in facts or circumstances related to a tax position.
Significant judgment is required in making this assessment, and, therefore, we re-evaluate uncertain tax positions and consider various factors, including, but not limited to, changes in tax law, the measurement of tax positions taken or expected to be taken in tax returns, the effective settlement of matters subject to audit, information obtained during in-process audit activities, and changes in facts or circumstances related to a tax position.
Bayer Collaboration Revenue Year Ended December 31, (In millions) 2022 2021 2020 Regeneron's share of profits in connection with commercialization of EYLEA outside the United States $ 1,317.4 $ 1,349.2 $ 1,107.9 Reimbursement for manufacturing of ex-U.S. commercial supplies (a) 91.4 60.1 78.2 One-time payment in connection with change in Japan arrangement 21.9 — — Total Bayer collaboration revenue $ 1,430.7 $ 1,409.3 $ 1,186.1 (a) Corresponding costs incurred by the Company in connection with such production is recorded within Cost of collaboration and contract manufacturing 83 Table of Contents Bayer records net product sales of EYLEA outside the United States.
Bayer Collaboration Revenue Year Ended December 31, (In millions) 2023 2022 2021 Regeneron's share of profits in connection with commercialization of EYLEA outside the United States $ 1,376.4 $ 1,317.4 $ 1,349.2 Reimbursement for manufacturing of ex-U.S. commercial supplies (a) 111.1 91.4 60.1 One-time payment in connection with change in Japan arrangement (b) — 21.9 — Total Bayer collaboration revenue $ 1,487.5 $ 1,430.7 $ 1,409.3 (a) Corresponding costs incurred by the Company in connection with such production is recorded within Cost of collaboration and contract manufacturing.
Our ability to generate profits and to generate positive cash flow from operations over the next several years depends significantly on the continued success in commercializing EYLEA and Dupixent, as well as on whether we are able to obtain regulatory approval for aflibercept 8 mg and are successful in commercializing it.
Our ability to generate profits and to generate positive cash flow from operations over the next several years depends significantly on the continued success in commercializing EYLEA and Dupixent, as well as whether we are successful in commercializing EYLEA HD.
Selling, general, and administrative expenses also included $256.4 million and $213.3 million of stock-based compensation expense in 2022 and 2021, respectively.
Selling, general, and administrative expenses also included $307.1 million and $256.4 million of stock-based compensation expense in 2023 and 2022, respectively.
As of December 31, 2022, our contingent reimbursement obligation to Bayer for EYLEA was approximately $273 million and our contingent reimbursement obligation to Sanofi in connection with the companies' Antibody Collaboration was approximately $2.864 billion.
As of December 31, 2023, our contingent reimbursement obligation to Bayer was approximately $293 million and our contingent reimbursement obligation to Sanofi in connection with the companies' Antibody Collaboration was approximately $2.330 billion.
When we have a combined unit of account which includes a license and providing research and development services to our collaborator, recognition of up-front payments and development milestones earned from our collaborator is deferred (as a liability) and recognized over the development period (i.e., over time) typically using an input method on the basis of our research and development costs incurred relative to the total expected cost which determines the extent of our progress toward completion (see "Results of Operations - Expenses - Other Operating (Income) Expense" below for further information related to amounts recognized in connection with such estimates).
When we have a combined unit of account which includes a license and providing research and development services to our collaborator, recognition of up-front payments and development milestones earned from our collaborator is deferred (as a liability) and recognized over the development period (i.e., over time) typically using an input method on the basis of our research and development costs incurred relative to the total expected cost which determines the extent of our progress toward completion.
Share repurchases may be made from time to time at management's discretion, and the timing and amount of any such repurchases will be determined based on share price, market conditions, legal requirements, and other relevant factors. There can be no assurance as to the timing or number of shares of any repurchases in the future.
Repurchases may be made from time to time at management's discretion, and the timing and amount of any such repurchases will be determined based on share price, market conditions, legal requirements, and other relevant factors. The program has no time limit and can be discontinued at any time.
We expect continued significant capital expenditures over the next several years in connection with the planned expansion of our Tarrytown, New York campus. Payments for Libtayo intangible asset of $1.027 billion in 2022 were related to our acquisition of the exclusive right to develop, commercialize, and manufacture Libtayo worldwide.
We expect continued significant capital expenditures over the next several years in connection with the planned expansion of our Tarrytown, New York campus. 86 Table of Contents Payments for the Libtayo intangible asset of $207.8 million and $1.027 billion in 2023 and 2022, respectively, were related to our acquisition (including contingent consideration paid) of the exclusive right to develop, commercialize, and manufacture Libtayo worldwide (as described in Part I, Item 1.
"Business - Collaboration, License, and Other Agreements - Sanofi," as (i) Sanofi is no longer reimbursing us for 50% of Libtayo development costs, and (ii) effective July 1, 2022, we recognize our 50% share of research and development expenses in connection with the Sanofi Antibody Collaboration.
"Business - "Collaboration, License, and Other Agreements - Sanofi", as (i) Sanofi is no longer reimbursing us for 50% of Libtayo development costs (such reimbursements were previously included in Reimbursement of research and development expenses by collaborators in the table above) and (ii) we recognize our 50% share of research and development expenses in connection with the Sanofi Antibody Collaboration.
(In millions) Rebates, Chargebacks, and Discounts Distribution- Related Fees Other Sales- Related Deductions Total Balance as of December 31, 2019 $ 80.3 $ 46.4 $ 29.4 $ 156.1 Provisions 762.9 279.9 94.1 1,136.9 Credits/payments (641.0) (249.1) (78.7) (968.8) Balance as of December 31, 2020 202.2 77.2 44.8 324.2 Provisions 1,047.1 363.6 150.4 1,561.1 Credits/payments (1,034.7) (360.8) (127.6) (1,523.1) Balance as of December 31, 2021 214.6 80.0 67.6 362.2 Provisions 1,537.3 431.1 141.1 2,109.5 Credits/payments (1,398.0) (399.7) (127.2) (1,924.9) Balance as of December 31, 2022 $ 353.9 $ 111.4 $ 81.5 $ 546.8 Sanofi Collaboration Revenue Year Ended December 31, (In millions) 2022 2021 2020 Antibody: Regeneron's share of profits in connection with commercialization of antibodies $ 2,082.0 $ 1,363.0 $ 785.2 Sales-based milestones earned 100.0 50.0 50.0 Reimbursement for manufacturing of commercial supplies (a) 633.7 488.8 368.0 Other 28.7 — — Total Antibody 2,844.4 1,901.8 1,203.2 Total Immuno-oncology 11.3 0.4 (16.8) Total Sanofi collaboration revenue $ 2,855.7 $ 1,902.2 $ 1,186.4 (a) Corresponding costs incurred by the Company in connection with such production is recorded within Cost of collaboration and contract manufacturing As the A&R IO LCA became effective July 1, 2022, the three months ended June 30, 2022 was the last period in which Sanofi collaboration revenue was recognized in connection with the immuno-oncology collaborative arrangement.
(In millions) Rebates, Chargebacks, and Discounts Distribution- Related Fees Other Sales- Related Deductions Total Balance as of December 31, 2020 $ 202.2 $ 77.2 $ 44.8 $ 324.2 Provisions 1,047.1 363.6 150.4 1,561.1 Credits/payments (1,034.7) (360.8) (127.6) (1,523.1) Balance as of December 31, 2021 214.6 80.0 67.6 362.2 Provisions 1,537.3 431.1 141.1 2,109.5 Credits/payments (1,398.0) (399.7) (127.2) (1,924.9) Balance as of December 31, 2022 353.9 111.4 81.5 546.8 Provisions 2,074.5 439.2 155.3 2,669.0 Credits/payments (1,972.7) (388.3) (157.5) (2,518.5) Balance as of December 31, 2023 $ 455.7 $ 162.3 $ 79.3 $ 697.3 Sanofi Collaboration Revenue Year Ended December 31, (In millions) 2023 2022 2021 Antibody: Regeneron's share of profits in connection with commercialization of antibodies $ 3,136.5 $ 2,082.0 $ 1,363.0 Sales-based milestones earned 50.0 100.0 50.0 Reimbursement for manufacturing of commercial supplies (a) 613.0 633.7 488.8 Other — 28.7 — Total Antibody 3,799.5 2,844.4 1,901.8 Total Immuno-oncology (b) — 11.3 0.4 Total Sanofi collaboration revenue $ 3,799.5 $ 2,855.7 $ 1,902.2 (a) Corresponding costs incurred by the Company in connection with such production is recorded within Cost of collaboration and contract manufacturing.
If the applicable collaboration is profitable, we have contingent contractual obligations to reimburse Bayer and Sanofi for a defined percentage (generally 50%) of agreed-upon development expenses funded by Bayer and Sanofi (i.e., "development balance").
"Collaboration, License, and Other Agreements," under our collaborations with Bayer and Sanofi, we and our collaborator share profits in connection with commercialization of drug products. If the applicable collaboration is profitable, we have contingent contractual obligations to reimburse Bayer and Sanofi for a defined percentage (generally 50%) of agreed-upon development expenses funded by Bayer and Sanofi (i.e., "development balance").
Antibody Global net product sales of Dupixent and Kevzara are recorded by Sanofi. The increase in our share of profits in connection with commercialization of antibodies during the year ended December 31, 2022, compared to 2021, was driven by profits associated with higher Dupixent sales, partly offset by the impact of the amendment to the Antibody License and Collaboration Agreement.
The increase in our share of profits in connection with commercialization of antibodies during the year ended December 31, 2023, compared to 2022, was driven by higher profits associated with Dupixent sales, partly offset by the impact of the amendment to the LCA.
Other Operating (Income) Expense Other operating (income) expense, net, includes recognition of a portion of amounts previously deferred in connection with up-front and development milestone payments, as applicable, received in connection with Sanofi IO, Teva, and MTPC collaborative arrangements.
Other Operating (Income) Expense Other operating (income) expense, net, in 2022 included the recognition of amounts previously deferred in connection with up-front and development milestone payments, as applicable, received in connection with our Sanofi IO, Teva, and Mitsubishi 84 Table of Contents Tanabe Pharma Corporation ("MTPC") collaborative arrangements.
Year Ended December 31, $ Change (In millions) 2022 2021 * 2020 * 2022 vs. 2021 2021 vs. 2020 Direct research and development expenses: Dupixent (dupilumab) $ 156.5 $ 146.4 $ 129.7 $ 10.1 $ 16.7 Libtayo (cemiplimab) 138.0 146.2 155.3 (8.2) (9.1) EYLEA and aflibercept 8 mg 81.2 102.2 72.2 (21.0) 30.0 Pozelimab 72.4 28.3 16.0 44.1 12.3 Odronextamab 66.0 34.9 35.0 31.1 (0.1) Linvoseltamab 45.5 18.7 11.4 26.8 7.3 Fianlimab 43.4 8.7 9.1 34.7 (0.4) REGEN-COV 32.8 309.8 290.7 (277.0) 19.1 Other product candidates in clinical development and other research programs 407.1 401.0 587.8 6.1 (186.8) Total direct research and development expenses 1,042.9 1,196.2 1,307.2 (153.3) (111.0) Indirect research and development expenses: Payroll and benefits 1,195.5 981.4 816.6 214.1 164.8 Lab supplies and other research and development costs 181.0 142.0 138.3 39.0 3.7 Occupancy and other operating costs 508.5 414.9 335.7 93.6 79.2 Total indirect research and development expenses 1,885.0 1,538.3 1,290.6 346.7 247.7 Clinical manufacturing costs 938.3 621.7 686.1 316.6 (64.4) Reimbursement of research and development expenses by collaborators (273.7) (496.1) (636.9) 222.4 140.8 Total research and development expenses $ 3,592.5 $ 2,860.1 $ 2,647.0 $ 732.4 $ 213.1 * Certain prior year amounts have been reclassified to conform to the current year's presentation 85 Table of Contents Total research and development expenses increased in 2022, compared to 2021, partially due to the impact of the amendments to the Sanofi collaboration agreements described above in Part I, Item 1.
Year Ended December 31, $ Change (In millions) 2023 2022 * 2021 * 2023 vs. 2022 2022 vs. 2021 Direct research and development expenses: Dupixent (dupilumab) $ 168.0 $ 156.5 $ 146.4 $ 11.5 $ 10.1 Fianlimab 112.2 43.4 8.7 68.8 34.7 Libtayo (cemiplimab) 105.3 138.0 146.2 (32.7) (8.2) Odronextamab 96.3 66.0 34.9 30.3 31.1 EYLEA HD (aflibercept) 8 mg 96.2 67.9 73.5 28.3 (5.6) Linvoseltamab 78.7 45.5 18.7 33.2 26.8 Itepekimab 70.3 26.5 — 43.8 26.5 Pozelimab 60.2 72.4 28.3 (12.2) 44.1 REGEN-COV (5.6) 32.8 309.8 (38.4) (277.0) Other product candidates in clinical development and other research programs 514.0 393.9 429.7 120.1 (35.8) Total direct research and development expenses 1,295.6 1,042.9 1,196.2 252.7 (153.3) Indirect research and development expenses: Payroll and benefits 1,537.0 1,195.5 981.4 341.5 214.1 Lab supplies and other research and development costs 210.6 181.0 142.0 29.6 39.0 Occupancy and other operating costs 518.2 508.5 414.9 9.7 93.6 Total indirect research and development expenses 2,265.8 1,885.0 1,538.3 380.8 346.7 Clinical manufacturing costs 1,053.9 938.3 621.7 115.6 316.6 Reimbursement of research and development expenses by collaborators (176.3) (273.7) (496.1) 97.4 222.4 Total research and development expenses $ 4,439.0 $ 3,592.5 $ 2,860.1 $ 846.5 $ 732.4 * Certain prior year amounts have been reclassified to conform to the current year's presentation. 83 Table of Contents Total research and development expenses increased in 2023, compared to 2022, partially due to the impact of the amendments to the Sanofi collaboration agreements (which were effective July 1, 2022) described above in Part I, Item 1.
Regeneron's share of profits in connection with commercialization of EYLEA outside the United States is summarized below: Year Ended December 31, (In millions) 2022 2021 2020 EYLEA net product sales outside the United States $ 3,382.8 $ 3,450.9* $ 2,820.7* Regeneron's share of collaboration profit from sales outside the United States $ 1,375.1 $ 1,408.3 $ 1,165.8 Reimbursement of development expenses incurred by Bayer in accordance with Regeneron's payment obligation (57.7) (59.1) (57.9) Regeneron's share of profits in connection with commercialization of EYLEA outside the United States $ 1,317.4 $ 1,349.2 $ 1,107.9 Regeneron's share of profits as a percentage of EYLEA net product sales outside the United States 39% 39% 39% * 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.
Regeneron's share of profits in connection with commercialization of EYLEA outside the United States is summarized below: Year Ended December 31, (In millions) 2023 2022 2021 EYLEA net product sales outside the United States $ 3,495.2 $ 3,382.8 $ 3,450.9 Regeneron's share of collaboration profit from sales outside the United States $ 1,436.1 $ 1,375.1 $ 1,408.3 Reimbursement of development expenses incurred by Bayer in accordance with Regeneron's payment obligation (a) (59.7) (57.7) (59.1) Regeneron's share of profits in connection with commercialization of EYLEA outside the United States $ 1,376.4 $ 1,317.4 $ 1,349.2 Regeneron's share of profits as a percentage of EYLEA net product sales outside the United States 39% 39% 39% (a) See "Liquidity and Capital Resources - Additional Funding Requirements" below for additional details on our contingent reimbursement obligation.
Therefore, we expect that, for the foreseeable future, a portion of our share of profits from sales under our collaborations with Bayer and Sanofi will be used to reimburse our collaborators for these obligations.
Therefore, we continue to expect that a portion of our share of profits from sales under our collaborations with Bayer and Sanofi will be used to reimburse our collaborators for these obligations. Future Impact of Recently Issued Accounting Standards See Note 1 to our Consolidated Financial Statements for a description of recently issued accounting standards.
As the A&R IO LCA became effective July 1, 2022, the three months ended June 30, 2022 was the last period in which such amounts were recognized in connection with our Sanofi immuno-oncology collaborative arrangement.
(b) As the A&R IO LCA became effective July 1, 2022, the three months ended June 30, 2022 was the last quarter in which Sanofi collaboration revenue was recognized in connection with the IO Collaboration.
As of December 31, 2022, $745.2 million remained available for share repurchases under the November 2021 program. The table below summarizes the shares of our Common Stock we repurchased under the programs described above and the cost of the shares, which were recorded as Treasury Stock.
As of December 31, 2023, $1.531 billion remained available for share repurchases under the program. 87 Table of Contents The table below summarizes the shares of our Common Stock we repurchased and the cost of the shares, which were recorded as Treasury Stock.
Inventories We capitalize inventory costs associated with our products prior to regulatory approval when, based on management's judgment, future commercialization is considered probable and the future economic benefit is expected to be realized; otherwise, such costs are expensed.
We adjust the amount of the liability to reflect any subsequent changes in the relevant facts and circumstances surrounding the uncertain tax positions. 75 Table of Contents Inventories We capitalize inventory costs associated with our products prior to regulatory approval when, based on management's judgment, future commercialization is considered probable and the future economic benefit is expected to be realized; otherwise, such costs are expensed.
We also anticipate continuing to incur substantial commercialization costs for our marketed products. Commercialization costs over the next few years will depend on, among other things, the market potential for product candidates, whether commercialization costs are shared with a collaborator, and regulatory approval of additional product candidates.
Commercialization costs over the next few years will depend on, among other things, the market potential for product candidates, whether commercialization costs are shared with a collaborator, and regulatory approval of additional product candidates. We expect that expenses related to the filing, prosecution, defense, and enforcement of patents and other intellectual property will be substantial.
There is also variability in the duration and costs necessary to develop a pharmaceutical product, potential opportunities and/or uncertainties related to future indications to be studied, and the estimated cost and scope of the projects. The lengthy process of seeking FDA and other applicable approvals, and subsequent compliance with applicable statutes and regulations, require the expenditure of substantial resources.
"Risk Factors." There is also variability in the duration and costs necessary to develop a pharmaceutical product, potential opportunities and/or uncertainties related to future indications to be studied, and the estimated cost and scope of the projects.
Selling, General, and Administrative Expenses Selling, general, and administrative expenses increased in 2022, compared to 2021, primarily due to higher headcount and headcount-related costs, an increase in commercialization-related expenses for Libtayo (as effective July 1, 2022, the Company became solely responsible for the commercialization of Libtayo worldwide), and higher contributions to an independent not-for-profit patient assistance organization, partly offset by costs in 2021 for educational campaigns related to COVID-19 that did not recur during 2022.
Selling, General, and Administrative Expenses Selling, general, and administrative expenses increased in 2023, compared to 2022, primarily due to higher headcount and headcount-related costs, an increase in commercialization-related expenses for Libtayo (including acquisition and integration-related costs for Libtayo outside the United States as effective July 1, 2022, the Company became solely responsible for the commercialization of Libtayo worldwide), and, to a lesser extent, commercialization-related expenses for various other products, and higher contributions to an independent not-for-profit patient assistance organization.
We expect continued increases in our expenditures, particularly in connection with our research and development activities (including preclinical and clinical programs).
We expect to continue to incur significant costs in connection with our research and development activities (including preclinical and clinical programs).
Expenses Year Ended December 31, Change (In millions, except headcount data) 2022 2021 2020 2022 vs. 2021 2021 vs. 2020 Research and development (a) $ 3,592.5 $ 2,860.1 $ 2,647.0 $ 732.4 $ 213.1 Acquired in-process research and development 255.1 48.0 88.0 207.1 (40.0) Selling, general, and administrative (a) 2,115.9 1,824.9 1,346.0 291.0 478.9 Cost of goods sold 800.0 1,773.1 491.9 (973.1) 1,281.2 Cost of collaboration and contract manufacturing (b) 760.4 664.4 628.0 96.0 36.4 Other operating (income) expense, net (89.9) (45.6) (280.4) (44.3) 234.8 Total operating expenses $ 7,434.0 $ 7,124.9 $ 4,920.5 $ 309.1 $ 2,204.4 Average headcount 11,115 9,884 8,495 1,231 1,389 (a) Includes costs incurred net of any cost reimbursements from collaborators who are not deemed to be our customers (b) Cost of collaboration and contract manufacturing includes costs we incur in connection with producing commercial drug supplies for collaborators and others. 84 Table of Contents Operating expenses in 2022, 2021, and 2020 included a total of $725.0 million, $601.7 million, and $432.0 million, respectively, of stock-based compensation expense related to equity awards granted under our long-term incentive plans.
In addition, Other revenue increased in 2023, compared to 2022, primarily due to the following: • higher reimbursements for the manufacture of commercial supplies for Sanofi related to Praluent outside the United States; • higher share of profits earned in connection with sales of ARCALYST pursuant to our license agreement with Kiniksa Pharmaceuticals, Ltd.; and • royalties earned in connection with our license agreement with Novartis, under which we receive royalties on worldwide sales of Novartis' Ilaris ® (canakinumab). 81 Table of Contents Expenses Year Ended December 31, Change (In millions, except headcount data) 2023 2022 2021 2023 vs. 2022 2022 vs. 2021 Research and development (a) $ 4,439.0 $ 3,592.5 $ 2,860.1 $ 846.5 $ 732.4 Acquired in-process research and development 186.1 255.1 48.0 (69.0) 207.1 Selling, general, and administrative (a) 2,631.3 2,115.9 1,824.9 515.4 291.0 Cost of goods sold 932.1 800.0 1,773.1 132.1 (973.1) Cost of collaboration and contract manufacturing (b) 883.7 760.4 664.4 123.3 96.0 Other operating (income) expense, net (2.1) (89.9) (45.6) 87.8 (44.3) Total operating expenses $ 9,070.1 $ 7,434.0 $ 7,124.9 $ 1,636.1 $ 309.1 Average headcount 12,698 11,115 9,884 1,583 1,231 (a) Includes costs incurred net of any cost reimbursements from collaborators who are not deemed to be our customers (b) Includes costs incurred in connection with producing commercial drug supplies for collaborators and others Operating expenses in 2023 and 2022 included a total of $885.0 million and $725.0 million, respectively, of stock-based compensation expense related to equity awards granted under our long-term incentive plans.
During the years ended December 31, 2021 and 2020, we recorded net product sales of REGEN-COV in connection with our agreements with the U.S. government.
EYLEA volumes in 2023 were impacted by the August 2023 launch of EYLEA HD and subsequent transition of EYLEA patients to EYLEA HD. During the year ended December 31, 2021, we recorded net product sales of REGEN-COV in connection with our agreements with the U.S. government.
Any failure by us to obtain, or delay in obtaining, regulatory approvals could materially adversely affect our business. We are unable to reasonably estimate if our product candidates in clinical development will generate material product revenues and net cash inflows.
We are unable to reasonably estimate if our product candidates in clinical development will generate material product revenues and net cash inflows.
Stock-based Compensation We recognize stock-based compensation expense for equity grants under our long-term incentive plans to employees and non-employee members of our board of directors (as applicable) based on the grant-date fair value of those awards. The grant-date fair value of an award is generally recognized as compensation expense over the award's requisite service period.
The estimates are revised, if necessary, in subsequent periods if our actual share of profits or losses differ from those estimates. Stock-based Compensation We recognize stock-based compensation expense for equity grants under our long-term incentive plans to employees and non-employee members of our board of directors (as applicable) based on the grant-date fair value of those awards.
As of December 31, 2022, unrecognized stock-based compensation expense related to unvested stock options and unvested restricted stock (including performance-based restricted stock units) was $572.0 million and $1.064 billion, respectively. We expect to recognize this stock-based compensation expense related to stock options and restricted stock over weighted-average periods of 1.8 years and 2.6 years, respectively.
As of December 31, 2023, unrecognized stock-based compensation expense related to unvested stock options and unvested restricted stock (including performance-based restricted stock units) was $589.6 million and $1.127 billion, respectively.
As of December 31, 2021, the Company had completed its final deliveries of drug product under its agreements with the U.S. government; as a result, there were no net product sales of REGEN-COV in the United States recorded during the year ended December 31, 2022. Refer to Part I, Item 1. "Business - Agreements Related to COVID-19 - U.S.
As of December 31, 2021, the Company had completed its final deliveries of drug product under its agreements with the U.S. government; as a result, there were no net product sales of REGEN-COV in the United States recorded during the years ended December 31, 2023 and 2022. 78 Table of Contents Revenue from product sales is recorded net of applicable provisions for rebates, chargebacks, and discounts; distribution-related fees; and other sales-related deductions.
Intangible Assets Intangible assets acquired in connection with an asset acquisition are recorded at cost. Intangible assets are amortized over the estimated useful lives of the assets based on the pattern in which the economic benefits of the intangible assets are consumed; if that pattern cannot be reliably determined, a straight-line basis is used.
Indefinite-lived intangible assets are subject to impairment testing until completion or abandonment of the associated research and development efforts. Definite-lived intangible assets are amortized over the estimated useful lives of the assets based on the pattern in which the economic benefits of the intangible assets are consumed; if that pattern cannot be reliably determined, a straight-line basis is used.
As of December 31, 2022, deferred tax assets increased by $746.4 million, compared to December 31, 2021, primarily related to the impact of the Tax Cuts and Jobs Act of 2017, which requires, for tax purposes, the capitalization and amortization of research and development expenses effective for years beginning after December 31, 2021. 2021 As of December 31, 2021, Accounts receivable had increased by $1.927 billion, compared to December 31, 2020, primarily due to REGEN-COV sales in connection with our September 2021 agreement to supply drug product to the U.S. government.
As of December 31, 2021, Accounts receivable increased by $1.927 billion, compared to December 31, 2020, primarily due to REGEN-COV sales in connection with our September 2021 agreement to supply drug product to the U.S. government.
Asset acquisition, net of cash acquired, of $230.3 million in 2022 was related to our acquisition of Checkmate. Cash Flows from Financing Activities Proceeds from issuances of Common Stock, in connection with exercises of employee stock options, were $1.520 billion during 2022, compared to $1.672 billion during 2021 and $2.575 billion during 2020.
Cash Flows from Financing Activities Proceeds from issuances of Common Stock, in connection with exercises of employee stock options, were $1.146 billion during 2023, compared to $1.520 billion during 2022 and $1.672 billion during 2021. For information related to repurchases of Common Stock, see " Share Repurchase Programs " section below.
We expect that expenses related to the filing, prosecution, defense, and enforcement of patents and other intellectual property will be substantial. Liabilities for unrecognized tax benefits totaled $542.8 million as of December 31, 2022. Due to their nature, there is a high degree of uncertainty regarding the period and amounts of potential future cash settlement with tax authorities.
Liabilities for unrecognized tax benefits totaled $696.4 million as of December 31, 2023. Due to their nature, there is a high degree of uncertainty regarding the period and amounts of potential future cash settlement with tax authorities. See Note 15 to our Consolidated Financial Statements.
We are also required to make monthly payments of basic rent during the term of the Restated Lease in an amount equal to a variable rate per annum, which was modified in connection with the Restated Lease, to be an adjusted one-month forward-looking term rate based on the Secured Overnight Financing Rate ("SOFR"), plus an applicable margin that varies with our debt rating and total leverage ratio.
Such advances accrue yield at a variable rate per annum based on the one-month forward-looking Secured Overnight Financing Rate ("SOFR") term rate, plus a spread adjustment, plus an applicable margin that varies with our debt rating and total leverage ratio.
We cannot predict whether or when new products or new indications for marketed products will receive regulatory approval or, if any such approval is received, whether we will be able to successfully commercialize such product(s) and whether or when they may become profitable.
We cannot predict whether or when new products or new indications for marketed products will receive regulatory approval or, if any such approval is received, whether we will be able to successfully commercialize such product(s) and whether or when they may become profitable. 73 Table of Contents Critical Accounting Estimates The preparation of financial statements in accordance with accounting principles generally accepted in the United States of America ("GAAP") requires management to make estimates and assumptions that affect reported amounts and related disclosures in the financial statements.
The original Participation Agreement and certain related agreements were amended and restated in order to, among other things, (i) effect a five-year extension of the original March 2022 maturity date of the $720.0 million lease financing and the end of the term of our lease of the Facility from the Lessor to March 2027, at which time all amounts outstanding thereunder will become due and payable in full, and (ii) modify the rate of the interest or yield that is payable to the Participants.
The Third Amended and Restated Lease and Third Amended and Restated Participation Agreement provide for a March 2027 maturity date of the $720.0 million lease financing (previously advanced by the Participants in March 2017 in connection with the acquisition by BAL of the Facility and our lease of the Facility from BAL) and the end of the term of our lease of the Facility from BAL, at which time all amounts outstanding thereunder will become due and payable in full.
The increase in reimbursements for manufacturing of commercial supplies in 2022, compared to 2021, was primarily due to higher Dupixent sales, as revenue for such cost reimbursements is recognized when the product is sold by Sanofi to third-party customers.
Reimbursements for manufacturing of commercial supplies primarily relate to Dupixent and are recognized when the product is sold by Sanofi to third-party customers; such reimbursements decreased during the year ended December 31, 2023, compared to 2022, primarily due to lower manufacturing costs resulting from the transition to a higher-yielding manufacturing process.
Stock-based compensation expense also includes an estimate, which is made at the time of grant, of the number of awards that are expected to be forfeited. This estimate is revised, if necessary, in subsequent periods if actual forfeitures differ from those estimates.
The grant-date fair value of an award is generally recognized as compensation expense over the award's requisite service period. Stock-based compensation expense also includes an estimate, which is made at the time of grant, of the number of awards that are expected to be forfeited.
Changes in any of these assumptions may materially affect the fair value of awards granted and the amount of stock-based compensation recognized in future periods. We use the Black-Scholes model to compute the estimated fair value of stock option awards.
We use the Black-Scholes model to compute the estimated fair value of stock option awards.
"Business - Additional Information - Clinical Development Programs - REGEN-COV (casirivimab and imdevimab)" for further information related to regulatory developments for REGEN-COV which negatively impacted the estimated realizable value of inventory on hand. 86 Table of Contents Cost of Collaboration and Contract Manufacturing Cost of collaboration and contract manufacturing increased in 2022, compared to 2021, primarily due to the recognition of costs in connection with manufacturing additional commercial supplies for Sanofi related to Praluent outside the United States and Dupixent, and manufacturing costs associated with EYLEA outside the United States.
Cost of Collaboration and Contract Manufacturing Cost of collaboration and contract manufacturing increased in 2023, compared to 2022, primarily due to the recognition of costs in connection with manufacturing commercial supplies for Sanofi related to Praluent outside the United States and for Bayer related to EYLEA outside the United States.
In addition, we reassess our forfeiture rate assumptions at least annually, considering both historical forfeiture experience and an estimate of future forfeitures for currently outstanding unvested awards. The assumptions used in computing the fair value of equity awards reflect our best estimates but involve uncertainties related to market and other conditions, many of which are outside our control.
The assumptions used in computing the fair value of equity awards reflect our best estimates but involve uncertainties related to market and other conditions, many of which are outside our control. Changes in any of these assumptions may materially affect the fair value of awards granted and the amount of stock-based compensation recognized in future periods.
In addition, the amount of our share of profits we earned in connection with commercialization of antibodies outside the United States was adversely impacted in 2022 by the U.S. dollar strengthening against foreign currencies, including the Japanese yen and the euro. 82 Table of Contents Regeneron's share of profits in connection with the commercialization of Dupixent, Praluent (through March 31, 2020), and Kevzara is summarized below: Year Ended December 31, (In millions) 2022 2021 2020 Dupixent, Praluent, and Kevzara net product sales (a) $ 9,039.2 $ 6,536.3 $ 4,394.5 Regeneron's share of collaboration profits 2,405.5 1,511.5 871.5 Reimbursement of development expenses incurred by Sanofi in accordance with Regeneron's payment obligation (266.6) (148.5) (86.3) One-time payment in connection with amendment to the Antibody License and Collaboration Agreement (56.9) — — Regeneron's share of profits in connection with commercialization of antibodies $ 2,082.0 $ 1,363.0 $ 785.2 Regeneron's share of collaboration profits as a percentage of Dupixent, Praluent, and Kevzara net product sales 23% 21% 18% (a) Global net product sales of Dupixent and Kevzara are recorded by Sanofi.
"Business - Collaboration, License, and Other Agreements - Sanofi - Antibody", on July 1, 2022, an amendment to the LCA became effective, pursuant to which the percentage of Regeneron's share of profits in any calendar quarter used to reimburse Sanofi for development costs which were funded by Sanofi increased from 10% to 20%. 79 Table of Contents Regeneron's share of profits in connection with the commercialization of Dupixent and Kevzara is summarized below: Year Ended December 31, (In millions) 2023 2022 2021 Dupixent and Kevzara net product sales $ 11,974.0 $ 9,039.2 $ 6,536.3 Regeneron's share of collaboration profits 3,596.3 2,405.5 1,511.5 Reimbursement of development expenses incurred by Sanofi in accordance with Regeneron's payment obligation (a) (459.8) (266.6) (148.5) One-time payment in connection with amendment to the Antibody License and Collaboration Agreement — (56.9) — Regeneron's share of profits in connection with commercialization of antibodies $ 3,136.5 $ 2,082.0 $ 1,363.0 Regeneron's share of profits as a percentage of Dupixent and Kevzara net product sales 26% 23% 21% (a) See "Liquidity and Capital Resources - Additional Funding Requirements" below for additional details on our contingent reimbursement obligation.
We currently have nine FDA-approved products that have received marketing approval and approximately 35 product candidates in clinical development, almost all of which were homegrown in our laboratories.
Overview Regeneron Pharmaceuticals, Inc. is a fully integrated biotechnology company that invents, develops, manufactures, and commercializes medicines for people with serious diseases. Our research and development efforts have led to eleven FDA-approved products that have received marketing approval and approximately 35 product candidates in clinical development, almost all of which were homegrown in our laboratories.
The share repurchase program was approved under terms substantially similar to the November 2019 share repurchase program. As of December 31, 2021, the Company had repurchased the entire $1.5 billion of its Common Stock that it was authorized to repurchase under the program.
As of June 30, 2023, the Company had repurchased the entire $3.0 billion of its Common Stock that it was authorized to repurchase under the program. In January 2023, our board of directors authorized an additional share repurchase program to repurchase up to $3.0 billion of our Common Stock.
See Note 8 to our Consolidated Financial Statements for further information related to our intangible assets. Contingencies We accrue, based on management's judgment, for an estimated loss when the potential loss from claims or legal proceedings is considered probable and the amount can be reasonably estimated.
If the projected undiscounted cash flows of the intangible asset are less than the carrying amount, the intangible asset is written down to its fair value in the period in which the impairment occurs. 76 Table of Contents Contingencies We accrue, based on management's judgment, for an estimated loss when the potential loss from claims or legal proceedings is considered probable and the amount can be reasonably estimated.
Sources and Uses of Cash for the Years Ended December 31, 2022, 2021, and 2020 As of December 31, $ Change (In millions) 2022 2021 2020 2022 vs. 2021 2021 vs. 2020 Cash flows provided by operating activities $ 5,014.9 $ 7,081.3 $ 2,618.1 $ (2,066.4) $ 4,463.2 Cash flows used in investing activities $ (3,784.6) $ (5,384.7) $ (70.6) $ 1,600.1 $ (5,314.1) Cash flows used in financing activities $ (1,009.0) $ (1,005.8) $ (1,970.5) $ (3.2) $ 964.7 Cash Flows from Operating Activities 2022 As of December 31, 2022, Accounts receivable had decreased by $707.8 million, compared to December 31, 2021, driven by the Company's collection of amounts due from the U.S. government in connection with REGEN-COV sales in the fourth quarter of 2021.
Sources and Uses of Cash for the Years Ended December 31, 2023, 2022, and 2021 Year Ended December 31, $ Change (In millions) 2023 2022 2021 2023 vs. 2022 2022 vs. 2021 Cash flows provided by operating activities $ 4,594.0 $ 5,014.9 $ 7,081.3 $ (420.9) $ (2,066.4) Cash flows used in investing activities $ (3,185.1) $ (3,784.6) $ (5,384.7) $ 599.5 $ 1,600.1 Cash flows used in financing activities $ (1,790.1) $ (1,009.0) $ (1,005.8) $ (781.1) $ (3.2) Cash Flows from Operating Activities As of December 31, 2023 and 2022, deferred tax assets increased by $837.8 million and $746.4 million, respectively, primarily related to the impact of the Tax Cuts and Jobs Act of 2017, which requires, for tax purposes, the capitalization and amortization of research and development expenses effective for years beginning after December 31, 2021.
These inventory write-offs and reserves were primarily related to REGEN-COV. Refer to Part I, Item 1.
Inventory write-offs and reserves were $102.3 million in 2023 compared to $258.7 million in 2022. The inventory write-offs and reserves in 2022 were primarily related to REGEN-COV.
Research and Development Expenses The following table summarizes our estimates of direct research and development expenses by clinical development program and other significant categories of research and development expenses.
We expect to recognize this stock-based compensation expense related to stock options and restricted stock over weighted-average periods of 1.8 years and 2.3 years, respectively. 82 Table of Contents Research and Development Expenses The following table summarizes our direct research and development expenses by clinical development program and other significant categories of research and development expenses.

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Item 7A. Quantitative and Qualitative Disclosures About Market Risk

Market Risk — interest-rate, FX, commodity exposure

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Biggest changeNonetheless, deterioration of the credit quality of an investment security subsequent to purchase may subject us to the risk of not being able to recover the full principal value of the security. In 2022, 2021, and 2020, we did not record any charges for credit-related impairments of our available-for-sale debt securities.
Biggest changeCredit Quality Risk We have an investment policy that includes guidelines on acceptable investment securities, minimum credit quality, maturity parameters, and concentration and diversification. Nonetheless, deterioration of the credit quality of an investment security subsequent to purchase may subject us to the risk of not being able to recover the full principal value of the security.
We also incur worldwide development expenses for clinical products we are developing independently, incur expenses outside of the United States in connection with our international operations, and, effective July 1, 2022, market Libtayo outside of the United States as a result of obtaining worldwide rights to Libtayo under an A&R IO LCA with Sanofi.
We also incur worldwide development expenses for clinical products we are developing independently, incur expenses outside the United States in connection with our international operations, and, effective July 1, 2022, market Libtayo outside the United States as a result of obtaining worldwide rights to Libtayo under an A&R IO LCA with Sanofi.
Therefore, significant changes in foreign exchange rates of the countries outside the United States where our products are sold, where development expenses are incurred by us or our collaborators, or where we incur operating expenses can impact our operating results and financial condition.
Therefore, significant changes in foreign exchange rates of the countries outside the United States where our products are sold, where development expenses are incurred by us or our collaborators, or where we incur operating expenses may impact our operating results and financial condition.
We estimate that a 100 basis point, or 1%, unfavorable change in interest rates would have resulted in approximately a $102.7 million and $120.0 million decrease in the fair value of our investment portfolio as of December 31, 2022 and 2021, respectively.
We estimate that a 100 basis point, or 1%, unfavorable change in interest rates would have resulted in approximately a $98.7 million and $102.7 million decrease in the fair value of our investment portfolio as of December 31, 2023 and 2022, respectively.
As of December 31, 2022, two customers accounted on a combined basis for 86% of our net trade accounts receivables. Foreign Exchange Risk As discussed further above, our collaborators market certain products outside the United States, and we share in profits and losses with these collaborators from commercialization of products.
As of December 31, 2023, two customers accounted on a combined basis for 83% of our net trade accounts receivables. 89 Table of Contents Foreign Exchange Risk As discussed further above, our collaborators market certain products outside the United States, and we share in profits and losses with these collaborators from commercialization of products.
Our marketable securities include equity investments in publicly traded stock of companies, including common stock of companies with which we have entered into collaboration arrangements. Changes in the fair value of our equity investments are included in Other income (expense), net on the Consolidated Statements of Income.
Our investments include equity securities of companies with which we have entered into collaboration arrangements. Changes in the fair value of our equity investments are included in Other income (expense), net on the Statements of Operations. We recorded $237.8 million and $39.8 million of net unrealized losses on equity securities in Other income (expense), net in 2023 and 2022, respectively.
We also monitor financial performance and credit worthiness so that we can properly assess and respond to any changes in collaborator and/or customer credit profiles. In 2022, 2021 and 2020, we did not recognize any charges for write-offs and allowances of accounts receivable related to credit risk for our collaborators or customers.
In 2023, 2022, and 2021, we did not recognize any charges for write-offs and allowances of accounts receivable related to credit risk for our collaborators or customers.
We are subject to credit risk associated with the receivables due from our collaborators, including Bayer and Sanofi. We are also subject to credit risk in connection with trade accounts receivable due from our customers from our product sales. We have contractual payment terms with each of our collaborators and customers.
In 2023, 2022, and 2021, we did not record any charges for credit-related impairments of our available-for-sale debt securities. We are subject to credit risk associated with the receivables due from our collaborators, including Bayer and Sanofi. We are also subject to credit risk in connection with trade accounts receivable due from our customers from our product sales.
We recorded $39.8 million of net unrealized losses and $386.1 million of net unrealized gains on equity securities in Other income (expense), net in 2022 and 2021, respectively. Item 8. Financial Statements and Supplementary Data The information required by this Item is set forth beginning on page F-1 of this report and is incorporated herein by reference. Item 9.
Item 8. Financial Statements and Supplementary Data The information required by this Item is set forth beginning on page F-1 of this report and is incorporated herein by reference. Item 9. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure None.
We continue to monitor our interest rate risk and may utilize derivative instruments and/or other strategies in the future to further mitigate our interest rate exposure. 92 Table of Contents Credit Quality Risk We have an investment policy that includes guidelines on acceptable investment securities, minimum credit quality, maturity parameters, and concentration and diversification.
Our interest rate exposure is offset by our investments in marketable securities. We continue to monitor our interest rate risk and may utilize derivative instruments and/or other strategies in the future to further mitigate our interest rate exposure.
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Our interest rate exposure is primarily offset by our investments in marketable securities.
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We have contractual payment terms with each of our collaborators and customers. We also monitor financial performance and credit worthiness so that we can properly assess and respond to any changes in collaborator and/or customer credit profiles.
Removed
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure None.

Other REGN 10-K year-over-year comparisons