REGENERON PHARMACEUTICALS, INC. This Quarterly Report on Form 10-Q contains forward-looking statements that involve risks and uncertainties relating to future events and the future performance ofRegeneron Pharmaceuticals, Inc. (where applicable, together with its subsidiaries, "Regeneron," "Company," "we," "us," and "our"), and actual events or results may differ materially from these forward-looking statements. Words such as "anticipate," "expect," "intend," "plan," "believe," "seek," "estimate," variations of such words, and similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements contain these identifying words. These statements concern, and these risks and uncertainties include, among others, the impact of SARS-CoV-2 (the virus that has caused the COVID-19 pandemic) on Regeneron's business and its employees, collaborators, and suppliers and other third parties on which Regeneron relies, Regeneron's and its collaborators' ability to continue to conduct research and clinical programs, Regeneron's ability to manage its supply chain, net product sales of products marketed or otherwise commercialized by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Products"), and the global economy; the nature, timing, and possible success and therapeutic applications of Regeneron's Products and product candidates being developed by Regeneron and/or its collaborators or licensees (collectively, "Regeneron's Product Candidates") and research and clinical programs now underway or planned, including without limitation EYLEA® (aflibercept) Injection, Dupixent® (dupilumab) Injection, Libtayo® (cemiplimab) Injection, Praluent® (alirocumab) Injection, Kevzara® (sarilumab) Injection, Evkeeza® (evinacumab), Inmazeb® (atoltivimab, maftivimab, and odesivimab-ebgn), REGEN-COV® (casirivimab and imdevimab), fasinumab, garetosmab, pozelimab, odronextamab, itepekimab, REGN5458, REGN5713-5714-5715, REGN1908-1909, Regeneron's other oncology programs (including its costimulatory bispecific portfolio), Regeneron's and its collaborators' earlier-stage programs, and the use of human genetics in Regeneron's research programs; the likelihood and timing of achieving any of 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, Bayer, and Teva Pharmaceutical Industries Ltd. (or their respective affiliated companies, as applicable), as well as Regeneron's agreement with Roche relating to the casirivimab and imdevimab antibody cocktail (known as REGEN-COV inthe United States and Ronapreve™ in other countries) and its REGEN-COV supply agreement with theU.S. government, to be cancelled or terminated; and risks associated with intellectual property of other parties and pending or future litigation relating thereto (including without limitation the patent litigation and other related proceedings relating to EYLEA, Dupixent, Praluent, and REGEN-COV described further in Note 12 to our Condensed 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 12 to our Condensed 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 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 II, Item 1A. "Risk Factors," which could cause actual events and results to differ 25 --------------------------------------------------------------------------------
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materially from those indicated by such forward-looking statements. We do not undertake any obligation to update (publicly or otherwise) any forward-looking statement, whether as a result of new information, future events, or otherwise. OverviewRegeneron Pharmaceuticals, Inc. is a fully integrated biotechnology company that discovers, invents, develops, manufactures, and commercializes medicines for serious diseases. Our commercialized medicines and product candidates in development are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases, and rare diseases. 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 options for preventing and treating human diseases. Selected financial information is summarized as follows: Three Months Ended
Nine Months Ended
September 30 ,
(In millions, except per share data) 2021 2020 2021 2020 Revenues$ 3,452.8 $ 2,294.0 $ 11,120.0 $ 6,074.2 Net income$ 1,632.2 $ 842.1 $ 5,846.3 $ 2,364.0 Net income per share - diluted$ 14.33 $ 7.39
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.
Products
Products that have received marketing approval are summarized in the table
below.
Territory
Product Disease Area U.S. EU Japan ROW(4)
EYLEA (aflibercept) - Neovascular age-related macular a a a a
Injection(1) degeneration ("wet AMD")
- Diabetic macular edema ("DME") a a a a
- Macular edema following retinal a a a a
vein occlusion ("RVO"), which
includes macular edema following
central retinal vein occlusion
("CRVO") and macular edema
following branch retinal vein
occlusion ("BRVO")
- Myopic choroidal neovascularization a a a
("mCNV")
- Diabetic retinopathy a
- Neovascular glaucoma ("NVG") a
Dupixent (dupilumab) - Atopic dermatitis (in adults and a a a a
Injection(2) adolescents)
- Atopic dermatitis (in pediatrics a a a
6-11 years of age)
- Asthma (in adults and adolescents) a a a a
- Asthma (in pediatrics 6-11 years of a
age)
- Chronic rhinosinusitis with nasal a a a a
polyposis ("CRSwNP")
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Territory
Product (continued) Disease Area U.S. EU Japan ROW(4)
Libtayo (cemiplimab) - Metastatic or locally advanced a a a
Injection(2) first-line non-small cell lung cancer
("NSCLC")
- Metastatic or locally advanced basal a a a
cell carcinoma ("BCC")
- Metastatic or locally advanced a a a
cutaneous squamous cell carcinoma
("CSCC")
Praluent (alirocumab) - LDL-lowering in heterozygous familial a a a
Injection(3) hypercholesterolemia ("HeFH") or
clinical atherosclerotic
cardiovascular disease ("ASCVD")
- Cardiovascular risk reduction in a a a
patients with established
cardiovascular disease
- Homozygous familial a
hypercholesterolemia ("HoFH")
REGEN-COV(5) - COVID-19 a aKevzara (sarilumab) Solution for - Rheumatoid arthritis ("RA")
a a a a
Subcutaneous Injection(2)
Evkeeza (evinacumab) Injection - HoFH (in adults and adolescents) a a
Inmazeb (atoltivimab, - Infection caused by Zaire ebolavirus a
maftivimab, and odesivimab-ebgn)
Injection
ARCALYST® (rilonacept) Injection - Cryopyrin-associated periodic a
for Subcutaneous Use(6) syndromes ("CAPS"), including
familial cold auto-inflammatory
syndrome ("FCAS") and Muckle-Wells
syndrome ("MWS") (in adults and
adolescents)
- Deficiency of interleukin-1 receptor a
antagonist ("DIRA") (in adults and
pediatrics)
- Recurrent pericarditis (in adults and a
adolescents)
ZALTRAP® (ziv-aflibercept) - Metastatic colorectal cancer ("mCRC") a a a a
Injection for Intravenous
Infusion(7)
Note 1: Refer to "Net Product Sales of Regeneron-Discovered Products" section below for information regarding whether net product sales for a
particular product are recorded by us or others.
Note 2: Product is approved for use in adults, unless otherwise noted, in the disease area described above
(1) In collaboration with Bayer outside the United States
(2) In collaboration with Sanofi
(3) Pursuant to a 2020 agreement, the Company is solely responsible for the development and commercialization of Praluent in the United States ,
and Sanofi is solely responsible for the development and commercialization of Praluent outside of the United States (and Sanofi pays us a
royalty on net product sales of Praluent outside the United States ).
(4) Rest of world. Checkmark in this column indicates that the product has received marketing approval in at least one country outside of the
United States , European Union ("EU"), or Japan .
(5) Known as REGEN-COV in the United States and Ronapreve in other countries
(6) Pursuant to a 2017 license agreement with Kiniksa Pharmaceuticals, Ltd., we granted Kiniksa the right to develop and commercialize certain
new indications for ARCALYST. In March 2021 , Kiniksa received marketing approval for its first new indication of ARCALYST in the United States ;
consequently we granted U.S. commercial rights to ARCALYST for all previously approved indications and Kiniksa pays us a share of ARCALYST
profits. Refer to "Collaboration, License, and Other Agreements - Kiniksa" section below for further details.
(7) Sanofi is solely responsible for the development and commercialization of ZALTRAP, and Sanofi pays us a percentage of aggregate net product
sales of ZALTRAP.
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REGEN-COV - Emergency and Temporary Use AuthorizationsUnited States InNovember 2020 , the antibody cocktail casirivimab and imdevimab administered together, known as REGEN-COV inthe United States , received Emergency Use Authorization ("EUA") from theU.S. Food and Drug Administration ("FDA") for the treatment of mild to moderate COVID-19 in adults, as well as in pediatric patients at least 12 years of age and weighing at least 40 kg, who have received positive results of direct SARS-CoV-2 viral testing and are at high risk for progressing to severe COVID-19 and/or hospitalization. InJune 2021 , the FDA updated the EUA for REGEN-COV, lowering the dose to 1,200 mg (which is half the dose originally authorized) and allowing for subcutaneous injections as an alternative when intravenous ("IV") infusion is not feasible and would lead to a delay in treatment. InJuly 2021 , the FDA also expanded the EUA to include post-exposure prophylaxis in people at high risk for progression to severe COVID-19, who are not fully vaccinated or are not expected to mount an adequate response to vaccination, and who have been exposed to a SARS-CoV-2 infected individual or are at high risk of exposure to an infected individual because of infection occurring in the same institutional setting (such as in nursing homes or prisons). For people who are not expected to mount an adequate immune response to vaccination, REGEN-COV can also now be administered monthly for the duration of ongoing exposure to SARS-CoV-2. The EUA is temporary and does not replace a formal Biologics License Application ("BLA") submission review and approval process. This use is authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use, unless terminated or revoked sooner. See information regarding ongoing clinical trials of REGEN-COV in the "Programs in Clinical Development" section below. Outsidethe United States InFebruary 2021 , theEuropean Medicines Agency's ("EMA") Committee for Medicinal Products for Human Use ("CHMP") issued a positive opinion, recommending that the casirivimab and imdevimab antibody cocktail be used to treat COVID-19 patients who do not require supplemental oxygen and are at high risk of progressing to severe COVID-19. The CHMP's positive opinion can be used by EU member states when making decisions on the possible use of the antibody cocktail at a national level prior to a market authorization. InAugust 2021 , theUnited Kingdom's ("UK") Medicines and Healthcare products Regulatory Agency ("MHRA") granted Conditional Marketing Authorization for the casirivimab and imdevimab antibody cocktail inEngland ,Scotland , andWales to prevent and treat acute COVID-19 infection. In addition, the MHRA authorized emergency supply of the antibody cocktail to prevent and treat acute COVID-19 infection inNorthern Ireland . Emergency or temporary pandemic use authorizations are also currently in place in certain other countries outsidethe United States , including within theEuropean Union ,India ,Switzerland , andCanada . 28 --------------------------------------------------------------------------------
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Net Product Sales of Regeneron-Discovered Products
Three Months Ended
September 30,
2021 2020 % Change
(In millions) U.S. ROW Total U.S. ROW Total (Total Sales)
EYLEA(a) $ 1,473.4 $ 930.8 $ 2,404.2 $ 1,318.3 $ 780.0 $ 2,098.3 15 %
Dupixent(b) $ 1,256.7 $ 406.2 $ 1,662.9 $ 851.2 $ 221.4 $ 1,072.6 55 %
Libtayo(c) $ 78.4 $ 41.1 $ 119.5 $ 71.6 $ 24.5 $ 96.1 24 %
Praluent(d) $ 44.8 $ 69.7 $ 114.5 $ 48.5 $ 43.0 $ 91.5 25 %
REGEN-COV(e) $ 676.7 $ 518.8 $ 1,195.5 $ 40.2 - $ 40.2 (h)
Kevzara(b) $ 58.5 $ 39.3 $ 97.8 $ 33.2 $ 36.8 $ 70.0 40 %
Evkeeza(f) $ 6.6 - $ 6.6 - - - (h)
ARCALYST(g) $ 12.1 - $ 12.1 $ 3.6 - $ 3.6 236 %
ZALTRAP(b) $ 1.2 $ 20.9 $ 22.1 $ 1.7 $ 22.5 $ 24.2 (9 %)
Nine Months Ended
September 30,
2021 2020 % Change
(In millions) U.S. ROW Total U.S. ROW Total (Total Sales)
EYLEA(a) $ 4,245.1 $ 2,658.9 $ 6,904.0 $ 3,604.0 $ 2,102.7 $ 5,706.7 21 %
Dupixent(b) $ 3,364.8 $ 1,060.0 $ 4,424.8 $ 2,300.6 $ 572.2 $ 2,872.8 54 %
Libtayo(c) $ 225.5 $ 111.7 $ 337.2 $ 196.6 $ 54.3 $ 250.9 34 %
Praluent(d) $ 130.0 $ 188.5 $ 318.5 $ 130.8 $ 127.1 $ 257.9 23 %
REGEN-COV(e) $ 3,530.1 $ 1,173.2 $ 4,703.3 $ 40.2 - $ 40.2 (h)
Kevzara(b) $ 119.9 $ 113.7 $ 233.6 $ 105.0 $ 93.4 $ 198.4 18 %
Evkeeza(f) $ 9.1 - $ 9.1 - - - (h)
ARCALYST(g) $ 22.0 - $ 22.0 $ 9.3 - $ 9.3 137 %
ZALTRAP(b) $ 3.9 $ 66.1 $ 70.0 $ 4.9 $ 74.0 $ 78.9 (11 %)
(a) Regeneron records net product sales of EYLEA in the United States . Bayer records net product sales of EYLEA outside the United States . The Company records
its share of profits/losses in connection with sales of EYLEA outside the United States .
(b) Sanofi records global net product sales of Dupixent, Kevzara, and ZALTRAP. The Company records its share of profits/losses in connection with global sales
of Dupixent and Kevzara, and Sanofi pays the Company a percentage of net sales of ZALTRAP.
(c) Regeneron records net product sales of Libtayo in the United States and Sanofi records net product sales of Libtayo outside the United States . The parties
equally share profits/losses in connection with global sales of Libtayo.
(d) Effective April 1, 2020 , Regeneron records net product sales of Praluent in the United States . Also effective April 1, 2020 , Sanofi records net product
sales of Praluent outside the United States and pays the Company a royalty on such sales. Previously, Sanofi recorded global net product sales of Praluent and
the Company recorded its share of profits/losses in connection with such sales. Refer to "Collaboration, License, and Other Agreements - Sanofi" section below
for further details.
(e) Regeneron records net product sales of REGEN-COV in connection with its agreements with the U.S. government. Roche records net product sales of the
antibody cocktail outside the United States and the parties share gross profits from global sales. Refer to "Agreements Related to COVID-19" below for further
details.
(f) Regeneron records net product sales of Evkeeza in the United States
(g) Effective April 1, 2021 , Kiniksa records net product sales of ARCALYST in the United States and pays us a share of ARCALYST profits, if any. Prior to
April 1, 2021 , Regeneron recorded net product sales of ARCALYST in the United States . Refer to "Products" section above and "Collaboration, License, and Other
Agreements - Kiniksa" section below for further details.
(h) Percentage not meaningful
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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. We believe that our
ability to develop product candidates is enhanced by the application of
our VelociSuite® technology platforms. We continue to invest in the development
of enabling technologies to assist in our efforts to identify, develop,
manufacture, and commercialize new product candidates.
There are numerous uncertainties associated with drug development, including
uncertainties related to safety and efficacy data from each phase of drug
development (including any post-approval studies), uncertainties related to the
enrollment and performance of clinical trials, changes in regulatory
requirements, changes to drug pricing and reimbursement regulations and
requirements, and changes in the competitive landscape affecting a product
candidate. The planning, execution, and results of our clinical programs are
significant factors that can affect our operating and financial results.
We and our collaborators conduct clinical trials in multiple countries across
the world. The COVID-19 pandemic and the restrictions adopted around the globe
to reduce the spread of the disease have impacted and may continue to impact our
clinical development programs. We continue to evaluate the impact of the
COVID-19 pandemic on an individual trial basis and oversee trial management
while also working to ensure patient safety and provide sufficient supply of
product candidates for the studies. The ultimate impact (including possible
delays in recruiting and/or obtaining data) resulting from the COVID-19 pandemic
will depend, among other factors, on the extent of the pandemic in the areas
with study sites and patient populations. It is possible that the COVID-19
pandemic may cause clinical disruptions beyond those we have described. In
addition, there may be delays in the timing of regulatory review and other
projected milestones discussed in the table below.
Refer to Part II, Item 1A. "Risk Factors" for a description of these and other
risks and uncertainties that may affect our clinical programs, including those
related to the COVID-19 pandemic.
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Regulatory Select Upcoming
Clinical Program Phase 1 Phase 2 Phase 3 Review(h) 2021 Events to Date Milestones(i)
Ophthalmology
EYLEA (aflibercept)(b) -High-dose -Retinopathy of -ROP (Japan) -Initial results from -Submit supplemental BLA
formulation in wet prematurity National Institutes of ("sBLA") for
AMD ("ROP")(c) Health ("NIH")-sponsored every-16-weeks dosing
Protocol W trial in regimen in patients with
-High-dose non-proliferative diabetic NPDR (first half 2022)
formulation in wet retinopathy ("NPDR") were
AMD announced; data confirmed -Report results from
results from Phase 3 studies for
-High-dose Company-sponsored PANORAMA high-dose formulation in
formulation in DME trial and demonstrated wet AMD and DME (second
reduced risk of developing half 2022)
vision-threatening
complications with
every-16-weeks dosing
regimen
-Completed enrollment in
Phase 3 study for ROP
-Completed enrollment in
Phase 3 studies for
high-dose formulation in
wet AMD and DME
-Reported that Phase 2
trial of high-dose
formulation in wet AMD met
its primary safety and
efficacy endpoints
Immunology & Inflammation
Dupixent (dupilumab)(a) -Peanut allergy -Atopic dermatitis in -Asthma in -Reported that Phase 3 -Submit sBLA (Q4 2021) Antibody to IL-4R alpha pediatrics (6 pediatrics (6-11 trial for atopic and Marketing subunit -Grass allergy months-5 years of years of age) (EU) dermatitis
in pediatrics Authorization
age) (Phase 2/3)(d) (6 months-5 years of age) Application ("MAA")
-EoE in adults and met its primary and key (first half 2022) for
-Eosinophilic adolescents (U.S.) secondary endpoints atopic dermatitis in
esophagitis pediatric patients (6
("EoE")(c) in -InitiatedPhase 3 study months-5 years of age)
adults(d), in hand and foot atopic
adolescents(d), and dermatitis
pediatrics
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Select Upcoming
Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review(h) 2021 Events to Date Milestones(i)
Dupixent (dupilumab)(a) -Chronic obstructive -Approved by FDA for -European Commission
(continued) pulmonary disease asthma in pediatrics ("EC") decision on
("COPD") (6-11 years of age) regulatory submission for
asthma in pediatrics
-Bullous pemphigoid -Reported that Phase 3 (6-11 years of age)
(Phase 2/3)(c) trial in CSU met its (first half 2022)
primary and key secondary
-Chronic spontaneous endpoints -Complete rolling sBLA
urticaria ("CSU") submission for EoE in
-Reported that Phase 3 adults and adolescents
-Prurigo nodularis trial in prurigo (first half 2022)
nodularis met its primary
-Allergic and key secondary -Report results from
bronchopulmonary endpoints Phase 2 study in peanut
aspergillosis ("ABPA") allergy (first half 2022)
-Reported that Part B of
-Chronic inducible the Phase 3 trial in -Report results from
urticaria adults and adolescents additional Phase 3 CSU
with EoE met its study (first half 2022)
-Chronic rhinosinusitis co-primary endpoints
without nasal polyposis -Report results from
-Approved by FDA for 200 additional Phase 3
-Allergic fungal mg auto-injector prurigo nodularis study
rhinosinusitis (first half 2022)
-Reported that Phase 2
trial of Dupixent in
combination with Aimmune
Therapeutics' AR101, an
oral immunotherapy, in
pediatric patients with
peanut allergy met its
primary and key secondary
endpoint
Kevzara (sarilumab)(a) -Polyarticular-course
Antibody to IL-6R juvenile idiopathic
arthritis ("pcJIA")
-Systemic juvenile
idiopathic arthritis
("sJIA")
Itepekimab(a) (REGN3500) -COPD
Antibody to IL-33
REGN1908-1909(f) -Cat allergy -Reported that Phase 2
Multi-antibody therapy to Fel study in cat allergic
d 1 patients with mild asthma
met its primary and key
secondary endpoints
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Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review(h) 2021 Events to Date Select Upcoming Milestones(i)
REGN5713-5714-5715 -Birch allergy -Initial Phase 3 study in birch
Multi-antibody therapy to Bet allergic patients with allergic
v 1 rhinoconjunctivitis met its
primary endpoint
REGN6490 -Palmo-plantar pustulosis
Antibody to IL-36R
Solid Organ Oncology
Libtayo (cemiplimab)(a)(g) -Metastatic or -First-line NSCLC, -Second-line cervical -Approved by FDA and EC for -FDA decision on sBLA for
Antibody to PD-1 locally advanced chemotherapy combination cancer (U.S. ) first-line NSCLC, monotherapy cervical cancer (target CSCC(d) action date ofJanuary 30 , -Second-line cervical -Approved by FDA and EC for BCC 2022) -Neoadjuvant CSCC cancer(e) -Reported Phase 3 chemotherapy -Submit MAA for cervical -Second-line cervical -Adjuvant CSCC combination trial in NSCLC met cancer (Q4 2021) cancer, ISA101b its overall survival primary combination endpoint; trial stopped early -Submit sBLA (Q4 2021) and based on Independent Data MAA (Q1 2022) for NSCLC, Monitoring Committee ("IDMC") chemotherapy combination recommendation -Reported positive results from Phase 3 trial in cervical cancer, demonstrating an overall survival benefit; trial stopped early based on IDMC recommendation REGN4018(f) -Platinum-resistant ovarian -Report results from Phase 1 Bispecific antibody targeting cancer study in platinum-resistant MUC16 and CD3 ovarian cancer (2022) REGN5668 -Ovarian cancer Bispecific antibody targeting MUC16 and CD28 REGN5678 -Prostate cancer -Report results from Phase 1 Bispecific antibody targeting study in prostate cancer PSMA and CD28 (2022) 33
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Clinical Program Select Upcoming
(continued) Phase 1 Phase 2 Phase 3 Regulatory Review(h) 2021 Events to Date Milestones(i)
REGN5093 -MET-altered
Bispecific antibody advanced NSCLC
targeting two
distinct MET epitopes
REGN5093-M114 -MET overexpressing
Bispecific advanced cancer
antibody-drug
conjugate targeting
two distinct MET
epitopes
Fianlimab(f) -Solid tumors and -Presented positive -Initiate Phase 3
(REGN3767) advanced data from Phase 1 study in first-line
Antibody to LAG-3 hematologic trial in combination metastatic melanoma
malignancies with Libtayo in (2022)
advanced melanoma at
American Society of
Clinical Oncology
Annual Meeting
REGN6569 -Solid tumors
Antibody to GITR
REGN7075 -Solid tumors
Bispecific antibody
targeting EGFR and
CD28
Hematology
Odronextamab -Certain B-cell -B-cell -Resumed enrollment -Initiate Phase 3
(REGN1979) malignancies(c) non-Hodgkin of patients with program (2022)
Bispecific antibody lymphoma follicular lymphoma
targeting CD20 and ("B-NHL") ("FL") and diffuse
CD3 (potentially large B-cell lymphoma
pivotal study) ("DLBCL") following
protocol amendments
REGN5458(f) -Multiple myeloma -Expand into earlier
Bispecific antibody (potentially lines of multiple
targeting BCMA and pivotal study) myeloma therapy (first
CD3 half 2022)
REGN5459(f) -Multiple myeloma
Bispecific antibody
targeting BCMA and
CD3
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Select Upcoming
Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review(h) 2021 Events to Date Milestones(i)
Pozelimab(f) (REGN3918) -CD55-deficient -Myasthenia gravis, cemdisiran -Submit BLA for
Antibody to C5; studied as protein-losing combination(n) CD55-deficient
monotherapy and in combination enteropathy(c), protein-losing enteropathy,
with cemdisiran monotherapy (potentially monotherapy (first half
pivotal study) 2022)
-Paroxysmal nocturnal -Initiate Phase 3 study in
hemoglobinuria ("PNH"), PNH, cemdisiran combination
cemdisiran (2022)
combination(c)(n)
Cemdisiran(n) -Immunoglobulin A
siRNA therapeutic targeting C5 nephropathy
REGN7257 -Aplastic anemia
Antibody to IL2Rg
NTLA-2001(m) -Hereditary -Reported positive interim
TTR gene knockout using transthyretin data from Phase 1 trial in
CRISPR/Cas9 amyloidosis with ATTRv-PN
polyneuropathy
("ATTRv-PN")(c)
REGN9933 -Thrombosis
Antibody to Factor XI
General Medicine
REGEN-COV (casirivimab and -COVID-19 multi-dose -COVID-19 dose-ranging -COVID-19 treatment in -COVID-19 treatment -Reported that Phase 3 trials -FDA decision on BLA (target imdevimab)(e)(k)(l)
safety study virology study in non-hospitalized patients and prevention
(
non-hospitalized patients and EU) patients met primary and key 2022) and EC decision on
SARS-CoV-2 virus -COVID-19 treatment in secondary endpoints regulatory submission (Q4
hospitalized patients -EUA amendment to 2021) for COVID-19 treatment
add COVID-19 -New England Journal of of non-hospitalized patients
-COVID-19 prevention treatment for Medicine published positive and prevention
hospitalized results from Phase 3 trial in
-COVID-19 prevention in patients and non-hospitalized COVID-19 -Submit BLA (Q4 2021) and
immunocompromised patients pre-exposure patients MAA (Q1 2022) for COVID-19
prophylaxis treatment in hospitalized
-NIH COVID-19 Treatment patients
Guidelines updated to
strongly recommend REGEN-COV
be used in non-hospitalized
COVID-19 patients at high
risk of clinical progression
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Clinical Program (continued) Phase 1 Phase 2 Phase 3 Regulatory Review(h) 2021 Events to Date Select Upcoming Milestones(i)
REGEN-COV (casirivimab and -Reported that Phase 3
imdevimab)(e)(k)(l) trial in hospitalized
(continued) COVID-19 patients met its
primary endpoint
-Reported that all tested
doses in Phase 2
dose-ranging study in
non-hospitalized patients
met its primary endpoint
-FDA updated EUA,
lowering dose to 1,200
mg, allowing for
subcutaneous injections
in certain circumstances,
and to include
post-exposure prophylaxis
-Approved by Ministry of
Health, Labour and
Welfare ("MHLW") for
COVID-19 treatment in
Japan
-Reported that Phase 3
prevention trial in
uninfected household
contacts of SARS-CoV-2
infected individuals met
its primary and key
secondary endpoints
-Positive results
reported from Phase 3
RECOVERY trial in
hospitalized patients
Praluent (alirocumab) -HeFH in pediatrics -Approved by FDA for HoFH
Antibody to PCSK9
36
--------------------------------------------------------------------------------
Table of Contents
Clinical Program Select Upcoming
(continued) Phase 1 Phase 2 Phase 3 Regulatory Review(h) 2021 Events to Date Milestones(i)
Fasinumab(j)(f) (REGN475) -Osteoarthritis pain of -Report additional
Antibody to NGF the knee or hip(e) longer-term safety results
from Phase 3 studies in
osteoarthritis pain of the
knee or hip (Q4 2021)
-Continue discussions with
regulatory authorities and
determine next steps for
the program (Q4 2021)
Evkeeza (evinacumab)(f) -Acute pancreatitis -Approved by FDA and EC for HoFH
Antibody to ANGPTL3 prevention
-Completed Phase 2 study in severe
hypertriglyceridemia
Garetosmab(f) (REGN2477) -Fibrodysplasia ossificans -Further review trial data
Antibody to Activin A progressiva and determine next steps
("FOP")(c)(d)(e) for the program (2022)
(potentially pivotal study)
REGN4461(f) -Generalized
Agonist antibody to leptin lipodystrophy(e)
receptor ("LEPR")
REGN5381 -Heart failure
Agonist antibody to NPR1
ALN-HSD(n)
RNAi therapeutic targeting -Nonalcoholic steatohepatitis
HSD17B13 ("NASH")
37
-------------------------------------------------------------------------------- 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. (a) In collaboration with Sanofi (b) In collaboration with Bayer outside ofthe United States (c) FDA granted orphan drug designation (d) FDA granted Breakthrough Therapy designation (e) FDA granted Fast Track designation (f) Sanofi did not opt-in to or elected not to continue to co-develop the product candidate. Under the terms of our agreement, Sanofi is entitled to receive royalties on any future sales of the product candidate. (g) Studied as monotherapy and in combination with other antibodies and treatments (h) Information in this column relates toU.S. , EU, andJapan regulatory submissions only (i) As described in the section preceding the table above and Part II, Item 1A. "Risk Factors," development timelines may be further subject to change as a result of the impact of the COVID-19 pandemic. (j) In collaboration with Teva andMitsubishi Tanabe Pharma (k) Certain trials conducted with theNational Institute of Allergy and Infectious Diseases ("NIAID"), part of theNIH (l) In collaboration with Roche (m) In collaboration with Intellia (n) In collaboration with Alnylam 38 -------------------------------------------------------------------------------- Table of Contents General 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. We expect to continue to incur substantial expenses related to our research and development activities, a portion of which we expect to be reimbursed by our collaborators. Also, our research and development activities outside our collaborations, the costs of which are not reimbursed, are expected to expand and require additional resources. We also expect to incur substantial costs related to the commercialization of our marketed products. Our financial results may fluctuate from quarter to quarter and will depend on, among other factors, the net sales of our products; the scope and progress of our research and development efforts; the timing of certain expenses; the continuation of our collaborations, in particular with Sanofi and Bayer, including our share of collaboration profits or losses from sales of commercialized products and the amount of reimbursement of our research and development expenses that we receive from collaborators; and the amount of income tax expense we incur, which is partly dependent on the profits or losses we earn in each of the countries in which we operate. 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. Additional Information - Clinical Development Programs REGEN-COV (casirivimab and imdevimab) Treatment Study - Non-Hospitalized Patients InFebruary 2021 , the IDMC for the REGEN-COV Phase 3 trial in non-hospitalized patients with COVID-19 found clear clinical efficacy for reducing the rate of hospitalization and death with both the 1,200 mg and 2,400 mg doses of REGEN-COV compared to placebo, and recommended stopping enrollment in the placebo group. InMarch 2021 , we announced positive top-line results from the Phase 3 trial in non-hospitalized COVID-19 patients. The trial met its primary endpoint, showing that REGEN-COV reduced the risk of hospitalization or death by 70% (1,200 mg dose IV) and 71% (2,400 mg dose IV) compared to placebo. The trial also met key secondary endpoints, including the ability to reduce symptom duration. InMarch 2021 , the Company also announced that all tested doses (IV: 2,400 mg, 1,200 mg, 600 mg and 300 mg; subcutaneous injections: 1,200 mg and 600 mg) in the Phase 2 dose-ranging trial in non-hospitalized COVID-19 patients met the primary endpoint. InApril 2021 , the Company announced positive data from the Phase 3 treatment trial in recently infected asymptomatic COVID-19 patients. The trial was being jointly run with the NIAID and met all primary and key secondary endpoints. The trial demonstrated that the 1,200 mg subcutaneous injection of REGEN-COV reduced the risk of progressing to symptomatic COVID-19 by 31% (primary endpoint), and by 76% after the third day. Treatment Study - Hospitalized Patients InJune 2021 , positive results were reported from the Phase 3 UK-based RECOVERY trial in hospitalized patients with severe COVID-19. The trial found that adding REGEN-COV to usual care reduced the risk of death by 20% in patients who had not mounted a natural antibody response on their own against SARS-CoV-2, compared to usual care alone. We have shared these data with regulatory authorities and requested that the EUA be expanded to include COVID-19 treatment for appropriate hospitalized patients. We were subsequently notified by the sponsor of the RECOVERY trial of a Good Clinical Practices ("GCPs") inspection of the trial by theUK MHRA, which found certain deviations from GCP compliance. The MHRA report stated that it found no evidence that the identified issues had impacted the overall data integrity to such an extent that the data would be unreliable based on those findings. However, it noted that certain aspects of data quality could not be fully assured and requested that certain corrective and preventative actions be taken; the sponsor of the trial has been in discussions with the MHRA and is responding to these findings. We have shared this information with the FDA. In the Phase 2/3 portion of the treatment study in hospitalized patients being run by the Company, REGEN-COV met the primary virologic endpoint, showing that REGEN-COV reduced viral load in these hospitalized patients, but did not achieve statistical significance in the pre-specified primary clinical endpoint: reduction in mechanical ventilation or death from day 6 to day 29 in patients with high viral load at baseline. However, four out of five secondary clinical endpoints of the study were nominally significant including an endpoint preferred by the FDA: reduction in mechanical ventilation or death from day 1 to day 29 in all patients who were SARS-CoV-2 PCR-positive at baseline. The relative risk reduction with REGEN-COV versus placebo ranged from approximately 24% to 47% on these various clinical endpoints. In addition, an approximately 36% reduction in all-cause mortality was seen from day 1 to day 29, supporting the results of the RECOVERY trial. 39 -------------------------------------------------------------------------------- Table of Contents InSeptember 2021 , the Company announced that a Phase 3 trial in patients hospitalized with COVID-19 met its primary endpoint. The trial showed that REGEN-COV significantly reduced viral load within 7 days of treatment in patients who entered the trial without having mounted their own antibody response (seronegative) and required low-flow or no supplemental oxygen. Patients who received REGEN-COV in this trial experienced a 36% reduced risk of death within 29 days of receiving treatment, and in patients who were seronegative when they entered the trial the risk of death was reduced by 56%. The FDA is currently reviewing the Company's request to expand the EUA to include treatment in hospital settings. Prevention Study InApril 2021 , we announced positive results from the Phase 3 COVID-19 prevention trial in household contacts of SARS-CoV-2 infected individuals. The trial, which was jointly run with the NIAID, part of theNIH , met its primary and key secondary endpoints, showing that REGEN-COV 1,200 mg subcutaneous injection reduced the risk of symptomatic infections by 81% in those who were not infected. During the third quarter of 2021, we also initiated a Phase 2 trial in high-risk children aged 12 years and under to assess the safety and tolerability of REGEN-COV. Agreements Related to COVID-19 U.S. Government In the first quarter of 2020, the Company announced an expansion of its Other Transaction Agreement with theBiomedical Advanced Research Development Authority ("BARDA"), pursuant to which theU.S. Department of Health and Human Services ("HHS") was obligated to fund certain of our costs incurred for research and development activities related to COVID-19 treatments. InJuly 2020 , the Company announced a$466 million agreement with entities acting at the direction of BARDA and theU.S. Department of Defense to manufacture and deliver filled and finished drug product of REGEN-COV to theU.S. government. InJanuary 2021 , the Company announced an agreement with an entity acting on behalf of theU.S. Department of Defense and HHS to manufacture and deliver additional filled and finished drug product of REGEN-COV to theU.S. government. Pursuant to the agreement, theU.S. government was obligated to purchase all filled and finished doses of drug product delivered byJune 30, 2021 , up to 1.25 million doses, at the lowest treatment dose authorized or approved by the FDA for the indication authorized under the EUA, resulting in payments to the Company of$2.625 billion (as described under "Products - REGEN-COV - Emergency and Temporary Use Authorizations" above). The Company has completed its final deliveries of drug product under the agreements described above. InSeptember 2021 , the Company announced an amendment to itsJanuary 2021 agreement to supply theU.S. government with an additional 1.4 million doses of REGEN-COV. Pursuant to the agreement, theU.S. government is obligated to purchase all filled and finished doses of such additional drug product delivered byJanuary 31, 2022 , resulting in payments to the Company of up to$2.940 billion in the aggregate. A number of factors may impact the quantity and timing of filled and finished drug product supply, including manufacturing considerations. Additionally, Roche will supply a portion of the doses to Regeneron to fulfill our agreement with theU.S. government (see "Roche" below for further details regarding our collaboration agreement with Roche). See "Results of Operations - Revenues" below for REGEN-COV net product sales recognized in connection with these agreements. Roche InAugust 2020 , we entered into a collaboration agreement with Roche to develop, manufacture, and distribute the casirivimab and imdevimab antibody cocktail. We lead global development activities for casirivimab and imdevimab, and the parties jointly fund certain on-going studies, as well as any mutually agreed additional new global studies to evaluate further the potential of casirivimab and imdevimab in treating or preventing COVID-19. Under the terms of the agreement, each party is obligated to dedicate a certain amount of manufacturing capacity to casirivimab and imdevimab each year. We distribute the product inthe United States and Roche distributes the product outside ofthe United States . The parties share gross profits from worldwide sales based on a pre-specified formula, depending on the amount of manufactured product supplied by each party to the market. 40 -------------------------------------------------------------------------------- Table of Contents Collaboration, License, and Other Agreements Sanofi Antibody We are collaborating with Sanofi on the global development and commercialization of Dupixent, Kevzara, and itepekimab (the "Antibody Collaboration"). See discussion below for updates related to the development and commercialization of Praluent effectiveApril 1, 2020 . Under the terms of the Antibody License and Collaboration Agreement (the "LCA"), Sanofi is generally responsible for funding 80%-100% of agreed-upon development costs. We are obligated to reimburse Sanofi for 30%-50% of worldwide development expenses that were funded by Sanofi based on our share of collaboration profits from commercialization of collaboration products. However, we are only required to apply 10% of our share of the profits from the Antibody Collaboration in any calendar quarter to reimburse Sanofi for these development costs Under our collaboration agreement, Sanofi records product sales for commercialized products, and Regeneron has the right to co-commercialize such products on a country-by-country basis. We co-commercialize Dupixent inthe United States and in certain countries outsidethe United States . We supply certain commercial bulk product to Sanofi. We and Sanofi equally share profits and losses from sales withinthe United States . We and Sanofi share profits outsidethe 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 outsidethe United States at 55% (Sanofi)/45% (us). In addition to profit and loss sharing, we are entitled to receive sales milestone payments from Sanofi. In the third quarter of 2020, the Company earned the first$50.0 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outsidethe United States (including Praluent) exceeding$1.0 billion on a rolling twelve-month basis. In the third quarter of 2021, the Company earned the second$50.0 million sales-based milestone from Sanofi, upon aggregate annual sales of antibodies outsidethe United States (including Praluent) exceeding$1.5 billion on a rolling twelve-month basis. We are entitled to receive up to an aggregate of$150.0 million in additional sales milestone payments from Sanofi. InApril 2020 , the Company and Sanofi entered into an amendment to the LCA in connection with, among other things, the removal of Praluent from the LCA such that (i) effectiveApril 1, 2020 , the LCA no longer governs the development, manufacture, or commercialization of Praluent and (ii) the quarterly period endedMarch 31, 2020 was the last quarter for which Sanofi and the Company shared profits and losses for Praluent under the LCA. The parties also entered into a Praluent Cross License & Commercialization Agreement (the "Praluent Agreement") pursuant to which, effectiveApril 1, 2020 , the Company, at its sole cost, became solely responsible for the development and commercialization of Praluent inthe United States , and Sanofi, at its sole cost, is solely responsible for the development and commercialization of Praluent outside ofthe United States . Under the Praluent Agreement, Sanofi will pay the Company a 5% royalty on Sanofi's net product sales of Praluent outsidethe United States untilMarch 31, 2032 . The Company will not owe Sanofi royalties on the Company's net product sales of Praluent inthe United States . Although each party will be responsible for manufacturing Praluent for its respective territory, the parties have entered into definitive supply agreements under which, for a certain transitional period, the Company will continue to supply drug substance to Sanofi and Sanofi will continue to supply finished product to Regeneron. With respect to any intellectual property or product liability litigation relating to Praluent, the parties have agreed that, effectiveApril 1, 2020 , Regeneron and Sanofi each will be solely responsible for any such litigation (including damages and other costs and expenses thereof) inthe United States and outsidethe United States , respectively, arising out of Praluent sales or other activities on or afterApril 1, 2020 (subject to Sanofi's right to set off a portion of any third-party royalty payments resulting from certain patent litigation proceedings against up to 50% of any Praluent royalty payment owed to Regeneron). The parties will each bear 50% of any damages arising out of Praluent sales or other activities prior toApril 1, 2020 . Immuno-Oncology We are collaborating with Sanofi on the development and commercialization of antibody-based cancer treatments in the field of immuno-oncology (the "IO Collaboration"). EffectiveDecember 31, 2018 , the Company and Sanofi entered into an Amended and Restated Immuno-oncology Discovery and Development Agreement (the "Amended IO Discovery Agreement"), which narrowed the scope of the existing discovery and development activities conducted by the Company ("IO Development Activities") under the original 2015Immuno -oncology Discovery and Development Agreement (the "2015 IO Discovery Agreement") to developing therapeutic bispecific antibodies targeting (i) BCMA and CD3 (the "BCMAxCD3 Program") and (ii) MUC16 and CD3 (the "MUC16xCD3 Program") through clinical proof-of-concept. The Amended IO Discovery Agreement provided for, among other things, Sanofi's prepayment for certain IO Development Activities regarding the BCMAxCD3 Program and the MUC16xCD3 Program. Under the terms of the Amended IO Discovery Agreement, the Company was required to conduct development activities with respect to (i) the BCMAxCD3 Program through the earlier of clinical proof-of-concept or the expenditure of$70.0 million (the "BCMAxCD3 Program Costs Cap") and (ii) the MUC16xCD3 Program through the earlier of clinical proof- 41 -------------------------------------------------------------------------------- Table of Contents of-concept or the expenditure of$50.0 million (the "MUC16xCD3 Program Costs Cap"). We are obligated to reimburse Sanofi for half of the development costs they funded that are attributable to clinical development of antibody product candidates under the Amended IO Discovery Agreement from our share of profits from commercialized IO Collaboration products. With regard to the BCMAxCD3 Program and the MUC16xCD3 Program, when the applicable Program Costs Cap was reached, Sanofi had the option to license rights to the product candidate and other antibodies targeting the same targets for, with regard to BCMAxCD3, immuno-oncology indications, and with regard to MUC16xCD3, all indications, pursuant to theImmuno -oncology License and Collaboration Agreement (the "IO License and Collaboration Agreement"), as amended. During the first quarter of 2021, Sanofi did not exercise its options to license rights to these product candidates; as a result, we retain the exclusive right to develop and commercialize such product candidates and Sanofi will receive a royalty on sales (if any). Under the terms of the IO License and Collaboration Agreement, the parties are co-developing and co-commercializing Libtayo. We have principal control over the development of Libtayo, and the parties share equally, on an ongoing basis, development and commercialization expenses for Libtayo. With regard to Libtayo, we lead commercialization activities inthe United States , while Sanofi leads commercialization activities outside ofthe United States and the parties equally share profits from worldwide sales. Sanofi has exercised its option to co-commercialize Libtayo inthe United States . We will be entitled to a milestone payment of$375.0 million in the event that global sales of Libtayo equal or exceed$2.0 billion in any consecutive twelve-month period. Bayer EYLEA outsidethe United States We and Bayer are parties to a license and collaboration agreement for the global development and commercialization outsidethe United States of EYLEA. Under the agreement, we and Bayer collaborate on, and share the costs of, the development of EYLEA. Bayer markets EYLEA outsidethe United States , where, for countries other thanJapan , the companies share equally in profits and losses from sales of EYLEA. InJapan , we are entitled to receive a tiered percentage of between 33.5% and 40.0% of EYLEA net sales through 2021, and thereafter, the companies will share equally in profits and losses from the sales of EYLEA. We are obligated to reimburse Bayer for 50% of the development costs that it has incurred under the agreement from our share of the collaboration profits (including payments to us based on sales inJapan ). The reimbursement payment in any quarter will equal 5% of the then outstanding repayment obligation, but never more than our share of the collaboration profits in the quarter unless we elect to reimburse Bayer at a faster rate. Withinthe United States , we retain exclusive commercialization rights to EYLEA and are entitled to all profits from such sales. Teva Fasinumab We and Teva are parties to a collaboration agreement to develop and commercialize fasinumab globally, excluding certain Asian countries that are subject to our collaboration agreement withMitsubishi Tanabe Pharma Corporation ("MTPC"). In connection with the agreement, Teva made a$250.0 million non-refundable up-front payment. We lead global development activities, and the parties share equally, on an ongoing basis, development costs under a global development plan. As ofSeptember 30, 2021 , we had earned an aggregate of$120.0 million of development milestones from Teva and we are entitled to receive up to an aggregate of$340.0 million in additional development milestones and up to an aggregate of$1.890 billion in contingent payments upon achievement of specified annual net sales amounts. We are responsible for the manufacture and supply of fasinumab globally. Withinthe United States , we will lead commercialization activities, and the parties will share equally in any profits or losses in connection with commercialization of fasinumab. In the territory outside ofthe United States , Teva will lead commercialization activities and we will supply product to Teva at a tiered purchase price, which is calculated as a percentage of net sales of the product (subject to adjustment in certain circumstances). Alnylam In 2018, we and Alnylam Pharmaceuticals, Inc. entered into a collaboration to discover RNA interference ("RNAi") therapeutics for NASH and potentially other related diseases, as well as to research, co-develop and commercialize any therapeutic product candidates that emerge from these discovery efforts (including ALN-HSD, which is currently in Phase 1 clinical development). ALN-HSD is being co-developed with Alnylam with terms generally consistent with the form of a Co-Commercialization Collaboration Agreement in connection with the 2019 collaboration agreement as described below. Alnylam 42 -------------------------------------------------------------------------------- Table of Contents is conducting the Phase 1 clinical trial for ALN-HSD and Regeneron will be responsible for all other development as the lead party. The parties share equally, on an ongoing basis, development expenses for ALN-HSD. 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. Under the terms of the agreement, we made an up-front payment of$400.0 million to Alnylam. For each program, we will provide Alnylam with a specified amount of funding at program initiation and at lead candidate designation, and Alnylam is eligible to receive up to an aggregate of$200.0 million in clinical proof-of-principle milestones for eye and CNS programs. In addition, during 2019, the parties entered into a Co-Commercialization Collaboration Agreement for a silencing RNA ("siRNA") therapeutic targeting the C5 component of the human complement pathway being developed by Alnylam, with Alnylam as the lead party, and a License Agreement for a combination product consisting of cemdisiran and pozelimab, with us as the licensee. Under the C5 siRNA Co-Commercialization Collaboration agreement, the parties share costs equally and will split profits (if commercialized); and under the License Agreement, the licensee is responsible for its own costs and expenses. The C5 siRNA License Agreement contains a flat low double-digit royalty payable to Alnylam on our potential future net sales of the combination product only subject to customary reductions, as well as up to$325.0 million in commercial milestones. 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. NTLA-2001, which is in clinical development, is subject to a co-development and co-commercialization arrangement pursuant to which Intellia will lead development and commercialization activities and the parties share an agreed-upon percentage of development expenses and profits (if commercialized). InMay 2020 , we expanded our existing collaboration with Intellia Therapeutics, Inc. to provide us with rights to develop products for additional in vivo CRISPR/Cas9-based therapeutic targets and for the companies to jointly develop potential products for the treatment of hemophilia A and B, with Regeneron leading development and commercialization activities. In addition, we also received non-exclusive rights to independently develop and commercialize ex vivo gene edited products. In connection with theMay 2020 agreement, we made a$70.0 million up-front payment and purchased shares of Intellia common stock for an aggregate purchase price of$30.0 million . BARDA We and BARDA are parties to agreements pursuant to which HHS provided certain funding to develop, test, and manufacture a treatment for Ebola virus infection. InJuly 2020 , HHS exercised its option under an existing agreement to provide up to$344.6 million of additional funding for the manufacture and supply of Inmazeb. We expect to deliver a pre-specified number of Inmazeb treatment doses over the course of approximately six years. See "Agreements Related to COVID-19 -U.S. Government " section above for information related to our COVID-19 agreements. Kiniksa As described under "Products" above, pursuant to a 2017 license agreement, we granted Kiniksa the right to develop and commercialize certain new indications for ARCALYST. During the first quarter of 2021, Kiniksa received marketing approval inthe United States for a new indication of ARCALYST, recurrent pericarditis, and, as a result, we received a$20.0 million milestone payment from Kiniksa. The quarterly period endedMarch 31, 2021 was the last quarter for which the Company recorded net product sales of ARCALYST. Following this approval, Kiniksa is solely responsible for theU.S. development and commercialization of ARCALYST in all approved indications, and Regeneron will continue to supply clinical and commercial product to Kiniksa. Kiniksa will pay Regeneron 50% of its profits from sales of ARCALYST and the parties will not share in any losses incurred by Kiniksa in connection with commercialization of ARCALYST. Corporate Information We were incorporated in theState of New York in 1988 and publicly listed in 1991. Our principal executive offices are located at777 Old Saw Mill River Road ,Tarrytown, New York 10591, and our telephone number at that address is (914) 847-7000. We make available free of charge on or through our Internet website (http://www.regeneron.com) our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and, if applicable, amendments to those reports filed or 43 -------------------------------------------------------------------------------- Table of Contents furnished pursuant to Section 13(a) or 15(d) of the Exchange Act, as soon as reasonably practicable after we electronically file such material with, or furnish it to, theSecurities and Exchange Commission ("SEC"). 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. 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 ourSEC filings, press releases, conference calls, and webcasts. The information contained on our websites and social media channels is not included as a part of, or incorporated by reference into, this report. Results of Operations Three and Nine Months EndedSeptember 30, 2021 and 2020 Net Income Three Months Ended Nine Months Ended September 30, September 30, (In millions, except per share data) 2021 2020 2021 2020 Revenues$ 3,452.8 $ 2,294.0 $ 11,120.0 $ 6,074.2 Operating expenses 1,605.6 1,240.9 4,812.9 3,664.6 Income from operations 1,847.2 1,053.1 6,307.1 2,409.6 Other income (expense) (30.6) (54.8) 515.3 176.2 Income before income taxes 1,816.6 998.3 6,822.4 2,585.8 Income tax expense 184.4 156.2 976.1 221.8 Net income$ 1,632.2 $ 842.1 $ 5,846.3 $ 2,364.0 Net income per share - diluted$ 14.33 $ 7.39 $ 52.29 $ 20.36 Revenues Three Months Ended Nine Months Ended September 30, September 30, (In millions) 2021 2020 $ Change 2021 2020 $ Change Net product sales in the United States: EYLEA$ 1,473.4 $ 1,318.3 $ 155.1 $ 4,245.1 $ 3,604.0 $ 641.1 Libtayo 78.4 71.6 6.8 225.5 196.6 28.9 Praluent 44.8 48.5 (3.7) 130.0 95.7 * * REGEN-COV 676.7 40.2 636.5 3,530.1 40.2 3,489.9 Evkeeza 6.6 - 6.6 9.1 - 9.1 ARCALYST - ** 3.6 ** 2.2 ** 9.3 ** Collaboration revenue: Sanofi 581.8 353.3 228.5 1,384.3 869.3 515.0 Bayer 365.0 299.9 65.1 1,036.9 825.5 211.4 Roche 127.1 - 127.1 361.8 - 361.8 Other revenue 99.0 158.6 (59.6) 195.0 433.6 (238.6) Total revenues$ 3,452.8 $ 2,294.0 $ 1,158.8 $ 11,120.0 $ 6,074.2 $ 5,045.8
* Net product sales of Praluent in
44
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Net Product Sales
Net product sales of EYLEA in the United States increased for the three and nine
months ended September 30, 2021 , compared to the same periods in 2020, primarily
due to higher sales volume (including the adverse impact of the COVID-19
pandemic on U.S. EYLEA demand during the three months ended June 30, 2020 ),
partly offset by an increase in sales-related deductions.
Effective April 1, 2020 , the Company became solely responsible for the
development and commercialization of Praluent in the United States and records
net product sales of Praluent in the United States . Refer to "Collaboration,
License, and Other Agreements - Sanofi - Antibody" section above for further
details.
During the three and nine months ended September 30, 2021 and 2020, net product
sales of REGEN-COV were recorded in connection with our agreements with the U.S.
government. Refer to "Agreements Related to COVID-19 - U.S. Government " section
above for further details.
Collaboration Revenue
Sanofi Collaboration Revenue
Three Months Ended Nine Months Ended
September 30, September 30,
(In millions) 2021 2020 2021 2020
Antibody:
Regeneron's share of profits in connection with
commercialization of antibodies $ 387.0 $ 212.8 $ 975.2 $ 555.6
Sales-based milestone earned 50.0 50.0 50.0 50.0
Reimbursement for manufacturing of commercial
supplies(1) 144.7 94.3 361.2 275.0
Total Antibody 581.7 357.1 1,386.4 880.6
Immuno-oncology:
Regeneron's share of losses in connection with
commercialization of Libtayo outside the United
States (3.0) (4.7) (12.6) (17.3)
Reimbursement for manufacturing of commercial
supplies(1) 3.1 0.9 10.5 6.0
Total Immuno-oncology 0.1 (3.8) (2.1) (11.3)
Total Sanofi collaboration revenue $ 581.8 (1) Corresponding costs incurred by us in connection with such production is recorded within Cost of collaboration and contract manufacturing
Antibody
Sanofi provides us with an estimate of our share of the profits or losses from commercialization of antibodies for the most recent fiscal quarter; these estimates are reconciled to actual results in the subsequent fiscal quarter, and our portion of the profits or losses is adjusted accordingly, as necessary. During the three and nine months endedSeptember 30, 2021 , the increase in our share of profits in connection with commercialization of antibodies, compared to the same periods of 2020, was driven by higher Dupixent profits. 45 -------------------------------------------------------------------------------- Table of Contents Regeneron's share of profits in connection with the commercialization of Dupixent, Praluent (throughMarch 31, 2020 ), and Kevzara is summarized below: Three Months Ended Nine Months Ended September 30, September 30, (In millions) 2021 2020 2021 2020 Dupixent, Praluent, and Kevzara net product sales(1) $ 1,760.7$ 1,142.6 $ 4,658.4$ 3,151.0 Regeneron's share of collaboration profits $ 425.8 $ 233.7 $ 1,080.2 $ 618.1 Reimbursement of development expenses incurred by Sanofi in accordance with Regeneron's payment obligation (38.8) (20.9) (105.0) (62.5) Regeneron's share of profits in connection with commercialization of antibodies $ 387.0 $ 212.8 $ 975.2 $ 555.6 Regeneron's share of collaboration profits as a percentage of Dupixent, Praluent, and Kevzara net product sales 22% 19% 21% 18%
(1) Global net product sales of Dupixent and Kevzara are recorded by Sanofi. The quarter ended
As described above under "Collaboration, License, and Other Agreements - Sanofi - Antibody", effectiveApril 1, 2020 , the Company became solely responsible for the development and commercialization of Praluent inthe United States . Under the new agreement, Sanofi is solely responsible for the development and commercialization of Praluent outside ofthe United States , and pays the Company a 5% royalty on Sanofi's net product sales of Praluent outsidethe United States . During the three months endedSeptember 30, 2021 and 2020, the Company earned$50.0 million sales-based milestones from Sanofi, upon aggregate annual sales of antibodies outsidethe United States (including Praluent) exceeding$1.5 billion and$1.0 billion , respectively, on a rolling twelve-month basis. Bayer Collaboration Revenue Three Months Ended Nine Months Ended September 30, September 30, (In millions) 2021 2020 2021 2020 Regeneron's net profit in connection with commercialization of EYLEA outside the United States$ 351.0 $ 287.9 $ 995.3 $ 772.6 Reimbursement for manufacturing of commercial supplies(1) 14.0 12.0 41.6 52.9 Total Bayer collaboration revenue$ 365.0
(1) Corresponding costs incurred by us in connection with such production is recorded within Cost of collaboration and contract manufacturing
Regeneron's net profit in connection with commercialization of EYLEA outside
Three Months Ended Nine Months Ended
September 30, September 30,
(In millions) 2021 2020 2021 2020
EYLEA net product sales outside the United
States $ 930.8 $ 780.0 $ 2,658.9 $ 2,102.7
Regeneron's share of collaboration profit from
sales outside the United States $ 365.8 $ 302.5 $ 1,039.9 $ 816.0
Reimbursement of development expenses incurred
by Bayer in accordance with Regeneron's payment
obligation (14.8) (14.6) (44.6) (43.4)
Regeneron's net profit in connection with
commercialization of EYLEA outside the United
States $ 351.0 $ 287.9 $ 995.3 $ 772.6
Regeneron's net profit as a percentage of EYLEA
net product sales outside the United States 38% 37% 37% 37%
46
-------------------------------------------------------------------------------- Table of Contents Bayer records net product sales of EYLEA outsidethe United States . Bayer provides us with an estimate of our share of the profit, including the percentage of sales inJapan that we earned, from commercialization of EYLEA outsidethe United States for the most recent fiscal quarter; these estimates are reconciled to actual results in the subsequent fiscal quarter, and our portion of the profit is adjusted accordingly, as necessary. Roche Collaboration Revenue As described above under "Agreements Related to COVID-19 - Roche", Roche distributes and records net product sales of the casirivimab and imdevimab antibody cocktail outsidethe United States , and the parties share gross profits from worldwide sales, depending on the amount of manufactured product supplied by each party to the market. Each quarter, a single payment is due from one party to the other to true-up the global gross profits between the parties. If Regeneron is to receive a true-up payment from Roche, such amount will be recorded to Collaboration revenue. If Regeneron is to make a true-up payment to Roche, such amount will be recorded to Cost of goods sold. During the three and nine months endedSeptember 30, 2021 , true-up payments owed from Roche in connection with this agreement were$127.1 million and$361.8 million , respectively. Roche provides us with an estimate of its gross profits for the most recent fiscal quarter; these estimates are reconciled to actual results in the subsequent fiscal quarter, and the true-up of global gross profits is adjusted accordingly, as necessary. Other Revenue Other revenue decreased during the three and nine months endedSeptember 30, 2021 , compared to the same periods of 2020, primarily due to lower amounts recognized in connection with our agreement with BARDA related to funding of certain development activities for COVID-19 antibodies, and, to a lesser extent, Inmazeb. Expenses Three Months Ended Nine Months Ended September 30, September 30, (In millions, except headcount data) 2021 2020 $ Change 2021 2020 $ Change Research and development(1)$ 665.4 $ 684.6 $ (19.2) $ 2,122.5 $ 1,990.5 $ 132.0 Selling, general, and administrative(1) 445.0 326.9 118.1 1,265.3 1,042.5 222.8 Cost of goods sold(2) 238.8 131.0 107.8 961.4 312.3 649.1 Cost of collaboration and contract manufacturing(3) 214.4 143.0 71.4 493.5 454.5 39.0 Other operating expense (income), net 42.0 (44.6) 86.6 (29.8) (135.2) 105.4 Total operating expenses$ 1,605.6 $ 1,240.9 $ 364.7 $ 4,812.9 $ 3,664.6 $ 1,148.3 Average headcount 10,030 8,657 1,373 9,766 8,314 1,452 (1) Includes costs incurred as well as cost reimbursements from collaborators who are not deemed to be our customers (2) Cost of goods sold primarily includes costs in connection with producing commercial supplies for products that are sold by Regeneron inthe United States (i.e., for which we record net product sales), any royalties we are obligated to pay on such sales, and amounts we are obligated to pay to Sanofi for its share of LibtayoU.S. gross profits. (3) Cost of collaboration and contract manufacturing includes costs we incur in connection with producing commercial drug supplies for collaborators and others. Operating expenses included a total of$136.9 million and$101.2 million for the three months endedSeptember 30, 2021 and 2020, respectively, and$413.3 million and$310.5 million for the nine months endedSeptember 30, 2021 and 2020, respectively, of non-cash compensation expense related to equity awards granted under our long-term incentive plans. 47 -------------------------------------------------------------------------------- Table of Contents 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. Direct research and development expenses are comprised primarily of costs paid to third parties for clinical and product development activities, including costs related to preclinical research activities, clinical trials, and the portion of research and development expenses incurred by our collaborators that we are obligated to reimburse. Indirect research and development expenses have not been allocated directly to each program, and primarily consist of costs to compensate personnel, overhead and infrastructure costs to maintain our facilities, and other costs related to activities that benefit multiple projects. 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. The table below also includes reimbursements of research and development expenses by collaborators, as when we are entitled to reimbursement of all or a portion of such expenses that we incur under a collaboration, we record those reimbursable amounts in the period in which such costs are incurred. Three Months Ended Nine Months Ended September 30, September 30, (In millions) 2021 2020* $ Change 2021 2020* $ Change Direct research and development expenses: Libtayo (cemiplimab)$ 34.6 $ 46.9 $ (12.3) $ 112.6 $ 118.4 $ (5.8) Dupixent (dupilumab) 34.1 31.3 2.8 98.6 97.4 1.2 EYLEA 23.5 19.7 3.8 78.3 48.5 29.8 REGEN-COV 15.4 70.2 (54.8) 320.1 84.3 235.8 Fasinumab 6.6 39.9 (33.3) 58.3 123.6 (65.3) Up-front payments related to license and collaboration agreements - - - - 85.0 (85.0) Other product candidates in clinical development and other research programs 106.3 115.2 (8.9) 300.5 387.7 (87.2) Total direct research and development expenses 220.5 323.2 (102.7) 968.4 944.9 23.5 Indirect research and development expenses: Payroll and benefits 241.9 205.1 36.8 711.8 596.5 115.3 Lab supplies and other research and development costs 38.3 41.8 (3.5) 105.1 107.2 (2.1) Occupancy and other operating costs 104.1 83.0 21.1 297.8 245.8 52.0 Total indirect research and development expenses 384.3 329.9 54.4 1,114.7 949.5 165.2 Clinical manufacturing costs 163.5 177.8 (14.3) 450.9 539.3 (88.4) Reimbursement of research and development expenses by collaborators (102.9) (146.3) 43.4 (411.5) (443.2) 31.7 Total research and development expenses$ 665.4 $ 684.6 $ (19.2) $ 2,122.5 $ 1,990.5 $ 132.0
* Certain prior year amounts have been reclassified to conform to the current year's presentation
Research and development expenses for the nine months endedSeptember 30, 2020 included the$70.0 million up-front payment and the amount paid in excess of the fair value of the shares purchased, or$15.0 million , in connection with our collaboration agreement with Intellia (see "Collaboration and License Agreements - Intellia" above). Direct research and development expenses in 2020 also include costs incurred in connection with Kevzara for the treatment of COVID-19 patients (included within "Other product candidates in clinical development and other research programs" in the table above). 48 -------------------------------------------------------------------------------- Table of Contents Reimbursement of research and development expenses by collaborators included reimbursements from Roche related to REGEN-COV of$10.5 million and$138.3 million for the three and nine months endedSeptember 30, 2021 , respectively, and$9.5 million for both the three and nine months endedSeptember 30, 2020 . Research and development expenses included non-cash compensation expense of$73.1 million and$55.9 million for the three months endedSeptember 30, 2021 and 2020, respectively, and$213.7 million and$169.5 million for the nine months endedSeptember 30, 2021 and 2020, respectively. 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 II, Item 1A. "Risk Factors" (including those relating to the disruptions caused by the COVID-19 pandemic). 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. 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. Selling, General, and Administrative Expenses Selling, general, and administrative expenses increased for the three and nine months endedSeptember 30, 2021 , compared to the same periods in 2020, primarily due to higher headcount-related costs and an increase in commercialization-related expenses for EYLEA, including direct-to-consumer advertising. In addition, the nine months endedSeptember 30, 2021 included increased commercialization-related expenses for Libtayo and costs associated with educational campaigns related to COVID-19. Selling, general, and administrative expenses also included non-cash compensation expense of$48.7 million and$35.9 million for the three months endedSeptember 30, 2021 and 2020, respectively, and$149.1 million and$114.4 million for the nine months endedSeptember 30, 2021 and 2020, respectively. Cost of Goods Sold Cost of goods sold increased for the three and nine months endedSeptember 30, 2021 , compared to the same periods in 2020, primarily due to the recognition of manufacturing costs in connection with product sales of REGEN-COV. In addition, Cost of goods sold included inventory write-offs and reserves totaling$38.7 million and$188.0 million for the three and nine months endedSeptember 30, 2021 , respectively (primarily related to REGEN-COV for the nine months endedSeptember 30, 2021 ). Inventory write-offs and reserves were$11.8 million and$23.6 million for the three and nine months endedSeptember 30, 2020 , respectively. Cost of Collaboration and Contract Manufacturing Cost of collaboration and contract manufacturing increased for the three and nine months endedSeptember 30, 2021 , compared to the same periods in 2020, primarily due to the recognition of manufacturing costs associated with higher sales of Dupixent. The increase for the nine months endedSeptember 30, 2021 was partly offset by the recognition of process validation costs during 2020 in connection with manufacturing Inmazeb under our BARDA agreement; such costs did not recur during 2021. Other Operating Expense (Income) Other operating expense (income), 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. During the three months endedSeptember 30, 2021 , we updated our estimate of the total research and development costs expected to be incurred (which resulted in a change to the estimate of the stage of completion) in connection with the Sanofi IO Collaboration, and, as a result, recorded a cumulative catch-up adjustment of$66.9 million as a reduction to other operating income. Other Income (Expense) Other income (expense), net, for the nine months endedSeptember 30, 2021 , compared to the same period in 2020, was primarily impacted by the recognition of higher unrealized gains on equity securities. 49 -------------------------------------------------------------------------------- Table of Contents Income Taxes Three Months Ended Nine Months Ended September 30, September 30, (In millions, except effective tax rate) 2021 2020 2021 2020 Income tax expense $ 184.4$ 156.2 $ 976.1$ 221.8 Effective tax rate 10.2 % 15.6 % 14.3 % 8.6 % Our effective tax rate for the three and nine months endedSeptember 30, 2021 was positively impacted, compared to theU.S. federal statutory rate, primarily by stock-based compensation, income earned in foreign jurisdictions with tax rates lower than theU.S. federal statutory rate, the foreign-derived intangible income deduction, and federal tax credits for research activities. In addition, the effective tax rate for the nine months endedSeptember 30, 2021 was positively impacted by the reversal of liabilities related to uncertain tax positions. Our effective tax rate for the three and nine months endedSeptember 30, 2020 was positively impacted, compared to theU.S. federal statutory rate, primarily by stock-based compensation, and, to a lesser extent, income earned in foreign jurisdictions with tax rates lower than theU.S. federal statutory rate and federal tax credits for research activities. Liquidity and Capital Resources Our financial condition is summarized as follows: September 30, December 31, (In millions) 2021 2020 $ Change Financial assets: Cash and cash equivalents$ 3,432.4 $ 2,193.7 $ 1,238.7 Marketable securities - current 2,355.2 1,393.3 961.9 Marketable securities - noncurrent 5,631.3 3,135.6 2,495.7$ 11,418.9 $ 6,722.6 $ 4,696.3 Borrowings: Long-term debt$ 1,979.6 $ 1,978.5 $ 1.1 Working capital: Current assets$ 13,775.4 $ 9,779.1 $ 3,996.3 Current liabilities 3,714.8 2,697.4 1,017.4$ 10,060.6 $ 7,081.7 $ 2,978.9 As ofSeptember 30, 2021 , we also had borrowing availability of$750.0 million under a revolving credit facility. Sources and Uses of Cash for the Nine Months EndedSeptember 30, 2021 and 2020
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