Regeneron Pharmaceuticals : Next Generation Monoclonal Antibodies are Active Against All Known Variants of Concern, Including Both Omicron and Delta

December 16, 2021

Regeneron's Next Generation Monoclonal Antibodies are Active Against All Known Variants of Concern, Including Both Omicron and Delta

Currently authorized REGEN-COV® (casirivimab and imdevimab) antibodies have diminished potency versus Omicron, but are active against predominant Delta variant

Regeneron has confirmed that multiple 'next generation' monoclonal antibodies from its large collection of fully human monoclonal antibodies targeting SARS-CoV-2 are active against the Omicron (B.1.1.529) and Delta (B.1.617.2) variants, as well as against the other variants of concern. Pending regulatory discussions, we anticipate entering the clinic in the first quarter of 2022.

While Regeneron's currently authorized REGEN-COV antibodies have diminished potency against Omicron, they are active against Delta, which currently is the most prevalent variant in the U.S.

About the REGEN-COV Antibody Cocktail

REGEN-COV (casirivimab and imdevimab) is a cocktail of two monoclonal antibodies that was designed specifically to block infectivity of SARS-CoV-2, the virus that causes COVID-19, using Regeneron's proprietary VelocImmune® and VelociSuite® technologies. The two potent, virus-neutralizing antibodies that form the cocktail bind non-competitively to the critical receptor binding domain of the virus's spike protein, which diminishes the ability of mutant viruses to escape treatment and protects against most spike variants that have arisen in the human population, as detailed in Celland Science.

REGEN-COV has not been approved by the FDA, but is currently authorizedfor emergency use for the treatment and post-exposure prophylaxis in certain high risk individuals. In

the U.S., REGEN-COV is not authorized as a substitute for vaccination against COVID-19, or for pre-exposure prophylaxis for prevention of COVID-19, or for use in patients who are hospitalized due to COVID-19 or require oxygen therapy, or for people currently using chronic oxygen therapy because of an underlying comorbidity who require an increase in baseline oxygen flow rate due to COVID-19. This authorization is for the duration of the declaration that circumstances exist justifying the authorization of the emergency uses under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner. Additional information about REGEN-COV in the U.S. is below (authorized uses and important safety information).

In the U.S., REGEN-COV is available for free to eligible peopleas part of a U.S. government funded program, and in September Regeneron announceda new agreement with

the U.S. government to supply an additional 1.4 million 1,200 mg doses of REGEN-COV

by January 2022. Information on how to access REGEN-COV throughout the U.S. is available from the Department of Health and Human Servicesand the National Infusion Center Association.

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The development and manufacturing of REGEN-COV have been funded in part with federal funds from the Biomedical Advanced Research and Development Authority, part of the U.S. Department of Health and Human Services' Office of the Assistant Secretary for Preparedness and Response, under OT number: HHSO100201700020C.

About Regeneron

Regeneron (NASDAQ: REGN) is a leading biotechnology company that invents life- transforming medicines for people with serious diseases. Founded and led for over 30 years by physician-scientists, our unique ability to repeatedly and consistently translate science into medicine has led to nine FDA-approved treatments and numerous product candidates in development, almost all of which were homegrown in our laboratories. Our medicines and pipeline are designed to help patients with eye diseases, allergic and inflammatory diseases, cancer, cardiovascular and metabolic diseases, pain, hematologic conditions, infectious diseases and rare diseases.

Regeneron is accelerating and improving the traditional drug development process through our proprietary VelociSuite technologies, such as VelocImmune, which uses unique genetically humanized mice to produce optimized fully human antibodies and bispecific antibodies, and through ambitious research initiatives such as the Regeneron Genetics Center, which is conducting one of the largest genetics sequencing efforts in the world.

For additional information about the company, please visit www.regeneron.comor follow @Regeneron on Twitter.

AUTHORIZED USES AND IMPORTANT SAFETY INFORMATION

Treatment:

REGEN-COV is authorized for the treatment of mild to moderate coronavirus disease 2019 (COVID-19) in adults and pediatric patients (12 years of age and older weighing at least 40 kg) with positive results of direct SARS-CoV-2 viral testing, and who are at high risk for progression to severe COVID-19, including hospitalization or death

Limitations of Authorized Use (Treatment)

• REGEN-COVis not authorized for use in patients:

1. who are hospitalized due to COVID-19, OR

1. who require oxygen therapy due to COVID-19, OR

• 1. who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19 related comorbidity
• Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID-19 requiring high-flow oxygen or mechanical ventilation

Post-Exposure Prophylaxis:

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REGEN-COV is authorized in adult and pediatric individuals (12 years of age and older weighing at least 40 kg) for post-exposure prophylaxis of COVID-19 in individuals who are at high risk for progression to severe COVID-19, including hospitalization or death, and are:

• not fully vaccinated or who are not expected to mount an adequate immune response to complete SARS-CoV-2 vaccination (for example, individuals with immunocompromising conditions including those taking immunosuppressive medications) and

1. have been exposed to an individual infected with SARS-CoV-2 consistent with close contact criteria per Centers for Disease Control and Prevention (CDC) or

1. who are at high risk of exposure to an individual infected with SARS-CoV-2 because of occurrence of SARS-CoV-2 infection in other individuals in the same institutional setting (for example, nursing homes, prisons)

Limitations of Authorized Use (Post-Exposure Prophylaxis)

• Post-exposureprophylaxis with REGEN-COV is not a substitute for vaccination against COVID-19
• REGEN-COVis not authorized for pre-exposure prophylaxis for prevention of COVID- 19

REGEN-COV has not been approved, but has been authorized for emergency use by FDA

These uses are authorized only for the duration of the declaration that circumstances exist justifying the authorization of the emergency use under section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-3(b)(1), unless the authorization is terminated or revoked sooner

Healthcare providers should review the Fact Sheet for Healthcare Providersfor information on the authorized uses of REGEN-COV and mandatory requirements of the EUA and must comply with the requirements of the EUA. The FDA Letter of Authorizationis available for reference, as well as the Dear Healthcare Provider Letterand Patient Fact Sheet

Criteria for Identifying High Risk Individuals

Please refer to the Fact Sheet for Healthcare Providers for criteria for identifying high risk individuals

SARS-CoV-2 Viral Variants

Circulating SARS-CoV-2 viral variants may be associated with resistance to monoclonal antibodies. Healthcare providers should review the Antiviral Resistance information in Section 15 of the Fact Sheet for details regarding specific variants and resistance, and refer to

the CDC website (https://www.cdc.gov/coronavirus/2019-ncov/transmission/variant-cases.html) as well as information from state and local health authorities regarding reports of viral variants of importance in their region to guide treatment decisions

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Important Safety Information

REGEN-COV (casirivimab and imdevimab) is an unapproved investigational therapy, and there are limited clinical data available. Serious and unexpected adverse events may occur that have not been previously reported with REGEN-COV use

• Contraindication:
  REGEN-COV is contraindicated in individuals with previous severe hypersensitivity reactions, including anaphylaxis, to REGEN-COV
• Warnings and Precautions:

1. Hypersensitivity Including Anaphylaxis and Infusion-Related
   Reactions: Serious hypersensitivity reactions, including anaphylaxis, have been observed with administration of REGEN-COV. If signs or symptoms of a clinically significant hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration and initiate appropriate medications and/or supportive therapy. Hypersensitivity reactions occurring more than 24 hours after the infusion have also been reported with the use of REGEN-COV under EUA. Infusion-related reactions, occurring during the infusion and up to 24 hours after the infusion, have been observed with administration of REGEN-COV. These reactions may be severe or life threatening
2. • Signs and symptoms of infusion-relatedreactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), chest pain or discomfort, weakness, altered mental status, headache, bronchospasm, hypotension, hypertension, angioedema, throat irritation, rash including urticaria, pruritus, myalgia, vasovagal reactions (e.g., pre-syncope, syncope), dizziness, fatigue and diaphoresis. Consider slowing or stopping the infusion and administer appropriate medications and/or supportive care if an infusion-related reaction occurs

1. Clinical Worsening After REGEN-COVAdministration: Clinical worsening of COVID-19 after administration of REGEN-COV has been reported and may include signs or symptoms of fever, hypoxia or increased respiratory difficulty, arrhythmia (e.g., atrial fibrillation, tachycardia, bradycardia), fatigue, and altered mental status. Some of these events required hospitalization. It is not known if these events were related to REGEN-COV use or were due to progression of COVID-19

1. Limitations of Benefit and Potential for Risk in Patients with Severe COVID- 19: Monoclonal antibodies, such as REGEN-COV, may be associated with worse clinical outcomes when administered to hospitalized patients with COVID- 19 requiring high-flow oxygen or mechanical ventilation. Therefore, REGEN-COV is not authorized for use in patients who are hospitalized due to COVID-19, OR who require oxygen therapy due to COVID-19, OR who require an increase in baseline oxygen flow rate due to COVID-19 in those on chronic oxygen therapy due to underlying non-COVID-19-related comorbidity

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• Adverse Reactions:

1. COV-2067(Treatment): Infusion-related reactions (adverse event assessed as causally related by the investigator) of grade 2 or higher severity have been observed in 10/4,206 (0.2%) of those who received REGEN-COV at the authorized dose or a higher dose. Three subjects receiving the 8,000 mg dose of REGEN-COV, and one subject receiving the 1,200 mg casirivimab and 1,200 mg imdevimab, had infusion-related reactions (urticaria, pruritus, flushing, pyrexia, shortness of breath, chest tightness, nausea, vomiting, rash) which resulted in permanent discontinuation of the infusion. All events resolved. Anaphylactic reactions have been reported in the clinical program in subjects receiving REGEN-COV. The events began within 1 hour of completion of the infusion, and in at least one case required treatment including epinephrine. The events resolved

1. COV-2069 (Post-exposureprophylaxis): In subjects who were SARS-CoV-2 negative at baseline (Cohort A), injection site reactions (all grade 1 and 2) occurred in 55 subjects (4%) in the REGEN-COV group and 19 subjects (2%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were erythema and pruritus. Hypersensitivity reactions occurred in 2 subjects (0.2%) in the REGEN-COV group and all hypersensitivity reactions were grade 1 in severity. In subjects who were SARS-CoV-2 positive at baseline (Cohort B), injection site reactions, all of which were grade 1 or 2, occurred in 6 subjects (4%) in the REGEN-COV group and 1 subject (1%) in the placebo group. The most common signs and symptoms of injection site reactions which occurred in at least 1% of subjects in the REGEN-COV group were ecchymosis and erythema

• 1. COV-2093(Subcutaneous Dosing): Injection site reactions occurred in 12% and 4% of subjects following single dose administration in the REGEN-COV and placebo groups, respectively. Remaining safety finding following subcutaneous administration in the REGEN-COV group were similar to the safety findings observed with intravenous administration in COV-2067. With repeat dosing, injection site reactions occurred in 252 subjects (35%) in the REGEN-COV group and 38 subjects (16%) in the placebo group; all injection site reactions were grade 1 or 2 in severity. Hypersensitivity reactions occurred in 8 subjects (1%) in the REGEN-COV group; and all hypersensitivity reactions were grade 1 or 2 in severity. There were no cases of anaphylaxis
• Patient Monitoring Recommendations: Clinically monitor patients during dose administration and observe patients for at least 1 hour after intravenous infusion or subcutaneous dosing is complete
• Use in Specific Populations:
• 1. Pregnancy: There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. REGEN-

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