Regeneron?Pharmaceuticals, Inc.?(NASDAQ:?REGN) today?welcomed positive results from the largest trial assessing any monoclonal antibody treatment in patients hospitalized with severe COVID-19. The UK RECOVERY trial found that adding investigational 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 on its own. "These results are very exciting. The hope was that by giving a combination of antibodies targeting the SARS-CoV-2 virus we would be able to reduce the worst manifestations of COVID-19," said Sir?Peter Horby, Professor of Emerging Infectious Diseases in the Nuffield Department of Medicine,?University of Oxford, and Joint Chief Investigator for the RECOVERY trial. "There was, however, great uncertainty about the value of antiviral therapies in late-stage COVID-19 disease. It is wonderful to learn that even in advanced COVID-19 disease, targeting the virus can reduce mortality in patients who have failed to mount an antibody response of their own." RECOVERY is the first trial large enough to definitively determine whether REGEN-COV reduces mortality in patients hospitalized with severe COVID-19. Previous Phase 3 trials in non-hospitalized COVID-19 patients have shown that REGEN-COV reduced viral levels, shortened the time to resolution of symptoms and significantly reduced the risk of hospitalization or death. In a?Phase 1/2 trial?in hospitalized patients, REGEN-COV also rapidly reduced viral levels, with preliminary evidence suggesting that it lowered the risk of death or receiving mechanical ventilation, with the benefit driven by patients who entered the trial without having mounted a natural antibody response of their own (seronegative); and in the absence of REGEN-COV treatment, seronegative patients had higher mortality rates than patients who had already mounted their own immune response (seropositive). Based on the above Phase 1/2 data, the independently-run RECOVERY trial prospectively focused on seronegative patients. Similar to the prior trial, patients in RECOVERY who received usual care alone had double the mortality rate at day 28 if they were seronegative?(30%) compared to seropositive (15%); approximately one-third of hospitalized patients were seronegative (n=3,153), one-half were seropositive (n=5,272) and one-sixth had unknown serostatus (n=1,360). The mean age of patients for this comparison was 62 years, and more than 90% received corticosteroids across all groups. The primary outcome of RECOVERY showed that adding REGEN-COV 8,000 mg to usual care reduced all-cause mortality by 20% in seronegative patients (primary analysis population), compared to usual care alone (24% of patients in the REGEN-COV group died versus 30% in the usual care group by day 28; rate ratio [RR]: 0.80; 95% confidence interval [CI]: 0.70-0.91; p=0.001). When combining the larger seropositive group (as well as those with unknown status) with the seronegative patients, there was no longer a significant effect on 28-day mortality (overall 20% of patients in the REGEN-COV group died, versus 21% in the usual care group;?RR: 0.96; 95% CI: 0.86-1.03; p=0.17). "Definitive Phase 3 trials have now demonstrated that REGEN-COV can alter the course of COVID-19 infection from prevention, to very early infection, all the way through to when patients are on a ventilator in the hospital," said?George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at Regeneron. "We are incredibly grateful to the RECOVERY team, participating investigators and patients for conducting this in-depth analysis, and hope that the results mean that even more patients may soon be able to benefit from this life-saving medicine. We intend to rapidly discuss these results with regulatory authorities, including in the U.S. where we will ask for our EUA to be expanded to include appropriate hospitalized patients." Among seronegative patients in the RECOVERY trial, the median duration of hospital stay was 4 days shorter in the REGEN-COV group (13 days versus 17 days), and the proportion of patients discharged alive by day 28 was greater (64% versus 58%; RR: 1.19; 95% CI: 1.08-1.30). Among the seronegative patients not on invasive mechanical ventilation at baseline, the risk of progressing to the composite endpoint of invasive mechanical ventilation or death was lower among the REGEN-COV group than the usual care group (30% versus 37%; RR: 0.83; 95% CI: 0.75-0.92). No such benefits were seen in the overall trial population (combining patients with negative, positive, or unknown serostatus). "The RECOVERY trial has shown that in patients who had not made their own antibodies against SARS-CoV-2, treating them with REGEN-COV antibodies dramatically reduced their risk of dying or being on a ventilator, and also shortened how many days they remained in the hospital," said?David Weinreich, M.D., Executive Vice President, Global Clinical Development at Regeneron. "The trial was conducted at a time when most patients had not been fully vaccinated. These results provide hope to patients who have a poor immune response to either the vaccine or natural infection, as well as those who are exposed to variants for whom their existing antibodies might be sub-optimal." Multiple analyses, including a recent publication in?Cell, have shown that REGEN-COV retains potency against the main variants of concern circulating within the U.S.; consequently, REGEN-COV remains available for use in all 50 states. REGEN-COV retains potency against variants including P.1 (first identified in?Brazil, now classified by the World Health Organization [WHO] as Gamma), B.1.351 (first identified in?South Africa, now classified by the WHO as Beta) and B.1.162.2 (first identified in?India, now classified by the WHO as Delta). The combined frequency of the P.1 and B.1.351 variants now exceeds 10% of new COVID-19 diagnoses across eight states (Arizona,?California,?Florida,?Illinois,?Indiana,?Massachusetts,?Oregon?and?Washington), and the prevalence of these and other variants continues to be closely monitored. Today's data in hospitalized patients follow multiple positive Phase 3 results earlier this year from Regeneron-sponsored trials assessing the ability of REGEN-COV to treat outpatients already infected with SARS-COV-2 (including?symptomatic outpatients?and?recently infected asymptomatic patients), and also to?prevent infection?in close contacts of infected individuals. REGEN-COV has not been approved by the U.S. Food and Drug Administration (FDA), but is currently?authorized?in the U.S. under an Emergency Use Authorization (EUA) to treat mild-to-moderate COVID-19 in adults and pediatric patients (12 years of age and older weighing =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. This use is 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. Regeneron is in discussions with the FDA to expand the current EUA to other populations, including the prevention and hospitalized patient settings. Later this summer, Regeneron expects to submit a full Biologics License Application (BLA) for REGEN-COV. Regeneron is?collaborating?with Roche to increase global supply of REGEN-COV. Regeneron is responsible for development and distribution of the treatment in the U.S., and Roche is primarily responsible for development and distribution outside the U.S. The companies share a commitment to making the antibody cocktail available to COVID-19 patients around the globe and will support access in low- and lower-middle-income countries through drug donations to be made in partnership with public health organizations. The development and manufacturing of REGEN-COV have been funded in part with federal funds from the Biomedical Advanced Research and Development Authority (BARDA), 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 the Trial
The RECOVERY trial (Randomised Evaluation of COVid-19 thERapY) was conducted by the registered clinical trials units in the Nuffield Department of Population Health in partnership with the Nuffield Department of Medicine. The trial was supported by a grant to the?University of Oxford?from?UK Research and Innovation/National Institute for Health Research?(NIHR)?and by core funding provided by?NIHR Oxford Biomedical Research Centre,?Wellcome, the?Bill and Melinda Gates Foundation, the?Department for International Development,?Health Data Research?UK, the?Medical Research Council Population Health Research Unit?and?NIHR Clinical Trials Unit Support Funding. Between?September 18, 2020?and?May 22, 2021, 9,785 patients hospitalized with COVID-19 were randomly allocated to receive usual care plus REGEN-COV (8,000 mg by intravenous infusion) or usual care alone as part of the RECOVERY trial. Usual care was determined by individual facilities and clinicians, and could include steroids and remdesivir. Follow-up is complete for 99% of participants. The trial involved many thousands of doctors, nurses, pharmacists, and research administrators at 176 hospitals across the whole of the?UK, supported by staff at the NIHR Clinical Research Network,?NHS?DigiTrials,?Public Health England, Department of Health & Social Care, the Intensive Care National Audit & Research Centre, Public Health Scotland, the Secure Anonymised Information Linkage at?University of?Swansea, and the NHS in?England,?Scotland,?Wales?and Northern Ireland. About the REGEN-COV Antibody Cocktail
REGEN-COV (casirivimab and imdevimab) is a cocktail of two monoclonal antibodies (also known as REGN10933 and REGN10987) 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 spike variants that have arisen in the human population, as detailed in?Science. Under an EUA, REGEN-COV is available throughout the U.S. ? information on availability in your area is available from the?Department of Health and Human Services?and the?National Infusion Center Association. REGEN-COV can be administered by intravenous infusion (as short as 20 minutes) or by subcutaneous injection (four injections), which is an alternative when intravenous infusion is not feasible and would lead to a delay in treatment. It is now authorized as a co-formulated single vial, or in individual vials to be administered together. In the U.S., REGEN-COV is not authorized 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. About Regeneron's?VelocImmune?Technology
Regeneron's?VelocImmune?technology utilizes a proprietary genetically engineered mouse platform endowed with a genetically humanized immune system to produce optimized fully human antibodies. When Regeneron's President and Chief Scientific Officer?George D. Yancopoulos?was a graduate student with his mentor?Frederick W. Alt?in 1985, they were the first to?envision?making such a genetically humanized mouse, and Regeneron has spent decades inventing and developing?VelocImmune?and related?VelociSuite?technologies. Dr. Yancopoulos and his team have used?VelocImmune?technology to create approximately a quarter of all original, FDA-approved fully human monoclonal antibodies currently available. This includes REGEN-COV?(casirivimab and imdevimab), Dupixent^??(dupilumab), Libtayo^??(cemiplimab-rwlc), Praluent^??(alirocumab), Kevzara^??(sarilumab), Evkeeza^??(evinacumab-dgnb) and Inmazeb? (atoltivimab, maftivimab and odesivimab-ebgn). AUTHORIZED USE AND IMPORTANT SAFETY INFORMATION
REGEN-COV, (casirivimab and imdevimab) co-formulated product and REGEN-COV (casirivimab and imdevimab) supplied as individual vials to be administered together, 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. [see Limitations of Authorized Use]

• REGEN-COV has not been approved, but has been authorized for emergency use by FDA
• This use is 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 Providers?for information on the authorized use of REGEN-COV and mandatory requirements of the EUA and must comply with the requirements of the EUA. The?FDA Letter of Authorization?is available for reference,?as well as the?Dear Healthcare Provider Letter?and?Patient Fact Sheet

Limitations of Authorized Use

• REGEN-COV (casirivimab and imdevimab) 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
• Benefit of treatment with REGEN-COV has not been observed in patients hospitalized due to 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

Definition of High Risk Patients
The following medical conditions or other factors may place adults and pediatric patients (age 12-17 years and weighing at least 40 kg) at higher risk for progression to severe COVID-19:

• Older age (for example, age =65 years of age)
• Obesity or being overweight (for example, BMI >25 kg/m², or if age 12-17, have BMI =85th percentile for their age and gender based on CDC growth charts,?https://www.cdc.gov/growthcharts/clinical_charts.htm)
• Pregnancy
• Chronic kidney disease
• Diabetes
• Immunosuppressive disease or immunosuppressive treatment
• Cardiovascular disease (including congenital heart disease) or hypertension
• Chronic lung diseases (for example, chronic obstructive pulmonary disease, asthma [moderate-to-severe], interstitial lung disease, cystic fibrosis and pulmonary hypertension)
• Sickle cell disease
• Neurodevelopmental disorders (for example, cerebral palsy) or other conditions that confer medical complexity (for example, genetic or metabolic syndromes and severe congenital anomalies)
• Having a medical-related technological dependence (for example, tracheostomy, gastrostomy, or positive pressure ventilation (not related to COVID 19))

Other medical conditions or factors (for example, race or ethnicity) may also place individual patients at high risk for progression to severe COVID-19 and authorization of REGEN-COV under the EUA is not limited to the medical conditions or factors listed above. For additional information on medical conditions and factors associated with increased risk for progression to severe COVID, see the CDC website:?https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Healthcare providers should consider the benefit-risk for an individual patient. 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. 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

• Warnings and Precautions:
  • 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
    • Signs and symptoms of infusion-related reactions may include: fever, difficulty breathing, reduced oxygen saturation, chills, nausea, arrythmia (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
  • Clinical Worsening After REGEN-COV Administration:?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, arrythmia (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
  • Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19:?Benefit of treatment with?REGEN-COV has not been observed in patients hospitalized due to 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
• Adverse Reactions:
  • In a pooled phase 1/2/3 analysis of COV-2067, 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
  • Overall, in Phase 1/2/3, 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
  • The safety with subcutaneous administration is based on analysis from HV-2093, a randomized double-blind, placebo-controlled trial evaluating the safety and pharmacokinetic profile in healthy volunteer adult subjects. Subjects were randomized 3:1 to REGEN-COV (n=729) or placebo (n=240).?Injection site reactions were observed in 12% and 4% of subjects following single dose administration in the casirivimab and imdevimab, and placebo arms respectively; the remaining safety findings with subcutaneous administration in the casirivimab and imdevimab arm were similar to the safety findings observed with intravenous administration in COV-2067
• Patient Monitoring Recommendations: Clinically monitor patients during infusion and observe patients for at least 1 hour after intravenous infusion or subcutaneous dosing is complete
• Use in Specific Populations:
  • Pregnancy:?There are insufficient data to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. REGEN-COV should only be used during pregnancy if the potential benefit outweighs the potential risk for the mother and the fetus
  • Lactation:?There are no available data on the presence of casirivimab and/or imdevimab in human milk or animal milk, the effects on the breastfed infant, or the effects of the drug on milk production. The development and health benefits of breastfeeding should be considered along with the mother's clinical need for REGEN-COV and any potential adverse effects on the breastfed child from REGEN-COV or from the underlying maternal condition

About Regeneron
Regeneron (NASDAQ:?REGN) is a leading biotechnology company that invents life-transforming medicines for