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Copyright © 2021 BLUE ROOM™
By Ian Carter
ANOTHER
COVID-19
THERAPY
MAY BE
ON ITS WAY
EVERYTHING TO KNOW
"As we expected, the virus continues to mutate, and these data show the continued
ability of REGEN-COV™ to neutralize emerging strains, further validating our
multi-antibody cocktail approach to infectious diseases," 1
George D. Yancopoulos, M.D., Ph.D.
President and Chief Scientific Officer at Regeneron
1
The two potent, virus-neutralizing antibodies that form REGN-COV2 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.
Regeneron
REGEN—COV
THE TIMELINE
The following details Regeneron’s vaccine timeline from the onset of the first wave of COVID-19
until January 27, 2021. (It has been nearly 12 months since Regeneron began publishing press
releases in regards to their COVID-19 therapies.)
The United States recorded its first case of the novel Coronavirus SARS-CoV-2 on January 21,
2020 and Regeneron began its collaboration with the U.S. HHS to find a therapy to treat infected
persons.
They believed that their Kevzara IL-6, an antibody developed within their VelocImmune®
technology, had therapeutic attributes that could potentially lighten the body's hyperactive
immune response to the COVID-19 virus. Kevzara IL-6 was designed to stop lung inflammation,
which was hypothesized to significantly reduce the chance of severe cases and potentially even
death.
This drug, however, proved ineffective and its clinical trials were cancelled after a significant
portion of patients participating in the study experienced adverse reactions to the treatment.
Luckily, Regeneron was also working on an antibody “cocktail” or a mixture of two different
monoclonal antibodies called “REGN-COV”, specifically designed to bind to the receptor points
of the Coronavirus’ spike protein.
So far the trials seem to be effective and the United States Government has agreed to accept
up to 1.5 million doses of REGN-COV for Emergency Use Authorization (EUA).
Everything To Know
2
Regeneron
REGEN—COV
While other large pharmaceutical companies are trying and failing to develop their own vaccine
candidates, it will be interesting to see if Regeneron can create a viable COVID-19 vaccine that
will join the likes of Pfizer-BioNtech and Moderna. As of now the CDC expects Astrazeneca,
Janssen and Novavax to finish development of their own vaccine candidates because they have
been in Phase 3 trials since at least December 28th, 2020.
COVID-19 ~ Clinical Trials Timeline
Kevzara IL-6 to stop lung inflammation & Antibody cocktail therapy
February 4. 2020: Regeneron Expands Collaboration with the U.S. Department of Health and
Human Services (HHS) to Develop Antibody Treatments for New Coronavirus
“The life-saving results seen with our investigational Ebola therapy last year underscore
the potential impact of Regeneron’s rapid response platform for addressing emerging
outbreaks”
George D. Yancopoulos, M.D., Ph.D. President and CSO of Regeneron
Everything To Know
3
Regeneron
REGEN—COV
March 16, 2020: Regeneron and Sanofi Begin Global Kevzara (Sarilumab) Clinical Trial
Program in Patients with Severe COVID-19
● Kevzara is a fully-human monoclonal antibody that inhibits the interleukin-6 (IL-6)
pathway by binding and blocking the IL-6 receptor. IL-6 may play a role in driving the
overactive inflammatory response in the lungs of patients who are severely or critically ill
with COVID-19.
○ Scientists have preliminary evidence that IL-6 may play a key role in driving the
inflammatory response that causes acute respiratory distress syndrome in
patients critically ill from COVID-19
○ 21-patient trial in China
○ Patients experienced rapidly reduced fevers and 75% of patients (15 out of 20)
reduced their need for supplemental oxygen within days of receiving a different
IL-6 receptor antibody (tocilizumab)
● “Regeneron is also rapidly advancing a novel antibody cocktail for the prevention and
treatment of COVID-19, which we hope to have available for human testing this summer”
March 17, 2020: Regeneron Announces Important Advances in Novel COVID-19 Antibody
Program
● Regeneron scientists have now isolated hundreds of virus-neutralizing, fully human
antibodies from the company’s VelocImmune® mice, which have been genetically
modified to have a human immune system
● Regeneron has also isolated antibodies from humans who have recovered from
COVID-19, in order to maximize the pool of potentially potent antibodies
● Will select the top two antibodies for a cocktail treatment based on potency and binding
ability to the SARS-CoV-2 spike protein.2 Using a multiple antibody approach allows for
targeting of different parts of the virus and may help protect against multiple viral
variants
● The company is working toward the goal of producing hundreds of thousands of
prophylactic doses per month by the end of the summer and hopes to have smaller
quantities available for initial clinical testing at the beginning of the summer
2
All coronaviruses have a single glycoprotein on the virus surface called the spike protein, which is the
protein on the virus cell surface that binds to the host cell and is required for infectivity. Regeneron’s
SARS-CoV-2 antibodies will target the spike protein in order to block its interaction with the host cell, and
thus neutralize the virus.
Everything To Know
4
Regeneron
REGEN—COV
March 30, 2020: First Patient Outside U.S. Treated in Global Kevzara (Sarilumab) Clinical Trial
Program for Patients with Severe COVID-19
● The global clinical program has now been initiated in Italy, Spain, Germany, France,
Canada, Russia and the United States - all countries that have been impacted by
COVID-19
● This is the second multi-center, double-blind, Phase 2/3 trial as part of the Kevzara
COVID-19 program, and the companies are continuing to work with health authorities
around the world to secure initiation at additional sites
● “These trials will provide important data to determine whether Kevzara ameliorates the
life-threatening complications of COVID-19 infections by counteracting the overactive
inflammatory immune response in the lungs when damages by the virus”
April 27, 2020: Regeneron and Sanofi Provide Update on U.S. Phase 2/3 Adaptive-Designed
Trial of Kevzara (Sarilumab) In Hospitalized COVID-19 Patients
● Independent Data Monitoring Committee recommended continuing ongoing Phase 3
trial only in the more advanced “critical” group with Kevzara higher-dose versus placebo
and discontinuing less advanced “severe” group
● Phase 3 trial will be amended to enroll only “critical” patients
● Phase 3 trial will also be amended to discontinue lower-dose Kevzara (200 mg); all new
patients to receive either higher-dose Kevzara (400 mg) or placebo
● No new safety findings were observed for Kevzara use in COVID-19 patients
June 1, 2020: Regeneron and Intellia Therapeutics Expand Collaboration to Develop
CRISPR/CAS9-Based Treatments (Not COVID-19 Related)
● Regeneron and Intellia to co-develop potential hemophilia A and B treatments using their
jointly-owned targeted transgene insertion capabilities
● Regeneron gains rights to develop products for additional in vivo targets and new rights
for ex vivo product development
● Intellia receives $100 million through upfront cash and equity investment
Everything To Know
5
Regeneron
REGEN—COV
June 11, 2020: Regeneron Begins First Clinical Trials Of Anti-Viral Antibody Cocktail
REGN-CoV2 For The Treatment And Prevention Of COVID-19
● The REGN-CoV2 clinical program will consist of four separate study populations:
○ Hospitalized COVID-19 patients
○ Non-Hospitalized symptomatic COVID-19 patients
○ Uninfected people in groups that are at high risk of exposure (such as healthcare
workers or first responders)
○ Uninfected people with close exposure to a COVID-19 patient
● REGN-COV2 is an investigational dual antibody cocktail for the prevention and treatment
of COVID-19
● “Ultimately, the world needs multiple solutions for COVID-19, and the innovative
biopharma industry is collectively working hard to help as many people as possible with
a variety of complementary approaches”
June 11, 2020: Two Science Publications Highlight Potential of REGN-COV2 Antiviral Antibody
Cocktail To Protect Against SARS-COV-2 Escape Mutants
● Regeneron utilized ‘rapid response’ VelociSuite technologies to identify pairs of potent
and complementary antibodies that could be combined into antibody ‘cocktails’ for
COVID-19
● Cocktail approach protects against viral mutants by requiring simultaneous mutation at
multiple genetic positions for viral escape
July 2, 2020: Regeneron and Sanofi Provide Update on Kevzara (Sarilumab) Phase 3 U.S. Trial
In COVID-19 Patients
● Regeneron and Sanofi today announced that the U.S. Phase 3 trial of Kevzara
(sarilumab) 400 mg in COVID-19 patients requiring mechanical ventilation did not meet
its primary and key secondary endpoints when Kevzara was added to best supportive
care compared to best supportive care alone (placebo)
● In the primary analysis group, adverse events were experienced by 80% of Kevzara
patients and 77% of placebo patients
● Serious adverse events that occurred in at least 3% of patients and more frequently
among Kevzara patients were multiorgan dysfunction syndrome (6% Kevzara, 5%
placebo) and hypotension (4% Kevzara, 3% placebo)
Everything To Know
6Regeneron
REGEN—COV
July 6, 2020: Regeneron Announces Start of REGN-COV2 Phase 3 COVID-19 Prevention Trial
In Collaboration With National Institute of Allergy and Infectious Diseases (NIAID)
● Antiviral antibody cocktail REGN-COV2 is also in Phase 2/3 treatment trials following
positive Phase 1 safety review
● Phase 3 trial will evaluate REGN-COV2’s ability to prevent infection among uninfected
people who have had close exposure to a COVID-19 patient (such as the patient’s
housemate), and is being run jointly with the National Institute of Allergy and Infectious
Diseases (NIAID)
July 7, 2020: Regeneron Announces Manufacturing And Supply Agreement For Barda And U.S.
Department of Defense For REGN-COV2 Antiviral Antibody Cocktail
● Regeneron is rewarded a $450 million contract to manufacture and supply REGN-COV2
for ‘Operation Warp Speed’ as implemented by the Biomedical Advanced Research and
Development Authority (BARDA)
August 19, 2020: Regeneron and ROCHE Collaborate to Significantly Increase Global Supply of
REGN-COV2 Investigational Antibody Cocktail for COVID-19
● REGN-COV2 is in late-stage clinical trials for the treatment and prevention of COVID-19
infection
● The companies will collaborate on developing and manufacturing REGN-COV2;
Regeneron will distribute REGN-COV2 in the U.S. and Roche will be responsible for
distribution outside the U.S.
● Under this agreement, overall capacity of REGN-COV2 is expected to increase by at least
three and a half times, substantially increasing the number of doses available to patients
in the U.S. and around the world
September 14, 2020: RECOVERY COVID-19 Phase 3 Trial to Evaluate Regeneron’s REGN-COV2
Investigational Antibody Cocktail in the UK
● One of the world’s largest efforts to find effective COVID-19 treatments will evaluate the
impact of REGN-COV2 on mortality, hospital stays, and the need for ventilation
● RECOVERY (Randomized Evaluation of COVID-19 Therapy)
● The open-label RECOVERY trial will assess the impact of adding REGN-COV2 to the usual
standard-of-care on all-cause mortality 28 days after randomization
Everything To Know
7Regeneron
REGEN—COV
September 29, 2020: Regeneron’s REGN-COV2 Antibody Cocktail Reduced Viral Levels and
Improved Symptoms in Non-Hospitalized COVID-19 Patients
● Greatest improvements in patients who had not mounted their own effective immune
response prior to treatment
● Plan rapidly to discuss results with regulatory authorities
● Regeneron to host investor and media webcast to discuss results at 4:30 pm ET today
October 28, 2020: Regeneron’s COVID-19 Outpatient Trial Prospectively Demonstrates That
REGN-COV2 Antibody Cocktail Significantly Reduced Virus Levels And Need For Further
Medical Attention
● Today’s data, involving an additional 524 patients from the ongoing Phase 2/3 trial,
provides definitive final virology results and meets the clinical endpoint of reducing
medical visits
● Regeneron has shared these results with the U.S. FDA, which is reviewing an Emergency
Use Authorization submission for the REGN-COV2 low dose in adults with
mild-to-moderate COVID-19 who are at high risk for poor outcomes
October 30, 2020: REGN-COV2 Independent Data Monitoring Committee Recommends
Holding Enrollment In Hospitalized Patients With High Oxygen Requirements And Continuing
Enrollment In Patients With Low Or No Oxygen Requirements
● The IDMC also recommends continuation of enrollment in the REGN-COV2 outpatient
trial
November 5, 2020: Recovery Trial Data Monitoring Committee Recommends Continuing
Evaluation Of REGN-COV2 In All Hospitalized Patients
● Regeneron announced today an update from the independent data monitoring
committee (DMC) for the United Kingdom-based RECOVERY trial evaluating REGN-COV2
in hospitalized patients with COVID-19. DMC advised that they saw no cogent reason to
modify the current protocol or intake to the study and recommended continuing
recruitment of eligible patients to all study arms
Everything To Know
8Regeneron
REGEN—COV
November 21, 2020: Regeneron’s Casirivimab And Imdevimab Antibody Cocktail For COVID-19
Is First Combination Therapy To Receive FDA Emergency Use Authorization
● First treatment of any kind to have prospectively confirmed and statistically significant
antiviral activity against SARS-CoV-2
● Authorized for recently diagnosed, mild to moderate COVID-19 in high-risk patients
● Initial doses will be made available to approximately 300,000 patients, with no
medication out-of-pocket costs, under U.S. government allocation program
December 17, 2020: New England Journal Of Medicine Publishes Positive Initial Regeneron
Antibody Cocktail Results In Non-Hospitalized Patients With COVID-19
● Casirivimab and imdevimab effectively reduced viral load and the need for
medically-attended visits, with the greatest benefit in patients who had not yet mounted
their own effective immune response or had high viral load at baseline
- David Weinreich, M.D., Senior Vice President and Head of Global Clinical
Development at Regeneron and lead author of the publication
December 29, 2020: Regeneron Announces Encouraging Initial Data From Covid-19 Antibody
Cocktail Trial In Hospitalized Patients On Low-Flow Oxygen
● Phase 3 Program in hospitalized patients to continue based on passing futility analysis
on ability to reduce incidence of death or mechanical ventilation
● As in earlier outpatient trial, immune status when patients entered the trial was a
stronger predictor of viral load and clinical outcomes
● First antibody therapy to demonstrate antiviral effect in patients hospitalized with
COVID-19
January 12, 2021: Regeneron Announces U.S. Government Agreement to Purchase Additional
COVID-19 Antibody Cocktail Doses
● New agreement covers 1.25 million additional doses of the casirivimab and imdevimab
antibody cocktail, brining total potential U.S. supply to over 1.5 million doses
● Doses are being supplied for use pursuant to the FDA Emergency Use Authorization for
high-risk patients with mild to moderate COVID-19 in order to reduce the risk of
progression to severe COVID-19 and/or hospitalization
Everything To Know
9Regeneron
REGEN—COV
RECENT NEWS
REGENERON REPORTS POSITIVE INTERIM DATA WITH REGEN-COV™ ANTIBODY COCKTAIL
USED AS PASSIVE VACCINE TO PREVENT COVID-19
TARRYTOWN, New York
January 26, 2021
7:00 AM EST
● Reduction in overall infections seen within first week, with 100% prevention of
symptomatic infections
● Markedly decreased levels and duration of viral shedding in asymptomatic infections
that still occurred in REGEN-COV™ group
● Confirmatory Phase 3 results expected early in second quarter
● Potential application in people who need immediate protection or respond poorly to
vaccination
● REGEN-COV™ 1,200 mg administered by subcutaneous injection, providing greater
convenience and efficiency than infusion 3
On January 26, 2021,
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced positive initial results from an
ongoing Phase 3 clinical trial evaluating REGEN-COV™ (casirivimab and imdevimab antibody
cocktail) used as a passive vaccine for the prevention of COVID-19 in people at high risk of
infection (due to household exposure to a COVID-19 patient).
The trial is being run jointly with the National Institute of Allergy and Infectious Diseases (NIAID),
part of the National Institutes of Health (NIH).
3
Subcutaneous means ‘under the skin’. A subcutaneous injection utilizes a short needle to inject a drug
directly into the tissue layer between the skin and muscle.
Everything To Know
10Regeneron
REGEN—COV
An exploratory analysis was conducted on the first approximately 400 evaluable individuals
enrolled in the trial, who were randomized to receive passive vaccination with REGEN-COV™
(1,200 mg via subcutaneous injections) or placebo.
Results included:
● Passive vaccination with REGEN-COV™ resulted in 100% prevention of symptomatic
infection (8/223 placebo vs. 0/186 REGEN-COV™ ) and approximately 50% lower overall
rates of infection (symptomatic and asymptomatic) (23/223 placebo vs. 10/186
REGEN-COV™ )
● The lower number of infections occurring with REGEN-COV™ therapy were all
asymptomatic, with decreased peak virus levels and short duration of viral shedding.
○ Infections occurring in the placebo group has, on average, more than 100-fold
higher peak viral load.
○ Infections in the REGEN-COV™ group lasted no more than 1 week, while
approximately 40% of infections in the placebo group lasted 3-4 weeks.
○ No infected individuals in the REGEN-COV™ group had high viral loads (>10^4
copies/mL) compared to 62% of the infected placebo group (13/21 placebo vs.
0/9 REGEN-COV™ ).
● REGEN-COV™ was associated with lower disease burden:
○ Fewer total viral shedding weeks (44 weeks placebo vs. 9 weeks REGEN-COV™ ).
○ Fewer total high viral shedding weeks (>10^4 copies/mL) (22 weeks placebo vs.
0 weeks REGEN-COV™ ).
○ Fewer total symptomatic weeks (18 weeks placebo vs. 0 weeks REGEN-COV™ ).
“These data using REGEN-COV™ as a passive vaccine suggest that it may both reduce
transmission of the virus as well as reduce viral and disease burden in those who still get
infected,” said George D. Yancopoulos, M.D., Ph.D., President and Chief Scientific Officer at
Regeneron. “Even with the emerging availability of active vaccines, we continue to see hundreds
of thousands of people infected daily, actively spreading the virus to their close contacts. The
REGEN-COV™ antibody cocktail may be able to help break this chain by providing immediate
passive immunity to those at high risk of infection, in contrast to active vaccines which take
weeks to provide protection. There are also many individuals who unfortunately may be
Everything To Know
11Regeneron
REGEN—COV
immunocompromised and not respond well to an active vaccine or are otherwise unable to be
vaccinated, and REGEN-COV™ has the potential to be an important option for these
individuals. Overall, the REGEN-COV™ development program has demonstrated definitive
anti-viral activity and the collective data strongly suggest it can be effective both as a
therapeutic and as a passive vaccine.”
In the safety assessment, adverse events occurred more frequently in participants on placebo
(18% placebo vs. 12% REGEN-COV™ ); this difference was driven by the increased rate of
SARS-CoV-2 infections in the placebo group. In the placebo group, there was one death and one
COVID-19-related hospitalization; there were no deaths or COVID-19 hospitalization in the
treatment group. Injection site reactions occured at a rate of approximately 2% in both
treatment and placebo groups.
“In this prevention trial, REGEN-COV™ was given as injections rather than an infusion, which
makes administration much more convenient and efficient for patients and overburdened
healthcare providers and facilities,” said David Weinrich, M.D., Executive Vice President and
Head of Global Clinical Development at Regeneron. “It’s notable that the few infections that did
occur after receiving REGEN-COV™ were all asymptomatic, and associated with markedly lower
viral load and duration of viral shedding, potentially further reducing transmission. We look
forward to seeing the full dataset early next quarter and will discuss the current results with
regulatory authorities, including the potential to expand the Emergency Use Authorization.”
The development and manufacturing of REGEN-COV™ has 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: HHS0100201700020C. Under agreements with
the U.S. Government, Regeneron is supplying up to approximately 1.5 million doses of
REGEN-COV™ for treatment of COVID-19 under the current Emergency Use Authorization
(EUA). In November, REGEN-COV™ was granted an EUA by the U.S. Food and Drug
Administration (FDA) for use in treating people with mild or moderate COVID-19 who are at high
risk of developing severe symptoms and requiring hospitalization and are not currently
hospitalized. The EUA is temporary and does not take the place of formal biologics license
application (BLA) review and approval process and the use of the antibody cocktail remains
investigational. Evaluation of its safety and efficacy is ongoing in multiple clinical trials.
Everything To Know
12Regeneron
REGEN—COV
About the REGN-COV Phase 3 Prevention Trial
This trial evaluated the use of REGEN-COV™ as a passive vaccine to prevent SARS-CoV-2
infections. Passive vaccination provides immediate short-term passive immunity, by delivering
protective virus-neutralizing antibodies, either through therapeutic antibody medicines like
REGEN-COV™ or from mother to child through breastmilk. Traditional vaccines work by
activating the immune system to develop its own antibodies, a process that typically takes
weeks but provides longer-term active immunity. The initial descriptive analysis included 409
evaluable participants enrolled early in the trial who did not have COVID-19 at baseline and
were "seronegative," meaning they did not have existing antibodies in their blood to
SARS-CoV-2. Individuals were eligible for the trial if they had a household member with
COVID-19. Participants were tested weekly by nasopharyngeal swab. The confirmatory results
will evaluate the ability of REGEN-COV™ to prevent asymptomatic and symptomatic COVID-19
infections as the primary endpoint. The trial has enrolled over 2,000 participants. Among the
first 409 participants, approximately 49% were Hispanic and 13% were African American. On
average, participants were 43 years of age, approximately 46% were male and 54% were
female. In addition to the Phase 3 trial for the prevention of COVID-19, REGEN-COV™ is being
studied in two late-stage hospitalized patient trials and a Phase 3 trial for the treatment of
non-hospitalized patients.
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13Regeneron
REGEN—COV
REGEN-COV™ ANTIBODY COCKTAIL IS ACTIVE AGAINST SARS-COV-2 VARIANTS FIRST
IDENTIFIED IN THE UK AND SOUTH AFRICA
TARRYTOWN, N.Y.
January 27, 2021
7:00 AM EST
Columbia University researchers and Regerneron have independently confirmed findings; data
included in bioRxiv paper and submitted for peer-reviewed publication
Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) announced that researchers in Dr. David
Ho’s Columbia University lab and Regeneron scientists have independently confirmed that
REGEN-COV™ (casirivimab and imdevimab antibody cocktail) successfully neutralizes the
circulating SARS- CoV-2 variants first identified in the UK (B.1.1.7) and South Africa (B.1.351).
Columbia’s findings were included in a paper posted to bioRxiv and submitted for peer-reviewed
publication on the changing resistance of SARS-CoV-2 variants to antibody neutralization.
Both teams of researchers assessed in vitro neutralization potency of numerous COVID-19
antibodies (including those that have received emergency authorization and those still in
development) against various mutated strains of the virus. Although some antibody therapies
were no longer effective against some of the variants, the REGN-COV antibody cocktail
continued to neutralize all variants tested. REGEN-COV™, which consists of the highly potent
neutralizing antibodies imdevimab (REGN10987) and carisirivimab (REGN 10933), retained its
potent neutralizing capability against the B.1.1.7 variant, with both antibodies retaining their
potency. REGEN-COV™ also retained its highly potent neutralizing capacity against the B.1.351;
imdevimab retained its potency against this variant, and while casiririvimab potency was
reduced, it was still comparable to the potency that other single antibodies in development have
against the original virus.
The variant first identified in Brazil (1.1.248) and recently seen in a patient in the United States
contains the same receptor binding domain mutations as the B.1.351 variant, therefore
REGEN-COV™ is expected to remain similarly potent.
Regeneron is conducting additional preclinical research against this particular variant strain to
confirm this.
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14Regeneron
REGEN—COV
“As we expected, the virus continues to mutate, and these data show the continued ability of
REGN-COV to neutralize emerging strains, further validating our multi-antibody cocktail
approach to infectious diseases,” said George D. Yancopoulos, M.D., Ph.D., President and Chief
Scientific Officer at Regeneron. “With two complimentary antibodies in one therapeutic, even if
one has reduced potency, the risk of the cocktail losing efficacy is significantly diminished,
since the virus would need to mutate in multiple distinct locations to evade both antibodies.
Thanks to our proprietary VelocImmune® technology, we have hundreds of additional potent,
neutralizing antibodies in our labs that could form new combinations that might be useful
against future variants. We are evaluating potential next steps with these novel candidates.”
“In the face of this daunting pandemic, we appreciate the open exchange of pre-publication data
and the opportunity to confirm important findings with one of the world’s leading academic
laboratories,” said Christos A. Kyratsous, Ph.D., Vice President of Research, Infectious
Diseases and Viral Vector Technologies at Regeneron.
The development and manufacturing of REGEN-COV™ has been funded in part with federal
funds for 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: HHS0100201700020C.
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REGEN—COV
THE PRODUCT
About the REGN-COV Antibody Cocktail
REGEN-COV™ (casirivimab and imdevimab) is a cocktail of two monoclonal antibodies (also
known as REGN 10933 and REGN 10987) and was designed specifically to block infectivity of
SARS-CoV-2, the virus that causes COVID-19.
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.
Regeneron has done something similar in the past with the Ebola virus vaccine therapy, using a
three-antibody cocktail called REGN-EB3.
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REGEN—COV
In November 2020,
REGEN-COV™ received Emergency Use Authorization (EUA) from the 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.
The clinical evidence from Regeneron’s outpatient trial suggests the monoclonal antibodies
such as casirivimab and imdevimab have the greatest benefit when given early after diagnosis
and in patients who are seronegative and/or have high viral load.
The criteria for ‘high-risk’ patients are described in the Fact Sheet for Health Providers.
In the U.S., casirivimab and imdevimab are 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.
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REGEN—COV
Regeneron is collaborating with Roche to increase the global supply of REGEN-COV™.
Regenron 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.
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THE TECHNOLOGY
VelociSuite
VelociSuite consists of VelocImmune, VelociGene, VelociMouse, Veloci-Bi, VelociT, and other
related technologies. The VelocImmune mouse platform is utilized to produce fully human
antibodies. VelocImmue was generated by leveraging our VelociGene technology (see below), in
a process in which six megabases 4 of mouse immune gene loci 5 were replaced, or
“humanized,” with corresponding human immune gene loci.
VelocImmune mice can be used efficiently to generate fully human antibodies to targets of
therapeutics interest. VelocImmune and our entire VelociSuite offer the potential to increase
the speed and efficiency through which human antibody therapeutics may be discovered and
validated, thereby improving the overall efficiency of our early stage drug development
activities. We are utilizing the VelocImmune technology to produce our next generation of drug
candidates for preclinical and clinical development.
Our VelociGene platform allows custom and precise manipulation of very large sequences of
DNA to produce highly customized alterations of a specified target gene, or genes, and
accelerates the production of knock-out6 and transgenic expression models without using
either positive/negative selection or isogenic DNA. In producing knock-out models, a color or
fluorescent marker may be substituted in place of the actual gene sequence, allowing for
high-resolution visualization of precisely where the gene is active in the body during normal
body functioning as well as in disease processes. For the optimization of preclinical
development and pharmacology programs, VelociGene offers the opportunity to humanize
targets by replacing the mouse gene with the human homolog. Thus, VelociGene allows
scientists to rapidly identify the physical and biological effects of deleting or over-expressing
the target gene, as well as to characterize and test the potential therapeutic molecules.
Our VelociMouse technology platform allows for the direct and immediate generation of
genetically altered mice from embryonic stem cells (“ES cells”), thereby avoiding the lengthy
process involved in generating and breeding knockout mice from chimeras. Mice generated
4
A megabase is a term used in genetics to measure the length (number of base pairs) of a genome
segment. Megabases measure the physical distance of a genome region whereas a centiMorgan is used
to measure the genetic distance.
5
In genetics, a locus (plural loci) is a specific, fixed position on a chromosome where a particular gene or
genetic marker is located.
6
A knockout mouse is a genetically modified mouse (Mus musculus) in which researchers have
inactivated, or “knocked out”, an existing gene by replacing it or disrupting it with an artificial piece of
DNA.
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REGEN—COV
through this method are normal and healthy and exhibit a 100% germ-line transmission.
Furthermore, mice developed using our VelociMouse technology are suitable for direct
phenotyping or other studies. We have also developed our VelociMab platform for the rapid
screening of antibodies and rapid generation of expression cell lines for our Traps and our
VelocImmune human antibodies.
We have utilized our VelociSuite technologies to develop a class of potential drug candidates,
known as bi-specific antibodies7. Veloci-Bi allows for the generation of full-length bi-specific
antibodies similar to native antibodies that are amenable to production by standard antibody
manufacturing techniques, and are likely to have favorable antibody-like pharmacokinetic
properties8. In the area of immunotherapies in oncology, we are exploring the use of bi-specific
antibodies that target tumor antigens and the CD3 receptor on T-cells to harness the oncolytic
properties of T-cells. Our first such CD-3 bi-specific antibody, REGN1979, targets CD20. We are
exploring additional indications and applications for our bi-specific technologies, such as other
CD3 bi-specific antibodies to MUC16 (REGN4018) and BCMA (REGN5458 and REGN5459), as
well as a new class of CD28 costimulatory bi-specifics, including an antibody that targets PSMA
(REGN5678).
The VelociT mouse extends our research and drug discovery capabilities into cell mediated
immunity and therapeutic TCRs for oncology and other indications. VelociT was developed by
using our VelociGene technology to humanize genes encoding TCRa and TCRb variable
sequences, CD4 and CD8 co-receptors, Beta2m and class-I and -II major histocompatibility
complexes. As a result, VelociT mice generate fully human TCRs, providing for customized
modeling of T-cell function in different diseases and a powerful platform for the discovery of
unique TCR-based therapies.
7
A bispecific monoclonal antibody is a type of synthetically generated antibody that can bind to two types
of antigens.
8
Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics is the
study of how a drug affects an organism.
Everything To Know
21Regeneron
REGEN—COV
COMPETITIVE LANDSCAPE
VACCINE NAME: Comirnaty (also known as tozinameran or BNT162b2 )
EFFICACY: 95%
EUA DETAILS: 100 MILLION DOSES
DOSE: 2 doses, 3 weeks apart
TYPE: Muscle injection
STORAGE: Freezer storage only at –94°F (–70°C)
VACCINE NAME: mRNA-1273
EFFICACY: 94.5%
EUA DETAILS: 200 MILLION DOSES
DOSE: 2 doses, 4 weeks apart
TYPE: Muscle injection
STORAGE: 30 days with refrigeration, 6 months at –4°F (–20°C)
Everything To Know
22Regeneron
REGEN—COV
VACCINE NAME: REGN-COV
EFFICACY: 100% 9
EUA DETAILS: 1.5 MILLION DOSES
DOSE: unconfirmed
TYPE: Subcutaneous Injection
STORAGE: Unknown
Currently, Regeneron’s vaccine is being studied for its application and efficacy in patients at
high-risk or with mild to moderate COVID-19 in order to reduce the risk of progression to severe
COVID-19. Their current focus is more nuanced than Moderna and Pfizer meaning their EUA
agreement will contain fewer doses than its competitors, however if the trials are successful in
slowing/preventing viral shedding, Regeneron may see a big chance to become a relevant player
in the COVID-19 vaccine race. Until then, REGEN-COV can only be administered in emergency use
cases.
REGEN-COV™ JOINS 5 OTHER TRIAL PHASE 3 INVESTIGATIONAL MEDICINES
REPRESENTING A SMALL PART VELOCIMMUNE® INNOVATION
|INFINITE| |OPPORTUNITIES|
9
From symptomatic infections in a study of 400 subjects
Everything To Know
23Regeneron
REGEN—COV
Everything To Know
24Regeneron
REGEN—COV
THE STOCK
Regeneron Pharmaceuticals, Inc. | REGN | NASDAQ | Healthcare | Biotech |
Shares Outstanding10 106,700,000 as of January 27, 2021
10.00% 10,670,000 shares
1.00% 1,067,000
0.10% 106,700
0.01% 10,670
Market Capitalization $55.01B as of January 27, 2021
$550.00 per share $58.690B
$600.00 per share $64.02B
$700.00 per share $74.70B
$800.00 per share $85.35B
$900.00 per share $96.04B
$1,000.00 per share $106.700B
Team 8,314 Full Time Employees (As of January 19, 2021)
10
Regeneron has never paid cash dividends on its Common Stock or Class A Stock and does not
anticipate paying any in the foreseeable future.
Everything To Know
25Regeneron
REGEN—COV
AUTHORIZED USE AND IMPORTANT SAFETY INFORMATION
Authorized Emergency Use
Casirivimab and imdevimab injection is an investigational combination therapy and has been
authorized by FDA for the emergency use described above. Casisrivimab and imdevimab
injection is not FDA approved for any use. Safety and effectiveness of casisrivimab and
imdevimab injection have not yet been established for the treatment of COVID-19.
This authorized use is 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.
Limitations of Authorized Use
● Casirivimab and imdevimab injection 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 baselines 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 casirivimab and imdevimab injection has not been observed in
patients hospitalized due to COVID-19. Monoclonal antibodies, such as casirivimab and
imdevimab, may be associated with worse clinical outcomes when administered to
hospitalized patients requiring high flow oxygen or mechanical ventilation with
COVID-19.
Everything To Know
26Regeneron
REGEN—COV
Definition of High-Risk Patients
High-risk is defined as patients who meet at least one of the following criteria:
● Have a body mass index (BMI) of equal to, or greater than 35
● Have chronic kidney disease
● Have diabetes
● Have immunosuppressive disease
● Are currently receiving immunosuppressive treatment
● Are 65 years of age or older
● Are 55 years of age AND have
●
○ Cardiovascular disease, or
○ Hypertension, or
○ Chronic obstructive pulmonary disease/other chronic respiratory disease.
● Are 12 to 17 years of age AND have
○ (BMI) in 85th percentile, or higher,. for their age and gender based on CDC growth
charts, or
○ Sickle cell disease, or
○ Congenital or acquired heart disease, or
○ Neurodevelopmental disorders, for example, cerebral palsy, or
○ A medical-related technological dependence, for example, tracheostomy,
gastrostomy, or positive pressure ventilation (not related to COVID-19), or
○ Asthma, reactive airway or other chronic respiratory disease that requires daily
medication for control.
Everything To Know
27Regeneron
REGEN—COV
Warnings and Precautions:
● Hypersensitivity Including Anaphylaxis and Infusion-Related Reactions: There is a
potential for serious hypersensitivity reaction, including anaphylaxis, with administration
of casirivimab and imdevimab injection. If signs or symptoms of a clinically significant
hypersensitivity reaction or anaphylaxis occur, immediately discontinue administration
and initiate appropriate medications and/or supportive therapy. Infusion-related
reactions have been observed with administration of casirivimab and imdevimab
injection. Signs and symptoms of infusion related reactions may include fever, chills,
nausea, headache, bronchospasm, hypotension, angioedema, throat irritation, rash
including urticaria, pruritus, myalgia, and/or dizziness. If an infusion-related reaction
occurs, consider slowing or stopping the infusion and administer appropriate
medications and/or supportive care.
● Limitations of Benefit and Potential for Risk in Patients with Severe COVID-19: Benefit
of treatment with casirivimab and imdevimab injection has not been observed in
patients hospitalized due to COVID-19. Monoclonal antibodies, such as casirivimab and
imdevimab, may be associated with worse clinical outcomes when administered to
hospitalized patients requiring high flow oxygen or mechanical ventilation with
COVID-19. Therefore, casirivimab and imdevimab injection is not authorized for use in
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:
● Serious adverse events (SEAs) were reported in 4 (1.6%) patients in the casirivimab and
imdevimab injection 2,400 mg group, 2 (.08%) of patients in casirivimab and imdevimab
injection 8,000 mg group and 6 (2.3%) in patients in the placebo group. None of the SAEs
were considered to be related to study drugs. SAEs that were reported as Grade 3 or 4
adverse events were pneumonia, hyperglycemia, nausea and vomiting (2,400 mg
casirivimab and imdevimab injection), intestinal obstruction and dyspnea (8,000 mg
casirivimab and imdevimab injection) and COVID-19, pneumonia and hypoxia (placebo).
Casirivimab and imdevimab injection are not authorized at the 8,000 mg dose (4,000 mg
casirivimab and 4,000 mg imdevimab injection).
Patient Monitoring Recommendations:
Clinically monitor patients during infusion and observe patients for at least 1 hour after infusion
is complete.
Everything To Know
28Regeneron
REGEN—COV
Use in Specific Populations
● Pregnancy: There is currently limited clinical experience in the use of casirivimab and
imdevimab injection in COVID-19 patients who are pregnant. Casirivimab and imdevimab
injection therapy should be used during pregnancy only if the potential benefit justifies
the potential risk for the mother and fetus.
● Nursing Mothers: There is currently no clinical experience in use of casirivimab and
imdevimab injection in COVID-19 patients who are breastfeeding. The development and
health benefits of breastfeeding should be considered along with the mother’s clinical
need for casirivimab and imdevimab injection and any potential adverse effects on the
breastfed child from casirivimab and imdevimab injection or from the underlying
maternal condition.
Everything To Know
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