GS - COVID Toolkit 2.0 (7.17.20) PDF

17 July 2020 | 4:00AM EDT
Global Healthcare
COVID-19 toolkit 2.0: The GS roadmap for the path ahead
Healthcare companies across our coverage (including MRNA, PFE/BNTX, Salveen Richter, CFA
+1(212)934-4204 |
AZN/University of Oxford, JNJ, GILD, REGN, LLY, ROG, BDX, ABT, ADPT, Takeda, salveen.richter@gs.com
Goldman Sachs & Co. LLC
CSL, Grifols) are making significant progress towards addressing the global need for
Terence Flynn, Ph.D.
vaccines, treatments and diagnostics to address COVID-19. In this report, we update +1(212)357-5057 |
terence.flynn@gs.com
our “COVID-19 toolkit” to highlight learnings and debates regarding COVID-19 Goldman Sachs & Co. LLC
biology, the treatment landscape (ROG, LLY and potentially REGN data mid-year), Amit Hazan
+1(212)357-0315 | amit.hazan@gs.com
diagnostic testing dynamics and importantly, progress, timelines and regulatory Goldman Sachs & Co. LLC
For the exclusive use of HAN.MATTHEW@OUTLOOK.COM
guidelines on the vaccine front (notably, from MRNA, PFE/BNTX and AZN/University Keyur Parekh
+44(20)7552-9939 |
keyur.parekh@gs.com
of Oxford (Ph1 data is imminent), which alongside INO and SNV, should be in Ph3 Goldman Sachs International
this summer) - we believe a vaccine may gain US approval in 2H20. Akinori Ueda, Ph.D.
+81(3)6437-9910 | akinori.ueda@gs.com
Goldman Sachs Japan Co., Ltd.
Ross Weinreb
PM Summary +1(212)357-0031 |
ross.weinreb@gs.com
Veronika Dubajova, CFA

We revisit our initial April 6, 2020 report, The COVID-19 toolkit: Navigating a +44(20)7774-1901 |
veronika.dubajova@gs.com
once-in-a-century global pandemic, and highlight the progress in understanding Goldman Sachs International
COVID-19 biology, and advances in drug development and diagnosis. On the vaccine Chris Cooper, CFA
+61(2)9320-1489 | chris.cooper@gs.com
front, the following five programs are anticipated, per disclosed timelines, to be in Goldman Sachs Australia Pty Ltd
Phase 3 trials in the summer: (1) Moderna’s (MRNA) mRNA-1273 - Ph1 data from Paul Choi
+1(212)902-5217 | paul.k.choi@gs.com
the elderly and older adult cohorts (early-to-mid August), Ph2 data in Goldman Sachs & Co. LLC
93f15d4c5e4d11d89860be55d934f058
August/September and final Ph3 efficacy data in 4Q20 (by late-November/4Q20) Graig Suvannavejh, Ph.D.
+1(212)902-6393 |
- two potential interim analyses of the Ph3 study (~53 and ~106 events) may graig.suvannavejh@gs.com
provide the opportunity for early approval. MRNA has guided to deliver ~500mn
doses per year, and potentially up to 1bn doses per year, beginning in 2021; (2) Pfizer
(PFE)/ BioNTech (BNTX) - Post recent Ph1 BNT162b1 data, we expect additional data
from three other candidates (BNT162a1, BNT162b2, BNT162c2) over the coming
weeks to enable selection of a lead candidate. Ph2b/3 data in September (approval
by October/YE20; 100mn doses available this year, and >1.2bn in 2021); (3)
AstraZeneca (AZN)/University of Oxford’s AZD1222 – Ph1 data is imminent; UK
Ph2/3 data in mid-autumn (EUA/approvals as early as September). AZN expects to
supply >2bn doses across UK (potentially up to 100mn doses), US (300mn doses),
EU (400mn doses), low/middle income countries (1bn doses); (4) INOVIO’s (INO)
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INO-4800 – Ph2/3 trial initiation this summer (millions of doses produced by YE20) and
(5) Sinovac’s (SNV) CoronaVac – Ph3 enrollment to begin in July (100mn doses
manufactured per year).
The four traditional companies involved in prophylactic viral vaccine development are: (1)
GlaxoSmithKline (GSK/Clover; Ph1 with preliminary data in August); (2) Johnson &
Johnson (JNJ; Ph1 trial initiation in late July; Ph3 initiation in September; 1bn doses
manufactured by YE21); (3) Merck (MRK; preclinical development ongoing with Ph1
initiation in 2H20) and (4) Sanofi (SNY; Ph1 trial initiation in 4Q20; 100mn doses
available by June 2021 and a total capacity of 1bn by 2021).
We look to approvals of multiple COVID-19 vaccines in order to meet global demand

(~7.8bn).
We are positive on the mRNA-based vaccines from MRNA and PFE/BNTX, which
have the potential to be amongst those first-to-market. Further, the mRNA technology
platform (vs. DNA, adenoviral and traditional approaches) positions both companies well
to quickly develop a second vaccine should the virus mutate. In terms of patient use,
mRNA-based vaccines can likely be used in all individuals, whereas vaccines using an
adenoviral vector (AZN/University of Oxford and CanSino Biologics) are expected to
only be effective in a subset of individuals given pre-existing antibodies.
On the therapeutic side, Gilead’s (GILD) remdesivir, an anti-viral, is approved in the UK

(Veklury, treatment of SARS-CoV-2 infection) and available under Emergency Use
Authorization (EUA) in the US for treatment of severe COVID-19 patients. We next look
to Roche’s (ROG) Actemra, an IL-6, with data in severe COVID-19 pneumonia in July,
Regeneron’s (REGN) Ph2/3 REGN-COV2 data in hospitalized and ambulatory COVID-19
patients potentially later this summer, and Eli Lilly’s (LLY) Ph2 LY-CoV555 data in mild to
moderate COVID-19 patients in September. In terms of convalescent plasma therapy
against COVID-19, we highlight Takeda (trial initiation in July; data YE20), CSL Behring
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(CSL) and Grifols (trials in 3Q20). Here, the expectation is that antibodies from
recovered patients will trigger antibody production in the recipients. However, one
potential limitation in this approach is that it requires donor plasma; hence, there could
be limitations on scaling broadly to meet demand. To that end, we note, CSL/SAB
Biotherapeutics are developing highly potent, human polyclonal antibodies that mimic
convalescent plasma without the need for blood plasma donations from recovered
patients.
While many unanswered questions around the COVID-19 biology exist, we highlight the
most up-to-date scientific advances on the virus, and layout the key debates and
challenges that lie ahead in ensuring the successful development, supply and
manufacturing of a COVID-19 vaccine.
1. Despite significant scientific progress on understanding the virus, unknowns

persist regarding its biology and the resulting human immune response - most
importantly on the length of protection conferred by viral antibodies. Per the
CDC, there remains no conclusive evidence that antibodies developed in response
to infection with SARS-CoV-2 will be protective, and even if so, the antibody titer
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levels deemed to be protective are unknown. On how long antibodies derived from
a vaccine might offer protection, Dr. Anthony Fauci, Director of National Institute of
Allergy and Infectious Disease (NIAID), has stated that we can assume antibodies
will provide a degree of protection, but we must also assume that it is going to be
finite. A recent poll conducted by The Associated Press-NORC Center for Public
Affairs Research found that 49% of Americans planned to get vaccinated against
SARS-CoV-2, below the 70-85% (CDC/NIH estimate) required for herd
immunity. While our KOLs are optimistic on the potential for early vaccines, the
frequency of dosing needed to drive sufficient protection and the durability of
response remain outstanding questions. As it relates to concerns of antibody
dependent enhancements (ADEs) seen in Zika and Dengue virus, our KOLs pointed
to the lack of robust evidence of ADEs in coronaviruses.
2. There are multiple hurdles related to the development, manufacturing and
distribution of a COVID-19 vaccine. To accelerate the time-to-market for a COVID-19
vaccine, WHO and global groups (such as Gavi, the vaccine alliance and the Coalition
for Epidemic Preparedness Innovations (CEPI)) have established an $18bn program
to deliver 2bn COVID-19 vaccine doses by YE21 in countries with the greatest need.
In order to expedite the development of a vaccine, Operation Warp Speed
(OWS), a US government program, has funded Novavax (NVX; not covered;
$1.6bn for pivotal trials and manufacturing of 100mn doses) and has selected INO
and Vaxart (VXRT; not covered) to participate in non-human challenge studies. As
highlighted by Dr. Fauci, four vaccines (of 197 in development, per the Milken
Institute), likely MRNA, PFE/BNTX, AZN/University of Oxford and INO, will begin
late-stage trials between July and October with harmonized trial protocols
that include the same endpoints. Per recent FDA guidelines, a COVID-19 vaccine
should demonstrate at least 50% more effectiveness than placebo in preventing
disease; however, a vaccine with only 50% efficacy may fall short of the levels that
some researchers have estimated would be necessary to suppress a COVID-19
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outbreak. We note potential challenges in enrolling a diverse set of patients, with
clinical trials likely to be competing for the same participants in geographic regions
where community transmission of SARS-CoV-2 exists (~25k–30k volunteers is
needed for sufficient powering). Outside of clinical development challenges,
companies may face operational challenges as vaccines require special shipping
containers to ensure the vaccine remains frozen (promotes stability) during
transport.
3. On the diagnostic front, we break down the market opportunity into lab-based viral
tests, point of care antigen tests, and both lab and point of care based antibody
tests. Beginning with the viral lab side of the market, our updated analysis suggests
theoretical testing capacity in the US of between 21-29mn tests per month vs. our
prior estimate of 20-25mn. Since our last deep dive on COVID diagnostics, US
testing volume has increased meaningfully to ~22mn per month based on the latest
7-day run rate (vs. 10mn at the time of our last report). We had previously suggested
that bottlenecks would limit major upside to viral lab-based testing and believe we
are now starting to see those result in longer test result turnaround times as we
have previously cited. Critically, this dynamic sets up for other testing modalities to
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play a key role in further expansion in the US. Specifically, we see point of care
antigen testing (BDX’s Veritor platform, among others) as a likely source of further
testing capacity expansion as we describe below. Turning to antibody testing,
theoretical capacity exceeds 200mn tests per month, although we remain
somewhat cautious on the opportunity given potential lack of demand (relative to
supply), the limited role for antibody testing in diagnosis and screening of COVID-19,
and a much lower price point for these tests.
4. Within diagnostics on the company side, we see strong tailwinds accruing to
exposed viral testing companies, with positive views on Roche (ROG) and Becton
Dickinson (BDX), and a conservative view on Abbott (ABT) relative to high Street
expectations. For Roche (ROG), the company is one of the best positioned given the
broad installed bases of diagnostics machines, two validated tests with very high
accuracy (1 PCR and 1 serology test) and amongst the highest capacities globally for
these tests all combine to provide ROG with an opportunity to off-set the headwinds
they see in the other parts of their routine diagnostics business. ABT is likely a
disproportionate early beneficiary of COVID testing given approvals on multiple
platforms ahead of many other players, but ultimately we see its share as settling
along pre-COVID lines based on the installed base and throughput relative to key
competitors. For BDX, we are increasingly optimistic in the company’s potential to
drive upside from the Veritor point-of-care antigen test which has seen a recent FDA
approval ahead of our expected timelines with initial capacity above our projections.
In addition, BDX recently secured a large initial order from The US Department of
Health and Human Services (HHS), which we believe is the start of a large revenue
opportunity given the unique benefits including an ability to be used in screening
and diagnosis of COVID-19, setting flexibility, speed to result, and availability. We
highlight Adaptive Biotechnologies (ADPT)’s T cell receptor-based diagnostic for
COVID-19, which may be the first of its kind - and a more accurate test for infection.
ADPT expects to pursue an Emergency Use Authorization (EUA) regulatory pathway
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over the summer.
Key COVID-19 questions
1. What is the mutational risk of SARS-CoV-2?
Our due diligence with virologists/epidemiologists suggests that the mutational rate of
SARS-CoV-2 is lower than other viruses such as the flu. On average, SARS-CoV-2 is
estimated to have a mutation rate of ~25 mutations per year (LINK), compared to the
seasonal flu, which has a mutation rate of ~50 mutations per year. The flu genome is
segmented and carries a higher likelihood of recombination and translocation, compared
to SARS-CoV-2, which is a single, positive-stranded RNA sequence. Further, per our
KOLs, there is no evidence to indicate that viral mutations seen to-date make the virus
more infectious or pathogenic in nature — however, we note recent evidence that a
mutation could have made the virus more contagious.
A mutation in the spike protein, which has been associated with COVID-19 outbreaks in
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Europe and New York, was identified by researchers at Northwestern University. The
mutation resulted in one of the amino acids coding the spike protein (aspartic acid) to be
replaced with glycine — known as the “G” mutation. Notably, ~70% of the ~50,000
sequenced genomes that researchers have shared in a global digital database carry this
mutation. We note that there have been laboratory experiments suggesting the
mutation makes the virus more infectious, although we caveat that not all have been
peer reviewed. Results from a study from the Los Alamos National Laboratory and
published in the scientific journal Cell (LINK) demonstrated that patients infected with
SARS-CoV-2 containing the G variant have a higher viral load, increasing their likelihood
of infecting others. Another research paper (LINK), which was not peer-reviewed and
was posted online as a “pre-print”, demonstrated that viruses containing the G variant
had more spike proteins, and the outer parts of those proteins had a reduced likelihood
of breaking off — which made the virus ~10X more infectious in a lab experiment. The
authors noted that the mutation does not seem to lead to worse outcomes or alter the
virus’s response to antibodies from infected patients that did not contain the specific
variant. This suggests that a vaccine being developed against the original genetic
sequence of the virus could also be efficacious against the potential new strain. Based
on technological advantages of mRNA-based vaccines (see below), it will likely be easier
for Moderna (MRNA; SARS-CoV-2 sequence to shipping GMP product within 40 days),
Pfizer (PFE)/ BioNTech (BNTX) and Sanofi (SNY)/Translate Bio (TBIO; not covered) to
rapidly re-design a new vaccine in the event of a newly mutated SARS-CoV-2 strain.
2. What is the duration of protection conferred by antibodies to SARS-CoV-2?
The duration of protection conferred by SARS-CoV-2 antibodies is a key outstanding

question and will play a key role in determining the dosing frequency of a vaccine. Per a
discussion with one KOL, the durability of a vaccine should be at least as long as a
season, and neutralizing antibodies (NAbs) are expected to decline over eight
months — in which case a booster vaccine may be necessary to extend durability.
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Post-vaccine, per our KOLs (LINK), most individuals will have a burst of antibodies and a
robust response, followed by a decay in the antibodies over the course of several
months before reaching a plateau. We note that the majority of vaccines on the market
are against viruses to which people can develop lifelong immunity (i.e. smallpox or
measles). While determining the durability of response and the frequency of dosing of
vaccines that will provide long-term immunity remains outstanding, conversations with
one KOL indicate confidence that some early vaccines will be sufficiently protective and
provide a good immune response. KOLs have also noted the importance of examining
the durability of the immune response from other coronaviruses to inform SARS-CoV-2.
For example, MERS convalescent-treated patients developed neutralizing antibodies that
waned over a couple of years, demonstrating that lifelong immunity does not always
occur in respiratory viruses. One KOL estimates that, based on the length of immune
response seen in follow-ups of clinical trials, a booster dose may be needed every 1-2
years. Studies have shown that circulating antibodies against SARS-CoV or MERS-CoV
can last for at least 1 year, and sustained IgG levels were maintained for more than 2
years after SARS-CoV infection.
However, we note evidence from a recent peer-reviewed paper in Nature Medicine that
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antibodies to SARS-CoV-2 may fade within 2-3 months following the onset of
infection. The study examined the immune response to the virus in asymptomatic
(n=37) and symptomatic (n=37) patients with mild disease, and showed >90% declines
in the level of SARS-CoV-2-specific immunoglobulin G (IgG) antibodies in both groups
within two to three months following the onset of infection. However, we note disease
severity may play a role in antibody durability, with more severe disease potentially
leading to increased antibody durability. In addition, 40% of the asymptomatic group
tested negative for IgG antibodies eight weeks after being released from isolation. We
note that low levels of potent neutralizing antibodies can be protective; however, these
results provide challenges for the idea of “immune certificates” for individuals who have
recovered from the virus and support the prolongation of public health interventions.
Adding support to the hypothesis that antibodies may fade over a short period of time,
an article published in medRxiv (LINK) by scientists at King’s College London found that
antibody levels peaked approximately three weeks after the onset of COVID-19
symptoms and then declined. Further, the levels of a patient’s antibody peak can
determine the length of time the antibodies are present, which is in line with the study
in mild patients (noted above). A mathematical model published in Science projected

that if immunity to the virus wanes in a similar manner to related coronaviruses,
recurring outbreaks occurring during the wintertime are likely in coming years given the
seasonal variation in SARS-CoV-2 transmission. Per our KOLs, while there have been
reports of reinfection, these represent a small data set and based on the length of
immune response seen in clinical trial follow-ups of various viral vaccines, a booster
dose may be needed every 1-2 years (LINK).
The role of T cell and B cell responses to SARS-CoV-2 is increasingly being examined.
While the majority of COVID-19 vaccines in development mainly focus on
antibody-driven immune responses, largely to the Spike protein, T cells and B cells also
play a role in viral immunity. We note that T cells play an important function during viral
infection: CD4 T cells assist B cells in antibody production and organize the response of
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other immune cells, whereas CD8 T cells kill infected cells and reduce viral burden. T
lymphocytes expressing CD4 are also known as helper T cells (prolific cytokine
producers), which can be further subdivided into Th1 and Th2 cells; the cytokines they
produce are known as Th1-type cytokines and Th2-type cytokines. Th1-type cytokines
tend to produce the pro-inflammatory responses while Th2-type cytokines produce an
anti-inflammatory response. In diseases such as Zika and Dengue, non-neutralizing
antibodies are thought to stimulate a bias towards Th2 immune response, resulting in
the formation of immune complexes and tissue damage called antibody dependent
enhancements (ADEs). Per our discussions with key opinion leaders (KOLs), there is
no robust evidence for ADEs in coronaviruses. In addition, they noted that when a
vaccine elicits a strong immune response, the risk of ADE is reduced, highlighting that
ADEs are only a concern if a person gets infected post a weak vaccinal immune
response.
Per a paper published on the scientific pre-print website medRxiv (LINK), exposure to
SARS-CoV-2 can induce virus-specific T cell responses without seroconversion (i.e.
without antibody development), suggesting that epidemiological data that is solely
reliant on the detection of antibodies to SARS-CoV-2 could potentially lead to an
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underestimation of previous exposure to the virus. The paper examined the humoral and
cellular immune responses against SARS-CoV-2 in seven families, and suggests that T
cell responses may be more sensitive indicators of SARS-CoV-2 exposure than
antibodies. Importantly, research completed at the La Jolla Institute for Immunology
demonstrated that T cells react to several of the SARS-CoV-2 viral proteins, suggesting
that vaccines that target regions outside of the spike protein could be effective.
3. Re-infection risk remains an outstanding question.
Given that lifelong immunity does not always occur in respiratory viruses, a key question
is whether COVID-19 infected individuals are capable of being re-infected. Since the
virus has only been in circulation for ~6 months, data on this front is new and emerging.
The CDC states that there has been no firm evidence produced to-date that
antibodies developed in response to infection are protective, and in addition, if
antibodies are protective, the antibody titers that are associated with protection from
reinfection are unknown (LINK). Further, despite encouraging observations made
to-date, researches are unable to conclude that individuals with persistent or recurrent
detection of SARS-CoV-2 RNA are no longer infectious. However, the CDC does cite
evidence that individuals who have tested persistently or recurrently positive for
SARS-CoV-2 RNA have demonstrated stable or improving signs of illness. The CDC
points to experiments in such persons in South Korea and the US, which failed to isolate
live virus from tissue cultures of those patients. The CDC also noted that there exists
no evidence that clinically recovered persons with either persistent or recurrent
detection of viral RNA have transmitted COVID-19 to others. Further, in some
individuals that test negative by RT-PCR in two consecutive samples, later samples can
test positive. Per the CDC, the consistent, repeated detection of SARS-CoV-2 RNA in
these individuals has been noted to carry fewer copies of viral RNA than was found in
samples collected shortly after or during clinical illness — meaning the viral load
decreases over time.
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We note that false positives of SARS-CoV-2 tests may further convolute estimates of
re-infection. For example, in May, the U.S. Navy reported that 13 sailors from the USS
Theodore Roosevelt who had been infected with COVID-19 and received negative test
results later tested positive; however, it is not clear if the patients were reinfected or
had false-negative test results. False-negative test results could occur if an individual is
tested during a low period of viral shedding during infection and prior to clearing the
virus completely from the body. We further note that performance standards, such as
sensitivity and specificity, for the burgeoning number of serologic assays and the
potential of cross-reactivity to other coronaviruses (which may lead to false-positives)
have yet to be determined (see Diagnostics).
4. What level of antibody response is necessary to be protective?
The levels of antibody in the blood in humans who have been infected by SARS-CoV-2
and recovered from SARS-CoV-2 disease (i.e. convalescent sera) is used as a benchmark
for what is considered “protective” for vaccine trials, given past research on
coronaviruses indicates that an immune response will likely offer some protection over
the medium term (at least 1 year), followed by a potential decline in effectiveness
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(LINK), a sentiment echoed by our KOLs (LINK) and MRNA, who noted that individuals
that contracted SARS-CoV-2 appear at least, in the short term, to be resistant to a
secondary infection.
In addition, our KOL noted that it is difficult to compare titer levels across different
labs/companies, as they are all using their own in-house assays. For MRNA’s Ph1 study,
we note a variety of severity in the 38 individuals in the convalescent sera group had a
wide spectrum of disease: 15% were classified as having severe symptoms
(hospitalization requiring intensive care and/or ventilation), 22% had moderate
symptoms and 63% had mild symptoms. For the PFE/BNTX clinical trial (LINK),
convalescent sera was taken from 38 subjects that had PCR confirmed SARS-CoV-2
infection, including from 34 with symptomatic COVID-19 and one patient who was
hospitalized — which management commented reflects a spectrum between less
severe disease in young people and more severe disease in older adults.
During infection, we note that the levels of a neutralizing response may be less
important than the exact antibodies elicited. Per a study of 149 COVID-19 convalescent
individuals published in Nature Medicine, most convalescent plasma obtained from

individuals who have recovered from COVID-19 do not contain high levels of neutralizing
activity to distinct epitopes on the receptor binding domain (RBD). However, rare but
recurring antibodies that are specific to the receptor binding domain (RBD) of
SARS-CoV-2 with potent antiviral activity were found in all individuals that were tested,
suggesting that a vaccine designed to elicit such antibodies could be broadly effective.
Recall, the RBD protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor,
which mediates the entry of the virus into cells. As a whole, the plasma neutralizing
activity was low in patients who recovered - however, the specific receptor-binding
domain antibodies against SARS-Cov2 that were found within the plasma were
observed to have potent neutralizing activity.
We note the clinical bar for a protective neutralizing antibody response is difficult to
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pinpoint because the exact correlate of protection (i.e. measurable signs that a person is
immune to a virus) for COVID-19 is not currently known by the scientific community;
however, preclinical animal models can offer guidance. On average, vaccines studies
look for 4x titer levels for seroconversion. On the potential for SARS-CoV-2 preclinical
studies to contribute to correlates of protection, the goal would be to demonstrate that
the same antibodies that can be elicited in humans with the vaccine are protective in
non-clinical species. There are two ways this can be achieved: 1) achieving levels of
neutralizing antibodies that are achievable with vaccine, as measured on the same
assay, and 2) passive transfer studies, whereby serum from humans that have been
vaccinated is shown to meet clinical endpoints in animal models.
For reference, in MRNA’s preclinical data from mouse challenge studies (LINK),
neutralizing activity was elicited by 1ug of mRNA-1273, reaching 819, 89, and 1115
reciprocal IC50 geometric mean titer (GMT) across the three mouse strains. Neutralizing
antibody levels post a single vaccination with the 10ug dose reached an average of 315
IC50 GMT, demonstrating that neutralizing activity can be elicited with a single dose.
While all mice that received two 1ug doses of mRNA-1273 were entirely protected from
viral replication in lungs after challenge at a 5- or 13-week interval post-boost, one
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mouse (out of seven total) had detectable viral replication in nasal turbinates (nasal
samples). We note that MRNA achieved successful translation from preclinical studies
to in-human results for its other prophylactic vaccine programs, including its MERS, Zika
and CMV vaccines, leading to our confidence in MRNA’s approach and the data seen
to-date.
Pre-clinical data from AstraZeneca (AZN)/University of Oxford also demonstrated that

prime-boost pigs (two doses of vaccine) had a higher immunogenicity profile (peripheral
mononuclear cells; Ab titers and CD4+ /CD8+ T cells) than prime-only pigs (single dose
of vaccine). Moreover, a single vaccination in rhesus macaques induced a humoral and
cellular immune response as evidenced by a reduced viral load in bronchoalveolar lavage
fluid and respiratory tract tissue of vaccinated animals (n=6) (vs. control animals, n=3).
While the research demonstrated a single dose of the vaccine prevented all vaccinated
monkeys from developing pneumonia, the same amount of virus genome was detected
in the noses of both the vaccinated and unvaccinated animals. The findings suggest that,
while viral loads in bronchoalveolar lavage (BAL) fluid from the lungs and lung tissue of
the vaccinated animals were significantly reduced (which suggests vaccination prevents
viral replication in the lower respiratory tract), those vaccinated could potentially still
transmit the virus to others.
INOVIO’s (INO) INO-4800 demonstrated robust NAb and spike specific T-cell immune
responses against SARS-CoV-2 in mice and guinea pigs. Importantly, the investigators
used three separate neutralization assays to test the vaccine’s ability to generate Abs
against SARS-CoV-2 (we await further details).
Similarly, Sinopharm reported favorable pre-clinical data in animal studies (mice, rats,
guinea pigs, rabbits and non-human primates), which demonstrated high levels of
neutralizing antibodies without triggering any serious adverse events. In mice,
neutralizing antibodies were detected after immunization at all three dose levels, and in
monkeys, the placebo group had high viral loads in contrast to the viral loads in the low
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(significantly lower) and high dose (undetectable) groups.
Per CanSino Biologics, the company has provided few details on its pre-clinical data but
noted pre-clinical animal data (injected with Ad5-nCorV) demonstrated a robust immune
response and favorable safety profile.
5. Vaccination rate of 70-85% is estimated to be required for herd immunity.
As we recently highlighted (LINK), once there is a safe and effective COVID-19 vaccine
available we expect the next focal question to be “how widely will it be used?”. The
CDC/NIH estimated 70%-85% of the US population would need to be vaccinated in
order to provide herd immunity and that 5-8% of the population have been exposed to
the virus. A recent poll conducted by The Associated Press-NORC Center for Public
Affairs Research found that 49% of Americans planned to get vaccinated against
SARS-CoV-2, below the 70-85% estimate required for herd immunity noted above.
Vaccination coverage for the flu vaccine (≥1 dose) during the 2018-2019 influenza season
was 45.3% among adults ≥18 years and 62.6% among children 6 months through 17
years. A method for increasing vaccine uptake may be to require it, which we note has
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been effective for childhood vaccines, such as the vaccines for measles, mumps and
rubella. The NEJM editorial further noted that when a COVID-19 vaccine approaches
approval in the US, the Advisory Committee on Immunization Practices (ACIP) should
develop recommendations, including that only recommended groups should be
considered for mandatory vaccination.
Mandatory vaccination presents a potential method to increase the uptake of a

COVID-19 vaccine. While vaccine mandates have proven effective for childhood
immunizations, we question whether such mandates would be realistically feasible for
adults given concerns around compliance and the likelihood of a mandate being
enacted. A recent NEJM editorial suggests the following six criteria should be achieved
prior to a US state imposing a SARS-CoV-2 vaccine mandate:
1. Covid-19 is not adequately contained in the state.

2. The Advisory Committee on Immunization Practices has recommended vaccination
for the groups for which a mandate is being considered.
3. The supply of vaccine is sufficient to cover the population groups for which a
mandate is being considered.
4. Available evidence about the safety and efficacy of the vaccine has been
transparently communicated.
5. The state has created infrastructure to provide 1) access to vaccination without
financial or logistic barriers, 2) compensation to workers who have adverse effects
from a required vaccine, and 3) real-time surveillance of vaccine side effects.
6. In a time-limited evaluation, voluntary uptake of the vaccine among high-priority
groups has fallen short of the level required to prevent epidemic spread.
GS published COVID-19 related research notes
Below, we highlight key previously published research notes on COVID-19:
93f15d4c5e4d11d89860be55d934f058
n MRNA: Ph1 COVID-19 vaccine data in NEJM impresses (7/15); (LINK).
n PFE: Initial PFE/BNTX COVID-19 vaccine data encouraging; Ph2b/3 trial could start
later this month (7/1); (LINK)
n Healthcare: Pharmaceuticals: The next question to ask once we have a COVID-19
vaccine (7/1); (LINK)
n FDA releases guidelines for COVID-19 vaccines (6/30); (LINK).
n GS 41st Annual Global Healthcare Conference 2020 - Key Takeaways from the
COVID-19 panel (6/10); (LINK).
n Global Healthcare: Emerging Themes In A Post Pandemic World (6/7); (LINK).
n Outlook for a COVID-19 vaccine from our call with CEPI (6/2); (LINK).
n COVID-19 Testing: a Deep Dive into the Challenges and Opportunities Ahead (5/31);
(LINK).
n GILD: Remdesivir receives Emergency Use Authorization from FDA, an expected
positive (5/1); (LINK)
17 July 2020 10
n MRNA: Vaccines Day highlights the core modality and COVID-19 vaccine (4/15);
(LINK).
n The COVID-19 toolkit: Navigating a once-in-a-century global pandemic (4/6); (LINK).
n COVID-19 Discussion with Epidemiologist/Virologist (3/17); (LINK).
Summary: Vaccines/Therapeutics in development
According to the World Health Organization (WHO), global confirmed cases of COVID-19
have reached c.13mn (July 16), presenting a clinical need for both preventative
therapeutics, such as prophylactic vaccines, and therapeutics that address the disease.
These can be broadly segregated into two groups: pipeline therapies (vaccines,
antibodies, anti-inflammatory therapies, antivirals and convalescent plasma, RNAi,
among others) and approved treatments (such as drugs used for COVID-19 related
cytokine storm and inflammation). Below, we provide an overview on the current state
of pipeline therapies.
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17 July 2020 11
Exhibit 1: Summary of lead vaccines in development

Company Compound Category GS comment Event
Vaccines
Moderna (MRNA) reported positive Ph1 interim data and is dosing patients in its Ph2 trial, which is fully enrolled. Management guided to
potential for full Ph3 efficacy data (151 events) around Thanksgiving (11/26)/4Q20 - however, there are two interim reads at 53 and 106
We look to additional mRNA-1273 data publications this
events - which could enable earlier approval (pursuing a rolling submission; Fast Track designation). MRNA and partner Lonza expect to
summer, from non-human primate challenge studies, the
generate ~500mn doses per year, with the possibility to scale up to 1 bn doses per year beginning in 2021, pending continued optimization
elderly and older adult cohorts of the Ph1 study (early-to-
MRNA mRNA-1273 Vaccine efforts. MRNA is also collaborating with Catalent for the manufacturing of fill-finish commercial product (3Q20) and Ph3 clinical trial drug.
mid August), in addition to Ph2 data in August/September
The interim analysis of the Ph1 study published in the New England Journal of Medicine (NEJM) showed neutralizing antibody titers
and full Ph3 efficacy data in 4Q20 (potentially by late-
observed in all evaluable participants; we note at 100ug, the geometric mean titer (GMT) levels were 4.1X higher than those seen in
November) - with two prior interim reads.
reference convalescent sera, and mRNA-1273 elicited a Th1-biased CD4 T cell response, which bodes well for the risk of antibody
dependent enhancements. There were no serious adverse events.
AstraZeneca (AZN)/University of Oxford are running Ph1/2 (>1,000 healthy volunteers; 18-55yrs) and Ph2/3 trials in the UK (~10k
volunteers), but noted the possibility of delays due to dropping infection rates. In addition to the UK study, we note that AZN are also doing
other Phase III studies with enrolment already initiated in Brazil and South Africa (US is imminent). AZN expects to enrol c.30K incremental
patients beyond the UK study. We note positive pre-clinical data where prime-boost pigs had a higher immunogenicity profile than prime- Ph1 data anticipated as early as July
AZN/Univeristy of Oxford AZD1222 Vaccine
only pigs. AZN is also collaborating with IQVIA (IQV) as part of Operation Warp Speed to drive faster delivery of clinical studies in the US. UK Ph2/3 data anticipated in early-mid autumn
Post approval, AZN plans to manufacture and deliver potentially up to 100mn doses to the UK, 300mn to the US (first doses as early as
October, 2020), 400mn doses to EU (France, Germany, Italy and Netherlands; starting YE20) and 1bn doses to low- and middle- income
countries (via a licensing deal with the Serum Institute of India; 400mn by YE20) for a total supply of >2bn doses per year.
Pfizer (PFE) and BioNTech (BNTX) are developing four different vaccines targeting the spike protein or receptor binding domain (RBD) of
Data from the German trials expected in the next few
SARS-CoV-2. Preliminary data from vaccine 162b1 (targeting the RBD; tested across three cohorts: 10ug, 30ug and 100ug), demonstrated
weeks
robust RBD IgG levels in the 10ug and 30ug cohorts with higher mean neutralizing titers post the second doses of 10ug and 30ug. The
Ph2/3 trials to begin in late July
PFE/BNTX BNT162 Vaccine safety profile across the lower doses was favorable with all adverse events mild to moderate in nature (1 patient in the 100ug cohort
Pivotal data expected in August/September
experienced severe pain). Per PFE, they will be moving the 10ug and 30ug doses into Ph2/3 trials (20k-30k participants). Pending
Regulatory approval anticipated by YE20 (as early as
successful development of the vaccine and regulatory approval (received fast track designation), the company expects to have 100mn
October)
doses by YE20 and >1.2bn doses by 2021.
INOVIO (INO) has recently been selected by Operation Warp Speed to conduct non-human challenge studies. Based on positive interim
Ph1 data (n=36; 94% overall immunological response rate) from the first two cohorts, INO will be expanding its Ph1 trial to add older
INO INO-4800 Vaccine Ph2/3 trial initiations in the summer
patients in additional cohorts (full data will be published in an academic journal). Preclinical studies in animals show robust immune
response. INO aims to produce 1mn doses by YE20.
Sinovac’s (SVA) CoronaVac showed favorable immunogenecity in Ph2 (n=600) and triggerd neutralizing antibodies within 14 days of
SVA CoronaVac Vaccine vaccination (two doses) with a seroconversion rate >90%. Ph3 will be conducted in Brazil with partner Institut Butantan (timelines not Ph3 trials will be conducted in Brazil
disclosed). Sinovac aims to manufacture 100mn doses of the vaccine per year (in China).
Sinopharm announced positive results (97.6% seroconversion at the low and middle dose; 100% at high dose) from its placebo-controlled
Ph1/2 trial for BBIBO-CorV (inactivated vaccine) and has received approval to begin Ph3 trials in the UAE. Interestingly, per news reports,
China’s State-owned Assets Supervision and Administration Commission (a government body that oversees state-run enterprises such as
Sinopharm BBIBO-CorV Vaccine Sinovac and Sinopharm) is already offering SVA’s CoronaVac and Sinopharm’s BBIBO-CorV vaccines to employees of large state-owned Ph3 trials will be conducted in UAE
(Chinese) companies who intend to travel overseas. Pre-clinical studies in rodents, rabbits and monkeys were able to induce high level
neutralizing antibodies. Per news reports, 200mn doses will be manufactured per year across Sinopharm’s BBIBO-CorV/ Sinovac’s
CoronaVac.
CanSino reported positive results from its Ph1 dose escalation trial. However, we note that the mean neutralization titer in the high dose
CanSino Biologics Ad5-CorV Vaccine group was 34 -- well below FDA’s recommended titer of 160 for convalescent plasma. The vaccine has also been approved for use among
members of the Chinese military.
Ph1/2 trials are ongoing. Novavax (NVX) has received the largest CEPI funding (total $388mn) to date. Operation Warp Speed has also Ph1 preliminary data expected in at end of July 2020.
Novavax NVX-CoV2373 Vaccine provided $1.6bn in funding for pivotal trials (c.30k participants) and manufacturing of 100mn doses of its NVX-CoV2373 vaccine (targets Ph2 to begin following successful Ph1 results
spike protein) by YE20. Ph3 trial to begin in the fall
Post positive pre-clinical studies, Curevac will begin Ph1 dose escalation (2ug-8ug; n=168) trials in Germany and Belgium promptly. The
CureVac CVnCoV Vaccine primary goal is to determine the safety and immunogenicity profile of the vaccine. Tesla will be collaborating with CureVac to build RNA Ph1 trials to begin in Germany and Belgium promptly
microfactories that could potentially speed up the global supply chain manufacturing process.
Clover has produced an S-Trimer subunit vaccine that resembles the native trimeric viral spike, which is currently being tested in a Phase I
GSK/Clover clinical study assessing the potential of combining its COVID-19 S-Trimer vaccine with GlaxoSmithKline’s (GSK) pandemic adjuvant
S-Trimer Vaccine Preliminary data expected in August
Biopharmaceuticals system, which can reduce the amount of protein required per vaccine dose. Clover is responsible for manufacturing since it has one of the
largest in-house, commercial scale cGMP manufacturing facilities in China.
Ph1/2a trials to begin in late July 2020

Johnson & Johnson (JNJ) has identified a vaccine candidate for clinical development and plans to initiate Ph1/2a clinical studies by late July
Non-human challenge data in the coming weeks
2020. The company continues to engage with the NIAID with the goal to initiate Ph3 study ahead of schedule. JNJ intends to scale
JNJ Ad26-SARS-CoV-2 Vaccine Ph3 trial likely to initiate in late September
production in parallel to enable supply of >1bn doses through 2021. JNJ anticipates the the vaccine could be available for emergency use
Efficacy and safety data expected by YE20
authorization in early 2021.
Vaxart (VXRT) has been selected to participate in a non-human primate (NHP) challenge study by Operation Warp Speed for an oral
COVID-19 vaccine which is based on its validated propreitary oral vaccine platform (VAAST). While the COVID-19 oral vaccine is still in pre- Ph1 study (open label; dose ranging) to begin in 2H20,
VXRT - Vaccine
clinical studies, VXRT has contracted Emergent BioSolutions and Kindred Biosciences to produce bulk vaccine under cGMP for upcoming possibly as early as summer
clinical trials and the company notes that tech transfers are complete. The vaccine tablets will be manufactured at VXRT.
Preliminary Ph1/2 data likely by December

Sanofi (SNY) and GSK have entered into an agreement to use SNY’s S protein antigen in combination with GSK’s pandemic adjuvant
93f15d4c5e4d11d89860be55d934f058
Ph3 trial initiation in January 2021
SNY/GSK - Vaccine technology to develop a vaccine against SARS-CoV-2. If successful, SNY/GSK aim to have the vaccine ready by 1H21 and reach 100
potential FDA EUA by January 2021; approval by June
million doses as early as June 2021 with a total capacity of 1 billion doses in 2021.
2021
Initial human trials will begin in 4Q20; data YE20
SNY is developing a novel, recombinant, protein-based vaccine in partnership with BARDA using SNY’s recombinant DNA platform. Ph3 trials to begin in January 2021
SNY - Vaccine
Company has stated capacity of 100 million doses as early as June 2021 with a total capacity of 1 billion doses in 2021. potential FDA EUA by January 2021; approval by June
2021
Novel mRNA COVID-19 vaccine using Translate Bio’s (TBIO) mRNA platform. SNY expects to have capacity for 90-360mn doses by 1H21 Initial human trials will begin in 4Q20; approval anticipated
SNY/TBIO - Vaccine
is are working towards increasing capacity. 2H21
Merck (MRK) and IAVI are collaborating to develop an investigational COVID-19 vaccine based on the recombinant vesicular stomatitis
Pre-clinical development ongoing, clinical studies to begin
MRK/IAVI - Vaccine virus (rVSV) technology. The platform uses an attenuated strain of VSV that has been modified to express proteins which can stimulate an
in 2H20
immune response. MRK and IAVI previously collaborated to develop MRK’s Ebola Zaire virus vaccine, ERVEBO, using this same platform.
MRK recently acquired Themis (completed 6/19) - an EU biotech developing several vaccines for infectious disease, including COVID-19,
using a proprietary measles vector platform (originally developed at Institut Pasteur). The platform, which has been used in the development Pre-clinical development ongoing, clinical studies to begin
MRK/Themis - Vaccine
of vaccines for various infectious diseases including SARS, Chikungunya, MERS, and Lassa fever, uses a modified (live attenuated in 2H20
replicating) measles vaccine virus as a vector.
Subsidiary UMN Pharma is developing a recombinant protein vaccine for COVID-19 that uses insect cells. Rhabdovirus contamination of
Shionogi & Co. - Vaccine Nov, 2020 IND, March 2021 Topline/NDA
insect cells had been a concern, but the company said this issue has been solved.
AnGes aims to develop a vaccine using plasmid DNA drug discovery technology. While no DNA vaccine has ever been commercialized, if
AnGes AG0301-COVID19 Vaccine the vaccine shows efficacy and proceeds to large-scale phase 3 trials, the focus will be on news flow regarding the countries where the trials Ph1/2 Ongoing, NDA in 2020
will take place, and on fund procurement.
ReproCELL is participating in an international R&D consortium that aims to develop an mRNA vaccine that is administered intranasally. The
ReproCELL Inc. - Vaccine IND in early 2021
company aims to contribute through its technologies for introducing mRNA into cells.
Daiichi Sankyo aims to develop a vaccine using its proprietary nucleic acid platform. Although it has yet to launch any nucleic acid
Daiichi Sankyo - Vaccine treatments, it is making progress with development of DS-5141, a treatment for muscular dystrophy that uses the company’s ENA modified March 2021 IND
nucleic acid.
Eisai had previously reported that it envisaged use of its selective toll-like receptor (TLR) 4 agonist E6020 with influenza vaccines (PMID:
Eisai E6020 Vaccine -
19255727), but there is a possibility it could be effective used alone or with other adjuvants in COVID-19 vaccine development.
CSL Behring (CSL) is partnering with the University of Queensland (UQ, Australia) and CEPI to develop a “molecular clamp” enabled
COVID-19 vaccine (anticipated by 2021). Early preclinical data demonstrated that the vaccine candidate can trigger high levels of
CSL - Vaccine neutralizing antibodies. Funding contributions from both CSL and CEPI will be used to support clinical trials (Ph1 underway), and
manufacturing with a potential goal of producing millions of doses per year (100mn doses by YE21). Pending approval, CSL will distribute all
vaccine doses through COVAX.
Source: Company data, compiled by Goldman Sachs Investment Research
17 July 2020 12
Exhibit 2: Summary of lead therapies in development

Company Compound Category GS comment Event
Approved therapies
Veklury (remdesivir) has conditional approval in EU for the treatment of COVID-19 in adults and adolescents from 12 years of age with
pneumonia who require supplemental oxygen. On May 1, the FDA granted remdesivir emergency use authorization (EUA) for the treatment Results from expansion phases expected in the coming
GILD Veklury (remdesivir) Antiviral therapy
of severe COVID-19 patients and is also approved in Japan. In our view, the company sponsored Ph3 study in moderate/severe patients months
and an NIAID sponsored study in hospitalized patients suggests that the drug is a potential treatment for COVID-19.
Pipeline therapies
Eli Lilly (LLY) has begun dosing patients in the world’s first study of a potential antibody against SARS-CoV-2. If Ph1 shows that the Preliminary clinical data expected as early as late June
LLY/Abcellera LY-CoV555 Antibody therapy treatment is safe in hospitalized COVID-19 patients, LLY expects to move into testing in non-hospitalized COVID-19 patients with a goal of 2020
having several hundred thousands doses by YE20. Potential authorization for early use by September
LLY LY3127804 Antibody therapy LLY is currently recruiting for Ph2 trial in hospitalized COVID patients with pneumonia. Data readouts expected in early summer
Regeneron (REGN) has initiated Ph1/2 clinical trials which will test the antibody cocktail in COVID-19 patients that are hospitalized and non-
REGN REGN-COV2 Antibody therapy hospitalized. Ph1 endpoints include virology and safety; Ph2 endpoints include virology and clinical outcomes. Data from Ph1/2 will inform Initial data in the summer
Ph3 trial size and endpoints.
Vir Biotechnology (VIR) has identified antibody candidates (VIR-7831/VIR-7832) which it is now developing in partnership with GSK. The
Ph2 trials to begin in the summer pending regulatory
VIR/GSK VIR-7831/32 Antibody therapy companies are additionally utilizing VIR’s CRISPR screening and machine learning approach and GSK’s vaccine technologies to further
review
other initiatives in search for a vaccine for COVID-19.
VIR has identified two antibodies (VIR-7831/32) which are modified to i) extend its half-life, and ii) increase its short term (vaccinal) potency.
VIR/BIIB VIR-7831/32 Antibody therapy Clinical trials to begin in July-September 2020
One will be produced with and one without the vaccinal mutation.
Under a memorandum of understanding with AMGN, ADPT is leveraging its platform’s drug discovery capabilities to discover fully human ADPT expects to complete their discovery of candidate
AMGN/ADPT - Antibody therapy
neutralizing antibodies to potentially speed the recovery from or prevent COVID-19. neutralizing antibodies in 2H20.
Junshi has dosed its first healthy volunteer with JS016 in its Ph1 US trial. The recombinant fully human monoclonal neutralizing antibody
LLY/ Junshi JS016 Antibody therapy targets the SARS-CoV-2 surface spike protein. LLY will receive exclusive license to develop, manufacture and distribute the drug outside of
Greater China.
VIR has partnered with WuXi to expedite the development of their lead COVID-19 candidate. WuXi is responsible for and is in early stages
VIR/WuXi Biologics - Antibody therapy
of cell-line development, formulation and initial manufacuturing.
EIDD-2801 is an orally available antiviral candidate (ribonucleoside analog) currently in early clinical development. Ph1 studies have
demonstrated that EIDD-2801 is well-tolerated and has potent antiviral properties against multiple coronavirus strains including SARS-CoV-
MRK/Ridgeback Bio EIDD-2801 Antiviral drug 2. Two Ph2 trials were initiated in mid-June to evaluate the virologic efficacy and further assess the safety of EIDD-2801 — one focusing on Ph2 Ongoing
newly hospitalized COVID-19 patients (estimated enrollment of 60) and the other focusing on COVID-19 outpatients (estimated enrollment
of 44).
PFE is developing a protease inhibitor (that was initially developed during the SARS epidemic) for the treatment of COVID-19. Based on
Pre-clinical studies are ongoing
PFE - Antiviral therapy initial screenings and preliminary data, the compound is a potent inhibitor of the SARS-CoV-2 3CL protease and shows anti-viral activity
Ph1 trial is expected to start in August
against SARS-CoV-2.
The therapy will be developed as an inhalation formulation. VIR-2703 has predicted reactivity to >4300 SARS-CoV-2 genomes available in The companies plan to meet with regulatory authorities to
VIR/ALNY VIR-2703 Antiviral therapy
public databases and against the SARS-CoV genome from the 2003 SARS outbreak. discuss potential acceleration of filing and IND by YE20.
SRPT - Antiviral therapy In collaboration with USAMRIID, SRPT will identify antisense oligoneucleotides against SARS-CoV-2 using its PMO platform
Three preclinical Plans to develop treatments by taking a three-pronged approach: (1) identify peptides that block viral contact with human cells, (2) develop
PeptiDream Inc. projects Antiviral drugs peptides that block virus entry into human cells, and (3) develop peptides that introduce antiviral agents and immune cells into the virus.
Alliance with MRK Company has also partnered with Merck to jointly develop peptide therapeutics that are effective against multiple coronavirus strains.
Antiviral drug Has already acquired more highly active compounds than Remdesivir and Favipiravir (Avigan) in vitro . The company said it is also
Shionogi & Co. - Anti-inflammatory developing antiviral drugs that can cope with mutated versions of the virus going forward. It also showed interest in developing treatments Treatment: March 2021 IND
drug for severe/critical cases.
Data from severe COVID-19 patients show promise. Company is moving towards a global Ph2/3 trial and an investigator-initiated placebo- Preparing for registrational program in severe COVID-19
KNSA mavrilimumab Anti-inflammatory
controlled study in the US. associated pneumonia and hyperinflammation
Probably aimed at prevention/treatment of acute respiratory distress syndrome (ARDS) via neutralization of granulocyte-macrophage colony-
Eisai gimsilumab Anti-inflammatory Ph2 Ongoing
stimulating factor (GM-CSF), which is involved in cytokine storms. Out-licensee Roivant is conducting clinical trials.
Sponsoring the investigator-initiated STOP-COVID19 trial, investigating the potential for brensocatib to reduce the incidence of ARDS in Sample size reassessment expected in 3Q20 (after
INSM brensocatib Anti-inflammatory hospitalized COVID-19 patients. Prior positive data in bronchiectasis has shown efficacy in limiting neutrophil-mediated pulmonary enrolling & treating 100 patients), with full data (in up to
inflammation. 300 patients) expected in late 2020/early 2021.
Developed as treatment for severe sepsis arising from bacterial infection by antagonising toll-like receptor (TLR) 4. While safety of the
compound was confirmed, Phase 3 trials did not show efficacy in the original indication. Although the company has hopes for the compound
Eisai eritoran Anti-inflammatory Jun 2020 IND
as a blocker of signals that can cause cytokine storms, (1) it is unlikely that the novel coronavirus is directly involved in TLR4 signal
activation, and (2) the compound is unlikely to show efficacy in secondary bacterial infections.
In Japan, Healios is developing HLCM051 as a treatment for ARDS, including COVID-19 induced ARDS. In the US, Athersys, from whom
Healios HLCM051 Anti-inflammatory Healios licenses the pipeline , is currently assessing efficacy against COVID-19. It is hoped that the treatment will suppress the overactive TBD
immune response.
In early March, Takeda announced plans to develop treatments leveraging plasma derived therapy (PDT) technologies, a first among global
companies. We think this could boost expectations for CoVIg-19, currently being developed by a 10-company global consortium, given Jul, 2020 IND
Takeda Pharmaceutical CoVIg-19 Plasma therapy
clinical trial data showing promising efficacy/safety results of convalescent plasma against. COVID-19 have already been reported in The Topline results expected by the end of 2020
Journal of the American Medical Association (JAMA).
The company is exploring two separate treatment approaches: 1) it has started to use convalescent plasma in treating patients in hospital,
and recorded initial positive, albeit small-scale, feedback. 2) Similar to Takeda, Grifols intends to fractionate the convalescent plasma into
Grifols - Plasma therapy Clinical trials to begin in 3Q20
an H-IG treatment and test it in the clinic in 3Q20; we note that the company has started production in early June and used this approach
also during the Ebola outbreak.
SAB-185 is a high-potency immunotherapy delivering human polyclonal antibodies targeted to SARS-CoV-2. The advantage of this
CSL/SAB Biotherapeutics SAB-185 Plasma therapy approach is that it allows for the development of human polyclonal antibodies that deploy the same natural immune response to fight the
disease without the need for blood plasma donations from recovered patients.
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Development progressing as a cancer immunotherapy via inhibition of SUMOylation. Could be aiming for viral clearance via
Takeda Pharmaceutical TAK-981 Others Jun, 2020 IND (IIS)
immunostimulation also in COVID-19 cases.
Commercial therapies (under evaluation for COVID-19)
ROG is starting a second Ph3 global placebo controlled study (REMDACTA; n=450) with Actemra + remdesivir in severe COVID-19
Actemra/
ROG Anti-IL-6 pneumonia patients in June. The Actemra monotherapy Ph3 trial (COVACTA) has almost completed enrollment (n=450). Patients in both COVACTA trial data expected in July
RoActemra
trials are receiving SoC.
Anti-IL-6 receptor antibody. Prescribed mainly as rheumatoid arthritis treatment. Expected to function as cytokine storm inhibitor in COVID-
19. Has suspended clinical trials of Kevzara (RGEN/Sanofi), which has the same mode of action, as it has not shown efficacy. However,
Actemra (RA drug) Actemra: Topline result in early July 2020
Chugai Pharmaceutical Antibody Actemra has shown efficacy in clinical trials being implemented in French hospitals, and expectations remain high. Has adopted the same
Neutralizing antibody Neutralizing antibody: TBD
trial design as the global trials being conducted by ROG. Could apply for approval in Japan in 2020 if ROG data (due soon) and results from
global trials show efficacy.
First patient has been enrolled in the Ph2 ACTT-2 trial where NIAID is testing efficacy of combination treatment of Olumiant with remdesivir
LLY/NIAID Olumiant JAK inhibitor Results are expected during the summer 2020
in contrast to remdesivir alone. Focus is on time to recovery (evaluated as time to be discharged from hospital).
First patient have been enrolled in the Ph3 trial where the company is testing efficacy of combination treatment of Olumiant with SoC in
LLY Olumiant JAK inhibitor contrast to placebo with SoC in hospitalized COVID-19 patients (n=400). Focus is on mortality, recovery or ventilation requirements by Day Data is expected in the next few months
28.
Used currently to treat hereditary angioedema (HAE) via inhibition of vascular permeability through bradykinin B2 receptor blockade. Could
Takeda Pharmaceutical Firazyr Others also show efficacy in serious/critical COVID-19 cases, as increased permeability of pulmonary blood vessels could lead to critical respiratory Jun, 2020 IND (IIS)
dysfunction.
Used currently to treat HAE via inhibition of vascular permeability through kallikrein blockade. Could also show efficacy in serious/critical
Takeda Pharmaceutical Takhzyro Others Jun, 2020 IND (IIS)
COVID-19 cases, as increased permeability of pulmonary blood vessels could lead to critical respiratory dysfunction.
Based on a study reported in March by German research group that Foipan inhibits novel coronavirus entry into cells. An oral drug, if proven
Ono Pharmaceutical Foipan Antiviral drug Ph1 Ongoing (until Aug 2020)
to be effective, Foipan would be easy to administer.
REGN/SNY recently reported that their Ph 3 US trial of Kevzara 400 mg in COVID-19 patients requiring mechanical ventilation did not meet
its primary endpoint (Kevzara’s impact on fever) and key secondary endpoint (need for supplemental oxygen) when Kevzara was added to
REGN/SNY Kevzara Anti-IL-6 Ph2 ex-US data in 3Q20
best supportive care vs. best supportive care alone (placebo). The ex-US Ph 3 study, currently evaluating a higher dose of Kevzara in c.400
patients, will continue with results expected in Q3 2020
Based on report by a Tokyo University research group that Nafamostat shows higher efficacy than Camostat (Foipan). The existing
Nafamostat
Daiichi Sankyo Antiviral drug Nafamostat product is an injectable compound. The company has embarked on development of an inhalation formulation, leveraging March 2021 IND
(Inhalant)
inhalation formulation technology used with anti-influenza inhaler Inavir.
While Ph2 (n=50) trials are underway in the US, Japan is expected to ship drug to 43 countries for clinical studies. Additionally, the company
Fujifilm Holdings Avigan Anti-flu is working to increase monthly production to 100k treatment courses (14 days) by July and 300k treatment courses by September. It has
already reported that clinical trials in China suggested that the drug is effective in the treatment of COVID-19.
Incyte (INCY) and Novartis (NVS) are conducting a global Ph3 trial (RUXCOVID; n=400; >12yrs) to evaluate the safety and efficacy of Jakafi
(JAKi)/ standard of care (SoC) versus SoC in the treatment of patients with COVID-19 associated cytokine storm (uncontrolled
INCY/NVS Jakafi JAK inhibitor
inflammation). INCY will initiate an open-label emergency Expanded Access Program (EAP) in the US to allow eligible COVID-19 patients to
receive Jakafi .
Alexion (ALXN) is conducting a TACTIC-R study in the UK where less severe COVID-19 patients will receive lower doses of Ultomiris. In the
US, ALXN plans to conduct a 2:2:1 randomized open-label study (n=270) in addition to standard of care in severe COVID-19 patients with
ALXN Ultomiris C5 inhibitor
mechanical ventilation. The primary endpoint will be mortality at month one and will also evaluate other measures such as need for
mechanical ventilation. Management will provide updates on timelines and enrollment as the sites open up across the US and EU.
Source: Company data, compiled by Goldman Sachs Global Investment Research
17 July 2020 13
Vaccines - Key debates
WHO and partners have established a $18bn program to expedite R&D,

manufacturing and distribution of COVID-19 vaccines
World Health Organization (WHO) and global groups such as Gavi, the Vaccine Alliance
and the Coalition for Epidemic Preparedness Innovations (CEPI) have established a
$18bn program to expedite the R&D process for all countries and simultaneously
establish manufacturing and distribution for a global rollout. The group aims to deliver
2bn COVID-19 vaccine doses by the end of 2021 in countries with the greatest need.
We note that this is part of a larger program ($31.3bn) for COVID-19 vaccines,
therapeutics and diagnostics. Thus far, $3.4bn has been raised for the initiative with
$2.6bn earmarked for the vaccines campaign. In the interim, CEPI is in the process of
matching manufacturing capabilities at biopharma companies with the requirements for
leading vaccine candidates, with a goal of manufacturing 4bn vaccine doses by YE21.
There is concern that the US and EU have signed agreements to secure supplies
(pending success of candidates), that would make it difficult for low- and middle-income
countries to secure immediate access. We note AZN/University of Oxford have entered
into a $750mn deal to provide its vaccine to developing countries. Furthermore, to
ensure an equitable allocation an alliance of global health organizations, national
governments and private companies has been formed (see below for details).
COVAX to assist lower income countries in obtaining sufficient doses of vaccine

by establishing vaccine pools
As most vaccine programs progress towards pivotal trials and potential approval, a
coalition of global health organizations, national governments and private companies has
joined together to ensure equitable access to vaccines for lower income countries, in
particular, and to head-off the possibility that panic buying of vaccines by high income
93f15d4c5e4d11d89860be55d934f058
countries does not exhaust global supply (seen during the 2009 H1N1 influenza
pandemic). This coalition, a global purchasing pool, called the COVID-19 Vaccine Global
Access (COVAX) Facility, established by the Access to COVID-19 Tools (ACT) Accelerator,
uses the Gavi Advanced Market Commitment for COVID-19 Vaccines (Gavi Covax AMC)
as a financing instrument. The purpose of COVAX is to negotiate advance purchase
commitments for vaccines by guaranteeing manufacturers the sale of specific quantities
at predetermined prices. Then, COVAX will allow countries to either buy a share in a
vaccine pool or to sign a separate agreement on the payment/receipt of vaccines based
on the countries’ income levels. High- and upper-middle income countries will fund
COVAX by making upfront financial contributions which will serve as down-payments,
securing future vaccine deliveries and thus far, the initiative has raised $500mn of an
initial target of $2bn (estimates c.1.7bn doses needed 2021-22; c.9bn doses in 2021-26).
The purchasing pool will allow all self-financing countries to access vaccines for their
higher priority populations (20% of total population), post which they will be asked to
delay drawing additional vaccines from the pool until all other countries in the pool have
enough vaccine for 20% of their populations. Vaccines will be provided to lower-income
and lower-middle income countries as soon as it becomes available and will be allocated
17 July 2020 14
according to a framework that WHO is developing. However, we note that the success
of COVAX is highly dependent on the number of countries that participate due to
economies of scale.
Usage of adenoviral vectors could lead to lower pool of target patients
While initial data from CanSino Biologics has been favorable, we note that both
CanSino’s Ad5-CorV and AZN/University of Oxford’s AZN1222 vaccines use an
adenoviral vector (vaccine backbone), a key factor given that, on average, ~30% (AAV5)
of people are immune to the adenovirus, making these vaccines ineffective in such
populations. Furthermore, data suggests that immunity to the adenovirus increases with
age and use of adenovirus based vaccines could be an issue if a second dose (i.e
booster) is required for vaccination in the future.
Ph3 trials will require agility to recruit a diverse population and address
fluctuating infection dynamics
We note companies expected, per their guidance, to be in Ph3 trials this summer
include Moderna (MRNA), Pfizer (PFE)/ BioNTech (BNTX), AstraZeneca

(AZN)/University of Oxford (Ph3 currently underway), INOVIO (INO) and Sinovac (SVA;
we also note Sinopharm has received Ph3 approval however exact timelines of study
initiation have not been disclosed). While not naming the vaccine candidates, we note
that NIAID director, Dr. Anthony Fauci, highlighted that four vaccines which are
scheduled to begin late-stage trials between July and October have harmonized trial
protocols and will include the same endpoints. Based on respective trial timelines, these
vaccines likely include the MRNA’s mRNA-1273 (c.30k participants; trial start likely in
July), PFE/BNTX’s BNT162 (c.30k participants; trial start likely in July), and INO’s
INO-4800 - all are supported by Operation Warp Speed. We further note that Ph2/3
enrollment for AZN/University of Oxford’s AZD1222 is underway. These companies will
likely face challenges, as they look to recruit ~25,000–30,000 volunteers for sufficient
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powering - FDA guidance requires the delta between the placebo and treatment arm
should be at least 50% across all endpoints (and interim analyses) for registrational
studies of a COVID-19 vaccine.
In addition, these large trials may face hurdles, such as reduced community infection
rates (depending on geography), blurred efficacy (will require stringent testing) and
potentially prolonged timelines vs. expectations (if not nimble with regard to a
fluctuating infection dynamics). Further, multiple trials may likely be competing for the
same participants in geographic regions where community transmission exists. To
address these challenges, MRNA has noted its intention to enroll its Ph3 study at sites
across the US and be nimble, given unknowns on the geographic variability of the virus’
attack rate.
Requirement for cold storage of vaccines could impact distribution
Finally, as many vaccine programs approach pivotal trials and companies look to
distribute their vaccine products globally, a key concern is the stability of the vaccine
and associated storage requirements. For example, PFE/BNTX has noted that the
BNT162b1 vaccine is currently stored at -80C. However, due to the large anticipated
17 July 2020 15
distribution footprint, PFE/BNTX will need special shipping containers to ensure the
vaccine remains frozen (promotes stability) during transport (~10 days). PFE/BNTX is
conducting studies to estimate the short-term storage requirements at a range of
temperatures and as it looks to lifecycle management, PFE/BNTX expects to have a
lyophilized formulated vaccine by 4Q21. We note that CureVac (private company) has
also highlighted the possibility that its vaccine candidate could be stable at room
temperature. For MRNA, its mRNA-1273 vaccine can be stored at -2 to 5 degrees
Celsius, with a shelf life of 3-6 months, which the company has guided to as sufficient in
a pandemic given the likelihood of product being used immediately is high. MRNA will
not lyophilize the formulation, as it does with its CMV vaccine. We note that the
requirement for cold chain distribution may present logistical hurdles to providing the
vaccine to remote areas or countries with limited infrastructure.
Advantages of mRNA prophylactic vaccines
We see advantages to mRNA based vaccines given mRNA mimics aspects of natural
viral infection and can overcome certain limitations of DNA vaccines. When the mRNA
vaccines enters a cell, it produces viral antigen proteins (a process by which natural viral
infections occur) which can potentially enhance/improve the immune response (B and T
cell responses). Notably, unlike DNA vaccines, mRNA vaccines do not need to enter a
cell’s nucleus to be translated into protein (mRNA is translated in the cytosol) and
therefore limit the risk of DNA integration. As a result, mRNA vaccines require only
1/1000 the dose of DNA vaccines and do require special delivery devices to enter the
nucleus.
While mRNA vaccines generally have advantages over DNA-based vaccines, we note
MRNA has platform-specific benefits that will likely position them ahead of DNA and
other mRNA based vaccines, both for its COVID-19 and for other programs. MRNA uses
an in silico (computer-based) production process to design, produce and test antigens in
preclinical models thus accelerating vaccine selection. This capability positions MRNA
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well to adapt quickly should SARS-CoV-2 mutate. MRNA’s production process stands in
contrast to traditional vaccines, which use dedicated cell-cultures and/or
fermentation-based manufacturing to test potential vaccines. Additionally, mRNA
vaccine production does not involve either pathogens or the development of
target-specific cell culture or fermentation - there is no need to grow the vaccine
(required for traditional vaccines).
International guidance on COVID-19 vaccines
Per WHO (as of July 15), there are 23 COVID-19 vaccine candidates in clinical trials and
140 in pre-clinical studies. In order to rule out the licensure of weakly effective vaccines,
the International Coalition of Medicines Regulatory Authorities (ICMRA) released a
report on July 9 defining the criteria required to proceed to Ph3 trials and the optimal
Ph3 trial design.
Below we summarize the key takeaways from ICMRA guidance:
17 July 2020 16
Ph3 trial design criteria
n COVID-19 vaccine Ph3 trials should be randomized, double-blind, controlled

(placebo or active comparator), diverse (eg. race, ethnicity and age >55yrs, people
with underlying co-morbidities and children) and adequately powered. Sponsors
should provide eligibility criteria to include pregnant women and those of
childbearing potential who are not actively avoiding pregnancy. Additionally, studies
that use adaptive design elements should include pre-specified criteria.
n Endpoints need to be standardized across trials to allow the effectiveness and
safety of different SARS-CoV-2 vaccine candidates to be compared. The primary
endpoint should be laboratory-confirmed COVID-19 of any severity, while other
important endpoints include confirmed SARS-CoV-2 infection and severity of disease
as measured by hospitalization, mechanical ventilation or death. Success criteria
must include efficacy point estimates that should be specified in initial clinical
efficacy trials.
n On safety, sponsors must include pre-specified criteria for halting or pausing
the study based on signals of potential vaccine-induced enhanced disease with a

minimum study follow up of one year in order to evaluate safety, duration of
immune response and risk of disease enhancement as antibody titers wane.
Criteria to move into Ph3 trials
n Pre-clinical and clinical data requirements must be met prior to progression

towards Ph3. Non-clinical data characterizing vaccine-induced response derived from
studies of animal models will be needed, including an evaluation of immune markers
of potential enhanced respiratory disease (ERD) outcomes (including neutralizing
antibodies).
n The decision to proceed to Ph3 will be based on the specific SARS-CoV-2
vaccine construct, and the totality of data available (pre-clinical and clinical).
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ICMRA highlighted that adequate safety and immunogenicity characterization must
be undertaken at each dose level and age group prior to Ph3.
FDA guidance on COVID-19 vaccines
The FDA recently released industry guidance on June 30 (LINK) for the development
and licensure of vaccines to prevent COVID-19 (LINK). Notably, the guidance
recommended that prevention of COVID-19 infection is used as a primary endpoint
– however, in acknowledgment that this is a high bar to achieve, the FDA is also
permitting it to be used as a secondary endpoint. For example, MRNA’s primary
endpoint will be the prevention of symptomatic COVID-19 disease, with secondary
endpoints that include prevention of severe COVID-19 disease (as defined by the need
for hospitalization) and prevention of infection by SARS-CoV-2 for its Ph3 study. Across
all endpoints (and interim analyses), the delta between the placebo and treatment
arm should be at least 50%. This compares relatively favorably to the flu vaccine,
which has demonstrated efficacy ranging from 19% to 60% since 2010 per the Centers
17 July 2020 17
for Disease Control and Prevention (CDC, LINK). However, we note that MRK’s Ebola
vaccine, Ervebo, which was developed to address the outbreak in 2014, was 100%
effective as demonstrated in a “ring” study of the vaccine (MRK is using the same
platform for one of its SARS-CoV-2 vaccines) - ring vaccination is a method of infection
control that entails vaccinating a cluster of high-risk individuals based on their social or
geographic connection to a known case. In addition, per WHO, most routine childhood
vaccines are effective for 85% to 95% of recipients. A vaccine with 50% efficacy may
fall short of the levels that some researchers have estimated would be necessary
to suppress a COVID-19 outbreak. For example, in a computer model, researchers
estimated that a vaccine would have been required to be at least 70% effective to stop
the spread of the virus, if it were given to 60% of the population within 90 days of the
outbreak starting. The FDA guidance further notes that Emergency Use Authorization
(EUA) could be appropriate for COVID-19 vaccines (ahead of a formal review) only if
studies demonstrate favorable safety and efficacy based on adequate and
well-controlled clinical trials or surrogate endpoints that are deemed reasonably likely to
predict clinical benefit. For vaccines granted accelerated approval, post- marketing
confirmatory trials are required to verify the efficacy.
WHO released a document on April 9 (LINK), noting two success benchmarks for
vaccines: 1) Ideally, a vaccine should demonstrate at least a 70% efficacy and durability
of at least a year in the setting of reactive use in an outbreak and/or protection for
individuals with high ongoing risk; and 2) a lower success bar of 50% efficacy with at
least a six-month durability is acceptable, and likely enough for frontline healthcare
workers - however it may not be sufficient to reach herd immunity.
Below, we summarize the key takeaways from the FDA guidance:
n The primary endpoint for a placebo-controlled trial of a COVID-19 vaccine should

demonstrate at least 50% more effectiveness than placebo in preventing
disease, and the lower bound of alpha-adj CI should be >30%, with the same
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criteria applying to any interim analysis. Further, late Phase studies should be
randomized, double-blind, placebo controlled studies and should include interim
analyses to assess risk of vaccine-associated enhanced respiratory disease (ERD;
potential safety risk) and futility.
n Accelerated approval may be considered based on clinical trials establishing effect
on a surrogate endpoint that is reasonably likely to predict clinical benefit, however
additional understanding of SARS-CoV-2 immunology is necessary.
n Non-inferiority comparison to a COVID-19 vaccine with proven efficacy is acceptable
and the lower bound of the CI on the primary efficacy endpoint should be >-10%.
n COVID-19 vaccine candidates should establish safety databases on par with
other preventative vaccines for infectious disease which typically consists of at
least 3k participants. Participants should be observed for at least 7 days post
vaccination to characterize reactogenicity (solicited local and systemic AEs), 21-29
days to evaluate unsolicited AEs, and 6 months for SAEs and other medically
attended AEs.
n The FDA guidance notes Emergency Use Authorization (EUA) may be
17 July 2020 18
appropriate for COVID-19 vaccines before the manufacturer has submitted

and/or FDA completed the formal BLA review but only once studies have
demonstrated the safety and effectiveness of the vaccine.
n The standardization of efficacy endpoints across clinical trials may facilitate
comparative evaluation of vaccines for deployment programs, provided that
such comparisons are not confounded by differences in trial design or study
populations. To this end, FDA recommends that either the primary endpoint or a
secondary endpoint (with or without formal hypothesis testing) be defined as
virologically confirmed SARS-CoV-2 infection with one or more of the following
symptoms: fever or chills, cough, shortness of breath or difficulty breathing, fatigue,
muscle or body aches, headache, new loss of taste or smell, sore throat, congestion
or runny nose, nausea or vomiting, diarrhea.
In addition, per a recent US Senate hearing on COVID-19, Dr. Fauci (director of NIAID)
noted he is cautiously optimistic on knowing the extent of efficacy for a COVID-19
vaccine in winter or the early part of 2021, with hope that doses will be available by
the beginning of 2021.
Vaccines in development: At least five programs in Ph3 this summer
PFE/BNTX, MRNA, AZN/University of Oxford, INO and SVA to be in Ph3 this summer
Vaccines are a type of prophylactic treatment that work to stimulate the body’s immune
system to recognize and combat foreign pathogens (i.e viruses or bacteria) through the
production of antibodies (Abs). While there are numerous types of vaccines in
development, most of them target the SARS-CoV-2 spike protein, which can bind to
human cells, allowing the virus to gain entry, and is the part of the virus most likely to
provoke an immune reaction in humans.
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There are various types of vaccines in development (inactivated virus, mRNA, DNA etc)
and each have corresponding pros and cons. As it relates to inactivated viral vaccines
such as Sinopharm‘s BBIBO-CorV and Sinovac’s (SVA) Coronavac, we note that these
vaccines tend to produce a weaker immune response than live viral vaccines (eg
Measles, Mumps and Rubella (MMR) vaccine; need multiple booster shots) and have
prolonged manufacturing timelines (due to inactivation of live viral cultures). Key
advantages of next generation vaccines, such as DNA and RNA vaccines, include faster
manufacturing timelines given the usage of synthetic genetic material. We note that the
four traditional vaccine companies Pfizer (PFE), Merck (MRK), GlaxoSmithKline (GSK)
and Sanofi (SNY), with the exception of PFE (given the collaboration with BNTX, using
the mRNA platform), are further behind on timelines for a COVID-19 vaccine.
Moderna (MRNA): Registration for the Ph3 “COVE” study of MRNA’s COVID-19 vaccine,
mRNA-1273, is expected to be available at study centers in the US beginning on July 21
with the study initiation on July 27. The Ph3 study protocol has been reviewed by the
FDA and is aligned to recent FDA guidance (LINK) on clinical trial design for COVID-19
vaccine studies and will evaluate the 100μg dose in ~30,000 participants in the US in a
17 July 2020 19
randomized 1:1 placebo-controlled trial. The primary efficacy analysis will be an

event-driven analysis based on the number of participants with symptomatic COVID-19
disease.
On powering assumptions, MRNA’s target vaccine efficacy (VE) against COVID-19 is

60% (higher than the FDA’s guidelines) (95% confidence interval to exclude a lower
bound >30%), and data will be reviewed by an independent Data Safety Monitoring
Board organized by the NIH. We note that the Ph3 design falls in line with the FDA
guidance, which stated that the statistical considerations for the primary efficacy
endpoint should demonstrate at least 50% efficacy in a placebo-controlled trial (required
for primary, secondary or interim analysis). The guidelines also indicate vaccine
candidates will be required to demonstrate efficacy on outcome/disease endpoints
(such as infections and symptoms). MRNA expects to complete two interim analyses (at
approximately 53 and 106 events), prior to a final event-driven analysis, at approximately
151 events. We note that these interim analyses may provide the opportunity for early
approval. The primary efficacy analysis will be an event-driven analysis based on the
number of participants with symptomatic COVID-19 disease. Key secondary endpoints

include prevention of severe COVID-19 disease (as defined by the need for
hospitalization) and prevention of infection by SARS-CoV-2. Overall, we are positive on
MRNA’s platform technology approach given the Ph1 data seen to-date and safety and
efficacy database the company has built across its other vaccine candidates. To-date,
MRNA has demonstrated positive Ph1 data readouts for seven prophylactic vaccines
(H10N8, H7N9, RSV, chikungunya virus, hMPV/PIV3, CMV and Zika), >1,600 participants
have been enrolled in MRNA’s infectious disease vaccine clinical studies.
n Potential areas of debate: There could be comparisons between competitors, such

as MRNA vs.PFE/BNTX), who are jointly developing mRNA-based vaccine
candidates against COVID-19, and others - including AZN/University of Oxford (with
data imminent). We note, due to different assays employed per company, amongst
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other factors, head-to-head comparisons are difficult. Nonetheless, the key point is,
multiple vaccines against COVID-19 will be required to treat the global population.
n While overall, we are positive on the mRNA-based vaccine approach for COVID-19,
and view data from both MRNA and PFE/BNTX as validating for the platform, we
note two key differences between the programs that preclude a full comparison of
efficacy between the vaccines: 1) MRNA targets the full spike protein whereas
PFE/BNTX’s candidate only targets the receptor binding domain (RBD); and 2) the
assays used to evaluate the neutralizing antibody response were different, with
PFE/BNTX utilizing a RBD-binding IgG assay - which may provide a less stringent bar
than MRNA’s PRNT80 assay. On dosing, while PFE/BNTX is evaluating lower dose
levels (10μg, 30μg, 100μg) of BNT162b1, because the vaccine construct codes for
the RBD only, and not the full spike S protein like mRNA-1273, this can account for
the discrepancy on a molar weight basis.
On MRNA’s Ph1 data, there were questions regarding the following: (i) a focus on
the peaks and subsequent declines in neutralizing antibodies (we would note this is
not unusual post vaccination, and declines stabilize over time - we look to more
data); (ii) the data incorporates only a younger patient cohort of 18-55 years of age
17 July 2020 20
(data for older patients are expected later this summer and while that population
likely has more co-morbidities, there have been no serious adverse events to date),
(iii) low CD8 T-cell response, which MRNA noted was measured at a time point that
may be suboptimal, and questions the overall relevance of CD8 T cell response
against the virus. We note given that little is known on the duration of protection
from neutralizing antibodies, we highlight the length of protection that is conferred
by mRNA-1273 (and other COVID-19 vaccines) as a key outstanding question.
MRNA stated that the evaluation of the durability of immune responses is ongoing,
and participants will be followed for one year after the second vaccination in the
Ph1, with scheduled blood collections throughout that period.
n Manufacturing plans: MRNA and partner Lonza expect to generate ~500mn doses
(two doses/person) of mRNA-1273 per year, with the possibility to scale up to 1bn
doses per year beginning in 2021. In addition, MRNA is in collaboration with Catalent
for large-scale, commercial fill-finish manufacturing of mRNA-1273 at Catalent’s
biologics facility in Indiana. We note MRNA has entered into two collaborations for
the fill-finish portion of manufacturing for its COVID-19 vaccine:
o In the US, MRNA is in collaboration with Catalent (CTLT), for large-scale,

commercial fill-finish manufacturing of mRNA-1273 at CTLS’s biologics facility
in Bloomington, Indiana. Per the agreement, CTLT will provide vial filling and
packaging capacity, in addition to staffing required for 24x7 manufacturing
operations at the site. This will support the production of an initial 100mn
doses of mRNA-1273, to supply to the US market starting in the 3Q20, per
the company. In addition, MRNA and CTLT are in discussions to secure
fill-finish capacity for continued production of hundreds of millions of
additional doses. CTLT will also provide clinical supply services from its
facilities in Philadelphia, Pennsylvania, including packaging and labeling, in
addition to storage and distribution to support the Ph3 trial.
o Outside the US, MRNA is in collaboration with Laboratorios Farmacéuticos
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Rovi, S.A. (BME: ROVI), for large-scale, commercial fill-finish manufacturing of
mRNA-1273 at its facility in Madrid, Spain. Per the agreement, ROVI will
provide vial filling and packaging capacity by procuring a new production line
and equipment for compounding, filling, automatic visual inspection and
labeling to support production of hundreds of millions of doses of
mRNA-1273. This is intended in principle to supply markets outside the US
starting in early 2021.
n Ongoing clinical trials: mRNA-1273 is currently being evaluated in Ph1 and Ph2
studies. For the NIH-led Ph1 study (details below), all cohorts, including those with
older adults (56-70 yrs) and elderly adults (71 yrs and above), have completed
enrollment, and the results from the elderly and older adult cohorts of the Ph1 study
are expected in early-to-mid August. The Ph2 placebo-controlled, dose-confirmation
study is evaluating the safety, reactogenicity and immunogenicity of two
vaccinations of mRNA-1273 given 28 days apart, and each participant will receive
placebo, a 50ug or a 100ug dose at both vaccinations. The Ph2 study is fully enrolled,
and consists of one cohort of younger adults ages 18-55 years (n=300) and one
cohort of older adults ages 55 years and older (n=300).
17 July 2020 21
n Immunogenicity data to-date: An interim analysis of MRNA’s open-label Ph1 study

of its mRNA-based COVID-19 vaccine (mRNA-1273) was published in the New
England Journal of Medicine (NEJM) detailing the immune response across three
dose levels (25, 100, 250 μg) in 45 healthy adults ages 18-55 years up to 57 days
post-vaccine (LINK). The data was positive, with neutralizing antibody titers observed
in all evaluable participants; we note at 100μg, the geometric mean titer (GMT)
levels were 4.1X higher than those seen in reference convalescent sera, and
mRNA-1273 elicited a Th1-biased CD4 T cell response, which bodes well for the risk
of antibody dependent enhancements.
As measured by the PRNT assay (the “gold standard”), following two vaccinations,
mRNA-1273 elicited robust neutralizing antibody titers. At day 43, neutralizing
activity against SARS-CoV-2 (PRNT80) was seen in all evaluated participants.
Neutralizing antibodies were quantified using geometric mean titer (GMT), which is
defined as the average antibody titer for a group of subjects calculated by
multiplying all values and taking the nth root of this number, where n is the number
of subjects with available data. At the Ph3 selected dose of 100μg, the GMT levels
were 4.1X higher (n=14, 654.3) than those seen in reference convalescent sera
(n=3, 158.3). At the lower dose of 25μg, the GMT levels were ~2.1X higher (n=13,
339.7) than reference convalescent sera, demonstrating a dose-response to the
vaccine. We note that the levels of neutralizing antibody titers in convalescent sera is
close to FDA guidance for using convalescent sera as a therapeutic. Per the
publication, due to the time-intensive nature of the PRNT assay, results were
available only for the day 1 and day 43 time points in the 25μg and 100μg dose
groups.
T-cell responses were also evaluated at the 25 μg and 100 μg dose levels (results not
available for the 250μg dose) on specimens collected at days 1, 29, and 43 and
assessed by an intracellular cytokine–staining assay. Following the second
vaccination, mRNA-1273 elicited Th1-biased CD4 T-cell responses without significant
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elevation of Th2-biased CD4 T-cell responses. We note that the role of T cell and B
cell responses to SARS-CoV-2 is increasingly being examined. While the majority of
COVID-19 vaccines in development mainly focus on antibody-driven immune
responses, largely to the Spike protein, T cells and B cells also play a role in viral
immunity. In diseases such as Zika and Dengue, non-neutralizing antibodies are
thought to stimulate a bias towards Th2 immune response, resulting in formation of
immune complexes and tissue damage called antibody dependent enhancements
(ADEs) - per discussions with key opinion leaders (KOLs), there is no robust
evidence for ADEs in coronaviruses, but we note it still remains a concern. Thus, a
CD4+ T cell response skewed towards Th1 response is viewed as a positive. On
CD8 T-cell response, MRNA noted that these cells are best measured a few days
post-vaccination, and was not able to sufficiently measure them due to timing.
Management further noted that day 43 is far from the ideal timepoint to examine
CD8 T cell response, and highlighted the early stage of the data - and questioned the
relevance of the CD8 T cell response against SARS-CoV-2.
n Safety and tolerability data to-date: On safety, mRNA-1273 was generally safe
and well-tolerated, with no serious adverse events reported through day 57. Study
17 July 2020 22
authors note that the safety profile is similar to those observed (LINK) in a report of
two trials of avian influenza mRNA vaccines (influenza A/H10N8 and influenza
A/H7N9) that were manufactured by MRNA with the use of an earlier lipid
nanoparticle capsule formulation. The adverse events (AEs) were generally transient
and mild to moderate in severity, with the most notable adverse events seen at the
250ug dose level - this included three of 14 participants (21%) reporting one or more
severe events. Solicited systemic adverse events were more common after the
second vaccination and occurred in seven of 13 (54%) participants in the 25ug
group, all 15 participants in the 100ug group and all 14 participants in the 250ug
group. The most commonly reported systemic AEs following second vaccination at
the 100ug dose were fatigue (80%), chills (80%), headache (60%) and myalgia
(53%), which were transient and mild or moderate in severity. At the 100ug dose,
the most common solicited local adverse event was pain at the injection site
(100%), which was also transient and mild or moderate in severity. Further, the
evaluation of clinical safety laboratory values Grade2 or greater and unsolicited AEs
did not reveal any patterns of concern.
Pfizer (PFE) and BioNTech (BNTX; not covered) are jointly developing mRNA-based
vaccine candidates against COVID-19. Initial Ph1 data from the first candidate
(BNT162b1) was released on July 1 (LINK) and demonstrated the ability to generate an
immune response (higher than that from a panel of plasma from recovered patients) and
an acceptable safety/tolerability profile at the 10/30ug doses. We expect additional data
from three other candidates (BNT162a1, BNT162b2, BNT162c2) over the coming weeks,
which will enable selection of a lead candidate to move into a larger Ph2b/3 trial that
could begin as early as July. This is generally consistent with our expectations given
recent commentary from PFE’s CEO (LINK) and he also noted the potential to have data
from this trial in September and a potential FDA approval by YE20 (or as early as
October), if timelines remain on track and the data are supportive. All four COVID-19
vaccine candidates are based on BNTX’s proprietary RNA vaccine platforms and include
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an unmodified mRNA vaccine (BNT162a1), two nucleoside-modified mRNA vaccines
(BNT162b1; BNT162b2), and a self-amplifying RNA vaccine (BNT162c2). Two of the
candidates include the full spike protein, and two contain the receptor binding domain
(RBD; targeted approach) from the spike protein.
n Potential areas of debate: mRNA vs. mRNA and vs DNA vaccine: RNA vaccines,
such as MRNA’s mRNA-1273 and PFE/BNTX’s BNT162b1, may be better positioned
than DNA plasmid-based vaccines (such as the vaccine candidate from INOVIO
Pharmaceuticals (INO, not covered)), at mobilizing the immune system to create
antibodies, and induce more potent immunity, potentially requiring lower doses.
However, RNA vaccines tend to be less stable than DNA-plasmid vaccines given
enzymes in the body can degrade them and heat can affect them - we note RNA
vaccines must generally be kept frozen or refrigerated, creating logistical challenges,
while DNA-plasmid vaccines are stable at higher temperatures.
n Manufacturing plans: PFE and BNTX stated they are scaling up manufacturing with
the goal of producing up to 100mn doses this year, and 1.2bn+ in 2021. The
potential vaccine will be jointly distributed worldwide (excluding China, where it will
17 July 2020 23
be developed and commercialized by BNTX/Fosun Pharma).

n Ongoing clinical trials: PFE and BNTX released initial Ph1 data from the ongoing
Ph1/2 study evaluating the safety, immunogenicity of BNT162b1 (10ug, 30ug and
100ug). BNT162b1 incorporates modified mRNA and encodes the receptor binding
domain (RBD) of the SARS-CoV-2 spike protein. The trial included 45 healthy adults
(ages 18-55) vaccinated on day 1 and 21 with 10ug (N=12) and 30ug (N=12), and on
day 1 with 100ug (N=12) or placebo (N=9). Patients randomized to 100ug dose level
did not receive a second vaccination based on the tolerability profile of the first
dose.
n Immunogenicity data to-date: BNT162b1 successfully induced immunogenicity

after the first dose which increased substantially with the second doses (10ug and
30ug arms). Importantly, substantial neutralizing antibody levels were observed at
day 28 (7 days post dose 2) and neutralizing geometric mean titers (GMTs) were
1.8-fold and 2.8-fold the GMT of the convalescent serum panel for the 10ug and
30ug doses, respectively. Modest increases in SARS-CoV-2 neutralizing geometric
mean titers were observed 21 days post dose 1 across all dose levels and
sustainably greater levels were observed 7 days post the second dose for 10ug and
30ug arms and reached 168-267, which compares to 94 for the convalescent serum
panel (derived from 38 PCR-confirmed COVID-19 patients). The authors noted that
the robust immune response observed relative to the convalescent serum panel
suggests an appropriate dose level may be between 10ug and 30ug. While the
immunogenicity data are encouraging, the authors note that a limitation is the kind
of immunity (T cells versus B cells or both) and level of immunity needed to protect
from COVID-19 are unknown. We believe this is likely a reason that the recent FDA
COVID-19 vaccine guidance is focused on disease/symptom outcomes from a
pivotal trial rather than antibody levels (LINK).
n Safety and tolerability data to-date: The 10/30ug doses appeared better tolerated
93f15d4c5e4d11d89860be55d934f058
than 100ug (patients in this cohort were not administered a second dose because of
a higher frequency of local reactions and systemic events and no increase in
immunogenicity). At the 10ug or 30ug dose levels, adverse reactions, including low
grade fever, were more common after the second dose than the first dose.
Following dose 2, 8.3% of participants who received 10ug and 75.0% of participants
who received 30ug BNT162b1 reported fever. Local reactions and systemic events
after injection with 10ug and 30ug of BNT162b1 were dose-dependent, generally
mild to moderate, and transient. Fevers generally resolved within 1 day of onset. No
Grade 4 systemic events or fever were reported. Most local reactions and systemic
events peaked by Day 2 after vaccination and resolved by Day 7. The most commonly
reported local reaction was injection site pain, which was mild to moderate, except
in one of 12 subjects who received a 100ug dose, which was severe. AEs were
reported by 50.0% (6/12) of participants who received either 10ug or 30ug, by
58.3% (7/12) of those who received 100ug vs. 11.1% (1/9) for placebo. Two
participants reported a severe adverse event: Grade 3 pyrexia 2 days after
vaccination in the 30ug group, and sleep disturbance 1 day after vaccination in the
100ug group. Related AEs were reported by 25% (3/12 in the 10 μg groups) to 50%
(6/12 each in 30ug and 100ug groups) and by 11.1% (1/9) for placebo. No serious
17 July 2020 24
adverse events were reported. Per the paper transient dose-dependent decreases in
lymphocytes (Grades 1-3) were observed within a few days after vaccination, with
lymphocyte counts returning to baseline within 6-8 days in all participants. These
laboratory abnormalities were not associated with clinical findings. Per the paper
RNA vaccines are known to induce type I IFN which has been associated with
transient migration of lymphocytes into tissues.
AstraZeneca (AZN) is partnered with the University of Oxford on their AZD1222

vaccine (previously known as ChAdOx1 nCoV-19), a replication-deficient simian
adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein, which is made
from a weakened version of the common cold virus (ChAdOx1 adenovirus) that causes
infections in chimpanzees and has been genetically modified to be expressed in
humans. Recall, the spike protein is usually found on the surface of the SARS-CoV-2
virus. The SARS-CoV-2 coronavirus uses its spike protein to bind to ACE2 receptors on
human cells to gain entry to the cells and cause an infection. AZN/University of Oxford
are running a Ph1/2 clinical trial in the UK (>1,000 healthy volunteers; 18-55 yrs of age)
with data expected imminently. In addition, AZN/University of Oxford are also

conducting a Ph2/3 trial of AZD1222 in ~10k volunteers in the UK, with data anticipated
in early to mid-autumn but noted the possibility of delays due to dropping infection
rates. In addition to the UK study, we note that AZN/University of Oxford are also
conducting other Ph3 studies with enrollment already initiated in Brazil (5k volunteers)
and South Africa, with US enrollment to occur shortly. AZN expect to enroll to c.30K
incremental patients beyond the UK study.
Per AZN management, if successful, FDA early use authorization (EUA) and UK
approvals could come as early as September. AZN is also collaborating with IQVIA (IQV,
covered by Bob Jones) in the accelerated development of a COVID-19 vaccine as part of
OWS. The collaboration will drive faster delivery of clinical studies in the US aimed at
demonstrating efficacy of AZN’s potential COVID-19 vaccine, AZD1222. This initiative
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includes an expansive subject study (enrollment this summer) and will leverage IQV’s
Virtual Trial solutions including Study Hub (enables virtual or hybrid study activities).
n Potential areas of debate: Despite speedy progress on development, we note the

vaccine utilizes an adenoviral vector, which may make it ineffective in a large
segment of recipients (~30% for AAV5) who have had prior exposure and are
immune.
n Manufacturing plans: AZN has contracted Symbiosis Pharmaceutical’s services for
fast track access to sterile vaccine drug product manufacturing capacity for clinical
trial supply. AZN is also partnered with Catalent on the manufacturing of the vaccine
for commercial use. If the vaccine is approved, Catalent will supply hundreds of
millions of doses from August 2020, potentially through March 2022 via its
manufacturing facility in Anagni, Italy. As part of the Operation Warp Speed initiative,
AZN has also signed a deal with Emergent BioSolutions ($87mn) to manufacture
doses of AZD1222 for US supply. In a deal with CEPI and GAVI, the vaccine alliance,
AZN will manufacture and distribute 300mn doses of the vaccine by YE20. Daiichi
Sankyo (covered by Akinori Ueda) has also stated that it is putting together a supply
deal (finish undiluted vaccine in its own facilities) while negotiations between AZN
17 July 2020 25
and the Japanese government are ongoing. All in, post approval, AZN plans to
manufacture and deliver potentially up to 100mn doses to the UK, 300mn to the US
(first doses as early as October 2020), 400mn doses to EU (France, Germany, Italy
and Netherlands; starting YE20) and 1bn doses to low- and middle-income countries
(via a licensing deal with the Serum Institute of India; 400mn by YE20) for a total
supply of >2bn doses per year.
n Ongoing clinical trial: Ph1 clinical trials were initiated in April and, to date, the
University of Oxford has immunized >1,000 healthy volunteers (18-55yrs)
randomized across two arms (active control and vaccine). The active control arm
received the MenACWY vaccine (targets group A, C, W and Y meningococcus and
protects against common causes of meningitis and sepsis). Per clinicaltrials.gov, the
Ph1/2 UK study tests the safety and immunogenicity of AZD1222 across four
cohorts (AZD1222 treatment arms: 1a, 2a, 2c-d, 3, 4a and 4c) where prime-only
cohorts 1/2a/4a received AZD1222 (5x1010vp), prime-full boost cohort 2c received
AZD1222 (5x1010vp) at week 0 and 8, prime-half boost cohort 2d received AZD1222
(5x1010vp) at week 0 and AZD1222 (2.5x1010vp) at week 8, prime-full boost cohort 3

received AZD1222 (5x1010vp) at week 0 and 4 and prime-only cohort 4c received
AZD1222 (5x1010vp) + paracetamol (active control arm also received paracetamol).
Ph1 results are expected in July (from University of Oxford). On the Ph2/3 trial
design in the UK, we note that per clinicaltrials.gov, cohorts 1 & 7 are 56-69yrs;
cohorts 2 & 8 are 70yrs+; cohort 3 is 5-12 yrs; cohort 4 and 6 are >18yrs; cohort 5 is
18-55 yrs. All cohorts will receive a matched MenACWY vaccine. Cohorts 1/2/4 will
receive AZD1222 as either prime-only (5x1010vp) or prime-boost (5x1010vp at week 0;
2.2x1010vp at week 4 or 6), cohort 3 will receive prime-only AZD1222 (2.5x1010vp),
cohorts 5/6 will receive prime-only AZD1222 (5x1010vp) and cohort 7/8 will receive
either prime-only or prime-boost AZD1222 (5x1010vp) at week 0 and 4 or 6.
n Pre-clinical data to-date: Positive data was reported from studies where pigs and
mice were injected with AZD1222. The data demonstrated that pigs that received
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two doses (prime-boost) of the vaccine had a higher immunogenicity profile than
pigs that received a single dose (prime only). Similar studies in mice showed no
difference between the two arms (prime vs prime boost), likely because immune
response was saturated. While the research demonstrated a single dose of the
vaccine prevented all vaccinated monkeys from developing pneumonia, the same
amount of virus genome was detected in the noses of both the vaccinated and
unvaccinated animals. The findings suggest that while viral loads in bronchoalveolar
lavage (BAL) fluid from the lungs and lung tissue of the vaccinated animals was
significantly reduced (which suggests vaccination prevents viral replication in the
lower respiratory tract), those vaccinated could potentially still transmit the virus to
others.
INOVIO (INO; not covered), recently selected by Operation Warp Speed (OWS) to
conduct non-human challenge studies, reported positive interim Ph1 data from the first
two cohorts treated with INO-4800, its vaccine candidate against SARS-CoV-2 (Ph2/3
trials anticipated this summer). Based on the data thus far, INO will be expanding its
Ph1 trial to add older patients in additional cohorts and has noted that it will publish the
17 July 2020 26
full data in an academic journal.
n Potential areas of debate: mRNA vs DNA vaccine: RNA vaccines, such as

MRNA’s mRNA-1273 and PFE/BNTX’s BNT162b1, may be better positioned than
DNA plasmid-based vaccines (such as the vaccine candidate from INO), at mobilizing
the immune system to create antibodies, and induce more potent immunity,
potentially requiring lower doses. However, RNA vaccines tend to be less stable
than DNA-plasmid vaccines given enzymes in the body can degrade them and heat
can affect them - we note RNA vaccines must generally be kept frozen or
refrigerated, creating logistical challenges, while DNA-plasmid vaccines are stable at
higher temperatures.
n Manufacturing plans: The company has not disclosed details.
n Ongoing clinical trials: Ph1 participants (n=40; ages 18-50) were given two 1mg or
2mg doses of INO-4800 four weeks apart (administered intradermally via INO’s
CELLECTRA 2000 device).
n
Immunogenicity data to-date: Based on preliminary assessment of the data, the

company reported 94% (34/36) of participants have demonstrated overall
immunological response rates (humoral (binding and neutralizing) and T cell immune
responses). One participant (1mg cohort) and two participants (2mg cohort) were
excluded from analysis as they tested positive for COVID-19 at study entry,
indicating prior infection. Additionally, one participant (2mg cohort) discontinued the
study for reasons unrelated to safety and tolerability.
n Safety and tolerability data to-date: The company noted a favorable safety profile
across both dose cohorts with no serious adverse events through week 8. Of the
ten reported adverse events, most were local injection site redness and were grade
1 in severity.
n Pre-clinical data to-date: INO also reported pre-clinical data where INO-4800
93f15d4c5e4d11d89860be55d934f058
demonstrated robust NAb and spike specific T-cell immune responses against
SARS-CoV-2 in mice and guinea pigs. Importantly, the investigators used three
separate neutralization assays to test the vaccine’s ability to generate Abs against
SARS-CoV-2: 1) an assay using live SARS-CoV-2 viruses; 2) an assay using a
pseudo-virus assay, where another virus displays the SARS-CoV-2 spike protein; and,
3) a novel high-throughput surrogate neutralization assay measuring the ability of
INO-4800-induced antibodies to block SARS-CoV-2 Spike binding to the host ACE2
receptor. However, we await further data from these studies.
Sinovac (SVA; not covered) announced positive preliminary data from its Ph1/2 trial for
Coronavac and has received approval from the Brazilian National Regulatory Agency,
Anvisa, to run a Ph3 trial in Brazil (sponsored by Instituto Butantan; c.9k participants;
enrollment to begin in July).
n Potential areas of debate: Despite being one of the first companies to progress
towards Ph3 clinical trials, we note that inactivated vaccines tend to produce a
weaker immune response than live viral vaccines (eg Measles, Mumps and Rubella
(MMR) vaccine) and might require multiple booster shots to be effective.
17 July 2020 27
n Manufacturing plans: Sinovac has also reported that it is building a commercial

plant in China which is expected to manufacture ~100mn doses of CoronaVac per
year. However, we note that manufacturing for the vaccine could be time-consuming
(vs. competitors with next generation DNA/RNA vaccines such as MRNA) since it
requires the growth of live viral cultures which need to be inactivated.
n Ongoing clinical trials: Sinovac conducted a randomized, double-blind and
placebo-controlled Ph1/2 trial (total n=743; Ph1 n = 143; Ph2 n =600; 18-59yrs) for
CoronaVac, an inactivated SARS-CoV-2 vaccine, in China. Participants were given
two doses of the vaccine on a 0-14 day schedule.
n Safety, tolerability and immunogenicity data to-date: While not providing
extensive details on the data, the company reported favorable safety and
immunogenicity profiles in the Ph2 trial. The company reported no severe adverse
events and noted that neutralizing antibodies (NAb) were triggered 14 days post-
vaccination with a seroconversion rate of >90% (full details expected in a
forthcoming academic publication).
CanSino Biologics (not covered) is developing a vaccine, Ad5-nCoV, against the spike
glycoprotein of SARS-CoV-2 and has reported positive results from its Ph1 dose
escalation trial. However, we note that the mean neutralization titer in the high dose
group was 34 — below FDA’s recommended titer of 160 for convalescent plasma. The
vaccine has also been approved for use among members of the Chinese military.
n Potential areas of debate: We note the vaccine utilizes an adenoviral vector, which
may make it ineffective in a large segment of recipients (~30%) who have had prior
exposure and are immune.
n Manufacturing: The company has not disclosed details.
n Clinical trial: The Ph1 trial was a single-center, open-label, non-randomized,
dose-escalation study (total n=108; n=36 per low (5 x 10 10), middle (1 x 10 11) and
93f15d4c5e4d11d89860be55d934f058
high (1.5x10 11) dose cohorts; administered as a single intramuscular injection) in
Wuhan, China. Key inclusion criteria included healthy adults (18-60yrs), who did not
have SARS-CoV-2 infection, confirmed by negative results of serum specific IgM and
IgG antibodies, negative nucleic acid for SARS-CoV-2 in pharyngeal, sputum and anal
swabs and a clear chest CT image with no evidence of lesions in the lungs at the
time of screening. The primary outcome was adverse events in the 7 days
post-vaccination, however, both safety (over 28 days) and immunogenicity (at days
14 and 28) were assessed post vaccination.
n Immunogenicity data to-date: On efficacy, the higher dose cohort had higher
immunogenicity, but also higher reactogenicity than the low and middle dose
cohorts. Additionally, participants with prior immunity to Ad5, experienced
compromised seroconversion of neutralizing antibodies. At day 14 the study showed
rapid binding antibody (Abs) responses to receptor binding domain (RBD) across all
three cohorts and at day 28, the higher dose cohort had higher binding Ab geometric
mean titers of 1445.8 than the middle dose (806) and low dose (615.8) cohorts with
a 4x increase in anti-RBD Abs noted in 97%/94%/100% of participants in the low/
middle/ high dose cohorts, respectively. Neutralizing Abs (NAbs) against live
17 July 2020 28
SARS-CoV-2 were all negative at day 0 and increased moderately at day 14, peaking
at 28 days post-vaccination. The NAb titers of the high dose cohort (34) were
significantly higher than the middle or low dose cohorts (16.2 and 14.5,
respectively). By day 28, a 4x increase in NAb titers was noted in 50% of low and
middle dose cohorts and 75% of the high dose cohort. Post-vaccination, similar
patterns of the binding Ab to spike glycoprotein and NAb titers to pseudovirus were
noted across all dose groups. Ad5 NAbs were significantly higher post vaccination
and multivariable analysis demonstrated that high pre-existing Ad5 NAb titers
compromised the seroconversion of NAbs post-vaccination, regardless of the
vaccine doses, with older recipients (45–60 yrs) having lower NAb seroconversion
than younger recipients. At days 14/ 28, despite the effect of high preexisting Ad5
immunity, positive responders were identified in all groups (low dose 75%/60%;
middle dose 95%/84%; high dose 94%/100% respectively). T-cell responses in the
high dose group were significantly higher than the low dose cohort (p<0·0010; no
statistical difference vs. middle dose) and pre-existing Ad5 NAb had a negative effect
on T-cell responses. Post-hoc analysis showed that 78%/92%/100% of participants
in the low/middle/high dose cohorts showed either positive T-cell responses to spike
glycoprotein or seroconversion of NAb to live SARS-CoV-2, at day 28
post-vaccination. All in, the high dose cohort had higher reactogenicity but also
higher immunogenicity than the low and middle dose cohorts. Since the safety
profiles of the low and middle dose cohorts were favorable at days 7 and 14
post-vaccination, CanSino will be moving forward with the two lower doses (5 x 10
10
and 1 x 10 11) in Ph2 trials which will also be expanded to include older
participants.
n Safety and tolerability data to-date: CanSino reported that a majority of
participants (81%; low and middle dose n=30/36 (83%) each; high dose n =27/36
(75%)) had at least one adverse event (AE) within the first seven days
post-vaccination. The most common injection site AE was pain (54%; low dose
93f15d4c5e4d11d89860be55d934f058
n=17/36 (47%); middle dose n=20/36 (56%); high dose n =21/36 (58%)) and the
most commonly reported systematic AEs were fever (46%; low and middle dose
n=15/36 (42%) each; high dose n =20/36 (56%)), fatigue (44%; low dose n=17/36
(47%); middle dose n=14/36 (39%); high dose n =16/36 (44%)), headache (39%; low
dose n=14/36 (39%); middle dose n=11/36 (31%); high dose n =17/36 (47%)), and
muscle pain (17%; low dose n=7/36 (19%); middle dose n=3/36 (8%); high dose n
=8/36 (22%)). Most adverse reactions were mild or moderate in severity. However,
a grade 3 fever with axillary temperature greater than 38·5C was noted in 8% of
participants (low and middle dose n=2/36 (6%) each; high dose n =5/36 (14%)). One
participant from the high dose cohort reported severe fever along with severe
symptoms of fatigue, dyspnoea (shortness of breath), and muscle pain. However,
the study noted that these reactions occurred within 24hrs post-vaccination,
persisted for no more than 48hrs and no SAE was reported within 28 days.
Interestingly, high preexisting Ad5 immunity (titer of >1:200 vs ≤1:200) was
associated with significantly fewer occurrences of fever post-vaccination (odds ratio
0.3, 95% CI 0.1–0.6).
Sinopharm (not covered) announced positive results from its placebo-controlled Ph1/2
17 July 2020 29
trial for BBIBO-CorV (inactivated vaccine) and has received approval to begin Ph3 trials in
the UAE. Per news reports, China’s State-owned Assets Supervision and Administration
Commission (a government body that oversees state-run enterprises such as Sinovac
and Sinopharm) is already offering SVA’s CoronaVac and Sinopharm’s BBIBO-CorV
vaccines to employees of large state-owned (Chinese) companies who intend to travel
overseas.
n Potential areas of debate: Despite being one of the first companies to progress
towards Ph3 clinical trials, we note that inactivated vaccines tend to produce a
weaker immune response than live viral vaccines (eg Measles, Mumps and Rubella
(MMR) vaccine) and might require multiple booster shots to be effective.
n Manufacturing plans: The company has highlighted the construction of two new
production facilities in Beijing and Wuhan, China where it anticipates the production
of 200mn doses of inactivated COVID-19 vaccines per year. However, we note that
manufacturing for the vaccine could be time-consuming (vs. competitors with next
generation DNA/RNA vaccines such as MRNA) since it requires the growth of live
viral cultures which need to be inactivated.

n Ongoing clinical trials: Participants (n=1,120) received two injections of the
vaccine, BBIBO-CorV (an inactivated vaccine similar to Sinopharm’s vaccine
CoronaVac), at low, middle or high dosing strengths at either 14-, 21- or 28- days
apart.
n Safety, tolerability and immunogenicity data to-date: According to its subsidiary,
China National Biotec Group’s (CNBG) Wuhan Institute of Biological Products, the
seroconversion rate for the 14- and 21-day schedules of the middle dose was 97.6%
and at 28-days was 100%. Sinopharm did not specify the NAb response rates at
either the low or high dose, but noted that the antibody titers were high and that no
serious AEs were observed.
n Pre-clinical data to-date: The vaccine induced high levels of NAbs in animals
93f15d4c5e4d11d89860be55d934f058
studies of mice, rats, guinea pigs, rabbits and non-human primates (cynomolgus
monkeys and rhesus macaques) without triggering any SAEs. In mice, NAbs were
detected after immunization at all three dose levels and in monkeys, the placebo
group had high viral loads in contrast to the viral loads in the low (significantly lower)
and high dose (undetectable) groups; no detectable viral load in their lungs,
demonstrating that the BBIBP-CorV vaccination efficiently blocks the infection of
SARS-CoV-2 in these animals.
Johnson & Johnson (JNJ) announced in June the accelerated development of their
COVID-19 vaccine candidate which will now enter the clinic in the second half of July
(vs. Sept prior). The vaccine candidate, Ad26.COV2-S, is a recombinant adenovirus
vector vaccine based on the company’s AdVac technology. Management noted the
acceleration was based on the strength of the preclinical data and interactions with
regulatory authorities. Management remains confident in their approach and highlighted
their experience in developing vaccines using their platform for Ebola and HIV (in Ph3).
n Potential areas of debate: Program is in early stages of development.
17 July 2020 30
n Manufacturing plans: JNJ is working to expand their manufacturing capacity with

the goal of being able to produce at least 1bn doses of the vaccine by the end of
2021 on a not-for-profit basis.
n Ongoing clinical trials: The randomized, double-blind, placebo-controlled Ph1/2a
study will evaluate safety, reactogenicity, and immunogenicity of the vaccine
candidate in 1,045 healthy volunteers (ages 18-55 and 65+). The company continues
to engage with the NIAID with the goal to initiate Ph3 study ahead of schedule
(likely late September), pending Ph1 data and approval of regulators. Per the 2Q20
EPS call, JNJ will publish results from non-human primate challenge studies in an
academic journal in the coming weeks.
n Safety, tolerability and immunogenicity data to-date: Initial Ph1/2a data
expected in September.
Novavax (NVX; not covered) is currently conducting Ph1/2 trials and has received
support from the Coalition for Epidemic Preparedness Innovations (CEPI; $388mn for
Ph1/2 trials), Operation Warp Speed (OWS; $1.6bn for Ph3 trials, manufacturing and
delivery of 100mn doses by YE20, at the earliest) and from the Department of Defense
(DoD; $60mn for exclusive manufacturing with US based CMO’s and delivery of 10mn
doses for Ph2/3 trials or early EUA).

n Manufacturing plans: Per the agreement with OWS, NVX will need to demonstrate
that it can rapidly stand up large-scale manufacturing and transition into ongoing
production (stockpiling capabilities; distribution of large quantities when needed) and
allows for a follow-on agreement with the U.S. government for additional production
and procurement to support OWS’ vaccine production goal (millions of doses by
2021).
n Ongoing clinical trials: NVX began Ph1/2 trials (n=130; 18-59yrs) for their
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NVX-CoV2373 vaccine in Australia in May with Ph2 scheduled to begin after positive
Ph1 data. The OWS-funded Ph3 trial will include c.30k participants and is scheduled
to begin in fall 2020.
n Safety, tolerability and immunogenicity data to-date: Ph1 data is expected at the
end of July.
CureVac (private company) has received regulatory clearance to begin dose escalation
Ph1 trials of CVnCoV, an mRNA vaccine encoding the full-length spike protein of
SARS-CoV-2 formulated with lipid nanoparticles (storage at room temperature is likely),
in Germany and Belgium.

n Manufacturing plans: CureVac will be using clinical supply drug from its
GMP-certified large scale mRNA production facility in Tubingen. In addition, per
recent new reports, Tesla (TSLA; covered by Mark Delaney) will be collaborating with
CureVac to build RNA microfactories that could potentially speed up the global
supply chain manufacturing process. Theoretically, the new approach could by-pass
cGMP manufacturing (time-consuming and expensive) and create a template that
17 July 2020 31
could be reproduced globally, enabling vaccine delivery in a compressed timeframe.

n Ongoing clinical trials: Ph1 trials (n=168; 18-60yrs; 2ug and 8ug). The goal of the
trial is to evaluate the safety and immune profile of the vaccine.
n Safety, tolerability and immunogenicity data-to-date: Company has not
disclosed timelines.
GlaxoSmithKline (GSK) has partnered with Clover Biopharmaceuticals (not covered) to

develop S-Trimer, a trimeric SARS-CoV-2 spike (S)-protein subunit vaccine candidate.
Coronavirus, like most other enveloped RNA viruses (HIV, RSV, influenza), has a trimeric
spike (S) protein on its viral envelope which is responsible for viral entry via binding to
the host cell surface receptor, ACE2. Clover has produced an S-Trimer subunit vaccine
that resembles the native trimeric viral spike.

n Manufacturing plans: Clover will be responsible for manufacturing since it has one
of the largest in-house, commercial-scale cGMP manufacturing facilities in China
which could potentially meet the rising demand.

n Ongoing clinical trials: The ongoing Ph1 trials are assessing the potential of
combining its COVID-19 S-Trimer vaccine with GSK’s pandemic adjuvant system,
which can reduce the amount of protein required per vaccine dose.
n Safety, tolerability and immunogenicity data-to-date: Preliminary safety and
immunogenicity results are expected in August.
Vaxart (VXRT; not covered) has been selected to participate in a non-human primate
(NHP) challenge study by OWS for an oral COVID-19 vaccine. The vaccine is based on its
proprietary oral vaccine platform (VAAST), which has been validated by data from VXRT’s
influenza oral vaccine which demonstrated a reduction in illness and infection rates
similar to Fluzone with favorable safety, tolerability and mucosal immunity in Ph1b/2
93f15d4c5e4d11d89860be55d934f058
trials. While the COVID-19 oral vaccine is still in pre-clinical studies, VXRT has contracted
Emergent BioSolutions (EBS; not covered) and Kindred Biosciences (KIN; not covered)
to produce bulk vaccine under cGMP for upcoming clinical trials and the company notes
that tech transfers are complete (vaccine tablets will be manufactured at VXRT). The
company stated it plans to submit an IND application soon with open-label, dose-ranging
Ph1 trials to being in 2H20 or as early as the summer.
Sanofi (SNY) entered into a partnership with the Biomedical Advanced Research and
Development Authority (BARDA) to develop a novel recombinant, protein-based vaccine
against COVID-19 which leverages SNY’s prior work for a SARS vaccine with a goal of
reaching a capacity of 100mn-600mn doses (goal to extend to >1bn doses by mid-2021).
SNY used its recombinant DNA platform to produce an exact genetic match to proteins
found on the surface of the virus. The DNA sequence encoding this antigen has been
combined into the DNA of the baculovirus expression platform. Since SNY’s
recombinant influenza product uses the same baculoviral expression platform, they will
be able to rapidly produce large quantities of the COVID-19 antigen and begin testing in
humans in 4Q20 with safety and efficacy data expected by YE20 and Ph3 initiation in
January 2021. The company intends to seek EUA in January 2021 with up to 100 million
17 July 2020 32
available doses and full regulatory approval as early as June 2021 (2H21 prior) with a
total capacity of 1 billion doses in 2021.
n SNY and Translate Bio (TBIO; not covered) have expanded their existing
collaboration to develop a novel mRNA COVID-19 vaccine. TBIO will use its mRNA
platform to identify, design and manufacture SARS-CoV-2 vaccine candidates.
Depending on the final dose of the vaccine, TBIO will likely be able to meet demand
for a pandemic response as it has already established 100gm single-batch
production with its clinical-stage platform. In addition, TBIO is partnered with a
contract manufacturing partner that can accommodate at least two 250gm batches
per month with a capacity of 90-360mn doses by 1H21. Clinical studies are
scheduled to begin in 4Q20 with approval anticipated in 2H21.
n SNY and GlaxoSmithKline (GSK) have entered into an agreement to use SNY’s
S-protein antigen in combination with GSK’s pandemic adjuvant technology to
develop a vaccine against SARS-CoV-2 with preliminary data from the Ph1/2 study
likely available in December and expected Ph3 study initiation in January. The
company intends to seek emergency use authorization in January 2021 with up to

100 million available doses and full regulatory approval as early as June 2021
(previously 2H21) with a total capacity of 1 billion doses in 2021 (LINK).
Merck (MRK) and the International AIDS Vaccine Initiative (IAVI; nonprofit scientific
research organization) entered into a collaboration in late May to develop an
investigational COVID-19 vaccine based on the recombinant vesicular stomatitis virus
(rVSV) technology. The platform uses an attenuated strain of VSV that has been modified
to express proteins which can stimulate an immune response. MRK and IAVI previously
collaborated to develop MRK’s Ebola Zaire virus vaccine, ERVEBO, using this same
platform. Under the agreement, the organizations will develop the vaccine jointly, with
MRK responsible for regulatory filings. MRK has also entered into an agreement with
BARDA who will provide initial funding for the effort. The vaccine is currently in
93f15d4c5e4d11d89860be55d934f058
pre-clinical development, with clinical studies planned to begin in 2H20.
n MRK recently acquired Themis (completed 6/19) - an EU biotech developing several

vaccines for infectious disease, including COVID-19, using a proprietary measles
vector platform (originally developed at Institut Pasteur). The platform, which has
been used in the development of vaccines for various infectious diseases including
SARS, Chikungunya, MERS, and Lassa fever, uses a modified (live attenuated
replicating) measles vaccine virus as a vector which can be engineered to express a
variety of antigens to trigger the targeted immune response. The COVID-19 vaccine
candidate is currently in pre-clinical development, with clinical studies slated to
begin in 2H20.
Shionogi (subsidiary of UMN Pharma) is developing a recombinant protein vaccine for

COVID-19, with support from the National Institute of Infectious Diseases (NIID).
Shionogi aims to start Ph1/2 clinical trials by around November and to obtain data/file for
approval in FY3/21. The company expects to have the structure in place by the end of
this year to produce 10mn units of the proposed vaccine and it sees potential to expand
capacity to 50mn units in the future. Management said the planned joint venture with
17 July 2020 33
Ping An Insurance could provide the opportunity to sell the vaccine in China (LINK).
In June, Daiichi Sankyo announced plans to develop a mRNA vaccine, leveraging its
proprietary nucleic acid platform technologies. Animal trials have confirmed a rise in
antibody titer. The company is planning to begin clinical trials in March 2021 (LINK).
In March, ReproCELL announced that it plans to participate in an international R&D

consortium that is looking to develop a vaccine for novel corona viruses (including the
causative virus for COVID-19). The consortium of several research institutions and
biotech companies will combine technologies to develop a versatile CoV-2 mRNA
vaccine administered intranasally, with the aim of entering clinical trials in early 2021
(LINK).
AnGes, Takara Bio, Osaka University et al.: Jointly developing a DNA vaccine for
COVID-19 (AG0301). Ph1/2 trials began on June 30 (Japic CTI-205328), and plans call for
approval in 2020, and a structure in place to produce 1mn units by March 2021.
CSL Behring (CSL) is partnering with the University of Queensland (UQ, Australia) and
CEPI to develop a “molecular clamp” enabled COVID-19 vaccine (anticipated by 2021).

The molecular clamp is an efficient mechanism to identify viral surface proteins that
drive host cell entry and infection. Early preclinical results demonstrated that the vaccine
candidate can trigger high levels of neutralizing antibodies. CSL will provide technical
expertise and its proprietary adjuvant technology, MF59, used in both seasonal and
pandemic influenza vaccines. UQ will use adjuvants that enable a stronger immune
response and increase the speed of viral production/output. Funding contributions from
both CSL and CEPI will be used to support clinical trials (Ph1 underway), and
manufacturing with a potential goal of producing millions of doses per year (100mn
doses by YE21). CSL also plans to subcontract with other global manufacturers to
increase the number of doses and broaden the geographical distribution of vaccine
production. Pending approval, CSL will distribute all vaccine doses through COVAX.
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Therapies: GILD’s remdesevir approved; Monitoring antibody approaches
Anti-viral therapies: GILD’s remdesevir has been granted FDA EUA in the US; approved
in UK
Recall, when an infection occurs, the body generates antibodies to fight it off. While
vaccines trigger the body to makes its own antibodies, anti-viral therapies (such as
nucleoside analogs) stop the function/replication of the virus at an enzymatic level,
thereby neutralizing it. Dr. Fauci highlighted the need for therapies to address early
stages of COVID-19 and noted that both GILD’s remdesivir and anti-inflammatory steroid
dexamethasone have demonstrated benefit. We note that GILD’s remdesivir has been
granted emergency use authorization (EUA) by the FDA for use in severe COVID-19
patients and is priced at $390/vial for all governments ($2,340 per patient for a 5-day
treatment course).
On May 1, the FDA granted GILD’s remdesivir (GS-5734, nuc inhibitor) Emergency Use
17 July 2020 34
Authorization (EUA) for the treatment of severe COVID-19 patients (for both 5 and 10
day duration), following the release of Ph3 data from the NIAID and GILD sponsored
studies (LINK). Per the authorization letter the FDA has concluded that it is reasonable to
believe the potential benefits of remdesivir outweigh the known and potential risks for
the treatment of hospitalized severe COVID-19 patients. Severe patients are defined as
those with SpO2 ≤ 94%, requiring supplemental oxygen, mechanical ventilation, or
extracorporeal membrane oxygenation (ECMO).
n GILD has set the price of remdesivir at $390/vial for all governments, which equates
to $2,340 per patient, assuming the majority of patients will receive a 5-day
treatment course (6 vials), and a price of $520/vial for private insurers in the US.
Given the patient population enrolled in the remdesivir studies and the IV
formulation its use will likely be limited to hospitalized patients. Regarding
manufacturing, the company expects to have more than 2mn treatment courses
manufactured by YE20 and many millions more by 2021. GILD is also developing an
inhaled formulation of remdesivir which is currently in Ph1 trials.
n Clinical trials: Several trials have evaluated remdesivir for the treatment of
COVID-19 and several more are ongoing (see Exhibit 3). Below we highlight the
results of the company sponsored Ph3 study in severe patients and the NIAID
sponsored Adaptive COVID-19 Treatment Trial (ACTT) in hospitalized patients.
Exhibit 3: Overview of remdesivir clinical trials

Trial initiation Data timing Sponsor Geography Trial N Patients Arms Primary endpoint
Bin Cao, China-Japan Remdesivir (9-day regimen) Time to clinical improvement on 6-pt scale,
Feb 6 Terminated China Ph3 237/453 Severe covid-19 patients
Friendship Hospital Pbo day 28
Time to clinical recovery (normalization of
Bin Cao, China-Japan Remdesivir (9-day regimen)
Feb 12 Suspended China Ph3 308 Mild/moderate covid-19 patients fever, respiratory rate, O2 saturation, and
Friendship Hospital Pbo
alleviation of cough), day 28
Met primary endpoint Remdesivir (10-day regimen)
Feb 21 NIAID Global ACTT 572 Hospitalized covid-19 patients Time to recovery, day 1-29
at interim Pbo
Remdesivir (10-day regimen) - no ventilator
Remdesivir (5-day regimen) -no ventilator Odds Ratio for Improvement on a 7-point
March 6 Completed GILD Global Ph3 6,000 Severe covid-19 patients
Remdesivir (10-day regimen) - ventilator Ordinal Scale on Day 14
Remdesivir (5- or 10-day regiment) - extension
Remdesivir (10-day regimen)
Remdesivir (5-day regimen) Odds Ratio for Improvement on a 7-point
93f15d4c5e4d11d89860be55d934f058
March 15 Late May 2020* GILD Global Ph3 1,600 Moderate covid-19 patients
Remdesivir (5- or 10-day regimen) - extension Ordinal Scale on Day 11
SOC
Lopinavir/ritonavir
Proportion of pts reporting each severity
Mar 22 Mar 2023 INSERM Europe DisCoVeRy 3,100 Hospitalized covid-19 patients Lopinavir/ritonavir + IFN beta
rating on 7-pt scale, day 15
Hydroxychloroquine
SOC
Hydroxychloroquine
WHO/Oslo University
Mar 26 Aug 2020 Global SOLIDARITY 700 Hospitalized covid-19 patients Lopinavir/ritonavir All cause in-hospital mortality, wk 3
Hospital
Lopinavir/ritonavir + IFN beta
SOC
Apr 1 - GILD UK Ph3 - Moderate-severe covid-19 patients - -
Apr 1 - GILD UK Ph3 - Moderate-severe covid-19 patients - -
The Camelot
Apr 11 Oct 2020 US Ph2/3 500
Foundation
Source: Company reports, clinicaltrials.gov
17 July 2020 35
Exhibit 4: Primary endpoint scale for GILD Ph3 trials
Source: Goldman Sachs Global Investment Research, clinicaltrials.gov
n GILD sponsored Ph3 trial in severe patients: The GILD sponsored Ph3 severe study
evaluated remdesivir (5- or 10-day regimens) in severe COVID-19 patients that were
not mechanically ventilated at baseline as part of the primary analysis. Severe
patients were defined as hospitalized COVID-19 patients (confirmed <4 days prior to
randomization) with SpO2 ≤94% or requiring supplement oxygen, but not
mechanical ventilation at screening. The primary efficacy endpoint was the odds
ratio for improvement on a 7-point ordinal scale on day 14 (Exhibit 4). At Day 14,
64.5% of patients in the 5-day treatment group and 53.8% of patients in the 10-day
treatment group achieved clinical recovery. The time to clinical improvement for 50%
of patients was 10 days in the 5-day treatment group and 11 days in the 10-day
treatment group. More than half of patients in both treatment groups were
discharged from the hospital by Day 14 (5-day: 60.0% vs. 10-day: 52.3%; p=0.14).
The study also demonstrated that patients receiving a 10-day treatment course
achieved similar improvement in clinical status compared with those taking a 5-day
treatment course. The mortality rate at 14 days was 8%/11% (5 day/10 day regimen)
or 7% outside of Italy, which is in the range of to below the mortality rates from the
literature in similar patient populations, however the lack of a control arm makes it
difficult to draw a definitive conclusion here. Remdesivir was generally well-tolerated
93f15d4c5e4d11d89860be55d934f058
in both the 5-day and 10-day treatment groups. The most common adverse events
occurring in more than 10 percent of patients in either group were nausea (5-day:
10.0%, n=20/200 vs. 10-day: 8.6%, n=17/197) and acute respiratory failure (5-day:
6.0%, n=12/200 vs. 10-day: 10.7%, n= 21/197). Grade 3 or higher liver enzyme (ALT)
elevations occurred in 7.3 percent (n=28/385) of patients, with 3.0 percent
(n=12/397) of patients discontinuing remdesivir treatment due to elevated liver
tests.
n NIAID sponsored ACTT in hospitalized patients: The NIAID study evaluating
remdesivir in hospitalized, severe COVID-19 patients was published in a leading
medical journal (New England Journal of Medicine). The study randomized 1,063
hospitalized COVID-19 patients to treatment with remdesivir (10-day regimen) or
placebo. The primary efficacy endpoint was the time to recovery, defined as the first
day on which a patient satisfied categories 1,2 or 3 in the 8-category ordinal scale
(Exhibit 5) during the 28 days after enrollment. The trial met the primary endpoint
based on an interim analysis - patients who received remdesivir had a 31% faster
time to recovery than those who received placebo (p<0.001). Per the NEJM paper,
patients who received remdesivir had a median recovery time of 11 days (95% CI
17 July 2020 36
9-12 days) compared with 15 days for placebo treated patients (95% CI 13-19 days)
p<0.001 (4 day delta, which is clinically meaningful). The results also suggested a
survival benefit, with a mortality rate of 8.0% for the group receiving remdesivir
versus 11.6% for the placebo group (p=0.059), but this was not statistically
significant. The NEJM authors noted that remdesivir’s benefit was most apparent in
patients that were less severe at baseline (requiring oxygen and not on ventilator)
and highlighted the need to identify COVID-19 patients and begin anti-viral treatment
earlier, before the pulmonary disease progresses and requires mechanical
ventilation. They also added that combination regimens should be evaluated to
improve patient outcomes given the high mortality rate of the disease. The authors
are awaiting final visits, data entry, monitoring, and data lock for the remaining
patients enrolled, after which an update of the results will be provided.
Exhibit 5: NIAID study ordinal scale

Source: Goldman Sachs Global Investment Research, NEJM
n A physician we previously spoke with had a generally positive view of the remdesivir
Ph3 and NIAID data and believes these data increase confidence in the efficacy of
the drug, especially if used earlier in the course of disease. On the NIAID study, the
physician views the 31% faster time to recovery (11 days vs 15 days), which he
considers a “hard endpoint”, as clinically meaningful, as it alleviates some burden on
the healthcare system and likely correlates with other “harder endpoints”, but would
93f15d4c5e4d11d89860be55d934f058
have liked to see a greater degree of benefit. He was also encouraged by the trend
in survival benefit, which he noted just missed statistical significance.
Merck (MRK) and Ridgeback Bio (privately held) have entered into a collaboration
agreement (closed 7/1) to develop EIDD-2801, an orally available antiviral candidate
(ribonucleoside analog) currently in early clinical development for the treatment of
COVID-19. Under the agreement, MRK has exclusive worldwide rights to develop
EIDD-2801 and will be responsible for clinical development, regulatory filings and
manufacturing, while Ridgeback Bio will receive an upfront payment, milestone
payments, and a share of the net proceeds, if approved.
n Clinical trials: Ph1 studies have demonstrated that EIDD-2801 is well-tolerated and
has potent antiviral properties against multiple coronavirus strains including
SARS-CoV-2. In addition, two animal studies had previously shown the ability of the
compound to improve pulmonary function, decrease body-weight loss, and reduce
the amount of virus in the lung. Two Ph2 trials were initiated in mid-June to evaluate
the virologic efficacy and further asses the safety of EIDD-2801 — one focusing on
newly hospitalized COVID-19 patients (estimated enrollment of 60) and the other
17 July 2020 37
focusing on COVID-19 outpatients (estimated enrollment of 44). Both trials are

randomized, double-blind, placebo-controlled studies. The hospitalized patients trial
will include three arms: 200mg, 300mg, and placebo, while the outpatients trial will
have two arms: 200mg and placebo. Per clinicaltrials.gov, the hospitalized patients
trial will include the following primary endpoints: number of participants that achieve
undetectable SARS-CoV-2 RNA in nasopharyngeal swabs by Day 5, number of
participants with any serious adverse events and number of participants with any
adverse events through Day 28. The outpatients trial will focus on the primary
endpoints of days until first non-detectable SARS-CoV-2 in nasopharyngeal swabs
and number of participants with any adverse effects, and the secondary endpoint of
number of participants with any Grade 2 or higher adverse effects.
PFE is also developing a protease inhibitor (that was initially developed during the SARS
epidemic) for the treatment of COVID-19. Based on initial screenings and preliminary
data, the compound is a potent inhibitor of the SARS-CoV-2 3CL protease and shows
anti-viral activity against SARS-CoV-2. Pre-clinical studies are ongoing, and a Ph1 trial is
expected to start in August.
VIR and Alnylam Pharmaceuticals (ALNY) announced the selection of a development

candidate (VIR-2703/ALN-COV), an investigational RNAi therapeutic targeting
SARS-CoV-2 that will be advanced as an enhanced formulation for the
treatment/prevention of COVID-19. In preclinical studies, this candidate demonstrated
an effective concentration for 50% inhibition of less than 100 picomal (EC50) of
infectious virion production and VIR-2703 has predictive reactivity against >99.9% of the
4,300 SAR-CoV-2 genomes available in public databases. The company expects to
complete an IND for this asset by year-end 2020.
Sarepta Therapeutics (SRPT) has entered into a Cooperative Research and Development
Agreement (CRADA) with the United States Army Medical Research Institute of
Infectious Diseases (USAMRIID) to jointly identify antisense oligonucleotides using
93f15d4c5e4d11d89860be55d934f058
SRPT’s proprietary phosphorodiamidate morpholino oligomer (PMO) platform with
activity against SARS-CoV-2 for the potential treatment of COVID-19. Previously
published clinical and preclinical studies of SRPT’s RNA technology have found evidence
of antiviral activity of SRPT’s PMO technology in coronaviruses and other viruses. Per
the CRADA, SRPT will design, synthesize, manufacture and provide to USAMRIID
multiple peptide-conjugated PMO (PPMO) constructs based on the genetic sequence of
SARS-CoV-2. USAMRIID will evaluate the constructs on characterized wild-type
SARS-CoV-2 viruses for their potential to inhibit viral infection. Based on the results,
SRPT and USAMRIID will consider collaborative funding proposals to advance the
development of treatments for COVID-19.
Shionogi plans to develop an antiviral treatment for COVID-19 patients, and has already
identified promising compounds. It aims to enter clinical trials in March 2021.
Ono has entered into clinical trials to examine potential treatments for COVID-19 using
Foipan (camostat mesilate). Plans call for Ph1 trials to begin between June 20 and
August 31 (Japic CTI-205326).
17 July 2020 38
Chugai Pharmabody Research, a Chugai Group research center in Singapore, started

joint research in May with the Agency for Science, Technology and Research (A*STAR) in
Singapore on a therapeutic antibody to fight COVID-19 (LINK). The center has already
identified a lead neutralizing antibody candidate, and is currently in the optimization
phase.
PeptiDream plans to develop treatments leveraging its special peptide technology

(LINK). It aims to take a three-pronged approach to development: (1) identify peptides
that block viral contact with human cells, (2) develop peptides that block virus entry into
human cells, and (3) develop peptides that introduce antiviral agents and immune cells
into the virus. In June, PeptiDream also announced a joint-development partnership with
Merck (LINK).
Daiichi Sankyo, Nichi-Iko, Universtity of Tokyo, RIKEN: Alliance partners are

beginning development of an inhalation formulation of pancreatitis treatment
Nafamostat (intravenous formulation) for COVID-19, and expect to begin clinical trials in
March 2021 (LINK).
Schrödinger (SDGR, not covered) is leveraging its partnership with Google’s (GOOGL,
covered by Heather Bellini) cloud computing division to screen novel potential antivirals
as part of its COVID-19 initiative (which also includes TAK, NVS, GILD and WuXi AppTec).
Schrödinger intends to virtually evaluate billions of small molecules using Google Cloud’s
parallel computing resources, totaling ~16 million compute hours of physics-based
modeling, to identify the molecules that can match with different protein targets.
Scientists will then synthesize the identified compounds and evaluate them in the lab
for their ability to stop SARS-CoV-2. Using GOOGL’s parallel computing resources will
allow Schrödinger to save months to years compared to a more traditional drug
discovery effort. Post the discovery phase, the initiative’s partners will progress the lead
molecules through optimization, synthesis and clinical testing.
93f15d4c5e4d11d89860be55d934f058
Antibody therapies: REGN and LLY in Ph2 trials for antibody therapy with data
potentially this summer
The SARS-CoV-2 spike protein present on the viral surface binds the host cell and
induces infection. Since all coronaviruses have a spike protein, companies are searching
for antibodies with the ability to block interaction with the host and neutralize the virus.
We note that Dr. Fauci has highlighted the need for viral targeting antibodies in the
treatment of COVID-19. Furthermore, the KOL we spoke to (LINK) had a positive view
on the monoclonal antibody approach given the relative ease of isolating and
manufacturing neutralizing antibodies. We note Regeneron’s (REGN) REGN-COV2
antibody cocktail, post favorable Ph1 safety results, has progressed to a Ph2/3 adaptive
trial (initial cohort n=30; data yet to be released) and a prevention trial to assess the
efficacy of REGN-CoV2 in preventing infection in uninfected people with close exposure
to a COVID-19 patient (e.g., patient’s housemate).
REGN is developing an antibody cocktail (REGN-COV2) that can be used as a

prophylactic before exposure to SARS-CoV-2 virus or as a treatment for those that are
already infected and entered clinical testing on June 11. REGN-COV2 contains two
17 July 2020 39
antibodies (REGN10933 + REGN10987) that target different parts of the spike protein.
The company has highlighted the importance of the dual-antibody approach to not only
protect against multiple viral variants but also decrease the potential for virus to escape
mutants that might arise in response to selective pressure from a single antibody
treatment. These antibody targets were identified by screening virus-neutralizing human
antibodies from REGN’s VelocImmune mice (genetically modified mice with human
immune system) and from humans who have recovered from COVID-19. This approach
is similar to REGN’s antibody cocktail for Ebola (REGN-EB3), which is currently under
FDA-review. REGN has guided to reaching clinical-scale production of hundreds of
thousands of prophylactic doses per month by the end of August 2020. On July 7, as
part of Operation Warp Speed, BARDA awarded REGN a $450mn contract to
manufacture and supply REGN-COV2. Per the press release, if EUA or product approval
is granted, the US government has committed to making the doses from this contract
(up to 300k treatment doses or 1.3mn prevention doses, depending on the final dosage
size) available to the American people at no cost.
n REGN initiated an adaptive clinical program of its antibody cocktail, REGN-COV2 in

June for hospitalized and ambulatory patients in the US. Although data has yet to be
released, on July 6 REGN announced that based on a review of the Ph1 safety
results (in an initial cohort of 30 patients) by the Independent Data Monitoring
Committee, REGN-COV2 has now moved into the Ph2/3 portion of these adaptive
trials, with preliminary data expected later this summer. The company also
announced that it has initiated a Ph3 trial to assess the efficacy of REGN-CoV2 in
preventing infection in uninfected people with close exposure to a COVID-19 patient
(e.g., patient’s housemate).
n Per REGN the first two Ph1 trials will include ~50-100 COVID-19 patients between
both studies and focus on safety, PK, and various virology measures (such as
reduction in viral shedding) following a single dose. The ambulatory patient trial will
randomize 1:1:1 to receive placebo, a low dose, or a high dose. The hospitalized
93f15d4c5e4d11d89860be55d934f058
patient trial will be divided into three cohorts: C1 on low-flow oxygen, C2 on high O2
no mechanical ventilation, and C3 on mechanical ventilation. Per clinicaltrials.gov, a
range of primary and secondary outcomes will be measured in the Ph1 trials. In the
ambulatory patients trial, primary endpoints include the proportion of patients with
at least one COVID-19 related medical visit, treatment-emergent SAEs, and change
in viral shedding. Secondary endpoints include the proportion of patients admitted to
a hospital or ICU, or requiring mechanical ventilation due to COVID-19, as well as
serum concentration, AUC, incidence of ADA, and time to negative PCR. In the
hospitalized patients trial, primary endpoints include the proportion of patients with
infusion-related reactions, treatment-emergent SAEs, and change in viral shedding.
Secondary endpoints include the proportion of patients with at least 1-point
improvement on a 7-Point Ordinal Scale in clinical status at various times, time to no
longer requiring supplemental oxygen, number of days of mechanical ventilation,
overall survival, serum concentration, and incidence of ADA. REGN is also
conducting an adaptive Ph2/3 trial (estimated hospitalized patients n=1,850 ;
ambulatory patients n=1,050; virologic and clinical endpoints), which will be
conducted in the US, Brazil, Mexico, and Chile and a prevention trial (n= 2,000 US)
17 July 2020 40
which will assess SARS-CoV-2 infection status. Details on the design for both trials
(adaptive Ph2/3 and prevention trial) have yet to be released.
LLY is developing a number of antibodies (LY-CoV555, JS016, as well as several in

pre-clinical development) designed to neutralize SARS-CoV-2. LY-CoV555 and JS016
entered the clinic in June and both antibodies are directed against the SARS-CoV-2 spike
protein, but bind different epitopes. The LY-CoV555 antibody was identified by AbCellera
and NIAID from a blood sample taken from one of the first recovered patients in the US
and LLY has guided toward the goal of having several hundred thousand doses available
by the end of the year. JS016 is being co-developed by Junshi Biosciences and LLY, with
Junshi leading development in China and LLY has exclusive rights in the rest of the
world. LLY intends to test both single antibodies and antibody cocktails. LLY initiated a
Ph1 trial of LY-CoV555 on June 1. A single dose of LY-CoV555 will be administered to 40
patients hospitalized for COVID-19 and evaluate the safety/tolerability, PK, and PD (viral
load). According to management, based on the results of the Ph1 trial the company has
now moved into Ph2 trial in the US. Per clinicaltrials.gov, the trial is a randomized,
placebo-controlled, double-blind study evaluating efficacy and safety in 400 people with
mild to moderate COVID-19 illness and data are expected in September. Endpoints
include change in viral load (at Day 11) and percentage of people who experience
COVID-related hospitalization, emergency room visit, or death (through day 29). LLY also
plans to study the drug in a preventative setting, focusing on vulnerable patient
populations who historically are not optimal candidates for vaccines.
n Junshi Biosciences dosed the first healthy volunteer in a study of JS016 on June 8.
Per the prior release LLY guided to begin dosing patients in a complementary US
Ph1 in the coming days. Both Ph1 studies are designed to evaluate the safety,
tolerability, PK and immunogenicity of the antibody in healthy participants who have
not been diagnosed with COVID-19.
Vir Biotechnology (VIR) is leveraging its differentiated platform to develop a potential
93f15d4c5e4d11d89860be55d934f058
therapy with vaccinal effect for COVID-19. The company is proceeding with two antibody
candidates (VIR-7831, VI-7832) that neutralize SARS-CoV-2, the second of which carries
a “vaccinal mutation” which in animal models leads to the generation of protective
CD8+ T cells that may provide long-term immunity such that this antibody could function
both therapeutically and as a vaccine. VIR has entered into agreement with GSK, WuXi
Biologics, Samsung Biologics, and BIIB for the manufacture/development of both agents
and the company plans to initiate human trials this summer.
n VIR has entered into partnerships with the NIH, NIAID, Biogen (BIIB), WuXi
Biologics, and Samsung Biologics to advance the characterization, development, and
manufacture of a human antibody against SARS-CoV-2. The company has identified
two assets, the first of which is engineered for an extended half-life and the second
of which is engineered for short-term potency and potential vaccinal effect. The
company will evaluate four potential use cases for these antibodies: i) prevention of
disease: prophylaxis in health care workers / high-risk individuals, ii) prevention of
progression to severe disease: treatment during the early phase of infection, iii)
treatment of severe disease, and iv) development of vaccines: understanding the
17 July 2020 41
epitopes that lead to effective neutralization can add the development of effective
vaccines. The company will bring these assets into the clinic this summer.
n VIR and GSK entered into a collaboration to research and develop solutions for
coronavirus. While their early efforts will focus on the advancement of VIR-7831 and
VIR-7832, the partners will leverage VIR’s antibody platform technology, GSK’s
expertise in functional genomics, and both of their capabilities in CRISPR
screening/AI to identify additional anti-coronavirus compounds, against both
SARS-CoV-2 and other coronaviruses.
Adaptive Biotechnologies (ADPT) has partnered with Amgen (AMGN) to leverage its
immune medicine platform to identify and develop neutralizing antibodies from the
blood of patients who are either actively fighting or have recently recovered from
COVID-19 in an effort to better understand the immune response on a population level.
While we note early successes using convalescent plasma therapy to boost the ability
of patients with severe cases of COVID-19 to fight off the infection through neutralizing
antibodies, this approach is difficult to scale and standardize - unlike ADPT’s
high-throughput method. The antibodies can be used to treat patients fighting the
disease and to potentially prevent disease in those with heightened exposure, such as
health-care workers. To identify neutralizing antibodies, ADPT is applying the same
approach as used to identify T cell receptors, by using its technology and machine
learning to assess hundreds of thousands of possible antibodies against a wide range of
targets to select those that best neutralize SARS-CoV-2. After identifying the most
promising antibodies, AMGN will then develop and manufacture the antibodies - given
SARS-CoV-2 is a slowly mutating large RNA virus, it lends itself to a highly efficacious
monoclonal antibody or cocktail of antibodies, per management. ADPT expects to
complete the discovery of candidate neutralizing antibodies in 2H20. While ADPT and
AMGN may not be the first COVID-19 antibody candidate to reach the clinic, we are
optimistic on the approach to select the best candidate that will be most efficacious. We
note ADPT’s immune-medicine platform technology can be easily leveraged to
93f15d4c5e4d11d89860be55d934f058
understand the immune response to COVID-19, and we highlight ADPT’s multi-pronged
efforts to decode the T cell response to the virus below:
n In addition to the work with AMGN, ADPT is leveraging machine learning to decode
the immune response to COVID-19. There are ~1,000 participants in immuneRACE,
ADPT and MSFT’s (covered by Heather Bellini) virtual clinical study towards
developing a novel diagnostic based on the immune response to COVID-19 (see
below in Diagnostics). ADPT will also examine ~4,000 samples from studies from
around the world as part of this effort. Further, ADPT is building out the
immuneCODE database, which shares data from T cells shown to recognize
antigens specific to COVID-19. The data released to-date from the immuneCODE
database identifies the regions of the virus that the immune system sees
(commonly targeted by T cells), including 9,000 TCRs (from 17 individuals) mapped
to these parts of the virus. ADPT expects the database to be updated every few
weeks, and it is publicly available on ADPT’s website. In total, there have been
222mn TCRs sequenced from 1,274 samples (the vast majority of which pertain to
distinct individuals). They represent a combination of data collected so far from
17 July 2020 42
institutions and partners around the world and some collected from immuneRACE.
n Using its proprietary MIRA (Multiplexed Identification of T cell Receptor Antigen
Specificity) technology, ADPT will map T cell receptors that are specific to
SARS-CoV-2, which can then be compared to negative controls. ADPT has already
confirmed ~1,000 TCRs specific for SARS-CoV-2, and ADPT intends to strengthen
the signal iteratively over time as more data is collected and generated.
n On applying its platform to vaccine and drug trials, ADPT intends to upgrade its
research use only (RUO) product with T cell receptor annotations, to examine
SARS-CoV-2 specific T cells expansion in trial participants over time. This data can be
integrated into vaccine and other drug trials inclusive of TCR signatures to measure
and monitor efficacy.
Plasma therapies: CSL developing a novel treatment

The use of plasma has been studied in prior outbreaks including the 2009-10 H1N1
influenza virus pandemic, 2003 SARS-CoV-1 epidemic and the 2012 MES-CoV epidemic.
Plasma accounts for ~55% of total blood volume and helps to carry important proteins,
antibodies and hormones. The rationale is that antibodies against the virus which are
present in plasma from a recovered patient circulate in the blood and treat the viral
infection in the recipient.
Takeda (TAK) announced that it started development of CoVIg-19 (a hyperimmune

globulin) in March, and it has now completed production of a clinical trial lot. The
company plans to start clinical trials in July with a target of announcing data in 2020.
Grifols (GRFS) continues to collaborate with BARDA and other global healthcare
agencies to collect plasma from convalescent COVID-19 patients. The company is
exploring two separate treatment approaches: 1) it has started to use convalescent
plasma in treating patients in hospital, and recorded initial positive, albeit small-scale,
feedback. In addition, Grifols is providing viral inactivation technology (methylene blue) to
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support the utilization of convalescent plasma for transfusion. This will help to ensure
inactivated plasma units are used for treatment. Concurrently, Grifols is in a collaboration
with donation centers and public hospitals in Spain and is conducting a clinical trial with
inactivated plasma from recovered patients. 2) Similarly to Takeda, Grifols intends to
fractionate the convalescent plasma into an H-IG treatment and test it in the clinic in
3Q20; we note that the company has started production in early June and used this
approach also during the Ebola outbreak.
CSL Behring (CSL) has joined the CoVIg-19 Plasma Alliance, an industry collaboration to
develop and deliver CoVIg-19, a potential plasma-derived therapy for treating those with
serious complications from COVID-19. CSL has also partnered with SAB
Biotherapeutics (not covered) in the development of, SAB-185, a high-potency
immunotherapy delivering human polyclonal antibodies targeted to SARS-CoV-2,
generated from SAB’s novel platform technology, DiversitAb (expected to enter clinic in
the summer). The advantage of this approach is that it allows for the development of
human polyclonal antibodies that deploy the same natural immune response to fight the
disease without the need for blood plasma donations from recovered patients.
17 July 2020 43
Approved treatments repurposed for COVID-19
An excessive inflammatory response to SARS-CoV-2 is thought to be a major cause of

disease severity and death in patients with COVID-19 and is associated with high levels
of circulating cytokines, profound lymphopenia and substantial mononuclear cell
infiltration in the lungs, heart, spleen, lymph nodes and kidney. Given that the morbidity
and mortality seen in COVID-19 is associated with excessive inflammation, dozens of
immunomodulatory agents are rapidly going into clinical trials. Preliminary data indicates
that anti interleukin-6 (IL-6) plays a key role in triggering the inflammatory immune
response causing acute respiratory distress syndrome (ARDS) in critically-ill COVID-19
patients. Based on these results, China approved the use of IL-6 inhibitors in the
treatment of severe or critical COVID-19. In Japan, Healios and Athersys’ MultiStem is
being developed to treat ARDS, which has been designated as a “Highly Relevant”
therapeutic for COVID-19 by BARDA. Other agents with immunomodulatory action
include JAK inhibitors (JAKi) and complement 5 inhibitors (C5).
Roche (ROG) initiated a global Ph3 clinical trial (COVACTA; n=450) in March evaluating
the efficacy and safety of Actemra/RoActemra (anti-IL6 biologic) in hospitalized adult
patients with severe COVID-19 pneumonia, in collaboration with BARDA. This is a
double-blind, placebo controlled, multicenter study, with initial data expected by July
(LINK). The primary and secondary endpoints include clinical status, mortality,
mechanical ventilation and intensive care unit (ICU) variables. Patients will be followed
for up to 60 days following randomization and an interim analysis will be conducted to
look for early evidence of efficacy. In addition, ROG is recruiting for a second Ph3 trial,
REMDACTA (n=450) which tests the efficacy of Actemra administered with remdesivir
vs. remdesivir and placebo therapy in hospitalized adult patients with severe COVID-19
pneumonia. While Actemra/RoActemra is not currently approved for use in COVID-19
patients with pneumonia, we note that it has been included in the 7th updated
93f15d4c5e4d11d89860be55d934f058
diagnosis and treatment plan for COVID-19 issued by China’s National Health
Commission (NHC) on March 3, 2020, after the anti-IL6 class has shown some potential
benefits in patients.
Sanofi (SNY) has partnered with Regeneron (REGN) to test Kevzara (anti-IL-6) in the
treatment of hospitalized patients with severe COVID-19. REGN/SNY recently reported
that their Ph 3 US trial of Kevzara 400 mg in COVID-19 patients requiring mechanical
ventilation did not meet its primary endpoint (Kevzara’s impact on fever) and key
secondary endpoint (need for supplemental oxygen) when Kevzara was added to best
supportive care versus best supportive care alone (placebo). In the primary analysis
group, adverse events were experienced by 80% of Kevzara patients and 77% of
placebo patients, while serious adverse events occurred in at least 3% of patients and
more frequently among Kevzara patients. These included multi-organ dysfunction
syndrome (6% Kevzara vs. 5% placebo) and hypotension (4% Kevzara vs. 3% placebo).
Based on the results, the US-based trial has been terminated. The ex-US Ph 3 study,
currently evaluating a higher dose of Kevzara in c.400 patients, will continue with results
expected in 3Q20.
17 July 2020 44
Incyte (INCY), in partnership with Novartis (NVS), is conducting a global, randomized,

double-blind, placebo-controlled Ph3 trial (RUXCOVID; n=400; >12yrs) to evaluate the
safety and efficacy of Jakafi (JAKi)/standard of care (SoC) versus SoC in the treatment of
patients with COVID-19 associated cytokine storm (uncontrolled inflammation).
RUXCOVID is funded by Incyte in the US and Novartis outside of the US. INCY will
initiate an open-label emergency Expanded Access Program (EAP) in the US to allow
eligible COVID-19 patients to receive Jakafi while it is being evaluated in clinical trials
separately.
Eli Lilly (LLY) is also evaluating the efficacy of the JAK-inhibitor baricitinib (OLUMIANT)
for the treatment of hospitalized COVID-19 patients in a Ph3 trial. Seperately NIAID is
running the Adaptive COVID-19 Treatment Trial (ACTT-2) to assess the efficacy and safety
of the combo treatment baricitinib plus GILD’s remdesivir, compared to remdesivir
alone. OLUMIANT is approved as a treatment for rheumatoid arthritis. LLY initiated a
Ph3 trial of baricitinib in hospitalized COVID-19 patients on 6/15. The randomized,
double-blind, placebo-controlled study will evaluate the safety and efficacy of baricitinib
for the treatment of COVID-19. The trial is expected to enroll 400 patients in the US,
Europe, and Latin America and will focus on hospitalized patients not on mechanical
ventilation (at entry) with at least one elevated marker of inflammation. Per the press
release, it is hypothesized that through JAK1/2 inhibition, baricitinib may be able to
reduce the cytokine storm associated with COVID-19 infection. Patients will be
randomized to receive baricitinib (4 mg) or placebo for up to 14 days or until discharged
from the hospital. All patients will also be administered background therapy. The primary
endpoint will be the proportion of patients who die or require non-invasive
ventilation/high-flow oxygen or invasive mechanical ventilation by Day 28. Secondary
endpoints include the proportion of patients with clinical improvement at various times,
time to recovery, duration of hospitalization, number of ventilator-free days and mortality
through Day 28. Per the company, data from the Ph3 trial is expected in the next few
months.
93f15d4c5e4d11d89860be55d934f058
n In May, NIAID initiated a randomized, controlled, double-blind clinical trial evaluating
the safety and efficacy of the combination treatment of GILD’s remdesivir plus
baricitinib compared to remdesivir alone. The trial is expected to enroll 1,000
hospitalized adults in the US with COVID-19 and evidence of lung involvement (e.g.,
need for supplemental oxygen, abnormal chest X-rays, or mechanical ventilation).
Participants will be randomized 1:1 to receive either remdesivir + barcitinib or
remdesivir + placebo. Per the NIAID press release, remdesivir will be administered
as one 200 mg IV dose, followed by a 100 mg once-daily IV dose for the duration of
hospitalization, up to a 10-day total course of treatment. Baricitinib will be
administered as a 4 mg oral dose for the duration of hospitalization, up to a 14-day
total course of treatment. The primary endpoint will be time to recovery, i.e., well
enough for hospital discharge. The study will look at a number of secondary
endpoints, including patient outcomes using an eight-point ordinal scale — see
exhibit Exhibit 6 (Day 15), and mortality alone.
17 July 2020 45
Exhibit 6: Eight-point ordinal scale
Source: Goldman Sachs Global Investment Research, NEJM
Alexion (ALXN) is conducting a TACTIC-R study in the UK where less severe COVID-19
patients will receive lower doses of Ultomiris, a C5 inhibitor. In the US, ALXN plans to
conduct a 2:2:1 randomized open-label study (n=270) in addition to standard of care in
severe COVID-19 patients with mechanical ventilation. The primary endpoint will be
mortality at month one and will also evaluate other measures such as need for
mechanical ventilation. Management will provide updates on timelines and enrollment
as the sites open up across the US and EU.
Chugai: The company launched domestic Ph3 trials for Actemra from May (LINK), while
Roche is currently undertaking global Ph3 trials into the same drug.
Takeda (TAK): The company plans to develop COVID-19 treatments using icatibant
(brand name: Firazyr), lanadelumab (brand name: Takhzyro) and TAK-981. Ph1/2 trials into
lanadelumab began on June 25 (NCT04422509), and Ph1 trials are also underway into
TAK-981, in parallel with anticancer indications (NCT03648372).
Kiniksa (KNSA), Insmed (INSM), Eisai, Healios, among others, have non approved drugs
in development to address COVID-related inflammatory response.
n KNSA has reported positive initial Ph1 data and is preparing to begin Ph2/3 trials to
evaluate mavrilimumab compared to placebo on top of standard of care, and also an
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investigator-initiated placebo-controlled study in the US. The company announced
28-day clinical outcomes data from mavrilimumab (mavri) in non-mechanically
ventilated patients with severe COVID-19 pneumonia and hyperinflammation, which
has also been published in The Lancet Rheumatology. Recall, mavri is KNSA’s
monoclonal antibody that targets GM-CSFRα which promotes inflammation. In the
treatment protocol, 13 non-mechanically ventilated patients with severe COVID-19
pneumonia and hyperinflammation were treated with a single IV dose of mavri (6
mg/kg) upon hospital admission. Another 26 non-mechanically ventilated patients
with severe COVID-19 pneumonia and hyperinflammation with similar baseline
characteristics (comorbidities, baseline inflammatory markers, respiratory
dysfunction) were utilized as a control group and received standard of care therapy,
including antibiotics and antivirals.
Overall, patients treated with mavri demonstrated earlier and improved clinical
outcomes. By Day 28, death occurred in no patients (0/13) treated with mavri
compared to 27% (7/26) of control-group patients (p=0.086). One patient treated
with mavri (1/13) progressed to mechanical ventilation compared to 35% (9/26) of
control-group patients who progressed to ventilation or died (p=0.077). All patients
17 July 2020 46
treated with mavri (13/13) achieved the clinical improvement endpoint (improvement
in clinical status of >2 categories on 7-point scale) compared to 65% (17/26) of
control-group patients. Lastly, fever resolved in 91% (10/11 febrile patients) of
mavri-treated patients by Day 14 compared to 61% (11/18 febrile patients) of control
group patients (p=0.0093)
The company has announced an active investigational new drug (IND) application for
its global randomized placebo-controlled Ph2/3 clinical trial which will evaluate mavri
compared to placebo on top of SOC, and also an investigator-initiated
placebo-controlled study in the US.
n INSM is sponsoring an investigator-initiated study of brensocatib, an oral reversible
inhibitor of dipeptidyl peptidase 1 (DPP1), in the treatment of COVID-19 related
Acute Respiratory Distress Syndrome (ARDS). DPP1 inhibition is a novel,
under-investigated mechanism of action (MOA) that works by attenuating
neutrophil-mediated inflammation. Brensocatib (previously INS1007) demonstrated
encouraging proof-of-concept data in the Ph2 WILLOW study in non-CF
Bronchiectasis (NCFBE), wherein a 25mg QD dose reduced incidence of pulmonary

exacerbations (i.e., flare-ups of inflammation) to 33% vs 48% for placebo over a
24-week period. Based on these data, brensocatib’s potential utility in COVID-19 is
being evaluated in an investigator-initiated trial called STOP-COVID19 (Superiority Trial
of Protease inhibition in COVID-19). STOP-COVID-19 is a randomized, double-blind
trial assessing the potential role of brensocatib in up to 300 hospitalized COVID-19
patients in the UK who are at material risk of needing supplementary oxygen and/or
ventilation, with a sample size reassessment performed once 100 patients have
been enrolled and treated. Patients will be randomized 1:1 to placebo or a daily
25mg oral dose of brensocatib on top of standard of care with a 28-day course of
treatment. The primary endpoint of the trial will be clinical status at Day 29, and
secondary endpoints will include mortality, use of ventilation/oxygenation and
duration of hospital stay. Currently, trial results are expected by the end of 2020.
93f15d4c5e4d11d89860be55d934f058
n Eisai: The company has announced plans to expand the development of severe
sepsis drug Eritoran (E5564) into a treatment for moderate to severe COVID-19
cases, citing potential for suppressing the cytokine storm (LINK).
n Healios: In April, Healios announced Ph2 clinical trials of cell therapy treatment
MultiStem (HLCM051), which it is developing for treatment of strokes and
pneumonia induced ARDS, for treatment of COVID-19 induced ARDS (LINK). It may
be in a position to complete patient enrollment in clinical trials by around fall 2020
and be ready to announce trial data by 1H2021 (LINK).
Anti-flu treatment:
Fujifilm Toyama Chemical (FUJIY) is currently conducting Ph3 trials in Japan, which it
had planned to conclude at end-June. The study is currently still underway due to delays
in enrolling patients, mainly because trials in Japan are often observational studies, and
owing to the small number of patients available. The Japanese Association for Infectious
Diseases published in May on its website an interim report of an observational study (n
= 2,158) on closely watched flu treatment Avigan. The rates of improvement at 7/14 days
17 July 2020 47
were 73.8%/87.8% for mild COVID-19 cases, 66.6%/84.5% for moderate cases, and
40.1%/60.1% for severe cases. However, this study lacked a placebo comparison group
and its design had a low evidence level, so no conclusions were reached regarding
efficacy.
Diagnostics: Assessing the current landscape
n As a follow-up to our deep dive report on COVID testing opportunities and

challenges, here we update our analysis with a focus on the latest testing volumes
and most recent updates of theoretical testing capacity from the manufacturers.
Types of Tests
n As we deconstruct the COVID diagnostic landscape, there are two settings for
testing and three main categories of tests that have been developed to support
diagnosis and surveillance of COVID-19.
a. Setting: Clinical Lab vs Point of Care

b. Test Type: Viral (PCR tests), Antigen, and Antibody (Serology tests)
n Broadly speaking, determining which test and which setting to use is based on the
purpose for the test, as we describe in the following illustration:
Exhibit 7: Screening to Research Continuum for Testing
Purpose
Screening Diagnosis Immunity Research
93f15d4c5e4d11d89860be55d934f058
POC - PCR Testing POC - PCR Testing POC - Antibody Testing POC - Antibody Testing
Test & Setting
Lab - PCR Testing Lab - PCR Testing Lab - Antibody Testing Lab - Antibody Testing
POC - Antibody Testing POC - Antigen Testing
Lab - Antibody Testing
POC - Antigen Testing
Asymptomatic Patients Symptomatic Patients Prevalence Studies Epidimiological Studies

Drivers
Population Level Testing Confirm Positive Screenings Immune Response Vaccine Studies
Surgery Candidates
At Risk Workers
Source: Goldman Sachs Global Investment Research
n Types of tests can be broken down into (1) molecular PCR tests (lab-based), (2)
antigen tests (point-of-care) and (3) antibody tests (point-of-care and lab-based).
Together these make up the landscape of available tests with each having their own
roles, capabilities, and drawbacks.
a. Molecular PCR - viral tests used to diagnose current infections. Accuracy of
the molecular PCR test is generally highest of the three modalities with
specificity and sensitivity frequently above 99% and around 100%,
respectively.
b. Antigen - viral test used to diagnose current infections at the point-of-care
17 July 2020 48
setting. Test utilizes spike-protein detection and is generally less accurate than
molecular PCR testing (though still accurate enough to be valuable) but at
much faster speeds. A typical test can yield results in as few as 15 minutes.
c. Antibody (serology) - test that detects the body’s own immune response,
often in the form of IgG or IgM. Both IgG and IgM are produced by the body in
the later stages of infection and so are generally not useful to confirm an
active infection, but instead are used for immunity detection and population
research. These tests can be lab based and/or point-of-care based and are
generally highly manufacturable, suggesting significant theoretical capacity for
this type of test.
Current Test Volume versus Theoretical Capacity

n Daily testing for COVID in the US has consistently risen since late April with the
current run-rate at over 5mn tests per week, or nearly 22mn tests per month. While
there have been some reports of antibody testing included in this daily tally, we
estimate that the vast majority are molecular PCR tests in the lab setting based on
data from states that report both separately.
Exhibit 8: US Daily Testing
900k 6.0M
800k
5.0M
700k
600k 4.0M
500k
3.0M
400k
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300k 2.0M
200k
1.0M
100k
0k 0.0M
9-Mar 16-Mar 23-Mar 30-Mar 6-Apr 13-Apr 20-Apr 27-Apr 4-May 11-May 18-May 25-May 1-Jun 8-Jun 15-Jun 22-Jun 29-Jun 6-Jul 13-Jul
Daily Tests (Left) Trailing 7-Day Tests (Right)
Source: The COVID Testing Project by The Atlantic, Goldman Sachs Global Investment Research
n For viral testing, those done over the trailing 7-day period imply a run rate of ~22mn
tests per month. This compares to our updated estimate of theoretical capacity in
the range of 21-29mn. With recent reports of extended turnaround time for test
results that we have previously highlighted, we believe bottlenecks exist in
delivering significantly higher volumes of lab-based PCR tests. Below we show how
we arrive at a theoretical capacity between 21-29mn tests per month vs. the current
run-rate of ~22mn tests performed per month in the US. As we describe below, this
leaves other testing modalities as key to further increasing US testing volume.
17 July 2020 49
Exhibit 9: Viral Testing Capacity - Molecular PCR and Antigen

US TEST PRODUCTION US TEST PRODUCTION
COMPANY COMPANY
ESTIMATE ESTIMATE
Thermo Fisher Scientific 5-10M DiaSorin 200,000
Hologic 4M - 5M GenMark Diagnostics 100,000
Roche 3M - 5M QIAGEN Not Available*
Abbott Laboratories 3,600,000 bioMerieux Not Available*
Cepheid (Danaher) 1,500,000 BGI Genomics Co. Ltd Not Available*
Siemens Healthineers 1,200,000 Mesa Biotech Inc. Not Available*
PerkinElmer 1,000,000 Atila BioSystems, Inc. Not Available*
Becton, Dickinson - PCR 900,000
Luminex 400,000 TOTAL CAPACITY 21M - 29M
n Some of the largest commercial labs in the country have acknowledged constraints
on meeting demand for COVID testing, with LabCorp recently flagging increased
turnaround time for results up to 3-5 days. Our recent diligence has also suggested
that testing capacity may be stretched especially in various parts of the country
where a recent acceleration in COVID infections has occurred.

n For antigen testing, given the constraints we have described for viral testing
volume in the lab setting and the manufacturability of antigen tests, we see
significant opportunity for volume to increase from here. Two key players in this
market are Becton Dickinson and Quidel, among others. On a combined basis, these
two players expect capacity to approach 15mn later this year, which could
significantly expand testing capacity in the US. While accuracy of these tests is
typically lower than lab-based viral tests, we would expect to see some utility for
them at physician offices, pharmacies, drive-through testing locations, and other
point-of-care settings at the very least, and at the most, there could be significant
theoretical potential for these tests to be utilized at home for screening on a regular
basis if accuracy hurdles can be overcome.
n On the antibody side, significantly greater testing capacity of more than 200mn
93f15d4c5e4d11d89860be55d934f058
per month should be available in theory, though, as we have previously described,
these tests are not as useful (compared to viral tests) in diagnosing current
infections given their measurement IgG/IgM which are produced by the body several
days into the infection at earliest. We believe that antibody testing capacity is
likely to outpace demand given the lower utility of these tests compared tests
that can be used in screening and diagnosis of COVID-19.
17 July 2020 50
Exhibit 10: Antibody (Serology) Testing Capacity - Monthly

TEST PRODUCTION
COMPANY IgG IgM Sensitivity Specificity
CAPACITY (monthly)
Roche yes pending 100.0% >99.8% Approx. 100 million tests by June
30M test in May, ramping to 60M

Abbott Laboratories yes pending 100.0% 99.6%
WW in June
Siemens Healthineers yes yes >99% >99% 50M by June
Danaher (Beckman Coulter) yes no 100.0% 99.8% Over 30M tests per month
1
Perkin Elmer yes no 100% 99.0% Over 10M per month
Thermo Fisher / Mayo Clinic / ramping production in US in next

yes yes n/a n/a
WuXi Diagnostics few weeks (dated May 13)
DiaSorin yes no Varies2 98.9% n/a
Bio-Rad yes yes 98.0% 99.0% n/a
Luminex yes no n/a n/a n/a
Ortho Clinical Diagnostics total only total only 83.0% 100.0% n/a
Mount Sinai Laboratory yes no n/a n/a n/a
1
From 0-10 days, 13.9%; 11-20 days, 61.1%; >21 days, 100%. 2Sensitivity: 25% <5 days, 90.5% at 5-15 days, 97.4% >15 days
Leading COVID diagnostics players: ROG, BDX, ABT
We see Roche (ROG) as one of the best positioned companies relative to the COVID-19
testing dynamics. One of the broadest installed bases of diagnostics machines, 2
validated tests with very high accuracy (1 PCR and 1 serology test) and amongst the
highest capacities globally for these tests all combine to provide ROG with an
opportunity to off-set the headwinds they see in the other parts of their routine
diagnostics business. Whilst ROG are currently working on a POC/antigen test we note
that their internal bar for the accuracy requirements of these tests (broadly on par with
93f15d4c5e4d11d89860be55d934f058
what they see on their PCR / Serology tests) could mean that they aren’t necessarily the
first out of the gates here, but we would note that if they are able to develop such a test
it would represent meaningful upside to our current estimates. In the mid-long term, we
believe the increased strategic value of diagnostics and increased demand for their
COBAS 6800/8800 machines (ROG noted that their current purchase orders are greater
than their installed base) is likely to mean a higher revenue growth outlook for a longer
duration. We currently model ROG’s diagnostics business to deliver a 5%-6% annual top
line growth (versus historic growth rates of 4%-5%), albeit do not model a sustainable
upside from COVID-19 testing in particular. All else being equal, every $500mn of
incremental COVID-19 testing revenues are likely to add c.400bp to the diagnostics
business growth rate and c.80bp to ROG’s overall growth rate. ROG remains one of our
preferred names in the EU biopharma group.
n Elecsys antibody test: Approved in May 2020 under emergency use, ROG’s
antibody test is performed on a cobas e analyser (cobas e 411, cobas e 601/602, or
cobas e 801), which requires different equipment and reagents than the cobas
6800/8800 systems. Per ROG, more than 3,000 cobas e analyzers of the four
models are installed in US. The assay detects high affinity antibodies including IgM,
17 July 2020 51
IgA, or IgG antibodies which appear in the late or convalescent Phase of infection,
using the double antigen sandwich (DAGS) format. ROG’s antibody test was
developed to bind two viral antigens (spike and capsid, the former being more
difficult to target and the latter being predominantly targeted by competitors).
According to ROG, its antibody test selects for more neutralising antibodies (not
detecting mature antibodies), and can provide rapid test results within 18 minutes
with a test throughput of up to 300 tests/hour, depending on the analyser. Data from
5,272 samples indicates that the assay has a specificity of c.99.8% and shows no
cross-reactivity with the common cold coronaviruses. The assay has also exhibited
100% clinical sensitivity for samples collected >14 days after PCR confirmation. The
company is currently ramping up its serology testing capacity with the aim of 100mn
tests per month for June and even more by August.
n On the antigen test, ROG has been less optimistic on this approach given the
low sensitivity of the tests. The company has stated that the low sensitivity of
antigen tests was a concern given the 80% accuracy. That said, ROG believes there
is more utility of using antigen tests in developing markets where there is a lack of
testing infrastructure.
n SARS-CoV-2 PCR test: ROG’s PCR test, which received EUA in March 2020, can be
run on fully automated cobas 6800/8800 systems through an oropharyngeal or
nasopharyngeal swab. Per ROG, there are c. 850 cobas 6800/8800 machines
installed globally (of which we estimate 100-150 being in the US), that can deliver
test results within 3.5 hours, with throughput to process 384/1,056 tests on the
cobas 6800/8800 systems respectively, over an 8-hour shift. Currently, 10mn tests
are performed per month and scaling efforts are well-underway with three more
production lines of consumables in June/July. ROG offers one of the best assays on
the market with high specificity and sensitivity, detecting as low as 25 viral
copies/mL in contrast to 100 copies/mL required by competitors. In terms of
capacity, ROG has previously highlighted (LINK) that their outstanding purchase
93f15d4c5e4d11d89860be55d934f058
orders (PO) for cobas 6800/8800 today equal or exceed the entirety of their existing
installed base - in a normal year new demand is expected to be 15%-20% of
installed capacity.
We believe Abbott (ABT) benefited from an early lead in developing and launching an
array of COVID tests in the US including molecular lab-based tests, point of care tests
(ID NOW), and serology tests. However, Abbott represents about a quarter of the
market for many major testing categories, and we believe that ultimate COVID testing
market share will likely settle along similar lines as pre-COVID market share. This is a
reflection of the installed base of various systems and their throughput which determine
the upward bounds on market share. ABT has also recently announced that it is
developing a point of care antigen test that will not require a reader, but rather will be
entirely self-contained. Details remain very limited around timing or potential capacity.
Finally, we remain skeptical that the demand for antibody testing will reach a material
level for ABT revenues given the much lower price point for those tests.
n Based on our prior deep dive report on the testing market opportunity, we estimate
that viral testing could drive between $150-200mn of revenue for ABT over the next
17 July 2020 52
several quarters. Our revenue estimates for the lateral flow antibody test for ABT are
largely immaterial at this time. For 2Q20, ABT reported a total of $615mn of revenue
from COVID-related diagnostics; the results were $283mn in revenue from
molecular testing, $152mn in revenue from antibody testing, and $180mn in
revenue for point of care testing on the ID NOW platform.
Our assessment of the opportunities for Becton Dickinson (BDX) are generally positive
(above Street) and driven predominately by potential upside from the Veritor
point-of-care antigen test. The company recently received FDA approval ahead of our
expected timeline and with initial capacity well above what we modeled. The Veritor
point-of-care test offers unique benefits including an ability to be used in screening and
diagnosis of COVID-19, setting flexibility, speed to result, and availability. Our
assumptions for the Veritor test was peak capacity of about 5M per quarter (in calendar
1Q21) but the company has since suggested upwards of 2M per week by September.
This strongly suggests upside to our estimates both in FY20 and FY21 from this
platform. BDX also has PCR testing via BD Max and a lateral-flow serology test (under
development).
n For the PCR test, we model revenue of roughly $30-40M per quarter driving FY20
revenue of $60M and FY21 revenue of $160M. On the lateral flow serology test
opportunity, our revenue estimates are currently immaterial, similar to ABT.
Adaptive Biotechnologies (ADPT)’s T cell receptor-based diagnostic for COVID-19

may overcome current shortcomings with existing diagnostics and be the first
T-cell based diagnostic on the market. ADPT is actively exploring the application of its
diagnostic platform, immunoSEQ Dx, to detect the T cell receptor response to COVID-19
based on the hypothesis that quantifying virus-specific T cells may provide important
diagnostic advantages given T cells appear earlier than antibodies and seem to persist
longer. ADPT’s initial focus for its COVID-19 efforts is to introduce a new and more
accurate test for past infection of COVID-19, or to identify who has had the disease,
93f15d4c5e4d11d89860be55d934f058
which is currently measured with serology testing. Future utility of the diagnostic
includes detecting signs of COVID-19 infection early, applications to vaccines, and to
identify T cell receptors associated with better patient outcomes. Management
anticipates that a T cell receptor-based diagnostic that examines the cellular response to
confirm past infection will have very little to no false positives, which will help provide
reassurance as society begins reopening. In parallel, ADPT is testing if the T cell
receptor-based signature can be used across the diagnostic paradigm from exposure
(including in asymptomatic patients), to infection to recovery. ADPT will assess whether
the dynamics of the T cell receptors are also able to help triage newly diagnosed
patients and predict the severity of response, to determine whether a person may
develop mild COVID-19 or whether someone will require hospitalization. ADPT expects
to pursue an EUA regulatory pathway (estimated to occur over the summer), and notes
plans to discuss an expedited path to approval with the FDA.
17 July 2020 53
Disclosure Appendix
Reg AC
We, Salveen Richter, CFA, Terence Flynn, Ph.D., Amit Hazan, Keyur Parekh, Akinori Ueda, Ph.D., Ross Weinreb, Veronika Dubajova, CFA, Chris Cooper,
CFA, Paul Choi and Graig Suvannavejh, Ph.D., hereby certify that all of the views expressed in this report accurately reflect our personal views about
the subject company or companies and its or their securities. We also certify that no part of our compensation was, is or will be, directly or indirectly,
related to the specific recommendations or views expressed in this report.
Unless otherwise stated, the individuals listed on the cover page of this report are analysts in Goldman Sachs’ Global Investment Research division.
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Distribution of ratings/investment banking relationships
Goldman Sachs Investment Research global Equity coverage universe
Rating Distribution Investment Banking Relationships
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Buy Hold Sell Buy Hold Sell
Global 47% 36% 17% 65% 58% 54%
As of July 1, 2020, Goldman Sachs Global Investment Research had investment ratings on 3,015 equity securities. Goldman Sachs assigns stocks as
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17 July 2020 54
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17 July 2020 56

GS - COVID Toolkit 2.0 (7.17.20) PDF

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17 July 2020 | 4:00AM EDT

COVID-19 toolkit 2.0: The GS roadmap for the path ahead

Veronika Dubajova, CFA

We look to approvals of multiple COVID-19 vaccines in order to meet global demand

On the therapeutic side, Gilead’s (GILD) remdesivir, an anti-viral, is approved in the UK

1. Despite signiﬁcant scientiﬁc progress on understanding the virus, unknowns

Key COVID-19 questions

1. What is the mutational risk of SARS-CoV-2?

2. What is the duration of protection conferred by antibodies to SARS-CoV-2?

The duration of protection conferred by SARS-CoV-2 antibodies is a key outstanding

in mild patients (noted above). A mathematical model published in Science projected

3. Re-infection risk remains an outstanding question.

4. What level of antibody response is necessary to be protective?

individuals published in Nature Medicine, most convalescent plasma obtained from

Pre-clinical data from AstraZeneca (AZN)/University of Oxford also demonstrated that

5. Vaccination rate of 70-85% is estimated to be required for herd immunity.

Mandatory vaccination presents a potential method to increase the uptake of a

1. Covid-19 is not adequately contained in the state.

GS published COVID-19 related research notes

Below, we highlight key previously published research notes on COVID-19:

Summary: Vaccines/Therapeutics in development

Exhibit 1: Summary of lead vaccines in development

Ph1/2a trials to begin in late July 2020

Preliminary Ph1/2 data likely by December

Source: Company data, compiled by Goldman Sachs Investment Research

Exhibit 2: Summary of lead therapies in development

Source: Company data, compiled by Goldman Sachs Global Investment Research

Vaccines - Key debates

WHO and partners have established a $18bn program to expedite R&D,

COVAX to assist lower income countries in obtaining sufﬁcient doses of vaccine

Usage of adenoviral vectors could lead to lower pool of target patients

include Moderna (MRNA), Pﬁzer (PFE)/ BioNTech (BNTX), AstraZeneca

Requirement for cold storage of vaccines could impact distribution

Advantages of mRNA prophylactic vaccines

International guidance on COVID-19 vaccines

Below we summarize the key takeaways from ICMRA guidance:

Ph3 trial design criteria

n COVID-19 vaccine Ph3 trials should be randomized, double-blind, controlled

the study based on signals of potential vaccine-induced enhanced disease with a

Criteria to move into Ph3 trials

n Pre-clinical and clinical data requirements must be met prior to progression

FDA guidance on COVID-19 vaccines

conﬁrmatory trials are required to verify the efﬁcacy.

Below, we summarize the key takeaways from the FDA guidance:

n The primary endpoint for a placebo-controlled trial of a COVID-19 vaccine should

appropriate for COVID-19 vaccines before the manufacturer has submitted

the beginning of 2021.

Vaccines in development: At least ﬁve programs in Ph3 this summer

randomized 1:1 placebo-controlled trial. The primary efﬁcacy analysis will be an

On powering assumptions, MRNA’s target vaccine efﬁcacy (VE) against COVID-19 is

number of participants with symptomatic COVID-19 disease. Key secondary endpoints

n Potential areas of debate: There could be comparisons between competitors, such

o In the US, MRNA is in collaboration with Catalent (CTLT), for large-scale,

n Immunogenicity data to-date: An interim analysis of MRNA’s open-label Ph1 study

be developed and commercialized by BNTX/Fosun Pharma).

n Immunogenicity data to-date: BNT162b1 successfully induced immunogenicity

AstraZeneca (AZN) is partnered with the University of Oxford on their AZD1222

with data expected imminently. In addition, AZN/University of Oxford are also

n Potential areas of debate: Despite speedy progress on development, we note the

(5x1010vp) at week 0 and AZD1222 (2.5x1010vp) at week 8, prime-full boost cohort 3

full data in an academic journal.

n Potential areas of debate: mRNA vs DNA vaccine: RNA vaccines, such as

Immunogenicity data to-date: Based on preliminary assessment of the data, the