EVELO BIOSCIENCES: Discussion and analysis by management of the financial situation and operating results (form 10-K)

The following discussion and analysis should be read in conjunction with our
consolidated financial statements and related notes included elsewhere in this
Annual Report on Form 10-K. This discussion and analysis and other parts of this
Annual Report on Form 10-K contain forward-looking statements based upon current
beliefs, plans and expectations that involve risks, uncertainties and
assumptions, such as statements regarding our plans, objectives, expectations,
intentions and projections. Our actual results and the timing of selected events
could differ materially from those anticipated in these forward-looking
statements as a result of several important factors, including without
limitation those set forth under "Summary Risk Factors" and Part I, Item1A "Risk
Factors" and elsewhere in this Annual Report on Form 10-K. You should carefully
read the "Risk Factors" section of this Annual Report on Form 10-K to gain an
understanding of the important factors that could cause actual results to differ
materially from our forward-looking statements. Please also see the section
entitled "Special Note Regarding Forward-Looking Statements." A discussion of
the year ended December 31, 2019 compared to the year ended December 31, 2018,
as well as a discussion of our 2018 fiscal year, specifically, has been reported
previously in our Annual Report on Form 10-K for the year ended December 31,
2019, filed with the SEC on February 14, 2020, under the heading "Management's
Discussion and Analysis of Financial Condition and Results of Operations."

Overview

We are discovering and developing a new class of oral biologics that are
intended to act on cells in the small intestine to produce therapeutic effects
throughout the body. The target cells in the small intestine play a central role
in governing human immune, metabolic and neurological systems. We refer to this
biology as the small intestinal axis, or SINTAXTM. We have built a platform to
discover and develop novel oral medicines which target the small intestinal
axis. By harnessing the small intestinal axis, we have the potential to
transform healthcare via medicines that have the potential to be effective,
safe, convenient and affordable and to thereby treat patients at all stages of
diseases and to treat patients globally.
Our first product candidates are orally delivered pharmaceutical preparations of
naturally occurring, specific single strains of microbes. In preclinical models,
our product candidates engaged immune cells in the small intestine and drove
changes in systemic biology without any observed systemic exposure. We have
observed in early clinical trials and preclinical studies that our approach led
to modulated immune responses throughout the body by acting on the small
intestinal axis. Our most advanced product candidate, EDP1815 is being developed
for the treatment of inflammatory diseases and the hyperinflammatory response
associated with COVID-19. Additional product candidates include EDP1867 and
EDP2939 for the treatment of inflammatory disease and EDP1908 for the treatment
of cancer.

Impact of COVID-19

At March 11, 2020, WHO has declared the COVID-19 outbreak a pandemic. The outbreak has led governments around the world to implement stringent measures to help control the spread of the virus, including quarantines, “safe-in-place” and “stay-at-home” orders. travel, business closures and reductions, and school closings.

The COVID-19 pandemic has had, and for an extended period of time is expected to
have, negative impacts on our operations and supply chain. Our ability to
continue to operate without any significant negative impacts will, in part,
depend on our ability to protect our employees and our supply chain. We have
endeavored to follow recommended actions of government and health authorities to
protect our employees with particular measures in place for those working in our
laboratories, such as staggered work shifts and flexible schedules, and
telecommuting for office workers. We are working with our CMOs to minimize
delays and disruptions to scheduled manufacturing batch runs for our product
candidates and to ensure conformity to product specifications.

The COVID-19 pandemic has impacted and continues to impact our enrollment of new
patients into, and the retention of existing patients in, our ongoing clinical
trials, due primarily to lower patient participation. The pandemic likely will
impact enrollment and retention of patients in new and existing clinical trials.
We continue to recruit individuals in line with the local and national
guidelines of the clinical research sites. We are keeping in close contact with
our CROs and clinical sites to provide support and guidance to ensure the safety
of the patients in our clinical trials. We have prioritized our drug supply
operations to secure the re-supply of patients currently enrolled in our
clinical trials.


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The extent to which the COVID-19 pandemic impacts our business and finances will
depend on future developments, which are highly uncertain and cannot be
predicted with confidence, such as the duration of the pandemic, travel
restrictions and social distancing in the United States, the United Kingdom and
other countries, business closures or business disruptions and the effectiveness
of actions taken in the United States, the United Kingdom and other countries to
contain and treat the disease. See "Risk Factors - The COVID-19 pandemic has
adversely impacted and may continue to adversely impact our business, including
our preclinical studies and clinical trials and finances." in Part I, Item 1A of
this Annually Report on Form 10-K.

Clinical programs

We are advancing SINTAX medicines to potentially treat a spectrum of immune
mediated diseases with an initial focus on inflammatory diseases and oncology.
The efficiency of our platform has, in a relatively short period of time,
allowed us to advance multiple product candidates into clinical trials for a
range of diseases.

EDP1815, a whole microbe candidate for inflammatory diseases

EDP1815 is in clinical development for psoriasis, atopic dermatitis and COVID-19.

Psoriasis

Based on previously reported positive clinical data in two cohorts of
individuals with mild and moderate psoriasis in a Phase 1b clinical trial, we
have advanced EDP1815 into a Phase 2 dose ranging trial, evaluating three doses
of A' EDP1815 in capsules versus placebo in approximately 225 individuals with
mild and moderate psoriasis. The primary endpoint of the trial is the mean
reduction in PASI score at 16 weeks. Other clinical measures of psoriasis are
also being evaluated. We initiated the Phase 2 clinical trial in October 2020
and have completed enrollment and, therefore, now plan to report topline data in
the third quarter of 2021. Clinical data from this trial, if positive, may
enable us to advance directly into Phase 3 registrational trials, subject to end
of Phase 2 discussions with regulatory agencies.

We intend to evaluate EDP1815 in additional inflammatory disease indications,
depending on the results from the Phase 2 trial. Potential indications include
psoriatic arthritis, axial spondylarthritis and rheumatoid arthritis.

Atopic dermatitis

In November 2018, we initiated our ongoing Phase 1b double-blind
placebo-controlled dose-escalating safety and tolerability trial of EDP1815 in
healthy volunteers and individuals with mild and moderate psoriasis or atopic
dermatitis. The primary endpoint of the phase 1b trial is safety and
tolerability.

In December 2020 and January 2021, we reported positive clinical data from a
cohort of patients with mild and moderate atopic dermatitis (n=24), randomized
2:1 to receive EDP1815 in capsules or placebo for 56 days. Atopic dermatitis is
the most common type of eczema. EDP1815 was well-tolerated with no
treatment-related adverse events of moderate or severe intensity, and no serious
adverse events. Secondary endpoints included a range of established markers of
clinical efficacy in atopic dermatitis, such EASI, IGA* BSA, and SCORAD scores.

The data showed consistent improvements in percentage change from baseline
compared to placebo for all three clinical scores: EASI, IGA*BSA, and SCORAD. In
addition, 7 out of 16 (44%) patients treated with EDP1815 achieved an outcome of
a 50% improvement from baseline in EASI score by day 70, compared with 0% in the
placebo group, showing sustained improvement in those patients responding to
EDP1815.

In addition to physician-reported clinical outcomes, this trial also assessed
patient-reported outcomes. Treatment with EDP1815 resulted in clinically
meaningful improvement in the DLQI and POEM. These patient-reported outcomes
capture the important impact of the disease on patients, including the domains
of itch and sleep, both of which saw improvements in patients receiving EDP1815
in the trial. All five measures of itch within the Pruritus-NRS, SCORAD, POEM,
and DLQI showed greater improvements in the treated group at day 56 compared
with placebo. These results provide further evidence that modulating SINTAX can
drive significant clinical benefit without the need for systemic exposure.


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Subject to regulatory approval, we expect to launch a Phase 2 trial of EDP1815 in atopic dermatitis in the third quarter of 2021.

COVID-19[feminine

EDP1815 is being evaluated in two ongoing clinical trials for the treatment of
hospitalized COVID-19 patients. The first is a Phase 2 double-blind,
placebo-controlled clinical trial evaluating the safety and efficacy of EDP1815
for the treatment of individuals diagnosed with COVID-19 early in the course of
their disease. The clinical trial initially will evaluate 60 individuals to
determine if early intervention with EDP1815 can prevent the progression of
COVID-19 symptoms and the development of COVID-Related complications.
Individuals who have presented at the emergency room within the last 36 hours
and tested positive for SARS-CoV-2 are randomized 1:1 to receive the capsule
formulation of EDP1815 targeted for release in the small intestine or placebo
for 14 days, along with the standard of care. The primary endpoint is reduced
requirements for oxygen therapy, as measured by the ratio of oxygen saturation
(SpO2) / fraction of inspired oxygen (FiO2). Key secondary endpoints include
total symptom duration, progression along the WHO scale of disease severity, and
mortality. The trial is led by Reynold A. Panettieri, Jr., M.D., Vice Chancellor
for Translational Medicine and Science at Rutgers Biomedical and Health Sciences
and Professor of Medicine at Rutgers Robert Wood Johnson Medical School.

EDP1815 is also included as a treatment arm in the TACTIC-E clinical trial.
TACTIC-E is a Phase 2/3 randomized trial, sponsored by Cambridge University
Hospitals NHS Foundation Trust, that is expected to evaluate up to 469 patients
per arm at Addenbrooke's Hospital and other leading clinical centers in the
United Kingdom and select international sites. The trial is investigating the
safety and efficacy of certain experimental therapies in the prevention and
treatment of life-threatening complications associated with COVID-19 in
hospitalized individuals at early stages of the disease. The trial is enrolling
individuals with COVID-19 who have identified risk factors for developing severe
complications and are at risk of progression to the intensive care unit or
death. The primary outcome measure of the trial is time to incidence (up to day
14) of any one of the following: death, mechanical ventilation, extracorporeal
membrane oxygenation, cardiovascular organ support, renal failure,
hemofiltration or dialysis. Secondary outcome measures include duration of stay
in hospital, duration of oxygen therapy, changes in biomarkers associated with
COVID-19 progression, and time to clinical improvement.

As a result of the varying infection rates and resulting hospitalizations that
have occurred with the pandemic, we experienced slower than expected enrollment
early on in both trials and now expect to report data from the clinical trial
conducted at the Robert Wood Johnson University Hospital and interim safety data
and futility analysis from TACTIC-E in the second quarter of 2021. In order to
expedite patient recruitment and expand access to potential therapies for
COVID-19, new trial sites have been opened for TACTIC-E, including in the United
Kingdom and Mexico.

Modèle expérimental humain de l’inflammation

In addition to testing our product candidates in patients with inflammatory
disease, we also have employed a human experimental model of inflammation in
healthy volunteers. This model is very similar in design to a standard
preclinical model of T cell driven inflammation. We have recently used this
model to test two different concentrations of EDP1815 to investigate the
relative effectiveness of the different concentrations. A total of 32 volunteers
were enrolled into the trial and treated with either EDP1815 (n=12 per
formulation) or placebo (n=4 per formulation) daily for 28 days. The
participants were immunized with an antigen used in preclinical inflammation
experiments. After 28 days of daily oral dosing with EDP1815 or placebo, the
participants were given a skin challenge with the same antigen, which causes
measurable skin inflammation a day later. Inflammation was determined by
measuring five parameters in the skin at the challenge site.

The increased concentration of drug results from improvements made in the
commercial-scale manufacturing process, referred to as A2. This is the same
active drug at four times the concentration compared to a prior manufacturing
process, referred to as A'. Twelve participants were dosed with A' EDP1815.
Another 12 participants were given the higher concentration A2 EDP185. Eight
participants who received a placebo were divided between the two treatment
groups. The results are in the figure below.



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A2 EDP1815 is more effective than A' at same total dose in human experimental
model of inflammation
                    [[Image Removed: evlo-20201231_g4.jpg]]The higher concentration A2, given in fewer capsules, resulted in numerically superior reductions across the full range of skin scores compared to A 'and placebo.  A2 and A 'were given at the same total daily dose of drug.  These results are consistent with preclinical data that showed increased drug concentration resulted in increased activity.  This is a key advance in our understanding of how to get more benefit from SINTAX medicine candidates.  We plan to evaluate tablets and capsules containing the higher concentration A2 EDP1815 in patients with psoriasis in our on-going Phase 1b trial, and expect to report data in the third quarter of 2021. Results from the Phase 1b trial and our on-going Phase 2 trial in psoriasis will position us to go forward into Phase 3 trials with an optimized dose and formulation of EDP1815, which may further improve on the positive results already seen.

EDP1867 – a whole microbe candidate for inflammatory diseases

EDP1867 is an inactivated investigational oral biologic being developed for the
treatment of inflammatory diseases. EDP1867 was selected from a broad screen of
single strains of microbes in in vitro cellular assays and in vivo models of
inflammation. In preclinical studies EDP1867 was shown to resolve multiple
pathways of inflammation. This observed activity suggests a number of possible
initial clinical indications for EDP1867, including TH2-dependent inflammation
which underlies atopic diseases and a large spectrum of asthma. We initiated our
first Phase 1b clinical trial of EDP1867 in healthy volunteers and patients with
moderate atopic dermatitis in February of 2021 and expect to report interim data
in the fourth quarter of 2021.

EDP2939 – an extracellular vesicle (EV) candidate for inflammatory diseases

EDP2939 is an EV investigational oral biologic being developed for the treatment
of inflammatory diseases. EDP2939 is the first EV product candidate we have
nominated in our inflammation program and we anticipate initiation of clinical
development in 2022.

EDP1908 – an EV candidate for oncology

In December 2020, we announced EDP1908 as our lead candidate in oncology
following presentation of preclinical data at the Society for Immunotherapy for
Cancer meeting in November 2020. Preclinical data presented showed that orally
administered EDP1908, an EV, resulted in superior tumor growth control versus
the parent microbial strain or anti-PD-1 therapy, with an observed
dose-dependent reduction in tumor growth. We anticipate initiation of clinical
development in 2022.

Funding

We were incorporated and commenced operations in 2014. Since our incorporation,
we have devoted substantially all of our resources to developing our clinical
and preclinical candidates, building our intellectual property portfolio and
process development and manufacturing function, business planning, raising
capital and providing general and administrative support for these operations.
To date, we have financed our operations


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primarily with proceeds from sales of common and convertible preferred stock to
our equity investors and borrowings under loan and security agreements with
financial institutions.
Through December 31, 2020, we have received gross proceeds of $332.0 million
through the issuance of our common stock, convertible preferred stock and
borrowings under our loan and security agreements.
On July 19, 2019 we entered into a loan and security agreement, as amended, with
K2HV providing for up to $45.0 million in potential debt financing, the proceeds
of which were used to prepay our entire existing outstanding loan balance, and
additional amounts are intended for the advancement of our research and
development activities related to our pipeline of oral biologics and for general
corporate purposes. Under terms of the 2019 Credit Facility, the aggregate
principal amount of $45.0 million was available in three tranches of term loans
of $20.0 million, $10.0 million, and $15.0 million, respectively. At closing on
July 19, 2019, we borrowed $20.0 million, representing the first tranche under
the 2019 Credit Facility. On July 14, 2020, we drew down the second tranche of
$10.0 million and availability of the third tranche expired on January 15, 2021.
Interest on the outstanding loan balance accrues at a variable rate equal to the
greater of (i) 8.65% and (ii) the prime rate as published in the Wall Street
Journal, plus 3.15%. We are required to make monthly interest-only payments
through February 2022. Subsequent to the interest-only period, we are required
to make equal monthly principal payments plus any accrued interest until the
loans mature in August 2024. Upon final payment or prepayment of the loans, we
are required to pay a final payment equal to 4.3% of the loans borrowed.
In June 2020, we sold 13,800,000 shares of our common stock in an underwritten
public offering at a public offering price of $3.75 per share, for gross
proceeds of $51.8 million and net proceeds of $48.4 million, after deducting
underwriting discounts and commission and other offering expenses payable by us.
For the year ended December 31, 2020, pursuant to the June 2019 sales agreement
with Cowen and Company, LLC, we sold 1,232,131 shares of our common stock, in
"at-the-market" offerings under a registration statement on Form S-3 that we
previously filed with the SEC with offering prices ranging between $4.25 to
$11.15 per share for gross proceeds of $6.8 million and net proceeds of
$6.6 million, after deducting commission and other offering expenses payable by
us. In January 2021, we issued 139,734 additional shares of our common stock
with offering prices ranging between of $12.54 and $13.17 per share for gross
proceeds of $1.8 million and net proceeds of $1.7 million, after deducting
commission and other offering expenses payable by us.

On February 2, 2021, we sold 5,175,000 shares of our common stock in an
underwritten public offering at a public offering price of $15.00 per share,
including the underwriters' exercise of their option to purchase 675,000 shares
to cover over-allotment, generating gross proceeds of $77.6 million and net
proceeds of $73.0 million, after deducting underwriting discounts and
commissions, exclusive of other offering expenses payable by us.
On January 28, 2021, we entered into a stock purchase agreement with ALJ Health
Care & Life Sciences Company Limited ("ALJ"), pursuant to which on February 2,
2021, ALJ purchased $7.5 million of our common stock in a private placement at a
purchase price of $15.00 per share. The sale of these 500,000 shares was not
registered under the Securities Act.
We are a development stage company and have not generated any revenue. All of
our product candidates are in early clinical or preclinical development. Our
ability to generate product revenue sufficient to achieve profitability will
depend heavily on the successful development and eventual commercialization of
one or more of our product candidates. Since our inception, we have incurred
significant operating losses and we continue to incur significant research and
development and other expenses related to our ongoing operations. For the years
ended December 31, 2020 and 2019 our net loss was $93.7 million and $85.5
million, respectively. As of December 31, 2020, we had an accumulated deficit of
$292.5 million. We do not expect to generate revenue from sales of any products
for the foreseeable future, if at all.
We expect that our expenses will increase substantially in connection with our
ongoing activities, particularly as we:
•continue the ongoing clinical trials for EDP1815 and EDP1867;
•initiate additional clinical trials for EDP1815;
•initiate or advance the clinical development of additional product candidates;
•conduct research and continue preclinical development of potential product
candidates;
•make strategic investments in manufacturing capabilities, including potentially
planning and building our own manufacturing facility;


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•maintain our current intellectual property portfolio and opportunistically
acquire complementary intellectual property;
•increase research and development employees and employee-related expenses
including salaries, benefits, travel and stock-based compensation expense; and
•seek to obtain regulatory approvals for our product candidates.
In addition, if we obtain marketing approval for any of our product candidates,
we expect to incur significant commercialization expenses related to product
manufacturing, marketing, sales and distribution.
As a result, we will need additional financing to support our continuing
operations. Until such time as we can generate significant revenue from product
sales, if ever, we expect to finance our operations through a combination of
public or private equity or debt financings or other sources, which may include
collaborations with third parties. Adequate additional financing may not be
available to us on acceptable terms, or at all. Our inability to raise capital
as and when needed would have a negative impact on our financial condition and
our ability to pursue our business strategy. We will need to generate
significant revenue to achieve profitability, and we may never do so.
Because of the numerous risks and uncertainties associated with drug
development, we are unable to predict the timing or amount of increased expenses
or when or if we will be able to achieve or maintain profitability. Even if we
are able to generate revenue from product sales, we may not become profitable.
If we fail to become profitable or are unable to sustain profitability on a
continuing basis, then we may be unable to continue our operations at planned
levels and be forced to reduce or terminate our operations.
As of December 31, 2020, our principal source of liquidity is cash and cash
equivalents, which totaled approximately $68.9 million. During the first quarter
of 2021 we raised net proceeds of $82.2 million from the issuance of common
stock exclusive of certain other fees payable by us. We expect that our existing
cash and cash equivalents as of December 31, 2020, together with the net
proceeds raised in the first quarter of 2021 from the issuance of our common
stock, will enable us to fund our planned operating expenses and capital
expenditure requirements into the third quarter of 2022. We have based these
estimates on assumptions that may prove to be wrong, and we may use our
available capital resources sooner than we currently expect. See "Liquidity and
Capital Resources."

Financial Operations Overview
Revenue
We have not generated any revenue since our inception and do not expect to
generate any revenue from the sale of products in the near future if at all. If
our development efforts for our current product candidates or additional product
candidates that we may develop in the future are successful and result in
marketing approval or if we enter into collaboration or license agreements with
third parties, we may generate revenue in the future from a combination of
product sales or payments from such collaboration or license agreements.
Operating Expenses
Our operating expenses since inception have consisted primarily of research and
development activities and general and administrative costs.
Research and Development Expenses
Research and development expenses consist primarily of costs incurred for our
research activities, including our discovery efforts, and the development of our
product candidates, which include:
•expenses incurred under agreements with third parties, including investigative
sites, external laboratories and CROs, that conduct research, preclinical
activities and clinical trials on our behalf
•manufacturing process-development costs as well as technology transfer and
other expenses incurred with contract manufacturing organizations, or CMOs, that
manufacture drug substance and drug product for use in our preclinical
activities and any current or future clinical trials;
•salaries, benefits and other related costs, including stock-based compensation
expense, for personnel in our research and development functions;
•expenses to acquire technologies to be used in research and development;
•costs of outside consultants, including their fees, stock-based compensation
and related travel expenses;


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•the cost of laboratory supplies and acquiring, developing and manufacturing
preclinical and clinical trial materials;
•costs related to compliance with regulatory requirements; and
•facility-related expenses, which include direct depreciation costs and
allocated expenses for rent and maintenance of facilities and other operating
costs.
We expense research and development costs as incurred. We recognize external
development costs based on an evaluation of the progress to completion of
specific tasks using information provided to us by our vendors and our clinical
investigative sites. Payments for these activities are based on the terms of the
individual agreements, which may differ from the pattern of costs incurred, and
are reflected in our consolidated financial statements as prepaid or accrued
research and development expenses. Nonrefundable advance payments for goods or
services to be received in the future for use in research and development
activities are deferred and capitalized, even when there is no alternative
future use for the research and development. The capitalized amounts are
expensed as the related goods are delivered or the services are performed.
Our primary focus of research and development since inception has been building
a platform to enable us to develop medicines based on an understanding of the
gut-body network and to show potential clinical utility and develop the first
set of clinical assets. Our platform and program expenses consist principally of
costs, such as preclinical research, process development research, clinical and
preclinical manufacturing activity costs, clinical development costs, licensing
expense as well as an allocation of certain indirect costs, facility and office
related expenses. We do not allocate personnel costs, which include salaries,
discretionary bonus and stock-based compensation costs, as such costs are
separately classified as research and development personnel costs.
Research and development activities are central to our business model. Product
candidates in later stages of clinical development generally have higher
development costs than those in earlier stages of clinical development,
primarily due to the increased size and duration of later-stage clinical trials.
We expect that our research and development expenses will continue to increase
in the foreseeable future as we continue our ongoing clinical trials for our
product candidates, including EDP1815 and EDP1867, initiate additional clinical
trials of other product candidates, including EDP2939 and EDP1908, continue to
discover and develop additional product candidates, hire additional research and
development personnel, build manufacturing capabilities and expand into
additional therapeutic areas.
At this time, we cannot reasonably estimate or know the nature, timing and
estimated costs of the efforts that will be necessary to complete the
development of, and obtain regulatory approval for, any of our product
candidates. We are also unable to predict when, if ever, material net cash
inflows will commence from sales or licensing of our product candidates. This is
due to the numerous risks and uncertainties associated with drug development,
including the uncertainty of:
•our ability to add and retain key research and development personnel;
•our ability to successfully develop, obtain regulatory approval for, and then
successfully commercialize, our product candidates;
•our successful enrollment in and completion of clinical trials;
•the costs associated with the development of our current product candidates
and/or any additional product candidates we identify in-house or acquire through
collaborations;
•our ability to discover, develop and utilize biomarkers to demonstrate target
engagement, pathway engagement and the impact on disease progression of our
product candidates;
•our ability to establish an appropriate safety profile with IND-enabling
toxicology studies;
•our ability to establish and maintain agreements with CMOs and other entities
for clinical trial supply and future commercial supply, if our product
candidates are approved;
•the terms and timing of any collaboration, license or other arrangement,
including the terms and timing of any milestone payments thereunder;
•our ability to obtain and maintain patent, trade secret and other intellectual
property protection and regulatory exclusivity for our product candidates if and
when approved;
•our receipt of marketing approvals from applicable regulatory authorities;


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•our ability to commercialize products, if and when approved, whether alone or
in collaboration with others; and
•the continued acceptable safety profiles of the product candidates following
approval.
A change in any of these variables with respect to the development of any of our
product candidates would significantly change the costs, timing and viability
associated with the development of that product candidate. We expect our
research and development expenses to increase at least over the next several
years as we continue to implement our business strategy, advance our current
programs, expand our research and development efforts, seek regulatory approvals
for any product candidates that successfully complete clinical trials, identify
and develop additional product candidates and incur expenses associated with
hiring additional personnel to support our research and development efforts.
General and Administrative Expenses
General and administrative expenses consist primarily of salaries and other
related costs, including stock-based compensation, for personnel in our
executive, finance, corporate and business development, and administrative
functions. General and administrative expenses also include legal fees relating
to patent and corporate matters; professional fees for accounting, auditing, tax
and administrative consulting services; insurance costs; administrative travel
expenses; and facility-related expenses, which include direct depreciation costs
and allocated expenses for rent and maintenance of facilities and other
operating costs.
We anticipate that our general and administrative expenses will increase in the
future as we increase our headcount to support the expected growth in our
research and development activities and the potential commercialization of our
product candidates. We also expect to incur increased expenses associated with
being a public company, including increased costs of accounting, audit, legal,
regulatory and tax-related services associated with maintaining compliance with
exchange listing and SEC requirements, director and officer insurance costs and
investor and public relations costs.
Interest (Expense) Income, Net
Interest income (expense), net consisted primarily of interest earned on our
cash, cash equivalents and short-term investments balances offset by interest
expense at the stated rate on borrowings under our loan and security agreement,
amortization of deferred financing costs and interest expense related to the
accretion of debt discount associated with the loan and security agreement.
Other (Expense) Income, Net
For the year ended December 31, 2020, other income (expense), net primarily
consists of foreign currency gains and government grants related to our
operations in the United Kingdom.
Income Taxes
Income tax expense primarily relates to tax expense at our UK subsidiary.
Since our inception in 2014, we have not recorded any U.S. federal or state
income tax benefits for the net losses we have incurred in each year or our
earned research and development tax credits, due to our uncertainty of realizing
a benefit from those items.


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Results of Operations
Comparison of Years Ended December 31, 2020 and 2019
The following table summarizes our results of operations for the years ended
December 31, 2020 and 2019 (in thousands):
                                       Year Ended December 31,            Increase/
                                         2020               2019         (Decrease)
Operating expenses:
Research and development         $      69,616           $  63,128      $     6,488
General and administrative              22,270              23,229             (959)
Total operating expenses                91,886              86,357            5,529
Loss from operations                   (91,886)            (86,357)          (5,529)
Other (expense) income:
Interest (expense) income, net          (2,109)              1,049           (3,158)
Other income, net                          738                  26              712
Other (expense) income, net             (1,371)              1,075           (2,446)
Net loss before income taxes           (93,257)            (85,282)          (7,975)
Income tax expense                        (409)               (190)            (219)
Net loss                         $     (93,666)          $ (85,472)     $    (8,194)

Research and development costs (in thousands):

                                                                Year Ended December 31,                  Increase/
                                                                2020                    2019             (Decrease)
Platform expenses                                      $      11,487                $  10,468          $     1,019
Inflammation programs                                         30,467                   25,161                5,306
Oncology programs                                              5,487                    9,226               (3,739)

Research and development personnel costs (including stock-based compensation)

                                     22,175                   18,273                3,902
Total research and development expenses                $      69,616        

$ 63,128 $ 6,488

Research and development expenses were $69.6 million for the year ended
December 31, 2020, compared to $63.1 million for the year ended December 31,
2019. The increase of $6.5 million was primarily driven by a $5.3 million
increase in inflammation program costs due to the progression of EDP1815 to
Phase 2, the addition of COVID-19 studies utilizing EDP-1815, and costs incurred
in contract manufacturing to enable EDP1867 Phase 1 clinical trials partially
offset by the closeout of the EDP1066 program. In addition, personnel costs
increased by $3.9 million due to increases in clinical development and technical
operations headcount to support increased clinical program activities. Finally,
there was a $1.0 million increase for platform expenses which is in line with
our strategy to maximize the potential of our platform. These increases were
partially offset by a $3.7 million decrease in our oncology program costs,
primarily related to the clinical trial stage and the impact of the COVID-19
pandemic on patient recruitment. Overall, we expect that our research and
development expenses will continue to increase in the foreseeable future as we
continue our clinical trials for our product candidates, including EDP1815 and
EDP1867, initiate new clinical trials, potentially expand into additional
therapeutic areas, continue discovery and development efforts for additional
product candidates, hire additional research and development personnel, and seek
to increase manufacturing capabilities.
General and Administrative Expenses (in thousands):
                                                                 Year Ended December 31,                  Increase/
                                                                 2020                    2019             (Decrease)

General and administrative staff costs (including stock-based compensation)

                               $      12,261                $  12,345          $       (84)
Professional fees                                               5,513                    6,725               (1,212)
Facility costs, office expense and other                        4,496                    4,159                  337
Total general and administrative expenses               $      22,270                $  23,229          $      (959)




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General and administrative expenses were $22.3 million for the year ended
December 31, 2020, compared to $23.2 million for the year ended December 31,
2019. The decrease of $1.0 million was primarily driven by $1.2 million lower
cost associated with legal, consulting and other professional fees, partially
offset by higher IT, facilities and other office expenses costs. We expect this
decrease to be temporary and general and administrative expenses to increase due
to higher personnel and related costs, professional, legal, and patent fees and
consulting expenses in support of our continued growth.
Other (Expense) Income, Net
Other income (expense), net for the year ended December 31, 2020 was expense of
$1.4 million compared to income of $1.1 million for the year ended December 31,
2019. This decrease was primarily driven by a decrease in interest income as a
result of lower interest rates and a lower cash and cash equivalent balance and
an increase in interest expense as a result of a higher interest rate on a
greater principal balance from the 2019 Credit Facility, partially offset by
foreign currency gains and a grant related to our operations in the United
Kingdom.
Net Loss

Net loss was $93.7 million for the year ended December 31, 2020, compared to
$85.5 million for the year ended December 31, 2019. The increase of $8.2 million
was primarily the result of the increase in research and development expenses
and decrease in other income (expense), net discussed above, partially offset by
the decrease in general and administrative expenses discussed above.

Liquidity and Capital Resources
To date, we have financed our operations primarily with the proceeds from
issuance of our common stock combined with proceeds from previous sales of our
convertible preferred stock to our equity investors and borrowings under loan
and security agreements. From our inception through December 31, 2020, we have
received gross proceeds of $332.0 million from such transactions, including
$30.0 million borrowed under the 2019 Credit Facility. As of December 31, 2020,
we had cash and cash equivalents of $68.9 million and an accumulated deficit of
$292.5 million. During the first quarter of 2021 we raised net proceeds of $82.2
million from the issuance of common stock exclusive of certain other fees
payable by us. We expect that our existing cash and cash equivalents as of
December 31, 2020, together with the net proceeds raised in the first quarter of
2021 from the issuance of our common stock, will enable us to fund our planned
operating expenses and capital expenditure requirements into the third quarter
of 2022.

On June 3, 2019, we filed a Registration Statement on Form S-3 (File No.
333-231911) (the "Shelf") with the SEC under which we can offer from time to
time common stock, preferred stock, debt securities, warrants and/or units of
any combination thereof in an aggregate amount of up to $200.0 million over a
period of up to three years from the date of its effectiveness on June 6, 2019.
We also simultaneously entered into a sales agreement with Cowen and Company,
LLC, as sales agent, providing for the offering, issuance and sale by us of up
to an aggregate $50.0 million of our common stock from time to time in
"at-the-market" offerings under the Shelf. For the year ended December 31, 2020,
we had issued 1,232,131 shares of our common stock with offering prices ranging
between $4.25 to $11.15 per share for gross proceeds of $6.8 million and net
proceeds of $6.6 million, after deducting commission and other offering expenses
payable by us. In January 2021, we issued 139,734 additional shares of our
common stock with offering prices ranging between $12.54 and $13.17 per share
for gross proceeds of $1.8 million and net proceeds of $1.7 million, after
deducting commission and other offering expenses payable by us.
On February 2, 2021, we sold 5,175,000 shares of our common stock in an
underwritten public offering at a public offering price of $15.00 per share,
including the underwriters' exercise of their option to purchase 675,000 shares
to cover over-allotment, generating gross proceeds of $77.6 million and net
proceeds of underwriting discounts and commission of $73.0 million, exclusive of
certain other offering expenses payable by us.
On January 28, 2021, we entered into a stock purchase agreement with ALJ,
pursuant to which on February 2, 2021, ALJ purchased $7.5 million of our common
stock in a private placement at a purchase price of $15.00 per share. The sale
of such shares will not be registered under the Securities Act.
Debt financing
On July 19, 2019 we entered into the 2019 Credit Facility with K2HV providing
for up to $45.0 million of current and future potential debt financing. The
aggregate principal amount was available in three tranches of term loans of
$20.0 million, $10.0 million, and $15.0 million, respectively. At closing on
July 19, 2019, we borrowed $20.0 million,


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representing the first tranche under the 2019 Credit Facility. On July 14, 2020,
we drew down the second tranche of $10.0 million and availability of the third
tranche expired on January 15, 2021.

Interest on the outstanding loan balance will accrue at a variable rate equal to
the greater of (i) 8.65% and (ii) the prime rate as published in the Wall Street
Journal, plus 3.15%. We are required to make monthly interest-only payments
through February 2022. Subsequent to the interest-only period, we are required
to make equal monthly principal payments plus any accrued interest until the
loans mature in August 2024. Upon final payment or prepayment of the loans, we
are required to pay a final payment equal to 4.3% of the loans borrowed. We have
an option to prepay the loans in whole, subject to a prepayment fee of 2% of the
amount prepaid or, if the prepayment occurs after the 18-month anniversary of
the funding date of the loans, 1% of the amount prepaid.
Contemporaneous with the closing of the first tranche of funding described
above, we repaid the entire $15.0 million loan balance outstanding under an
existing loan and security agreement with a separate financial institution. In
accordance with the agreement underlying the prior debt facility, we paid an
additional 0.5% prepayment fee as additional expense.
We have incurred losses and generated negative operating cash flows since our
inception and anticipate that we will continue to incur losses for at least the
next several years. We incurred net losses of approximately $93.7 million and
$85.5 million for the years ended December 31, 2020 and 2019, respectively.
Until such time, if ever, as we can generate revenue from product sales, we
expect to finance our cash needs through a combination of equity offerings, debt
financings and potential collaborations, license and development agreements. To
the extent that we raise additional capital through future equity offerings or
debt financings, the ownership interest of common stockholders will be diluted,
and the terms of these securities may include liquidation or other preferences
that adversely affect the rights of the common stockholders. Debt and equity
financings, if available, may involve agreements that include covenants limiting
or restricting our ability to take specific actions, such as incurring
additional debt, making capital expenditures or declaring dividends. There can
be no assurance that such financings will be obtained on terms acceptable to us,
if at all. If we are unable to raise additional capital in sufficient amounts or
on terms acceptable to us, we may have to significantly delay, scale back or
discontinue our research and development programs or future commercialization
efforts. If we raise additional funds through collaborations, strategic
alliances or marketing, distribution or licensing arrangements with third
parties for one or more of our current or future drug candidates, we may be
required to relinquish valuable rights to our technologies, future revenue
streams, research programs or drug candidates or to grant licenses on terms that
may not be favorable to us. Our failure to raise capital as and when needed
would have a material adverse effect on our financial condition and our ability
to pursue our business strategy.
Cash Flows
The following table summarizes our sources and uses of cash for each of the
periods presented (in thousands):
                                                                        

End of year the 31st of December,

                                                                        2020                   2019
Cash used in operating activities                               $     (73,063)             $  (71,980)
Cash (used in)/provided by investing activities                        (1,315)                 51,970
Cash provided by financing activities                                  65,465                   4,992

Net decrease in cash, cash equivalents and restricted cash ($ 8,913)

             $  (15,018)


Operating Activities
Net cash used in operating activities for the year ended December 31, 2020, was
$73.1 million, primarily due to our net loss of $93.7 million. This was
partially offset by non-cash charges, including stock-based compensation expense
of $8.5 million, depreciation expense of $2.0 million, lease expense of $2.0
million and reduction in working capital of $7.8 million.
Net cash used in operating activities for the year ended December 31, 2019,
was $72.0 million, primarily due to our net loss of $85.5 million. This was
partially offset by non-cash charges, including stock-based compensation expense
of $8.2 million, depreciation expense of $1.8 million, and reduction in working
capital of $3.5 million.
Investing Activities
Net cash used in investing activities for the year ended December 31, 2020, was
$1.3 million, primarily due to the purchase of capital equipment.


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Net cash provided by investing activities for the year ended December 31, 2019,
was $52.0 million, primarily consisting of maturity of investments totaling
$55.0 million, slightly offset by the purchase of capital equipment totaling
$3.0 million during the year.
Financing Activities
Net cash provided by financing activities for the year ended December 31, 2020
was $65.5 million, primarily due to proceeds from issuance of commons stock
totaling $55.0 million, issuance of long-term debt under our 2019 Credit
Facility totaling $10.0 million and proceeds from the issuance of common stock
in connection with the exercise of options totaling $0.5 million.
Net cash provided by financing activities for the year ended December 31, 2019
was $5.0 million, primarily due to proceeds from the issuance of long-term debt
under our 2019 Credit Facility and proceeds from the issuance of common stock in
connection with the exercise of options totaling $0.5 million, partially offset
by the repayment of our prior debt facility.
Funding Requirements
We have incurred losses and cumulative negative cash flows from operations since
our inception. As of December 31, 2020, we had an accumulated deficit of $292.5
million. We anticipate that we will continue to incur significant losses for at
least the next several years. We expect that our research and development and
general and administrative expenses will continue to increase. As a result, we
will need additional capital to fund our operations, which we may raise through
a combination of the sale of equity, debt financings, or other sources,
including potential collaborations.
We expect our expenses to increase substantially in connection with our ongoing
development activities related to the initiation of clinical studies and
preclinical work on additional monoclonal microbial product candidates, which
are still in development, and our follow-on therapeutics and other programs. In
addition, we expect to incur additional costs associated with increased
personnel and operating as a public company. We anticipate that our expenses
will increase substantially if and as we:
•continue our proof of concept clinical trials of EDP1815;
•advance the clinical development of any additional monoclonal microbial product
candidates;
•conduct research and continue preclinical development of potential product
candidates;
•make strategic investments in manufacturing capabilities, including potentially
planning and building a small-scale commercial manufacturing facility;
•maintain our current intellectual property portfolio and opportunistically
acquire complementary intellectual property;
•seek to obtain regulatory approvals for our product candidates;
•potentially establish a sales, marketing and distribution infrastructure
and scale-up manufacturing capabilities to commercialize any products for which
we may obtain regulatory approval;
•add clinical, scientific, operational, financial and management information
systems and personnel, including personnel to support our product development
and potential future commercialization efforts and to support our transition to
a public company; and
•experience any delays or encounter any issues with any of the above, including
but not limited to failed studies, complex results, safety issues or other
regulatory challenges.
During the first quarter of 2021 we raised net proceeds of $82.2 million from
the issuance of common stock exclusive of certain other fees payable by us. We
expect that our cash and cash equivalents as of December 31, 2020 together with
the net proceeds raised in the first quarter of 2021 from the issuance of our
common stock, will enable us to fund our planned operating expenses and capital
expenditure requirements into the third quarter of 2022. Our forecast of the
period of time through which our financial resources will be adequate to support
our operations is a forward-looking statement and involves risks and
uncertainties, and actual results could vary as a result of a number of factors.
Our forecast is based on assumptions that may prove to be wrong, and we may use
our available capital resources sooner than we currently expect.

Because of the numerous risks and uncertainties associated with the development
of EDP1815 and EDP1867, any additional monoclonal microbial product candidates
or any follow-on programs and because the extent to which we may enter into
collaborations with third parties for development of these product candidates is
unknown, we are


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unable to estimate the amounts of increased capital outlays and operating
expenses associated with completing the research and development of our product
candidates. Our future capital requirements for our technology platform or our
other programs will depend on many factors, including:
•the progress and results of clinical studies of EDP1815 and EDP1867;
•the cost of manufacturing clinical supplies of our product candidates;
•the scope, progress, results and costs of preclinical development, laboratory
testing for any other potential product candidates;
•the costs, timing and outcome of regulatory review of our product candidates;
•the costs and timing of future commercialization activities, including
manufacturing, marketing, sales and distribution, for any of our product
candidates for which we receive marketing approval;
•the revenue, if any, received from commercial sales of our product candidates
for which we receive marketing approval;
•the costs and timing of preparing, filing and prosecuting patent applications,
maintaining and enforcing our intellectual property rights and defending any
intellectual property-related claims;
•the effect of competing technological and market developments; and
•the extent to which we acquire or invest in businesses, products and
technologies, including entering into licensing or collaboration arrangements
for product candidates, although we currently have no commitments or agreements
to complete any such acquisitions or investments in businesses.
Identifying potential product candidates and conducting preclinical testing and
clinical trials is a time consuming, expensive and uncertain process that takes
years to complete, and we may never generate the necessary data or results
required to obtain marketing approval and achieve product sales. In addition,
our product candidates, if approved, may not achieve commercial success. Our
commercial revenues, if any, will be derived from sales of products that we do
not expect to be commercially available for many years, if ever. Accordingly, we
will need to obtain substantial additional funds to achieve our business
objectives.
Adequate additional funds may not be available to us on acceptable terms, or at
all. To the extent that we raise additional capital through the sale of equity
or convertible debt securities, the ownership interest of existing stockholders
will be diluted, and the terms of these securities may include liquidation or
other preferences that adversely affect the rights of common stockholders.
Additional debt financing and preferred equity financing, if available, may
involve agreements that include covenants limiting or restricting our ability to
take specific actions, such as incurring additional debt, making capital
expenditures or declaring dividends and may require the issuance of warrants,
which could potentially dilute the ownership interest of existing stockholders.
The terms of our 2019 Credit Facility with K2HV preclude us from paying
dividends on our equity securities without their consent. If we lack sufficient
capital to expand our operations or otherwise capitalize on our business
opportunities, our business, financial condition and results of operations would
be materially adversely affected.
If we raise additional funds through collaborations, strategic alliances or
licensing arrangements with third parties, we may have to relinquish valuable
rights to our technologies, future revenue streams, research programs, or
product candidates or grant licenses on terms that may not be favorable to us.
If we are unable to raise additional funds through equity or debt financings
when needed, we may be required to delay, limit or terminate our product
development programs or any future commercialization efforts or grant rights to
develop and market product candidates to third parties that we would otherwise
prefer to develop and market ourselves.
Contractual Obligations and Commitments
We are a smaller reporting company, as defined by Rule 12b-2 of the Exchange
Act, and are not required to provide this information.

Off-Balance Sheet Arrangements
As of December 31, 2020, we did not have, and we do not currently have, any
off-balance sheet arrangements, as defined in the rules and regulations of the
SEC.


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Critical Accounting Policies and Use of Estimates
Our management's discussion and analysis of financial condition and results of
operations are based on our consolidated financial statements which are prepared
in accordance with generally accepted accounting principles, or GAAP, in the
United States of America. The preparation of our consolidated financial
statements and related disclosures requires us to make estimates and assumptions
that affect the reported amount of assets, liabilities, revenue, costs and
expenses, and related disclosures. We believe that the estimates and assumptions
involved in the accounting policies described below may have the greatest
potential impact on our consolidated financial statements and, therefore,
consider these to be our critical accounting policies. We evaluate our estimates
and assumptions on an ongoing basis using historical experience, known trends
and events and various other factors that are believed to be reasonable under
the circumstances, the results of which form the basis for making judgments
about the carrying values of assets and liabilities that are not readily
apparent from other sources. Our actual results may differ from these estimates
under different assumptions and conditions.
Accrued Research and Development Expenses
As part of the process of preparing our consolidated financial statements, we
are required to estimate our accrued research and development expenses. This
process involves reviewing open contracts and purchase orders, communicating
with our personnel to identify services that have been performed on our behalf
and estimating the level of service performed and the associated costs incurred
for the services when we have not yet been invoiced or otherwise notified of the
actual costs. The majority of our service providers invoice us in arrears for
services performed, on a pre-determined schedule or when contractual milestones
are met; however, some require advanced payments. We make estimates of our
accrued expenses as of each balance sheet date in our consolidated financial
statements based on facts and circumstances known to us at that time. Examples
of estimated accrued research and development expenses include fees paid to:
•CROs in connection with performing research services on our behalf including,
but not limited to, clinical trials and preclinical studies;
•investigative sites and other providers in connection with clinical trials and
preclinical studies;
•other research and development service providers such as academic institutions
and laboratory services providers in connection with discovery, preclinical and
clinical development activities; and
•vendors related to product manufacturing, development and distribution of
clinical supplies.
We base our expenses related to clinical trials and preclinical studies on our
estimates of the services received and efforts expended pursuant to quotes and
contracts with multiple CROs, investigative sites, laboratories and other
providers that conduct and manage those studies on our behalf. The financial
terms of these agreements are subject to negotiation, vary from contract to
contract and may result in uneven payment flows. There may be instances in which
payments made to our vendors will exceed the level of services provided and
result in a prepayment of the clinical expense. Payments under some of these
contracts depend on factors such as the successful enrollment of patients and
the completion of milestones. In accruing service fees, we estimate the time
period over which services will be performed, enrollment of patients, number of
sites activated and the level of effort to be expended in each period. If the
actual timing of the performance of services or the level of effort varies from
our estimate, we adjust the accrual or amount of prepaid expense accordingly.
Although we do not expect our estimates to be materially different from amounts
actually incurred, our understanding of the status and timing of services
performed relative to the actual status and timing of services performed may
vary and may result in us reporting amounts that are too high or too low in any
particular period. To date, we have not made any material adjustments to our
prior estimates of accrued research and development expenses.
Stock-Based Compensation
We measure stock options and other stock-based awards granted to employees and
directors based on the fair value on the date of grant and recognize the
corresponding compensation expense of those awards over the requisite service
period, which is generally the vesting period of the respective award.
Generally, we issue stock options and restricted stock awards with only
service-based vesting conditions and record the expense for these awards using
the straight-line method, adjusting for pre-vesting forfeitures in the period in
which the forfeitures occur. We measure stock-based awards granted to
consultants and non-employees based on the fair value of the award on the date
of the grant. Compensation expense is recognized over the period during which
services are rendered by such consultants and non-employees until completed.
Prior to January 1, 2020, we accounted for these awards in accordance with the
provisions of ASC Subtopic 505-50, Equity-Based Payments to Non-employees ("ASC
505-50"). Under ASC 505-50, share-based awards to nonemployees were subject to
periodic fair value re-measurement at the end of each financial reporting period
prior to completion of the service.


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As discussed in Note 2 (Significant Accounting Policies) to our consolidated
financial statements included elsewhere in this Annual Report on Form 10-K under
the heading "New Accounting Pronouncements - Adopted during the current period,"
we adopted ASU No. 2018-07, Stock-based Compensation: Improvements to
Nonemployee Share-based Payment Accounting (Topic 718), on January 1, 2020. As a
result, our accounting for nonemployee awards is now generally consistent with
that of employee awards. Beginning on January 1, 2020, the measurement date for
nonemployee awards is the date of grant without any subsequent changes in the
fair value of the award.

We estimate the fair value of each stock option grant using the Black-Scholes
option-pricing model. Use of this model requires that we make assumptions as to
the volatility of our common stock, the expected term of our stock options, the
risk-free interest rate for a period that approximates the expected term of our
stock options, and our expected dividend yield. Prior to May 2018, we were a
privately-held company with limited operating history and no company-specific
historical and implied volatility information and accordingly, we estimate our
expected volatility based on the historical volatility of a group of publicly
traded peer companies. We expect to continue to do so until such time as we have
adequate historical data regarding the volatility of our traded stock price. We
use the simplified method prescribed by SEC Staff Accounting Bulletin No. 107,
Share-Based Payment, to calculate the expected term of options granted to
employees and directors. We base the expected term of options granted to
consultants and non-employees on the contractual term of the options. We
determine the risk-free interest rate by reference to the U.S. Treasury yield
curve in effect at the time of grant of the award for time periods approximately
equal to the expected term of the award. Expected dividend yield is based on the
fact that we have never paid cash dividends and do not expect to pay any cash
dividends in the foreseeable future.

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