UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
(Mark One)
☒
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2021
OR
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD
FROM TO
Commission File Number 001-38470
Unity Biotechnology, Inc.
(Exact name of Registrant as specified in its Charter)
Delaware
( State or other jurisdiction of
incorporation or organization)
285 East Grand Ave.
South San Francisco, CA
(Address of principal executive offices)
26-4726035
(I.R.S. Employer
Identification No.)
94080
(Zip Code)
Registrant’s telephone number, including area code: (650) 416-1192
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Common Stock, par value $0.0001
Trading Symbol(s)
UBX
Name of each exchange on which registered
The Nasdaq Global Select Market
Indicate by check mark if the Registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. YES ☐ NO ☒
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the Registrant is not required to file reports pursuant to Section 13 or 15(d) of the Act. YES ☐ NO ☒
Indicate by check mark whether the Registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding
12 months (or for such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. YES ☒ NO ☐
Indicate by check mark whether the Registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of
this chapter) during the preceding 12 months (or for such shorter period that the Registrant was required to submit such files). YES ☒ NO ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company.
See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer
Non-accelerated filer
Emerging growth company
Accelerated filer
Smaller reporting company
☐
☒
☒
☐
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If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial
accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the Registrant has filed a report on and attestation to its management assessment of the effectiveness of its internal control over financial reporting
under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐
Indicate by check mark whether the Registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). YES ☐ NO ☒
The aggregate market value of the voting and non-voting common equity held by non-affiliates of the Registrant, based on the closing price of the shares of common stock on The
Nasdaq Global Select Market on June 30, 2021 was $202,106,452.
The number of shares of Registrant’s Common Stock outstanding as of March 10, 2022 was 68,927,851.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the Registrant’s Definitive Proxy Statement relating to the 2022 Annual Meeting of Shareholders, scheduled to be held on [June 24], 2022, are incorporated by reference
into Part III of this Report. Such proxy statement will be filed with the Securities and Exchange Commission within 120 days of the end of the fiscal year covered by this Annual
Report on Form 10-K.
PART I
Item 1.
Item 1A.
Item 1B.
Item 2.
Item 3.
Item 4.
PART II
Item 5.
Item 6.
Item 7.
Item 7A.
Item 8.
Item 9.
Item 9A.
Item 9B.
Item 9C.
PART III
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
PART IV
Item 15.
Item 16.
Table of Contents
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
[Reserved]
Management’s Discussion and Analysis of Financial Condition and Results of Operations
Quantitative and Qualitative Disclosures About Market Risk
Financial Statements and Supplementary Data
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure
Controls and Procedures
Other Information
Disclosure Regarding Foreign Jurisdictions that Prevent Inspections
Directors, Executive Officers and Corporate Governance
Executive Compensation
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Certain Relationships and Related Transactions, and Director Independence
Principal Accounting Fees and Services
Exhibits, Financial Statement Schedules
Form 10-K Summary
Signatures
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Forward-Looking Statements
This Annual Report on Form 10-K contains “forward-looking statements” within the meaning of Section 21E of the Securities Exchange Act of
1934, as amended, or the Exchange Act. All statements other than statements of historical facts contained in this Annual Report on Form 10-K are
statements that could be deemed forward-looking statements reflecting the current beliefs and expectations of management with respect to future events or
to our future financial performance and involve known and unknown risks, uncertainties, and other factors that may cause our actual results, performance
or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements.
These statements are often identified by the use of words such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “due,”
“estimate,” “expect,” “goal,” “if,” “intend,” “may,” “objective,” “plan,” “predict,” “potential,” “positioned,” “seek,” “should,” “target,” “will,” “would,”
“until,” and similar expressions or variations. Forward-looking statements contained in this Annual Report on Form 10-K include, but are not limited to,
statements about:
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our expectations regarding the potential benefits, activity, effectiveness, and safety of our drug candidates;
our expectations with regard to the results of our clinical studies, preclinical studies, and research and development programs, including the
timing and availability of data from such studies;
our preclinical, clinical, and regulatory development plans for our drug candidates, including the timing or likelihood of regulatory filings and
approvals for our drug candidates;
our expectations with regard to our ability to acquire, discover, and develop additional drug candidates and advance such drug candidates into,
and successfully complete, clinical studies;
our expectations regarding the potential market size and size of the potential patient populations for our drug candidates, if approved for
commercial use;
our intentions and our ability to establish collaborations and/or partnerships;
the timing and amount of any milestone payments we are obligated to make pursuant to our existing license agreements and any future license or
collaboration agreements that we may enter into;
our commercialization, marketing, and manufacturing capabilities and expectations;
our intentions with respect to the commercialization of our drug candidates;
the pricing and reimbursement of our drug candidates, if approved;
the implementation of our business model and strategic plans for our business and drug candidates, including additional indications which we
may pursue;
the scope of protection we are able to establish and maintain for intellectual property rights covering our drug candidates, including the projected
terms of patent protection;
estimates of our expenses, future revenue, capital requirements, our needs for additional financing, and our ability to obtain additional capital;
developments and projections relating to our competitors and our industry, including competing therapies; and
other risks and uncertainties, including those listed under the caption “Risk Factors.”
We caution you that the foregoing list may not contain all of the forward-looking statements made in this Annual Report on Form 10-K.
Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or
achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. We
discuss these risks in greater detail in “Risk Factors” and elsewhere in this Annual Report on Form 10-K. Given these uncertainties, you should not place undue
reliance on these forward-looking statements. Also, forward-looking statements represent our management’s beliefs and assumptions only as of the date of this
Annual Report on Form 10-K. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the
reasons actual results could differ
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materially from those anticipated in these forward-looking statements, even if new information becomes available in the future.
This Annual Report on Form 10-K also contains estimates, projections, and other information concerning our industry, our business and the
markets for certain drugs, including data regarding the estimated size of those markets, their projected growth rates, and the incidence of certain medical
conditions. Information that is based on estimates, forecasts, projections or similar methodologies is inherently subject to uncertainties, and actual events or
circumstances may differ materially from events and circumstances reflected in this information. Unless otherwise expressly stated, we obtained this
industry, business, market, and other data from reports, research surveys, studies, and similar data prepared by third parties, industry, medical and general
publications, government data, and similar sources. In some cases, we do not expressly refer to the sources from which this data is derived. In that regard,
when we refer to one or more sources of this type of data in any paragraph, you should assume that other data of this type appearing in the same paragraph
is derived from the same sources, unless otherwise expressly stated or the context otherwise requires.
Trademarks
This Annual Report on Form 10-K includes trademarks, service marks, and trade names owned by us or other companies. All trademarks, service
marks and trade names included in this Annual Report on Form 10-K are the property of their respective owners.
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PART I
Item 1. Business.
Overview
Our mission is to slow, halt, or reverse diseases of aging. Our initial focus is on creating senolytic medicines to selectively eliminate senescent
cells and thereby treat diseases of aging, such as ophthalmologic diseases, with the opportunity to explore neurology and other therapeutic areas.
Diseases of aging cause considerable economic, personal, and societal burden. As individuals age, the prevalence of chronic disease increases,
with 80% of older Americans having at least one chronic disease and 50% having two or more. Diseases of aging negatively impact quality of life, are
typically chronic, and progress from the time of onset until death. It is estimated that providing healthcare for people over the age of 65 costs four to five
times more than for younger individuals. According to the United States Census Bureau, this elderly population of Americans is expected to increase nearly
50% by 2050, increasing the economic burden of aging dramatically. Any success increasing longevity without treating underlying diseases of aging would
only serve to increase this burden.
We believe that by creating medicines that target fundamental aging mechanisms, we can reduce the economic, personal, and societal burden of
aging and enhance quality of life.
In February 2022, we announced a restructuring to align resources to focus on our ongoing clinical programs and deliver on key development
milestones. These actions to prioritize our ophthalmology programs and implement cost saving measures were designed to enable us to achieve multiple
key clinical data readouts for UBX1325 as well as support the Tie2 and Tie2/VEGF bispecific program through advanced candidate nomination, with all
other pipeline programs paused to focus resources on these advanced programs.
Targeting Cellular Senescence and Other Biologies of Aging
We believe that the accumulation of senescent cells is a fundamental mechanism of aging and a driver of many common diseases of aging.
Cellular senescence is a natural biological state in which a cell permanently halts division. These cells are referred to as senescent. Senescent cells
accumulate with age, secreting large quantities of more than 100 proteins, including inflammatory factors, proteases, fibrotic factors, and growth factors,
that disturb the tissue micro-environment. This collection of secreted proteins is referred to as the Senescence Associated Secretory Phenotype, or SASP. In
addition to its effects on tissue function, the SASP contains factors that induce senescence in neighboring cells, setting off a cascade of events that
culminates in the formation of the functionally aged and/or diseased tissue that underlies a variety of age-related diseases.
We are developing senolytic medicines to eliminate senescent cells and thereby lower the production of the SASP, which we believe addresses a
root cause of age-related diseases. Many existing therapeutics, such as antibodies, target single SASP factors, but fail to remove the cells that continually
produce these factors. By stopping the production of the SASP at it source, we believe senolytic medicines could have a more durable impact by slowing,
halting, or reversing particular diseases of aging, and shift the treatment paradigm from chronic to intermittent dosing. Less frequent dosing may also
improve drug tolerability and patient adherence.
While our primary focus is on programs targeting cellular senescence, we are exploring other biologies of aging that may have a major impact on
diseases of aging. For instance, we have a preclinical program targeting Tie2 signaling. Tie2 is a receptor tyrosine kinase that is implicated in regulating
barrier function in blood vessels of the eye, which are affected in several prevalent eye diseases. Tie2 is also implicated in kidney disease. We also have a
preclinical program targeting both Tie2 and VEGF (Tie2/VEGF bispecific) designed to neutralize VEGF and activate Tie2, two major pathways involved in
retinal disease. We have outlicensed our program in α-Klotho, a protein that has been implicated in human cognition and may provide benefits in age-
related cognitive dysfunctions.
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Our Pipeline
We are targeting specific biological mechanisms implicated in diseases of aging. Our core therapeutic approach targets cellular senescence, and
we are currently advancing senolytic programs primarily in ophthalmologic disorders. In addition, we are advancing other programs based on other
biologies of aging to include an agonistic antibody to the Tie2 receptor and a Tie2/VEGF bispecific to treat vascular eye disease.
Ophthalmology Program
UBX1325 is our most advanced lead drug candidate for age-related diseases of the eye, including diabetic macular edema, or DME, age-related
macular degeneration, or AMD, and diabetic retinopathy, or DR. UBX1967 is our back-up compound to UBX1325. Each of these drug candidates are
potent small molecule inhibitors of Bcl-xL, a member of the Bcl-2 family of apoptosis regulating proteins, and has shown distinct tissue residence time
profiles in preclinical studies. UBX1325 and UBX1967 are designed to inhibit the function of proteins that senescent cells rely on for survival. In our
preclinical studies, we have demonstrated that targeting Bcl-xL with UBX1325 and UBX1967 preferentially eliminated senescent cells from diseased tissue
while sparing cells in healthy tissue. In July 2020, we filed an Investigational New Drug application, or IND, to commence a Phase 1 study of UBX1325.
In October 2020, we dosed our first patient in a Phase 1 clinical study of UBX1325 to evaluate ocular and systemic safety and tolerability of a single
intravitreal injection of UBX1325 by the incidence of dose limiting toxicities and treatment emergent adverse events reported up to 24 weeks after
administration. Based on prospectively determined safety criteria, the Phase 1 study was able to dose-escalate beyond the originally planned 5 mcg dose up
to 10 mcg, which informed the final dose for the Phase 2a study in DME. In July 2021, we announced positive 8-week data from this Phase 1 study of
UBX1325 in patients with DME and nAMD for whom anti-VEGF therapy was no longer considered beneficial. On October 5, 2021 we announced 12-
week data, on November 9, 2021 we announced 24-week data, and on February 14, 2022 we announced 24-week data from an additionally-enrolled cohort
of patients with AMD. UBX1325 was well-tolerated with no signs of intraocular inflammation or other related ocular adversities, and no dose-limiting
toxicities or adversities that preclude advancing UBX1325 into later stage clinical development. In DME, following a rapid improvement in BCVA, a mean
improvement of 9.5 ETDRS letters from baseline at 6 months in the higher dose cohorts (5, 10 mcg) and 6.9 ETDRS letters from baseline at 6 months in all
dose cohorts was observed. In AMD, following a rapid improvement in BCVA, there were improvements or stabilization of both BCVA and CST through 6
months post-injection. In both diseases, the majority of patients treated with UBX1325 showed durable improvement in vision and did not meet objective
rescue criteria requiring standard of care anti-VEGF treatment. Among patients who received anti-VEGF rescue, there was minimal change in either mean
BCVA or CST following treatment in all but one AMD patient.
In May 2021, we initiated our Phase 2a proof-of-concept study to evaluate the safety, efficacy, and durability of a single intravitreal injection of
UBX1325 in a broader population of patients with DME and dosed our first patient in June 2021. Approximately 62 patients will be enrolled, randomized
evenly between UBX1325 and sham-injected patients. An analysis of 12-week safety and efficacy data is expected by mid-2022, and patients will continue
to be followed through 48 weeks post-treatment in a long-term follow-up. Endpoints being explored in the study include safety and tolerability, changes in
BCVA, CST, SRF/IRF, proportion of patients requiring rescue treatment, and durability of effects.
In March 2022 we also enrolled our first patient in our Phase 2 proof-of-concept study in wet, or neovascular, AMD. This study is expected to
randomize 46 patients with wet AMD who have had at least three intravitreal injections of anti-VEGF therapy in the preceding six months and who have
residual sub- or intra-retinal fluid. Patients will have received their last anti-VEGF treatment approximately 4-8 weeks prior to screening, and all patients
will be followed for approximately 24 weeks after dosing with either UBX1325 or aflibercept. We expect to share 16-week data from this Ph2 study in wet
AMD in the fourth quarter of 2022.
Under our current amended license agreement with Ascentage Pharma Group Corp. Limited, or Ascentage, we have, among other things,
exclusive worldwide development and commercialization rights and non-exclusive manufacturing rights to UBX1325 outside of Greater China (China,
Hong Kong, Macau and Taiwan) in all non-oncology indications. Inside Greater China, we will be obligated to develop, manufacture and commercialize
UBX1325 through a joint venture with Ascentage. See “—Licenses and Collaborations.”
We also have a Tie2/VEGF bispecific program. Tie2 is a receptor tyrosine kinase that is implicated in regulating barrier function in blood vessels
of the eye, which are affected in several prevalent eye diseases. Tie2 is an important key regulator of the vascular endothelium in the eye and dysregulation
of this pathway leads to loss of
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barrier integrity and healthy vasculature. Preliminary studies suggest that cellular senescence in aging eyes may induce Ang-2 and therefore deactivate
Tie2, leading ocular edema.
The Tie2/VEGF bispecific has dual functionality on two validated targets for retinal diseases. In addition to direct activation of Tie2, the
bispecific candidate is designed to neutralize VEGF-A and VEGF-B. We believe that direct agonism of Tie2 may be superior to antagonism of Ang2 which
relies on adequate levels of endogenous Ang1 to activate the Tie2 pathway. We have identified Tie2/VEGF bispecific molecules that have pharmacological
activity on Tie2 and VEGF with potencies relevant for clinical benefit. Based on supporting preclinical data, we expect to designate an Advanced
Candidate by mid-2022. We also seek to initiate pilot preclinical toxicology experiments to support nomination of a Development Candidate that should
enable initiation of IND-enabling studies in the second half of 2023.
UBX2050 is our investigational, fully human anti-Tie2 agonist monoclonal antibody. Tie2 dysregulation is implicated in eye disease as well as
other indications. UBX2050 is derived from an asset that was acquired from Achaogen, Inc. in June 2020 through an Asset Purchase Agreement. UBX2050
was selected based on its potential to activate the Tie2 receptor in vitro and has demonstrated encouraging activity in preclinical models of ocular disease.
We believe UBX2050 may be an orthogonal approach to restoring barrier function and vascular function and are exploring a number of indications for
UBX2050, expecting to nominate a Development Candidate in 2022.
Neurology Program
We believe cellular senescence may play a fundamental role in neurodegeneration. Multiple lines of evidence suggest that senescent cells
accumulate in the nervous system during normal aging and neurodegenerative diseases. Several third-party preclinical proof of concept studies in mouse
models of aging and neurodegeneration have provided preliminary evidence that the removal of senescent cells via senolytic drugs or genetic methods have
the potential to improve brain function.
UBX2089, an α-Klotho hormone drug candidate, is a circulating hormone primarily produced in the kidneys and choroid plexus of the brain,
which is being researched for multiple neurology indications. Human genetic evidence links α-Klotho to cognitive function, and we have observed pro-
cognitive activity of recombinant α-Klotho in multiple preclinical rodent and non-human primate models. Our work focused on investigating the effect of
UBX2089 on engaging CNS circuits in preclinical animal models with the intent of advancement to clinical studies, and in December 2021, we announced
an exclusive licensing agreement of our α-Klotho asset to Jocasta Neuroscience, Inc. for development and commercialization.
Our Approach to Slowing, Halting, or Reversing Diseases of Aging
Targeting Cellular Senescence
Cellular senescence is a natural biological state in which a cell permanently halts division. Cells become senescent when they experience some
form of unresolvable cellular stress. These cellular stress events result in the activation of the tumor suppressor protein p53, which drives the production of
two cell-cycle dependent kinase inhibitors, or CDK inhibitors, p21 and p16. These two molecules are required for the establishment and subsequent
maintenance of the senescent cell state. The first CDK inhibitor to be produced is p21, which works through subsequent pathways to block the production
of numerous proteins that cells need to divide. The initial p21-driven signal is an acute response to cell damage and eventually decreases. In contrast, p16
permanently locks the cell into a non-dividing state and the production of p16 continues as long as the cell lives. Given that p16 production, in most cases,
continues indefinitely and is believed to be produced almost exclusively in senescent cells, it is a widely used marker to identify and quantify senescent
cells.
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The process through which stress mechanisms can induce cells to become senescent is illustrated in the figure below.
Figure 1: Illustration of induction of the senescent state and secretion of factors that can damage the microenvironment
How Senescent Cells Drive Diseases of Aging
Once cells become senescent, they begin secreting large quantities of proteins, including pro-inflammatory factors that recruit the immune
system, proteases that remodel the extra-cellular matrix, pro-fibrotic factors that drive the formation of dysfunctional matrix, and growth factors that
perturb the function of the tissue micro-environment. This collection of secreted proteins is referred to as the Senescence Associated Secretory Phenotype,
or SASP. In addition to affecting normal tissue function, the SASP contains factors that induce senescence in neighboring cells, setting off a cascade of
events that ultimately culminates in the formation of a functionally aged and/or diseased tissue that underlies a variety of age-related diseases.
Numerous SASP factors have been implicated as potentially contributing to human disease and it is now believed that the SASP is the primary
means by which senescent cells drive specific diseases of aging. For example, a variety of single SASP factors (e.g., TNF-α and VEGF-A) have been
demonstrated to drive human diseases by themselves and have been the target of well-known antibody therapeutics, including HUMIRA® and EYLEA®.
While these antibodies are able to modify human disease by removing the activity of a single factor, we believe the clearance of senescent cells will remove
the source of numerous SASP factors, providing improvement in both efficacy and duration-of-effect.
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Our Therapeutic Paradigm
We were founded on the principle that the selective elimination of senescent cells and their accompanying SASP has the potential to slow, halt,
or reverse diseases of aging. Our insights into senescent cell biology allow us to identify senescence-driven diseases, target the senescent cells driving a
particular disease, and selectively eliminate these cells. The figure below illustrates this process.
Figure 2: Illustration of the senolytic therapeutic hypothesis
In developing this approach, we have acquired significant expertise with respect to senescent cell survival pathways, which are the signaling
systems that senescent cells rely on for survival. When these pathways are targeted with specifically designed molecules, senescent cells undergo
programmed cell death. Through our research, we have identified several of these mechanistically distinct survival pathways, which differ depending on
cell type and the tissue in which the senescent cells reside.
Advantages of Our Approach
We believe that senolytic medicines that selectively eliminate senescent cells from diseased tissues may have several advantages over other
efforts to treat diseases of aging:
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Senolytic medicines target a root cause of diseases of aging. We believe that the accumulation of senescent cells is a root cause of many
diseases of aging. Unlike treatments that inhibit the activity of a single factor (such as antibodies targeting single pro-inflammatory proteins), we
believe a senolytic medicine that eliminates accumulated senescent cells and consequently also their associated SASP, could blunt the activity of
numerous factors contributing to disease. As a result, senolytic medicines could have improved efficacy because they target diseases at their
source and therefore may be able to normalize tissue levels of numerous disease-causing factors simultaneously.
Senolytic medicines can be dosed intermittently. The administration of senolytic medicines would remove senescent cells from diseased
tissue. As new senescent cells may take months or perhaps years to re-accumulate, senolytic medicines could potentially be dosed infrequently.
Intermittent dosing may also improve drug tolerability and patient adherence when compared to chronic therapies.
Senolytic medicines restore tissues to a healthy state. We believe senescent cells generally do not accumulate in young individuals and that the
accumulation of senescent cells in older individuals interferes with normal tissue function. Our goal for the administration of senolytic medicines
is to restore tissue to a functionally younger state.
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Ophthalmology Programs Targeting Cellular Senescence
Unmet Need and Therapeutic Rationale
Our Programs
The majority of significant eye diseases are age-related, with the prevalence of vision-threatening disease increasing significantly over the age of
75. Of the 285 million individuals worldwide living with visual impairment, 65% are over the age of 50. The individual diseases that are associated with
these figures include age-related macular degeneration, diabetic macular edema, and diabetic eye diseases, all of which have a high prevalence and
significant unmet need in either prevention or therapeutic options. The diseases we are evaluating as initial target indications for local administration of
senolytic therapy in the eye are age-related macular degeneration, diabetic macular edema, and diabetic retinopathy.
Diabetic Macular Edema
Diabetic macular edema is a condition in which the metabolic abnormalities associated with diabetes, including high levels of blood glucose, or
hyperglycemia, damage blood vessels in the central portion of the retina, or the macula, causing those vessels to leak fluid. The leaking fluid leads to
swelling and subsequently to abnormalities of vision. The prevalence of diabetic macular edema, or DME, in the United States ranges from approximately
4.0% to 6.8% of people with diabetes who are 40 years of age or older. In 2019, it was estimated that more than 20 million people worldwide are affected
by DME. There is a high burden of DME among non-Hispanic blacks and robust associations with higher hemoglobin A1c and longer duration of
underlying diabetes.
Despite the success achieved with anti-VEGF treatment for retinal disease like AMD that involve the proliferation of abnormal blood vessels, or
neovascularization, the impact of such treatment in DME has been more limited. This is due to the challenging nature of the therapeutic regimen (which
entails monthly and or bimonthly IVT injections for up to two years), the number of cases that are refractory to anti-VEGF treatment (approximately 50%
of DME patients), and the long-term complications of increased ischemia and retinal fibrosis associated with long-term treatment with anti-VEGF
injections. As a result, there is an unmet need in this group of patients. Although VEGF has been identified as a major factor for neovascular disease, other
factors, which we believe include SASP factors, are present in DME, including IL-1ß, TNF-a, IL-6, and TGF-ß, among others. Due to the multifactorial
nature of the disease, a significant opportunity exists to develop a more comprehensive approach to the treatment of DME, such as senolysis, that targets
the root cause of the disease.
Age-Related Macular Degeneration
Age-related macular degeneration, or AMD, is the leading cause of irreversible vision loss in developed countries, particularly in people older
than 60 years. In 2014, it was projected that by 2020 the number of people worldwide with AMD would be 196 million and could increase to 288 million
by 2040. The prevalence of AMD increases significantly with advancing age, with a prevalence rate of 1.63% in those aged 65 to 69 years which increases
to 11.73% in those aged 80 years or older. AMD affects central vision, impairing functions such as reading, driving, and facial recognition, and has a major
impact on quality of life and the ability to live independently. AMD is defined in three stages: (i) “early,” in which visual function is affected in the
presence of signs of age-related changes in the retina such as drusen and pigmentary changes; (ii) “intermediate,” in which increasing degrees of macular
lipid deposition and structural changes are noted; and (iii) “late,” in which central vision is compromised due to abnormal blood vessel growth (known as
“wet” AMD) or advanced atrophy of the retina (known as “dry” AMD). AMD is a heterogenous, complex, multifactorial disease, with inflammatory,
degenerative, genetic, and vascular factors all contributing to its development and progression. The potential role of senescent cells and the associated
SASP in driving the two main presentations of the disease, both wet and dry forms, could prove a unifying mechanism across this complex disorder.
Current standard of care for AMD is the administration of anti-vascular endothelial growth factor, or anti-VEGF, antibody drugs which control
aspects of the wet form of the disease only. The development of therapeutic options for dry AMD has proven to be challenging and currently there are no
approved therapies available to halt
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progression or reverse disease. And while wet AMD has been significantly impacted by anti-VEGF therapy, that approach is limited by the need for
frequent eye injections over a long period of time, a significant percentage of patients not completing or being non-responsive or poorly-responsive to anti-
VEGF therapy, and the contribution of multiple other mechanisms at play in the disease beyond VEGF. Thus, there is considerable potential for a senolytic
approach to impact disease progression and achieve stabilization in AMD via modulation of senescent cell burden and the accompanying SASP. SASP
factors in AMD include molecules that promote abnormal blood vessel growth, inflammation, and fibrosis, all of which have been implicated in various
stages of the disease. We believe that a senolytic medicine could have a meaningful and prolonged impact on the AMD disease state and help restore the
cellular microenvironment to a more normal, pre-senescent state.
Diabetic Retinopathy
Diabetic retinopathy, or DR, is estimated to affect over 90 million people globally and approximately 28 million have vision-threatening stages of
disease. It is a leading cause of vision loss in middle-aged and elderly people and impacts 8% of the U.S. population over age 65. Due to the increasing
diabetic population arising from lifestyle changes in developing countries, the disease incidence is predicted to climb.
Diabetic retinopathy is a complex multifactorial disease, characterized by progression through a series of stages of increasing severity. The
metabolic abnormalities associated with diabetes incite a variety of inflammatory and metabolic stress-induced events which leads to proliferation of new
blood vessels and subsequent bleeding and swelling, which in turn causes scarring and vision loss or may lead to blood vessel occlusion, limiting blood
flow and leading to damage to the retinal photoreceptors and nerves supplied by those vessels. The risk of developing diabetic retinopathy and its severity
increase with the duration of underlying diabetes. It is also associated with poor glycemic control and the presence of additional coexistent diseases, such as
high blood pressure, high cholesterol levels, and impaired kidney function.
Current standard of care for diabetic retinopathy, which includes blood sugar control, anti-VEGF drugs, steroid injections, and laser therapy, is
modestly effective. The limitations of existing therapy include general challenges with achieving diabetes control, the need for frequent intravitreal
injections for the administration of anti-VEGF therapy, a significant percentage of patients not completing or being non-responsive to anti-VEGF therapy,
and tissue destruction with permanent side effects from laser therapy. This presents a significant opportunity to design and develop a treatment paradigm,
such as senolysis, that treats a root cause of the disease.
Evidence suggests that diabetic retinopathy is driven by the accumulation of senescent cells that are a direct result of elevated glucose levels in
patients with diabetes. These senescent cells are triggered by local stresses in the retina and their accumulation drives the production of the accompanying
ocular SASP factors, VEGF and platelet-derived growth factor, or PDGF. Overproduction of VEGF and IL-6 leads to ocular inflammation and abnormal
blood vessel growth, key signatures of diabetic retinopathy. Thus, a senolytic approach could target multiple aspects of the underlying causes of diabetic
retinopathy and ideally lead to greater therapeutic coverage in a wider range of patients. This elimination of senescent cell accumulation and accompanying
SASP factors could limit further disease progression, reduce vessel leakage and inflammation, and prevent vision loss.
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Evidence for Senescence Burden in Human Disease and Human Biomarker Discovery: AMD, DR and DME
We evaluated the presence of senescent cells by IHC staining for p16 in post-mortem retinal donor tissue from individuals who carried a pre-
mortem diagnosis of AMD, DR/DME, or neither. We believe the resulting data support our hypothesis that the accumulation of senescent cells is linked to
AMD and DR/DME. Quantification of IHC images indicated a significant increase in senescent cell burden (as measured by p16+ cells) in both AMD and
DR patient globes (Figure 3).
Figure 3: Quantification of senescent cell burden in AMD and DR/DME
We also compared the presence of senescence in human retinal microvascular endothelial cells, or HRMEC, versus retinal donor tissue from
human DME/DR patients by evaluating the gene expression of several disease-relevant factors. Quantitative polymerase chain reaction, or qPCR,
demonstrated elevations in the SASP factors VEGF, PDGF, IL1B, and TNF in senescent HRMEC, relative to non-senescent cells. These disease-relevant
mediators have been reported to be elevated in DME/DR patients. We believe this data is consistent with our hypothesis that senescent cell accumulation
and SASP factors play a central role in both DME and DR.
Mechanism of Action of UBX1325 (Inhibitors of the Bcl-2 Family)
UBX1325, our lead drug candidate (along with our backup compound in our ophthalmology program, UBX1967) is a potent small molecule
inhibitor of specific members of the Bcl-2 family of apoptosis regulating proteins. The B-cell lymphoma 2, or Bcl-2, gene family encodes more than 20
proteins that regulate the intrinsic apoptosis pathway and are fundamental to the balance between cell survival and cell death. Inhibition of certain Bcl-2
family proteins results in cell death in certain cell types. Targeting this pathway has been studied extensively in connection with the search for new
oncology medicines.
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In Vitro and In Vivo Pharmacology Studies with UBX1325
We conducted an in vitro assessment of binding and efficacy of UBX1325 to determine both its potency for the Bcl-2 family protein targets and
its potency at eliminating senescent cells. Biochemical assays for Bcl-2, Bcl-xL, and Bcl-w yielded binding affinities in the sub-nanomolar range.
UBX1325 is a phosphate pro-drug that releases the active parent molecule known as UBX0601. In order to assess the activity of UBX0601 on senescent
cells, we used a cell-based assay with radiation-induced senescence. Senescent cells were exposed to increasing concentrations of UBX0601 for 72 hours.
In this study, UBX0601 showed potent, concentration-dependent senolytic activity against human foetal lung cells, or IMR90, primary human umbilical
vein endothelial cells, or HUVEC, and HRMEC as measured by reduction of senescent cell survival. UBX0601 also demonstrated selectivity for
elimination of senescent HRMEC over non-senescent HRMEC which is observed as decreased potency in the non-senescent HRMEC (Figure 4).
Figure 4: Concentration- dependent induction of apoptosis in HRMEC cells by UBX0601 in vitro
We next studied the effects of UBX1325 in the retina in an in vivo model. We employed the mouse oxygen-induced retinopathy, or OIR, model,
which provides an in vivo model of retinopathy of prematurity, or ROP, and DR. In this model, UBX1325 demonstrated a statistically significant
improvement in the degree of retinal neovascularization (Figure 5).
Figure 5: Intravitreal injection of UBX1325 reduced retinal neovascularization in the mouse OIR model
Based on these results in this key OIR model, we believe a single ocular injection of UBX1325 has the potential to functionally inhibit
neovascularization and promote vascular repair. We believe the efficacy of UBX1325 in this OIR model is due to elimination of senescent cells and
accompanying SASP that propagates senescence in retinal cells and promotes neovascularization of retinal vessels.
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We then studied the in vivo efficacy of UBX1325 in a streptozotocin-induced diabetic mouse, or STZ, model to understand its effects in a
diabetic retina, which shows phenotypes similar to the human diseased condition. In this STZ model, UBX1325 demonstrated a significant reduction in
vascular leakage as measured by Evans Blue dye permeation (Figure 6A). UBX1325 also demonstrated an improvement in the electroretinogram, or ERG,
as a measure of retinal/photoreceptor function (Figure 6B). At a dose of 200 pmol delivered per eye, UBX1325 led to significant increase in the amplitude
of both the A- and B-waves (p<0.01 and p<0.0001, respectively) of the ERG when compared to the vehicle control group. Lastly, the expression of several
disease-relevant cytokines was elevated in the diabetic retina, but attenuation of those factors was not observed after administration of UBX1325.
Figure 6: Streptozotocin-induced diabetic mice have increased retinal vascular leakage (6A) and decreased A-wave amplitude in ERG (6B). Administration of UBX1325
attenuated each of these disease-relevant endpoints.
Non-clinical toxicology studies of UBX1325, as well as its manufacturing and associated testing, have been completed to support the evaluation
of the safety, tolerability, and pharmacokinetics of this molecule in further clinical studies.
UBX1325 Clinical Data and Development Plan
In July 2020, we filed an Investigational New Drug application, or IND, to commence a Phase 1 study of UBX1325 in patients with DME or
AMD. In October 2020, we dosed our first patient in a Phase 1 clinical study of UBX1325 to evaluate ocular and systemic safety and tolerability of a single
intravitreal injection of UBX1325 by the incidence of dose limiting toxicities and treatment emergent adverse events reported up to 24 weeks after
administration. Based on prospectively determined safety criteria, the Phase 1 study was able to dose-escalate beyond the originally planned 5 mcg dose up
to 10 mcg, which informed the final dose for the Phase 2a study in DME. In July 2021, we announced positive data from this Phase 1 study of UBX1325 in
patients with DME and nAMD for whom anti-VEGF therapy was no longer considered beneficial. On October 5, 2021 we announced 12-week data, on
November 9, 2021 we announced 24-week data, and on February 14, 2022 we announced 24-week data from an additionally-enrolled cohort of patients
with AMD. UBX1325 was well-tolerated with no signs of intraocular inflammation or other related ocular adversities, and no dose-limiting toxicities or
adversities that preclude advancing UBX1325 into later stage clinical development. In DME, following a rapid improvement in BCVA, a mean
improvement of 9.5 ETDRS letters from baseline at 6 months in the higher dose cohorts (5, 10 mcg) and 6.9 ETDRS letters from baseline at 6 months in all
dose cohorts was observed. In AMD, following a rapid improvement in BCVA, there were improvements or stabilization of both BCVA and CST through 6
months post-injection. In both diseases, the majority of patients treated with UBX1325 showed durable improvement in vision and did not meet objective
rescue criteria requiring standard of care anti-VEGF treatment. Among patients who received anti-VEGF rescue, there was minimal change in either mean
BCVA or CST following treatment in all but one patient.
In May 2021, we initiated our Phase 2a proof-of-concept study to evaluate the safety, efficacy, and durability of a single intravitreal injection of
UBX1325 in a broader population of patients with DME and dosed our first patient in June 2021. Approximately 62 patients will be enrolled, randomized
evenly between UBX1325 and sham-injected patients. An analysis of 12-week safety and efficacy data is expected by mid-2022, and patients will
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continue to be followed through 48 weeks post-treatment in a long-term follow-up. Endpoints being explored in the study include safety and tolerability,
changes in BCVA, CST, SRF/IRF, proportion of patients requiring rescue treatment, and durability of effects.
In March 2022, we also enrolled our first patient in our Phase 2 proof-of-concept study in nAMD. This study is expected to randomize 46
patients with wet AMD who have had at least three intravitreal injections of anti-VEGF therapy in the preceding six months and who have residual sub- or
intra-retinal fluid. Patients will have received their last anti-VEGF treatment approximately 4-8 weeks prior to screening, and all patients will be followed
for approximately 24 weeks after dosing with either UBX1325 or aflibercept. We expect to share 16-week data from this Ph2 study in wet AMD in the
fourth quarter of 2022.
As part of our continued commitment to our ophthalmology indications, we also continue to design alternative senolytic molecules with differing
mechanisms of action. We are also focused on the physiochemical properties of our small molecules and are developing approaches to optimize solubility,
permeability, and pharmacokinetic, or PK, parameters to create favorable ocular absorption, distribution, metabolism, and residency profiles.
Ophthalmology Program Targeting Tie2 Signaling
The angiopoietin-Tie2 signaling axis is believed to play a fundamental role in vascular biology. Dysregulation of the expression of Tie2-
regulating ligands angiopoietin-2 (a context dependent Tie2 antagonist ligand) and angiopoietin-1 (a Tie2 agonist ligand) has been observed in the vitreous
of patients with DME, AMD, and other ocular diseases. We believe that a highly specific and potent Tie2-activating antibody will restore Tie2 signaling in
ocular tissues, potentially leading to decreased vascular leak, lower levels of pathogenic angiogenesis, and a restoration of healthy blood vessels in
ischemic areas of the eye. UBX2050 is an investigational Tie2-specific agonist monoclonal antibody that was selected based on its optimal binding and
functional properties observed in in vitro assays. In primary human endothelial cells (HUVECs), UBX2050 treatment activated Tie2 as measured by
increased levels of cellular phospho-Tie2, and potently activated downstream signal transduction pathways as measured by increased levels of phospho-Akt
and phospho-Erk1/2 by western blotting (Figure 7).
Figure 7. Anti-Tie2 agonist antibody Tie2-3 (UBX2050) activated Tie2 signaling with a potency comparable to angiopoietin-1 in primary endothelial cells in
vitro.
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The in vivo activity of UBX2050 has been explored in a laser-induced choroidal neovascularization model in mice. In this model, UBX2050
was administered to mice via the intraperitoneal route at a dose of 10 mg/kg, one day prior to laser-induced rupture of Bruch’s membrane. UBX2050
treatment, but not treatment with a non-specific isotype control antibody, significantly inhibited the area of choroidal neovascularization nine days post-
injury as measured in retina/choroid flat mounts from treated animals (Figure 8). Based on this data, we believe UBX2050 has the potential to address
pathogenic angiogenesis in the eyes of patients with ocular diseases such as AMD and DME.
Figure 8. UBX2050 treatment significantly inhibited choroidal neovascularization in a laser-induced injury model in mice.
We believe that the investigational Tie2 antibody (UBX2050) may be an orthogonal approach to restoring barrier function and vascular
function. We are exploring a number of indications for UBX2050 and expect to nominate a Development Candidate in 2022.
Tie2/VEGF bispecific program
Tie2 is a receptor tyrosine kinase that is implicated in regulating barrier function in blood vessels of the eye, which are affected in several
prevalent eye diseases. Tie2 is an important key regulator of the vascular endothelium in the eye and dysregulation of this pathway leads to loss of barrier
integrity and healthy vasculature. Preliminary studies suggest that cellular senescence in aging eyes may induce Ang-2 and therefore deactivate Tie2,
leading ocular edema. The Tie2/VEGF bispecific has dual functionality on two validated targets for retinal diseases. In addition to direct activation of Tie2,
the bispecific candidate is designed to neutralize VEGF-A and VEGF-B. We believe that direct agonism of Tie2 may be superior to antagonism of Ang2
which relies on adequate levels of endogenous Ang1 to activate the Tie2 pathway. We have identified Tie2/VEGF bispecific molecules that have
pharmacological activity on Tie2 and VEGF with potencies relevant for clinical benefit. Based on supporting preclinical data, we expect to designate an
Advanced Candidate by mid-2022. We also seek to initiate pilot preclinical toxicology experiments to support nomination of a Development Candidate that
should enable initiation of IND-enabling studies in the second half of 2023.
Neurology Program
We believe cellular senescence may play a fundamental role in neurodegeneration. Multiple lines of evidence suggest that senescent cells
accumulate in the nervous system during normal aging and neurodegenerative disease. While the brain is composed of a diversity of post-mitotic (e.g.,
neurons) and proliferative (e.g., astrocytes, microglia, oligodendrocytes, endothelial cells, pericytes, neural progenitor cells, etc.) cells, glia appear to be
uniquely prone to enter a senescent state. Interestingly, neurons do not readily express canonical markers of
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senescence, perhaps due to their terminally differentiated state. In the human cortex, a significant increase in p16 positive astrocytes has been observed in
advanced age (78-90 years) relative to middle age (35-50 years) individuals. Cellular senescence has also been shown to be a hallmark of multiple
neurodegenerative diseases. The appearance of senescent cells precedes the formation of neurofibrillary tangles and phosphorylated tau in the cortex of
both human Alzheimer’s Disease and the mouse P301S MAPT tauopathy/FTD model, suggesting that cellular senescence may be an early driver of disease
pathophysiology. In Parkinson’s Disease, elevated levels of p16 and several SASP factors have been detected in the human substantia nigra pars compacta,
providing further evidence that astrocytes are prone to a senescent phenotype. Senescent astrocytes expressing elevated levels of p16, p21, and IL6 have
also been detected in the human Amyotrophic Lateral Sclerosis brain and spinal cord.
Several preclinical third-party proof of concept studies in mouse models of aging and neurodegeneration have provided preliminary evidence
that the removal of senescent cells via senolytic drugs or genetic methods can improve brain function. These early proof of concept studies provide
encouraging evidence that senolysis can ameliorate the pathophysiology associated with neurodegeneration.
UBX2089, a α-Klotho hormone drug candidate, is a circulating hormone primarily produced in the kidneys and choroid plexus of the brain,
which is being researched for multiple neurology indications. Human genetic evidence links α-Klotho to cognitive function, and we have observed pro-
cognitive activity of recombinant α-Klotho in multiple preclinical rodent and non-human primate models. Our work focused on investigating the effect of
UBX2089 on engaging CNS circuits in preclinical animal models with the intent of advancement to clinical studies, and in December 2021, we announced
an exclusive licensing agreement of our α-Klotho asset to Jocasta Neuroscience, Inc. for development and commercialization
Manufacturing
Our success will depend on our ability to deliver reliable, high-quality preclinical and clinical drug supply. As we mature and approach
commercial stage operations, securing reliable high-quality commercial drug supply will be critical. We contract with third parties for the manufacture of
our drug candidates for clinical studies. Because we rely on contract manufacturers, we employ personnel with extensive technical, manufacturing,
analytical, and quality experience. Our staff has strong project management discipline to oversee contract manufacturing and testing activities, and to
compile manufacturing and quality information for our regulatory submissions.
Manufacturing is subject to extensive regulation that imposes various procedural and documentation requirements and that governs record
keeping, manufacturing processes and controls, personnel, quality control and quality assurance, and more. Our systems and our contractors are required to
be in compliance with these regulations, and compliance is assessed regularly through monitoring of performance and a formal audit program.
Our current supply chains for our lead drug candidates involve several manufacturers that specialize in specific operations of the manufacturing
process, specifically, raw materials manufacturing, drug substance manufacturing, drug product manufacturing, and drug product labeling, packaging, and
storage. We currently operate under purchase order programs for our drug candidates with Material Service Agreements in place, and we intend to establish
long-term supply agreements in the future. We believe our current manufacturers have the scale, the systems, and the experience to supply all planned
clinical studies.
We do not currently require commercial manufacturing capabilities. Should our needs change, we will likely need to scale up our manufacturing
processes to enable commercial launch. To ensure continuity in our supply chain, we plan to establish supply arrangements with alternative larger scale
suppliers for certain portions of our supply chain, as appropriate.
We do not currently have, nor do we expect to have in the near term, any FDA-approved drugs in our portfolio. Therefore, we have not yet built
an infrastructure for sales, marketing, or commercial distribution.
Commercialization Plan
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Should any of our drug candidates move into pivotal clinical trials intended to support an application for market authorization, we intend to
develop a plan to commercialize them in the United States and other key markets, through an internal infrastructure or external partnerships.
Competition
The biotechnology and pharmaceutical industries, including the field of research in aging, are typically rife with rapid technological
developments, bold competition, and dependence on intellectual property. Like any biotechnology company, we face competition from multiple sources,
including large or established pharmaceutical, biotechnology, and wellness companies, academic research institutions, government agencies, and private
institutions. We believe our drug candidates will prevail amid the competitive landscape through their efficacy, safety, administration methods and
convenience, cost, public and institutional demand, intellectual property portfolio, and treatment of the root cause of many diseases of aging.
We are aware of other companies seeking to develop treatments to prevent or treat diseases of aging through various biological pathways,
including several large pharmaceutical companies that have exploratory programs as well as a number of earlier-stage companies. Most of these companies
are either in early stages of discovery research in senescence or have not yet disclosed pipeline candidates or mechanisms of interest, and those companies
that have disclosed pipeline candidates are targeting other pathways. Hence, we believe that we currently have the most advanced program addressing
cellular senescence.
Our drug candidates are likely to compete against current therapies from a wide range of companies and technologies, including therapies for
ophthalmology diseases: current standard of care treatments include anti-VEGF antibodies (bevacizumab, ranibizumab, aflibercept, brolucizumab);
VEGF/Ang2 bispecific antibodies (faricimab); intravitreal steroid (dexamethasone); and pan-retinal photocoagulation by laser for both neovascular AMD,
DR, and DME. There is no currently available treatment for geographic atrophy form of AMD. There are potentially disease-modifying therapeutics are
being developed by several pharmaceutical and biotechnology companies, including Roche/Genentech and Regeneron.
Many of our competitors, either alone or with strategic partners, have substantially greater financial, technical, and human resources than we
do. Accordingly, our competitors may be more successful in obtaining approval for treatments and achieving widespread market acceptance, rendering our
treatments obsolete or non-competitive. Accelerated merger and acquisition activity in the biotechnology and biopharmaceutical industries may result in
even more resources concentrated among a smaller number of our competitors. These companies also compete with us in recruiting and retaining qualified
scientific and management personnel, establishing clinical study sites, patient registration for clinical studies, and acquiring technologies complementary
to, or necessary for, our programs. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative
arrangements with large and established companies. Our commercial opportunity could be substantially limited in the event that our competitors develop
and commercialize products that are more effective, safer, more tolerable, more convenient, or less expensive than our comparable products. In geographies
that are critical to our commercial success, competitors may also obtain regulatory approvals before us, resulting in our competitors building a strong
market position in advance of our products’ entry. We believe the factors determining the success of our programs will be the efficacy, safety, and
convenience of our drug candidates.
Intellectual Property
Our success depends in large part upon our ability to obtain and maintain proprietary protection for our products and technologies and to operate
without infringing the proprietary rights of others. Our policy is to protect our proprietary position by, among other methods, filing U.S. and foreign patent
applications that relate to our proprietary technologies, inventions and improvements that are important to the development and implementation of our
business. We also rely on trademarks, know-how, continuing technological innovation and licensing opportunities to develop and maintain our proprietary
position.
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Patent Portfolio
Our patent portfolio consists of a combination of issued and allowed patents and pending patent applications that are owned or co-owned by us
and/or licensed to us from third parties. The majority of these patents and applications cover our cellular senescence program, and others pertain to our
programs that target aging mechanisms beyond cellular senescence, including the administration of a Tie2 receptor agonist or α-Klotho hormone. As of
March 1, 2022, we own, co-own, or have an exclusive license in certain fields of use to more than 150 patents and pending applications in the United States
and foreign jurisdictions. This portfolio includes 47 issued and allowed U.S. patents and applications and 38 granted and allowed foreign patents and
applications, respectively.
In general, patents have a term of 20 years from the earliest claimed non-provisional priority date. The patent term may be extendible by up to
five years in certain countries by means of patent term extension depending on the regulatory pathway and the remaining term upon marketing approval.
Certain other patents and patent applications directed to our patent portfolio, if they were to issue, may have later expiration dates. Any pending U.S.
provisional application is not eligible to become an issued patent until, among other things, we file a non-provisional patent application within 12 months
of filing the related provisional patent application. If we do not timely file any non-provisional patent application, we may lose our priority date with
respect to our provisional patent application and any patent protection on the inventions disclosed in our provisional patent application.
Ophthalmology Programs
We have a license with Ascentage to two patent families of issued and pending composition of matter patents directed to specific Bcl-xL
inhibitors including UBX0601, the active parent molecule of our lead drug candidate, UBX1325. This license grants us exclusive development and
commercialization rights and non-exclusive manufacturing rights to UBX1325 for all non-oncology indications outside of Greater China (China, Hong
Kong, Macau and Taiwan). Inside Greater China, we will be obligated to develop, manufacture and commercialize UBX1325 through a joint venture with
Ascentage. Patents in these two patent families have been granted in the United States, South Korea, New Zealand, South Africa, Australia, Canada, India,
Singapore, Japan and Europe, and others are pending in China, India, and Singapore. Patents that issue from these two patent families are expected to
expire in 2032 and 2034, excluding any patent term adjustments or extensions.
Our license agreement with Ascentage also grants us the right to continue our preclinical development efforts with UBX1967 (our back-up
compound to UBX1325) until the time we wish to submit an IND for UBX1967, at which point we would be required to either enter into a separate license
agreement with Ascentage covering UBX1967.
We co-own a patent family encompassing the use of Bcl-2 and Bcl-xL inhibitors generally to treat various age-related eye diseases by targeting
senescent cells (which also covers aspects of our neurology programs) with the Buck Institute and the Mayo Clinic. We have exclusive licenses from each
of the Buck Institute and the Mayo Clinic to this patent family in the field of senescence. To date, three U.S. patents have issued in this patent family which
are directed to treating age related eye diseases, including age-related macular degeneration. Other patent applications are pending in the United States,
Australia, Canada, China, Europe, Mexico, and Japan. Patents that issue from this family are expected to expire in 2035, excluding any patent term
adjustments and patent term extensions.
We also solely own a patent family that specifically claims the composition of matter of UBX1325 and closely related compounds, as well as
general methods of use of UBX1325. As of March 1, 2022 we have two issued U.S. patents and one pending U.S. application as well as pending
applications in Australia, Canada, China, Europe, Japan, Hong Kong, and South Korea. Future patents issued from this family are expected to expire in
2039, excluding any patent term adjustments and patent term extensions.
We solely own a patent family that specifically covers the sequence, epitope, alternative antibody formats, and use of UBX2050 not only for
ophthalmic diseases, but also other indications, including kidney. Future patents issuing from this family are expected to expire in 2040, excluding any
patent term adjustments and patent term extensions.
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Neurology Program
We have an exclusive license with The Regents of the University of California for a patent family directed to methods of treatment and the use of
α-Klotho hormone for the development of human therapeutics to treat cognitive decline. As of March 1, 2022, our patent portfolio includes three issued
U.S. patents, an issued patent in Australia, Europe, and Japan, one pending patent application in each of the United States, Australia, Canada, Europe, Hong
Kong, and India and two pending patent applications in China. Patents that issue from this family are expected to expire in 2036, excluding any patent term
adjustments and patent term extensions. In December 2021, we announced an exclusive agreement licensing our α-Klotho asset to Jocasta Neuroscience,
Inc. for development and commercialization.
We co-own a patent family encompassing the use of Bcl-2/xL inhibitors generally to treat neurodegenerative diseases by targeting senescent cells
(which also covers aspects of our ophthalmology program) with the Buck Institute and the Mayo Clinic. We have exclusive licenses from each of the Buck
Institute and the Mayo Clinic to this patent family in the field of senescence. Currently, we co-own a pending U.S. patent application for the use of Bcl-xL
inhibition to eliminate senescent cells to treat neurodegenerative disorders. Patents that issue from this family are expected to expire in 2035, excluding any
patent term adjustments and patent term extensions.
Other Intellectual Property
Our continuing research and development, technical know-how, and contractual arrangements supplement our intellectual property protection to
maintain our competitive position. Our policy is to require inventors who are identified on any Company-owned patent applications to assign rights to us.
We also have confidentiality agreements with our employees, consultants, and other advisors to protect our proprietary information. Our policy is to require
third parties that receive material UNITY confidential information to enter into confidentiality agreements with us.
We also protect our brand through procurement of trademark rights. As of March 1, 2022, the mark UNITY BIOTECHNOLOGY® and the
UNITY BIOTECHNOLOGY® design logo are registered in the United States, the European Union, or EU, China, and in Japan, as well as other foreign
jurisdictions. The mark UNITY® is also registered in the United States and in the EU. In order to supplement protection of our brand, we have also
registered several internet domain names.
Description of Ascentage Agreements
Licenses and Collaborations
In February 2016, we entered into several related agreements with Ascentage Pharma Group Corp. Limited, or Ascentage, which is
headquartered in Suzhou, China and listed on the Hong Kong Stock Exchange. These agreements include a compound library and option agreement, which
includes a template form of license agreement and in January 2019 we entered into a license agreement granting us development and commercialization
rights to UBX1967 and the right to continue preclinical development efforts with UBX1325, which is a phosphate pro-drug that releases the active parent
molecule known as UBX0601, or the Original Bcl Agreement. This Original Bcl Agreement was amended in the fourth quarter of 2019 to remove certain
field and territory limitations and to amend the schedule of licensed patents related to UBX1967, and then amended again in the first quarter of 2020 to
further amend and restate the schedule of licensed patents. This Original Bcl Agreement was amended a third time in June 2020 to switch the status of
UBX1967 from Licensed Compound to back-up compound, and conversely the status of UBX1325 from back-up to Licensed Compound.
Library Agreement and License Template
The compound library and option agreement, or library agreement, gives us access to Ascentage’s existing collection of Bcl-2/xL inhibitor
compounds, as well as any additional Bcl-2/xL inhibitor compounds developed during the term of the library agreement, in order to screen such
compounds for senolytic activity. The library
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agreement permits us to nominate up to 15 such compounds at any given time for further evaluation and subsequently to select up to five of such selected
compounds for preclinical development and an additional five as back-up compounds. Prior to commencing IND-enabling toxicology studies on an
Ascentage compound of interest, we must formally designate the compound as a development candidate under the library agreement and enter into a
separate license agreement with Ascentage covering that compound on the terms set forth in the template form of license agreement. The library agreement
includes exclusivity provisions that (i) prohibit us from developing Ascentage Bcl-2/xL compounds for oncology indications, (ii) prohibit Ascentage from
researching or developing certain Bcl-2/xL compounds for non-oncology indications under any circumstances, and (iii) prohibit Ascentage from
researching or developing certain other Bcl-2/xL compounds for a specified set of non-oncology indications under certain circumstances. The term of the
library agreement is determined by a formula that is linked to the term of the research services agreement, and expired in February 2022.
Under the terms of the template form of license agreement, Ascentage will grant us the following rights with respect to a selected Ascentage
compound for all non-oncology indications: (i) exclusive worldwide development rights, and (ii) exclusive commercialization rights outside of Greater
China (China, Hong Kong, Macau and Taiwan). Inside Greater China, we will be obligated to commercialize the licensed Ascentage compound through a
joint venture with Ascentage. Ascentage will also have the right to manufacture at least 50% of our supply requirements of the licensed compound,
provided they achieve and maintain certain manufacturing quality standards. We will be obligated to make certain milestone payments in the form of shares
of our common stock, subject to the equity cap described below, and other milestone payments in in the form of cash, not to exceed $38.0 million per
licensed product, based in each case, upon the achievement of certain clinical and commercial milestones. We will also be required to make low-single digit
royalty payments on net sales of the licensed product under the agreement. Our royalty payment obligations will expire on a country-by-country basis and
licensed product-by-licensed product basis upon the later to occur of (i) the expiration of the last valid claim of a licensed patent covering such licensed
product in such country, (ii) the expiration of regulatory exclusivity for such licensed product in such country, and (iii) the tenth anniversary of the first
commercial sale of such licensed product in any country. We have the right to credit certain royalty payments that we pay to third parties with respect to
certain licensed products against our royalty obligation to Ascentage. Any license agreement may be terminated by either party due to the other party’s
uncured material breach of the agreement.
Under the library agreement, we issued 133,334 shares of our common stock as an upfront license fee. Of such shares, 80% were issued to
Ascentage and 20% were issued to the University of Michigan in satisfaction of Ascentage’s obligation to pay a related sublicense fee to the University of
Michigan. we will also be obligated to issue 133,334 shares of our common stock as an upfront license fee to Ascentage and the University of Michigan for
each of the next two license agreements. The aggregate number of shares of our common stock we could be required to issue to Ascentage and the
University of Michigan pursuant to the library agreement, and any additional license agreements we enter into pursuant to the library agreement is capped
at (i) 933,337 shares of common stock in the event there is only one licensed product, and (ii) 1,333,338 shares of common stock in the event there are two
or more licensed products, in each case to be issued based on our achievement of certain preclinical and clinical development and sales milestone events.
UBX1967 License Agreement
In January 2019, we entered into a license agreement, the Bcl license agreement, with Ascentage granting rights to UBX1967 (which Ascentage
calls APG1197) on the template license terms described above, including up to $38.0 million of potential cash milestone payments and low-single digit
royalties. Under the terms of this license agreement, Ascentage has granted us exclusive development and commercialization rights and non-exclusive
manufacturing rights to UBX1967 for all non-oncology indications outside of Greater China. Inside Greater China, we will be obligated to develop,
manufacture and commercialize UBX1967 through a joint venture with Ascentage. The Bcl license agreement also grants us the right to continue our
preclinical development efforts with another Ascentage-controlled Bcl-2/xL inhibitor compound. In the event we wish to pursue clinical development of
the additional compound as well as UBX1967, we will be required to enter into a separate license agreement with Ascentage on the template license terms
described above. In connection with the Bcl license agreement, we issued 106,667 shares of common stock to Ascentage and 26,667 shares of common
stock to the University of Michigan as an upfront license fee in the first quarter of 2019. The Bcl license agreement may be terminated by either party due
to an uncured material breach of the agreement but the other party, and we may terminate for convenience on a
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licensed product-by-licensed product basis. In November 2019, we entered into an amendment to the Bcl license agreement that removed certain field and
territory limitations from a provision granting us exclusivity and amended the schedule of licensed patents to include certain additional patents relating to
UBX1967. In January 2020, we entered into a second amendment to the Bcl license agreement which further amended and restated the schedule of licensed
patents. In June 2020, we entered into a third amendment to the Bcl license agreement. Under the terms of the original Bcl license agreement, Ascentage
granted us exclusive development and commercialization rights and non-exclusive manufacturing rights to UBX1967 as well as the right to continue our
preclinical development efforts with another Ascentage-controlled Bcl inhibitor compound, known as UBX1325, that served as a back-up compound to
UBX1967. Under the terms of the third amendment to the Bcl license agreement, the status of UBX1967 and UBX1325 were switched such that UBX1325
became the licensed compound and UBX1967 became the back-up compound under the Bcl license agreement. As a result of the first patient dosed in the
UBX1325 study in the fourth quarter of 2020, we triggered, under the Bcl license agreement, a milestone payment of $1.0 million, which we elected to
settle in shares of our common stock to Ascentage Pharma. As a result of the first patient dosed in the Phase 2a UBX1325 study in June 2021, the
Company additionally triggered a milestone payment of $2.0 million for Ascentage Pharma, which the Company elected to settle in shares of the
Company’s common stock.
Additional License Agreements
We are party to three additional license agreements that support our senescence-related patent portfolio. These agreements are with The John
Hopkins University, or JHU, an entity affiliated with the Mayo Clinic, or Mayo, and the Buck Institute for Research on Aging, or Buck, and provide us
with a worldwide, exclusive, sublicensable license under those counter-parties’ rights to a patent family that is co-owned by JHU, Buck, Mayo and us to
develop and commercialize licensed products, including for the treatment of senescence-related diseases in therapeutic areas including osteoarthritis,
ophthalmology, and neurological diseases.
Under our June 2013 license with Mayo, we may be obligated to make development and sales milestone payments to Mayo of up to
$10.8 million in the aggregate, to pay Mayo a percentage of certain sublicensing revenue that is between the high-single digits and the low-teens, and to
pay Mayo running royalty payments ranging from less than 1% to low-single digit percentages on net sales of licensed products. Our obligation to pay
running royalties to Mayo under the agreement is subject to a non-material minimum annual royalty and could potentially extend until January 1, 2037. We
also issued 677,966 shares of our common stock to Mayo under this agreement. Our agreement with Mayo continues until the later of (i) the expiration of
the last valid claim within the licensed patents and (ii) 13 years after first commercial sale of the first licensed product. We may terminate the agreement for
convenience, and either party may terminate the agreement for the other party’s uncured material breach.
Under our January 2017 license with Buck, which includes similar rights to a second patent family that is co-owned only by Buck and us, we
may be obligated to make development and sales milestone payments to Buck of up to $5.4 million in the aggregate, to pay Buck a mid-single digit
percentage of certain sublicensing revenue, and to pay Buck running royalty payments ranging from less than 1% to low-single digit percentages on net
sales of licensed products. Our obligation to pay running royalties to Buck under the agreement is subject to a non-material minimum annual royalty and
could potentially extend until January 1, 2037. We also issued 132,203 shares of our common stock to Buck under this agreement. The term of our license
agreement with Buck continues until the expiration of all our payment obligations to Buck thereunder. We may terminate the agreement for convenience,
and either party may terminate the agreement for the other party’s uncured material breach.
Under our November 2016 license with JHU, which relates to patents that are relevant only to osteoarthritis indications, we may be obligated to
make development and sales milestone payments to JHU in the form of equity (22,033 shares of our common stock) and cash (of up to $2.6 million in the
aggregate), to pay JHU a low-single digit percentage of certain sublicensing revenue, and to pay JHU a running royalty payment of less than 1% on net
sales, in all cases, with respect to licensed products for the treatment of osteoarthritis, which we refer to as Royalty Products. Our obligation to pay running
royalties to JHU under the agreement is subject to a non-material minimum annual royalty, and may continue on a country-by-country basis until such time
as neither the manufacture, sale, nor use of such Royalty Product would infringe a valid claim of a licensed patent in the applicable country. Our agreement
with JHU continues on a country-by-country basis until the expiration of the last to expire licensed patent in such country (or until twenty years after the
effective date if no licensed patent issues in such country). We may
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terminate the agreement for convenience (as a whole, with respect to a licensed product, or with respect to a particular licensed patent). Either party may
terminate the agreement for the other party’s uncured material breach or bankruptcy or insolvency-related events.
We are also party to license agreements relating to our α-Klotho program. In May 2019, we entered into an exclusive license with The Regents of
the University of California for intellectual property and know-how for the development of human therapeutics to treat cognitive decline in exchange for
development and sales milestones and low single-digit percentages on net sales of licensed products. In December 2021, we signed an exclusive license
agreement licensing our rights in the α-Klotho asset to Jocasta Neuroscience, Inc. for development and commercialization, under which we received a $5
million upfront cash payment from Jocasta, and we will also receive additional payments based on development milestones, approval milestones, and sales-
based royalties, per indication.
Government Regulation
Government authorities in the United States (including federal, state and local authorities) and in other countries, extensively regulate, among
other things, the manufacturing, research and clinical development, marketing, labeling and packaging, storage, distribution, post-approval monitoring and
reporting, advertising and promotion, pricing, and export and import of pharmaceutical products, such as those we are developing. The process of obtaining
regulatory approvals and the subsequent compliance with appropriate federal, state, local and foreign statutes and regulations require the expenditure of
substantial time and financial resources.
U.S. Government Regulation
In the United States, the FDA regulates drugs under the Federal Food, Drug, and Cosmetic Act, or FDCA, and its implementing regulations, and
biologics under the FDCA and the Public Health Service Act, or PHSA, and its implementing regulations. FDA approval is required before any new
unapproved drug or dosage form, including a new use of a previously approved drug, can be marketed in the United States. Drugs and biologics are also
subject to other federal, state and local statutes and regulations. If we fail to comply with applicable FDA or other requirements at any time during the drug
development process, clinical testing, the approval process or after approval, we may become subject to administrative or judicial sanctions. These
sanctions could include the FDA’s refusal to approve pending applications, license suspension or revocation, withdrawal of an approval, warning letters,
product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, civil penalties or criminal prosecution.
The process required by the FDA before drug candidates may be marketed in the United States generally involves the following:
completion of extensive preclinical laboratory tests and preclinical animal studies, all performed in accordance with GLP regulations;
submission to the FDA of an IND, which must become effective before human clinical studies may begin;
approval by an independent institutional review board, or IRB, or ethics committee representing each clinical site before each clinical study may
be initiated;
performance of adequate and well-controlled human clinical studies to establish the safety and efficacy, or in the case of a biologic, the safety,
purity and potency, of the drug candidate for each proposed indication;
preparation of and submission to the FDA of a new drug application, or NDA, or biologics license application, or BLA, after completion of all
pivotal clinical studies;
review of the product application by an FDA advisory committee, where appropriate and if applicable;
a determination by the FDA within 60 days of its receipt of an NDA or BLA to file the application for review;
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satisfactory completion of an FDA pre-approval inspection of the manufacturing facilities where the drug candidate is produced to assess
compliance with current Good Manufacturing Practices, or cGMP; and
FDA review and approval of an NDA or BLA prior to any commercial marketing or sale of the drug or biologic in the United States.
An IND is a request for authorization from the FDA to administer an investigational new drug product to humans. The central focus of an IND
submission is on the general investigational plan and the protocol(s) for human studies. The IND also includes results of animal and in vitro studies
assessing the toxicology, pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product; chemistry, manufacturing and controls
information; and any available human data or literature to support the use of the investigational new drug. An IND must become effective before human
clinical studies may begin. An IND will automatically become effective 30 days after receipt by the FDA, unless before that time the FDA raises concerns
or questions related to the proposed clinical studies. In such a case, the IND may be placed on clinical hold and the IND sponsor and the FDA must resolve
any outstanding concerns or questions before clinical studies can begin. Accordingly, submission of an IND may or may not result in the FDA allowing
clinical studies to commence.
Clinical Studies
Clinical studies involve the administration of the investigational new drug to human subjects under the supervision of qualified investigators in
accordance with Good Clinical Practice regulations, or GCPs, which include the requirement that all research subjects provide their informed consent for
their participation in any clinical study. Clinical studies are conducted under protocols detailing, among other things, the objectives of the study, the
parameters to be used in monitoring safety and the efficacy criteria to be evaluated. A protocol for each clinical study and any subsequent protocol
amendments must be submitted to the FDA as part of the IND. Additionally, approval must also be obtained from each clinical study site’s IRB before the
studies may be initiated, and the IRB must monitor the study until completed. There are also requirements governing the reporting of ongoing clinical
studies and clinical study results to public registries.
The clinical investigation of a drug or biologic is generally divided into three or four phases. Although the phases are usually conducted
sequentially, they may overlap or be combined.
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Phase 1.The drug or biologic is initially introduced into healthy human subjects or patients with the target disease or condition. These studies are
designed to evaluate the safety, dosage tolerance, metabolism and pharmacologic actions of the investigational new drug in humans, the side
effects associated with increasing doses, and if possible, to gain early evidence on effectiveness.
Phase 2.The drug or biologic is administered to a limited patient population to evaluate dosage tolerance and optimal dosage, identify possible
adverse side effects and safety risks and preliminarily evaluate efficacy.
Phase 3.The drug or biologic is administered to an expanded patient population, generally at geographically dispersed clinical study sites to
generate enough data to statistically evaluate dosage, clinical effectiveness and safety, to establish the overall benefit-risk relationship of the
investigational product and to provide an adequate basis for product approval.
Phase 4.In some cases, the FDA may condition approval of an NDA or BLA for a drug candidate on the sponsor’s agreement to conduct
additional clinical studies after approval. In other cases, a sponsor may voluntarily conduct additional clinical studies after approval to gain more
information about the drug. Such post-approval studies are typically referred to as Phase 4 clinical studies.
A pivotal study is a clinical study that adequately meets regulatory agency requirements for the evaluation of a drug candidate’s efficacy and
safety such that it can be used to justify the approval of the product. Generally, pivotal studies are Phase 3 studies, but the FDA may accept results from
Phase 2 studies if the study design provides a well-controlled and reliable assessment of clinical benefit, particularly in situations where there is an unmet
medical need and the results are sufficiently robust.
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The FDA, the IRB or the clinical study sponsor may suspend or terminate a clinical study at any time on various grounds, including a finding that
the research subjects are being exposed to an unacceptable health risk. Additionally, some clinical studies are overseen by an independent group of
qualified experts organized by the clinical study sponsor, known as a data safety monitoring board or committee. This group provides authorization for
whether or not a study may move forward at designated check points based on access to certain data from the study. A sponsor may also suspend or
terminate a clinical study based on evolving business objectives and/or competitive climate.
Submission of an NDA or BLA to the FDA
Assuming successful completion of all required testing in accordance with all applicable regulatory requirements, detailed investigational new
drug product information is submitted to the FDA in the form of an NDA or BLA requesting approval to market the product for one or more indications.
Under federal law, the submission of most NDAs and BLAs is subject to a substantial application user fee. Applications for orphan drug products are
exempted from the NDA and BLA application user fees.
An NDA or BLA must include all relevant data available from pertinent preclinical and clinical studies, including negative or ambiguous results
as well as positive findings, together with detailed information relating to the product’s chemistry, manufacturing, controls and proposed labeling, among
other things. Data can come from company-sponsored clinical studies intended to test the safety and effectiveness of a use of a product, or from a number
of alternative sources, including studies initiated by investigators. To support marketing approval, the data submitted must be sufficient in quality and
quantity to establish the safety and effectiveness of the investigational product to the satisfaction of the FDA.
Once an NDA or BLA has been submitted, the FDA’s goal is to review the application within ten months after it accepts the application for
filing, or, if the application receives priority review, six months after the FDA accepts the application for filing. The review process is often significantly
extended by FDA requests for additional information or clarification.
Before approving an NDA or BLA, the FDA typically will inspect the facility or facilities where the product is manufactured. The FDA will not
approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to
assure consistent production of the product within required specifications. Additionally, before approving an NDA or BLA, the FDA will typically inspect
one or more clinical sites to assure compliance with GCP.
The FDA is required to refer an application for a novel drug or biologic to an advisory committee or explain why such referral was not made. An
advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a
recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an
advisory committee, but it considers such recommendations carefully when making decisions and typically follows such recommendations.
The FDA’s Decision on an NDA or BLA
After the FDA evaluates the NDA or BLA and conducts inspections of manufacturing facilities, it may issue an approval letter or a Complete
Response Letter. An approval letter authorizes commercial marketing of the drug or biologic with specific prescribing information for specific indications.
A Complete Response Letter indicates that the review cycle of the application is complete and the application is not ready for approval. A Complete
Response Letter may require additional clinical data and/or an additional pivotal Phase 3 clinical study(ies), and/or other significant, expensive and time-
consuming requirements related to clinical studies, preclinical studies or manufacturing. Even if such additional information is submitted, the FDA may
ultimately decide that the NDA or BLA does not satisfy the criteria for approval. The FDA could also approve the NDA or BLA with a Risk Evaluation
and Mitigation Strategy, or REMS, to mitigate risks, which could include medication guides, physician communication plans or elements to assure safe use,
such as restricted distribution methods, patient registries and
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other risk minimization tools. The FDA also may condition approval on, among other things, changes to proposed labeling, development of adequate
controls and specifications or a commitment to conduct one or more post-market studies or clinical studies. Such post-market testing may include Phase 4
clinical studies and surveillance to further assess and monitor the product’s safety and effectiveness after commercialization. Also, new government
requirements, including those resulting from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent
regulatory approval of our products under development.
Expedited Review and Accelerated Approval Programs
The FDA has various programs, including fast track designation, breakthrough therapy designation, accelerated approval, and priority review,
that are intended to expedite the development and approval of new drugs and biologics that address unmet medical needs in the treatment of serious or life-
threatening diseases and conditions. To be eligible for a fast track designation, the FDA must determine, based on the request of a sponsor, that a product is
intended to treat a serious or life-threatening disease or condition and demonstrates the potential to address an unmet medical need. The FDA may review
sections of the NDA for a fast-track product on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the
submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays
any required user fees upon submission of the first section of the NDA.
The FDA may give a priority review designation to drugs or biologics that are designed to treat a serious condition and, if approved, would
provide a significant improvement in safety or effectiveness compared to available therapies. A priority review means that the goal for the FDA to review
an application is six months, rather than the standard review of ten months. These six- and 10-month review periods are measured from the “filing” date
rather than the receipt date for NDAs for new molecular entities, which typically adds approximately two months to the timeline for review and decision
from the date of submission. Products that are eligible for fast-track designation may also be eligible for priority review.
In addition, products studied for their safety and effectiveness in treating serious or life-threatening illnesses and that provide meaningful
therapeutic benefit over existing treatments may be eligible for accelerated approval and may be approved on the basis of adequate and well-controlled
clinical studies establishing that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical
endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or
mortality or other clinical benefit, taking into account the severity, rarity or prevalence of the condition and the availability or lack of alternative treatments.
As a condition of approval, the FDA may require a sponsor of a drug receiving accelerated approval to perform post-marketing studies to verify and
describe the predicted effect on irreversible morbidity or mortality or other clinical endpoint, and the drug or biologic may be subject to expedited
withdrawal procedures if the sponsor fails to conduct the required post-marketing studies, or such post-marketing studies fail to confirm the predicted
clinical benefit.
Moreover, under the provisions of the Food and Drug Administration Safety and Innovation Act, or FDASIA, passed in July 2012, a sponsor can
request designation of a product candidate as a “breakthrough therapy.” A breakthrough therapy is defined as a drug or biologic that is intended, alone or in
combination with one or more other drugs or biologics, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates
that the product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial
treatment effects observed early in clinical development. This designation includes all of the features of fast track designation, as well as more intensive
FDA interaction and guidance. The breakthrough therapy designation is a distinct status from both accelerated approval and priority review, but these can
also be granted to the same product candidate if the relevant criteria are met. The FDA must take certain actions, such as holding timely meetings and
providing advice, intended to expedite the development and review of an application for approval of a breakthrough therapy.
Fast track designation, priority review, and breakthrough therapy designation do not change the standards for approval but may expedite the
development or approval process. Even if a product qualifies for one or more of these programs, the FDA may later decide that the product no longer meets
the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.
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Post-Approval Requirements
Drugs and biologics marketed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other
things, requirements relating to recordkeeping, periodic reporting, product sampling and distribution, advertising and promotion and reporting of adverse
experiences with the product. After approval, most changes to the approved product, such as adding new indications or other labeling claims are subject to
prior FDA review and approval. There also are continuing, annual user fee requirements.
Manufacturers are subject to periodic unannounced inspections by the FDA and state agencies for compliance with cGMP requirements. Changes
to the manufacturing process are strictly regulated and, depending on the significance of the change, may require prior FDA approval before being
implemented. FDA regulations also require investigation and correction of any deviations from cGMP and impose reporting and documentation
requirements upon us and any third-party manufacturers that we may decide to use. Accordingly, manufacturers must continue to expend time, money and
effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.
Discovery of previously unknown problems with a product or the failure to comply with applicable requirements may result in restrictions on a
product, manufacturer or holder of an approved NDA or BLA, including withdrawal or recall of the product from the market or other voluntary, FDA-
initiated or judicial action that could delay or prohibit further marketing. Also, new government requirements, including those resulting from new
legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.
The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the
product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or
frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new
safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other
restrictions under a REMS program. Other potential consequences include, among other things:
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complete withdrawal of the product from the market or product recalls;
fines, warning letters or holds on post-approval clinical studies;
refusal of the FDA to approve pending NDAs or BLAs or supplements to approved NDAs or BLAs, or suspension or revocation of product
licenses or approvals;
product seizure or detention, or refusal to permit the import or export of products; or
injunctions or the imposition of civil or criminal penalties.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs may be promoted
only for the approved indications and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and
regulations prohibiting the promotion of off-label uses, and a company that is found to have improperly promoted off-label uses may be subject to
significant liability.
Orphan Designation and Exclusivity
Under the Orphan Drug Act, the FDA may grant orphan designation to a drug or biologic intended to treat a rare disease or condition, defined as
a disease or condition with a patient population of fewer than 200,000 individuals in the United States, or a patient population greater than 200,000
individuals in the United States and when there is no reasonable expectation that the cost of developing and making available the drug or biologic in the
United States will be recovered from sales in the United States for that drug or biologic. Orphan drug designation
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must be requested before submitting a BLA or NDA. After the FDA grants orphan drug designation, the generic identity of the therapeutic agent and its
potential orphan use are disclosed publicly by the FDA.
If a product that has orphan drug designation subsequently receives the first FDA approval for a particular active ingredient for the disease for
which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications,
including a full NDA or BLA, to market the same drug or biologic for the same indication for seven years, except in limited circumstances, such as a
showing of clinical superiority to the product with orphan drug exclusivity or if FDA finds that the holder of the orphan drug exclusivity has not shown that
it can assure the availability of sufficient quantities of the orphan drug to meet the needs of patients with the disease or condition for which the drug was
designated. Orphan drug exclusivity does not prevent the FDA from approving a different drug or biologic for the same disease or condition, or the same
drug or biologic for a different disease or condition. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver
of the BLA or NDA application user fee.
A designated orphan drug many not receive orphan drug exclusivity if it is approved for a use that is broader than the indication for which it
received orphan designation. In addition, orphan drug exclusive marketing rights in the United States may be lost if the FDA later determines that the
request for designation was materially defective or, as noted above, if the second applicant demonstrates that its product is clinically superior to the
approved product with orphan exclusivity or the manufacturer of the approved product is unable to assure sufficient quantities of the product to meet the
needs of patients with the rare disease or condition.
Biosimilars and Exclusivity
The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or the Affordable Care Act,
signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated
approval pathway for biological products that are biosimilar to or interchangeable with an FDA-licensed reference biological product. To date, only a
handful of biosimilars have been licensed under the BPCIA, although numerous biosimilars have been approved in Europe. The FDA has issued several
guidance documents outlining an approach to review and approval of biosimilars.
Biosimilarity, which requires that there be no clinically meaningful differences between the biological product and the reference product in terms
of safety, purity and potency, can be shown through analytical studies, animal studies and a clinical study or studies. Interchangeability requires that a
product is biosimilar to the reference product and the product must demonstrate that it can be expected to produce the same clinical results as the reference
product in any given patient and, for products that are administered multiple times to an individual, the biologic and the reference biologic may be
alternated or switched after one has been previously administered without increasing safety risks or risks of diminished efficacy relative to exclusive use of
the reference biologic. However, complexities associated with the larger, and often more complex, structures of biological products, as well as the
processes by which such products are manufactured, pose significant hurdles to implementation of the abbreviated approval pathway that are still being
worked out by the FDA.
Under the BPCIA, an application for a biosimilar product may not be submitted to the FDA until four years following the date that the reference
product was first licensed by the FDA. In addition, the approval of a biosimilar product may not be made effective by the FDA until 12 years from the date
on which the reference product was first licensed. During this 12-year period of exclusivity, another company may still market a competing version of the
reference product if the FDA approves a full BLA for the competing product containing that applicant’s own preclinical data and data from adequate and
well-controlled clinical studies to demonstrate the safety, purity and potency of its product. The BPCIA also created certain exclusivity periods for
biosimilars approved as interchangeable products. At this juncture, it is unclear whether products deemed “interchangeable” by the FDA will, in fact, be
readily substituted by pharmacies, which are governed by state pharmacy law.
A biological product can also obtain pediatric market exclusivity in the United States. Pediatric exclusivity, if granted, adds six months to
existing exclusivity periods and patent terms. This six-month exclusivity, which runs
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from the end of other exclusivity protection or patent term, may be granted based on the voluntary completion of a pediatric study in accordance with an
FDA-issued “Written Request” for such a study.
The BPCIA is complex and continues to be interpreted and implemented by the FDA. In addition, recent government proposals have sought to
reduce the 12-year reference product exclusivity period. Other aspects of the BPCIA, some of which may impact the BPCIA exclusivity provisions, have
also been the subject of recent litigation. As a result, the ultimate impact, implementation, and impact of the BPCIA is subject to significant uncertainty.
Hatch-Waxman Amendments and Exclusivity
Section 505 of the FDCA describes three types of marketing applications that may be submitted to the FDA to request marketing authorization
for a new drug. A Section 505(b)(1) NDA is an application that contains full reports of investigations of safety and efficacy. A 505(b)(2) NDA is an
application that contains full reports of investigations of safety and efficacy but where at least some of the information required for approval comes from
investigations that were not conducted by or for the applicant and for which the applicant has not obtained a right of reference or use from the person by or
for whom the investigations were conducted. This regulatory pathway enables the applicant to rely, in part, on the FDA’s prior findings of safety and
efficacy for an existing product, or published literature, in support of its application. Section 505(j) establishes an abbreviated approval process for a
generic version of approved drug products through the submission of an Abbreviated New Drug Application, or ANDA. An ANDA provides for marketing
of a generic drug product that has the same active ingredients, dosage form, strength, route of administration, labeling, performance characteristics and
intended use, among other things, to a previously approved product. ANDAs are termed “abbreviated” because they are generally not required to include
preclinical (animal) and clinical (human) data to establish safety and efficacy. Instead, generic applicants must scientifically demonstrate that their product
is bioequivalent to, or performs in the same manner as, the innovator drug through in vitro, in vivo or other testing. The generic version must deliver the
same amount of active ingredients into a subject’s bloodstream in the same amount of time as the innovator drug and can often be substituted by
pharmacists under prescriptions written for the reference listed drug. In seeking approval for a drug through an NDA, applicants are required to list with the
FDA each patent with claims that cover the applicant’s drug or a method of using the drug. Upon approval of a drug, each of the patents listed in the
application for the drug is then published in the FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly known as the
Orange Book. Drugs listed in the Orange Book can, in turn, be cited by potential competitors in support of approval of an ANDA or 505(b)(2) NDA.
Upon submission of an ANDA or a 505(b)(2) NDA, an applicant must certify to the FDA that (1) no patent information on the drug product that
is the subject of the application has been submitted to the FDA; (2) such patent has expired; (3) the date on which such patent expires; or (4) such patent is
invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the application is submitted. Generally, the ANDA or
505(b)(2) NDA cannot be approved until all listed patents have expired, except where the ANDA or 505(b)(2) NDA applicant challenges a listed patent
through the last type of certification, also known as a paragraph IV certification. If the applicant does not challenge the listed patents, or indicates that it is
not seeking approval of a patented method of use, the ANDA or 505(b)(2) NDA application will not be approved until all of the listed patents claiming the
referenced product have expired.
If the ANDA or 505(b)(2) NDA applicant has provided a Paragraph IV certification to the FDA, the applicant must send notice of the Paragraph
IV certification to the NDA and patent holders once the application has been accepted for filing by the FDA. The NDA and patent holders may then initiate
a patent infringement lawsuit in response to the notice of the paragraph IV certification. If the paragraph IV certification is challenged by an NDA holder or
the patent owner(s) asserts a patent challenge to the paragraph IV certification, the FDA may not approve that application until the earlier of 30 months
from the receipt of the notice of the paragraph IV certification, the expiration of the patent, when the infringement case concerning each such patent was
favorably decided in the applicant’s favor or settled, or such shorter or longer period as may be ordered by a court. This prohibition is generally referred to
as the 30-month stay. In instances where an ANDA or 505(b)(2) NDA applicant files a paragraph IV certification, the NDA holder or patent owner(s)
regularly take action to trigger the 30-month stay, recognizing that the related patent litigation may take many months or years to resolve.
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The FDA also cannot approve an ANDA or 505(b)(2) application until all applicable non-patent exclusivities listed in the Orange Book for the
branded reference drug have expired. For example, a pharmaceutical manufacturer may obtain five years of non-patent exclusivity upon NDA approval of a
new chemical entity, or NCE, which is a drug containing an active moiety that has not been approved by FDA in any other NDA. An “active moiety” is
defined as the molecule responsible for the drug substance’s physiological or pharmacologic action. During that five-year exclusivity period, the FDA
cannot accept for filing (and therefore cannot approve) any ANDA seeking approval of a generic version of that drug or any 505(b)(2) NDA that relies on
the FDA’s approval of the drug, provided that that the FDA may accept an ANDA four years into the NCE exclusivity period if the ANDA applicant also
files a Paragraph IV certification.
A drug, including one approved under Section 505(b)(2), may obtain a three-year period of exclusivity for a particular condition of approval, or
change to a marketed product, such as a new formulation for a previously approved product, if one or more new clinical studies (other than bioavailability
or bioequivalence studies) was essential to the approval of the application and was conducted/sponsored by the applicant. Should this occur, the FDA
would be precluded from approving any ANDA or 505(b)(2) application for the protected modification until after that three-year exclusivity period has run.
However, unlike NCE exclusivity, the FDA can accept an application and begin the review process during the exclusivity period.
Other Healthcare Laws and Compliance Requirements
Pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the
states and foreign jurisdictions in which they conduct their business. Such laws include, without limitation, state and federal anti-kickback, fraud and abuse,
false claims, and physician sunshine laws and regulations. If their operations are found to be in violation of any of such laws or any other governmental
regulations that apply, they may be subject to penalties, including, without limitation, civil and criminal penalties, damages, fines, the curtailment or
restructuring of operations, exclusion from participation in federal and state healthcare programs and individual imprisonment.
Coverage and Reimbursement
Sales of any product depend, in part, on the extent to which such product will be covered by third-party payors, such as federal, state and foreign
government healthcare programs, commercial insurance and managed healthcare organizations and the level of reimbursement for such product by third-
party payors. Decisions regarding the extent of coverage and amount of reimbursement to be provided are made on a plan-by-plan basis. These third-party
payors are increasingly reducing reimbursements for medical products, drugs and services. For products administered under the supervision of a physician,
obtaining coverage and adequate reimbursement may be particularly difficult because of the higher prices often associated with such drugs. In addition, the
U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls,
restrictions on coverage and reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment
measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures, could further limit sales of any product. Decreases
in third-party reimbursement for any product or a decision by a third-party payor not to cover a product could reduce physician usage and patient demand
for the product and also have a material adverse effect on sales.
Healthcare Reform
In March 2010, former President Obama signed the Affordable Care Act, which substantially changed the way healthcare is financed by both
governmental and private insurers in the United States, and significantly affected the pharmaceutical industry. The Affordable Care Act contains a number
of provisions, including those governing enrollment in federal healthcare programs, reimbursement adjustments and fraud and abuse changes. Additionally,
the Affordable Care Act increases the minimum level of Medicaid rebates payable by manufacturers of brand name drugs from 15.1% to 23.1%; requires
collection of rebates for drugs paid by Medicaid managed care organizations; requires manufacturers to participate in a coverage gap discount program,
under which they must agree to offer 70 percent point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during
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their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and imposes a non-deductible
annual fee on pharmaceutical manufacturers or importers who sell “branded prescription drugs” to specified federal government programs.
Since its enactment, there have been judicial and Congressional challenges to certain aspects of the Affordable Care Act, and we expect there
will be additional challenges and other efforts to repeal or replace the Affordable Care Act in the future. Other legislative changes have been proposed and
adopted since the Affordable Care Act was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year and reduced
payments to several types of Medicare providers. Moreover, there has recently been heightened governmental scrutiny over the manner in which
manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed bills designed to, among other
things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government
program reimbursement methodologies for drug products. Individual states in the United States have also become increasingly active in implementing
regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain
product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and
bulk purchasing.
Privacy and Security Laws
Numerous state, federal and foreign laws, including consumer protection laws and regulations, govern the collection, dissemination, use, access
to, confidentiality and security of personal information, including health-related information. In the United States, numerous federal and state laws and
regulations, including data breach notification laws, health information privacy and security laws, including the federal Health Insurance Portability and
Accountability Act of 1996, or HIPAA, and federal and state consumer protection laws and regulations (e.g., Section 5 of the FTC Act), that govern the
collection, use, disclosure, and protection of health-related and other personal information could apply to our operations or the operations of our partners. In
addition, certain state and non-U.S. laws, such as the California Consumer Privacy Act, or the CCPA, the California Privacy Rights Act, or the CPRA, and
the General Data Protection Regulation, or the GDPR, govern the privacy and security of personal data, including health-related data in certain
circumstances, some of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same
effect, thus complicating compliance efforts. Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or
criminal penalties and private litigation. Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other
to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and
restrictions on data processing.
Employees and Human Capital Resources
As of December 31, 2021, we had 65 employees, all of whom were full-time. Approximately 36% of our employees hold advanced degrees. On
February 2, 2022, we implemented a corporate restructuring to align our resources to focus on its UBX1325 program while further extending operating
capital. The restructuring resulted in an elimination of approximately half of our workforce, reducing staff to 34 full-time employees by the middle of the
year.
The majority of our employees work in our corporate headquarters. None of our employees are represented by a labor union or a collective
bargaining agreement and we consider our relationship with our employees to be good.
Our human capital resources objectives are, as applicable, identifying, recruiting, retaining, incentivizing and integrating our existing and
additional employees. As such, we expend considerable time, attention, and financial resources on these activities. Our corporate culture, which is
underpinned by our company values, is the overarching framework we use to make decisions related to people practices, including total compensation,
short and long-term incentives, health and wellness, and employee engagement.
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Facilities
Our corporate headquarters are located in South San Francisco, California, where we currently lease approximately 62,000 square feet of office
and laboratory space pursuant to a lease dated February 28, 2019, of which approximately 23,000 square feet was subleased to Freenome Holdings, Inc. as
of June 2021 through August 31, 2024. The majority of our employees work at our corporate headquarters.
Legal Proceedings
We are not currently involved in any litigation or legal proceedings that, in management’s opinion, are likely to have any material adverse effect
on our company. While we know of no imminent legal action in which we are likely to be involved, we may in the future become engaged in litigation or
other legal proceedings. Regardless of the outcome, litigation can have an adverse impact due to defense fees, settlement costs, demands on management
attention, and other concerns.
We view our operations and manage our business as one reportable segment. See Note 1 in the Notes to Financial Statements included in this
Annual Report on Form 10-K.
Financial Information About Segments
About UNITY
We were incorporated in the State of Delaware on March 30, 2009. Our registered trademarks include UNITY BIOTECHNOLOGY®. Other
service marks, trademarks and trade names referred to in this document are the property of their respective owners.
Available Information
We are subject to the information requirements of the Securities Exchange Act of 1934, as amended and we therefore file periodic reports, proxy
statements and other information with the U.S. Securities and Exchange Commission, or SEC, relating to our business, financial statements and other
matters. The SEC maintains an Internet site, www.sec.gov, that contains reports, proxy statements and other information regarding issuers such as UNITY.
For more information about UNITY, including free access to our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports
on Form 8-K and amendments to those reports, visit our website, www.unitybiotechnology.com. The information found on or accessible through our
website is not incorporated into, and does not form a part of, this Annual Report on Form 10-K.
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Item 1A. Risk Factors
This Annual Report on Form 10-K contains forward-looking information based on our current expectations. Because our business is subject to many risks
and our actual results may differ materially from any forward-looking statements made by or on behalf of us, this section includes a discussion of important
factors that could affect our business, operating results, financial condition and the trading price of our common stock. Many of the following risks and
uncertainties have been and may continue to be exacerbated by the COVID-19 pandemic and any worsening of the global business and economic
environment as a result. This discussion should be read in conjunction with the other information in this Annual Report on Form 10-K, including our
financial statements and the notes accompanying those financial statements and “Management’s Discussion and Analysis of Financial Condition and
Results of Operations.” The occurrence of any of the events or developments described below could have a material adverse effect on our business, results
of operations, financial condition, prospects and stock price. Additional risks and uncertainties not presently known to us or that we currently deem
immaterial may also impair our business.
Risk Factor Summary
Below is a summary of the principal factors that make an investment in our common stock speculative or risky. This summary does not address all of the
risks that we face. Additional discussion of the risks summarized in this risk factor summary, and other risks that we face, can be found below under the
heading “Risk Factors” and should be carefully considered, together with other information in this Quarterly Report on Form 10-Q and our other filings
with the Securities and Exchange Commission, or SEC, before making investment decisions regarding our common stock.
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We are a clinical-stage biopharmaceutical company with a limited operating history and no products approved for commercial sale. We have
incurred significant losses since our inception, and we anticipate that we will continue to incur losses for the foreseeable future, which, together
with our limited operating history, make it difficult to assess our future viability.
Our financial condition raises substantial doubt as to our ability to continue as a going concern. We will require substantial additional financing
to achieve our goals, and a failure to obtain this necessary capital when needed on acceptable terms, or at all, could force us to delay, limit,
reduce or terminate our product development programs, commercialization efforts or other operations.
We will require substantial additional financing to achieve our goals, and a failure to obtain this capital when needed on acceptable terms, or at
all, could force us to delay, limit, reduce or terminate our product development, other operations or commercialization efforts.
Our core therapeutic approach to slow, halt, or reverse diseases of aging is based on our understanding of cellular senescence. Utilizing
senolytic molecules to treat diseases of aging is a novel therapeutic approach, which exposes us to unforeseen risks and makes it difficult to
predict the time and cost of drug development and potential for regulatory approval.
Our business is currently dependent on the successful development and regulatory approval of UBX1325.
Other than UBX1325, all of our other programs are preclinical and face significant development risk.
The COVID-19 pandemic could adversely impact our business, including our clinical trials, and financial condition.
We rely on third-party suppliers to manufacture preclinical and clinical supplies of our drug candidates and we intend to continue to rely on
third parties to produce such preclinical and clinical supplies as well as commercial supplies of any approved product. The loss of these
suppliers, costs and availability of inputs or supplies, supply issues whether or not related to the COVID-19 panademic, or the failure of those
manufacturers or suppliers to comply with applicable regulatory requirements or to provide us with
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sufficient quantities at acceptable quality levels or prices, or at all, would materially and adversely affect our business.
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We face significant competition in an environment of rapid technological and scientific change, and our drug candidates, if approved, will face
significant competition and our failure to effectively compete may prevent us from achieving significant market penetration. Most of our
competitors have significantly greater resources than we do, and we may not be able to successfully compete.
Our senolytic medicine platform and any future products that we commercialize could be alleged to infringe patent rights and other proprietary
rights of third parties, which may require costly litigation and, if we are not successful, could cause us to pay substantial damages and/or limit
our ability to commercialize our products. Even if we obtain regulatory approval for a drug candidate, our products will remain subject to
regulatory scrutiny.
Risks Related to Our Limited Operating History, Financial Condition, and Capital Requirements
We are a clinical-stage biopharmaceutical company with a limited operating history and no products approved for commercial sale. We have incurred
significant losses since our inception, and we anticipate that we will continue to incur losses for the foreseeable future, which, together with our limited
operating history, make it difficult to assess our future viability.
We are a clinical-stage biopharmaceutical company with a limited operating history. Biopharmaceutical product development is a highly speculative
undertaking and involves a substantial degree of risk. We have not yet sought approval for commercial sale of any products and therefore have no products
approved for commercial sale and have not generated any revenue from contracts with customers and have incurred losses in each year since our inception
in March 2009. We have only a limited operating history upon which you can evaluate our business and prospects. In addition, we have limited experience
and have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by companies in new and
rapidly evolving fields, particularly in the biopharmaceutical industry.
We have had significant operating losses since our inception. Our net loss for the years ended December 31, 2021 and 2020 was approximately $60.7
million and $93.8 million, respectively. As of December 31, 2021, we had an accumulated deficit of $400.0 million. Substantially all of our losses have
resulted from expenses incurred in connection with our research and development programs and from general and administrative costs associated with our
operations. We expect to continue to incur losses for the foreseeable future, and we anticipate these losses will increase as we continue to develop our drug
candidates, conduct clinical studies and pursue research and development activities. Even if we achieve profitability in the future, we may not be able to
sustain profitability in subsequent periods. Our prior losses, combined with expected future losses, have had and will continue to have an adverse effect on
our stockholders’ equity and working capital.
Our financial condition raises substantial doubt as to our ability to continue as a going concern.
Our financial statements have been prepared assuming that we will continue to operate as a going concern, which contemplates the realization of assets and
the satisfaction of liabilities in the normal course of business. Based on our current operating plans, we expect our existing capital resources will fund our
planned operating expenses into the first quarter of 2023 which is expected to fund key clinical data readouts for UBX1325, but less than 12 months from
the date of this Annual Report. We expect to continue to incur net operating losses for at least the next several years as we continue our research and
development efforts, advance our drug candidates through preclinical and clinical development, seek regulatory approval, prepare for and, if approved,
proceed to commercialization. We do not expect to generate revenue from any drug candidates that we develop until we obtain regulatory approval for one
or more of such drug candidates and commercialize our products or enter into collaborative agreements with third parties.
These conditions raise substantial doubt about our ability to continue as a going concern. Additionally, our independent registered public accounting firm
has included in its audit opinion for the year ended December 31,
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2021 an explanatory paragraph that there is substantial doubt as to our ability to continue as a going concern. There is no assurance that funding will be
available to us, will be obtained on terms favorable to us or will provide us with sufficient funds to meet our objectives. The reaction of investors to the
inclusion of a going concern statement by our auditors and our potential inability to continue as a going concern may materially adversely affect our share
price and our ability to raise new capital or enter into partnerships. If we become unable to continue as a going concern, we may have to liquidate our assets
and the values we receive for our assets in liquidation or dissolution could be significantly lower than the values reflected in our financial statements.
We will require substantial additional financing to achieve our goals, and a failure to obtain this capital when needed on acceptable terms, or at all,
could force us to delay, limit, reduce or terminate our product development, other operations or commercialization efforts.
Since our inception, we have invested a significant portion of our efforts and financial resources in research and development activities. Preclinical studies
and clinical studies for our drug candidates and additional research and development activities to discover and develop new drug candidates will require
substantial funds to complete. As of December 31, 2021, we had capital resources consisting of cash, cash equivalents, and marketable securities of $90.1
million. We believe that we will continue to expend substantial resources for the foreseeable future in connection with our programs, including the clinical
development of UBX1325, and the development of any other drug candidates we may choose to pursue. These expenditures will include costs associated
with conducting preclinical studies and clinical studies, obtaining regulatory approvals, and manufacturing and supply, as well as marketing and selling any
products approved for sale. In addition, other unanticipated costs may arise. Because the outcome of any preclinical study or clinical study is highly
uncertain, we cannot reasonably estimate the actual amounts necessary to successfully complete the development and commercialization of our current
drug candidates or any future drug candidates.
In February 2022, we announced a restructuring to align resources to focus on our ongoing clinical programs and deliver on key development milestones.
These actions to prioritize our ophthalmology programs and implement cost saving measures were designed to enable us to achieve multiple key clinical
data readouts for UBX1325 as well as support the Tie2 and Tie2/VEGF bispecific program through advanced candidate nomination, with all other pipeline
programs paused to focus resources on these advanced programs.
Based on our current operating plans, we expect our existing capital resources will fund our planned operating expenses into the first quarter of 2023 which
is expected to fund key clinical data readouts for UBX1325, but less than 12 months from the date of this Annual Report. Accordingly, our financial
statements have been prepared on a going concern basis, which contemplates the continuity of operations, realization of assets and the satisfaction of
liabilities and commitments in the ordinary course of business. We will need substantial additional capital to operate our business and continue our
development activities. Our operating plans may change as a result of many factors currently unknown to us, and we may need to seek additional funds
sooner than planned, through public or private equity or debt financings or other sources, such as strategic collaborations. Such financing may result in
dilution to stockholders, the imposition of burdensome debt covenants and repayment obligations, or other restrictions that may affect our business.
Adequate funding may not be available to us on acceptable terms, or at all, particularly in light of the current COVID-19 pandemic and associated
economic uncertainty and potential for local and/or global economic recession. In addition, we may seek additional capital due to favorable market
conditions or strategic considerations even if we believe we have sufficient funds for our current or future operating plans. If sufficient funds on acceptable
terms are not available when needed, we could be required to significantly reduce our operating expenses and delay, reduce the scope of, or eliminate one
or more of our development programs.
Our future capital requirements depend on many factors, including:
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the results of our ongoing clinical trials of UBX1325;
the scope, progress, results and costs of researching and developing our drug candidates, and conducting preclinical studies and clinical studies;
potential delays in or an increase in costs associated with our ongoing or planned preclinical studies or clinical trials as a result of the COVID-
19 pandemic;
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the timing of, and the costs involved in, obtaining regulatory approvals for our current drug candidates or any future drug candidates;
the number and characteristics of any additional drug candidates we develop or acquire;
the timing and amount of any milestone payments we are required to make pursuant to our license agreements;
the cost of manufacturing our current drug candidates or any future drug candidates and any products we successfully commercialize;
the expenses needed to attract, hire, and retain skilled personnel;
the cost of commercialization activities if our current drug candidates or any future drug candidates are approved for sale, including marketing,
sales and distribution costs;
our ability to maintain existing, and establish new, strategic collaborations, licensing or other arrangements and the financial terms of any such
agreements, including the timing and amount of any future milestone, royalty or other payments due under any such agreement;
any product liability or other lawsuits related to our products;
the costs associated with being a public company;
the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing our intellectual property portfolio; and
the timing, receipt and amount of sales of any future approved products, if any.
Additional funds may not be available when we need them, on terms that are acceptable to us, or at all. If adequate funds are not available to us on a timely
basis, we may be required to:
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delay, limit, reduce or terminate preclinical studies, clinical studies or other development activities for our current drug candidates or any future
drug candidate;
delay, limit, reduce or terminate our research and development activities; or
delay, limit, reduce or terminate our efforts to establish manufacturing and sales and marketing capabilities or other activities that may be
necessary to commercialize our current drug candidates or any future drug candidate, or reduce our flexibility in developing or maintaining our
sales and marketing strategy.
We also could choose or be required to seek funds through arrangements with collaborators or others that may require us to relinquish rights to some of our
technologies or drug candidates that we would otherwise pursue on our own. We do not expect to realize revenue from sales of products or royalties from
licensed products in the foreseeable future, if at all, and unless and until our drug candidates are clinically tested, approved for commercialization and
successfully marketed. To date, we have primarily financed our operations through the sale of equity securities. We will be required to seek additional
funding in the future and currently intend to do so through collaborations, public or private equity offerings or debt financings, credit or loan facilities or a
combination of one or more of these funding sources. Our ability to raise additional funds will depend on financial, economic and other factors, many of
which are beyond our control. For example, financial markets have been negatively impacted by the COVID-19 pandemic and associated economic
uncertainty, and such impact may be exacerbated as the COVID-19 pandemic evolves or by other unforeseen events or public health emergencies.
Additional funds may not be available to us on acceptable terms or at all. If we raise additional funds by issuing equity securities, our stockholders will
suffer dilution and the terms of any financing may adversely affect the rights of our stockholders. In addition, as a condition to providing additional funds
to us, future investors may demand, and may be granted,
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rights superior to those of existing stockholders. Debt financing, if available, is likely to involve restrictive covenants limiting our flexibility in conducting
future business activities, and, in the event of insolvency, debt holders would be repaid before holders of our equity securities received any distribution of
our corporate assets.
Our operating results may fluctuate significantly, which makes our future operating results difficult to predict and could cause our operating results to
fall below expectations.
Our quarterly and annual operating results may fluctuate significantly, making it difficult for us to predict our future operating results. These fluctuations
may occur due to a variety of factors, many of which are outside of our control and may be difficult to predict, including:
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the timing, cost and level of investment in research, development and, if approved, commercialization activities relating to our drug candidates,
which may change from time to time;
the timing and status of enrollment for our clinical studies;
the cost of manufacturing our drug candidates, as well as building out our supply chain, which may vary depending on the quantity of
production and the terms of our agreements with manufacturers;
expenditures we may incur to acquire, develop or commercialize additional drug candidates and technologies;
timing and amount of any milestone, royalty or other payments due under any collaboration or license agreement;
future accounting pronouncements or changes in our accounting policies;
the timing and success or failure of preclinical studies and clinical studies for our drug candidates or competing drug candidates, or any other
change in the competitive landscape of our industry, including consolidation among our competitors or partners;
the timing of receipt of approvals for our drug candidates from regulatory authorities in the United States and internationally;
coverage and reimbursement policies with respect to our drug candidates, if approved, and potential future drugs that compete with our
products;
the level of demand for our products, if approved, which may vary significantly over time; and
potential disruption caused by the COVID-19 pandemic or other unforeseen events and public health emergencies.
The cumulative effects of these factors could result in large fluctuations and unpredictability in our quarterly and annual operating results. As a result,
comparing our operating results on a period-to-period basis may not be meaningful. Investors should not rely on our past results as an indication of our
future performance.
This variability and unpredictability could also result in our failing to meet the expectations of industry or financial analysts or investors for any period. If
our revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts
we provide to the market are below the expectations of analysts or investors, the price of our common stock could decline substantially. Such a stock price
decline could occur even when we have met any previously publicly stated revenue or earnings guidance we may provide.
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Risks Related to Our Business and Product Development
Our core therapeutic approach to slow, halt, or reverse diseases of aging is based on our understanding of cellular senescence. Utilizing senolytic
molecules to treat diseases of aging is a novel therapeutic approach, which exposes us to unforeseen risks and makes it difficult to predict the time and
cost of drug development and potential for regulatory approval.
Our foundational science and lead drug candidate are based on senescence biology. We believe that we can develop drug candidates capable of eliminating
or modulating accumulated senescent cells, when administered locally. In our development efforts we intend to explore senolytic medicines that use
multiple modalities. However, our approach to treating diseases of aging is novel and the scientific research that forms the basis of our efforts to develop
senolytic medicines is ongoing. We have only recently begun testing our senolytic molecules in humans and the majority of our current data supporting our
hypothesis regarding senescence biology is limited to pre-clinical animal models and in vitro cell lines, the results of which may not translate into humans.
We currently have no conclusive evidence in humans, that the accumulation or modulation of senescent cells is the underlying cause of tissue damage and
dysfunction associated with many diseases of aging. For example, we announced the 12-week results from our Phase 2 study of UBX0101 in patients with
moderate-to-severe painful OA of the knee. There was no statistically significant difference between any arm of UBX0101 and placebo at the 12-week
primary endpoint for change from baseline in WOMAC-A, an established measurement of pain in OA. Given these results, we are not progressing
UBX0101 into pivotal studies and have narrowed our near-term focus to our ongoing ophthalmologic and neurologic disease programs.
Our current program, UBX1325, is a Bcl-xL inhibitor, and is intended to target senescent cells in the eye. While cellular senescence is a naturally occurring
biological process, the administration of senolytic medicines to eliminate or cause the elimination or modulation of accumulated senescent cells in humans
has not been widely tested and may potentially harm healthy tissue or result in unforeseen safety events, or fail to achieve the intended therapeutic purpose
entirely. We may also ultimately discover that our senolytic molecules do not possess certain properties required for therapeutic effectiveness, or that even
if found to be effective in one type of tissue, that such molecules will be effective in other tissues. In addition, given the novel nature of this therapeutic
approach, designing preclinical and clinical studies to demonstrate the effect of senolytic medicines is complex and exposes us to unforeseen risks. In
addition, the scientific evidence to support the feasibility of developing systemic senolytic medicines is based primarily on preclinical data and not human
clinical trials. We may spend substantial funds attempting to develop these drug candidates and never succeed in doing so.
No regulatory authority has granted approval for a senolytic medicine. As such, we believe the U.S. Food and Drug Administration, or the FDA, has
limited experience with senescence, which may increase the complexity, uncertainty and length of the clinical development and regulatory approval process
for our drug candidates. We may never receive approval to market and commercialize any drug candidate. Even if we obtain regulatory approval, the
approval may be for targets, disease indications or patient populations that are not as broad as we intended or desired or may require labeling that includes
significant use or distribution restrictions or safety warnings. We may be required to perform additional or unanticipated clinical studies to obtain approval
or be subject to post-marketing testing requirements to maintain marketing authorization. If our other senolytic molecules prove to be ineffective, unsafe or
commercially unviable, our entire senolytic platform and pipeline would have little, if any, value, which would have a material and adverse effect on our
business, financial condition, results of operations and prospects.
Our business is currently dependent on the successful development of UBX1325 which is in early stages of clinical development.
We have no products approved for sale and all of our drug candidates are in early stages of development. We have one product candidate, UBX1325, in
clinical development and we have ceased development of UBX0101 following our Phase 2 trial and are focused on advancing our ophthalmology program.
In particular, in October 2020, we initiated a Phase 1 clinical study of UBX1325 in patients with DME or nAMD for whom anti-VEGF therapy was no
longer considered beneficial, and in July, October, and November 2021, we announced positive data up to 24 weeks from this Phase 1 study. We initiated a
Phase 2a proof-of-concept clinical study of UBX1325 in DME in May 2021 and dosed the first patient in June 2021 and expect 12-week safety and
efficacy data by mid-2022. In March 2022 we also enrolled our first patient in our Phase 2 proof-of-concept study in nAMD, and we expect to share 16-
week
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data in the fourth quarter of 2022. However, the impact of the COVID-19 pandemic on the timing of study initiations, enrollment, visit adherence, and
completions is hard to assess due the continually evolving nature of the situation and it is possible that the study enrollment, visit adherence, and
completion may be delayed.
In February 2022, we announced a restructuring to align resources to focus on our ongoing clinical programs and deliver on key development milestones.
These actions to prioritize our ophthalmology programs and implement cost saving measures were designed to enable us to achieve multiple key clinical
data readouts for UBX1325. As a result, our business is currently dependent on the successful development of UBX1325. The success of our business,
including our ability to finance our company and generate any revenue in the future, will primarily depend on the successful development of UBX1325. If
UBX1325 does not demonstrate clinical benefit or we encounter safety issues with UBX1325, we may be required to significantly delay or abandon its
development. In the event UBX1325 is not successful in clinical development, we have limited resources and capital with which to develop additional drug
candidates and we may be forced to sell or liquidate our business.
The clinical and commercial success of UBX1325 and any other future drug candidates will depend on a number of factors, including the following:
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our ability to raise any additional required capital on acceptable terms, or at all;
our ability to complete IND-enabling studies and successfully submit an IND or comparable applications in foreign jurisdictions;
timely completion of our preclinical studies and clinical studies, which may be significantly slower or cost more than we currently anticipate
and will depend substantially upon the performance of third-party contractors, some of whom could be adversely impacted by unforeseen
events such as pandemics and public health emergencies, such as the COVID-19 pandemic;
whether we are required by the FDA or similar foreign regulatory agencies to conduct additional clinical studies or other studies beyond those
planned to support the approval and commercialization of our drug candidates or any future drug candidates;
acceptance of our proposed indications and primary endpoint assessments relating to the proposed indications of our drug candidates by the
FDA and similar foreign regulatory authorities;
our ability to demonstrate to the satisfaction of the FDA and similar foreign regulatory authorities the safety, efficacy, and acceptable risk-to-
benefit profile of our current drug candidates or any future drug candidates;
the prevalence, duration and severity of potential side effects or other safety issues experienced with our drug candidates or future approved
products, if any;
the timely receipt of necessary marketing approvals from the FDA and similar foreign regulatory authorities;
achieving and maintaining, and, where applicable, ensuring that our third-party contractors achieve and maintain compliance with our
contractual obligations and with all regulatory requirements applicable to our current drug candidates or any future drug candidates or approved
products, if any;
the willingness of physicians, professional societies, operators of clinics, hospitals, and patients to recommend, utilize, or adopt any of our
future drug candidates to treat diseases of aging;
the ability of third parties with whom we contract to manufacture adequate clinical study and commercial supplies of our current drug
candidates or any future drug candidates, to remain in good standing with regulatory agencies and develop, validate and maintain commercially
viable manufacturing processes that are compliant with current good manufacturing practices, or cGMP;
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our ability to successfully develop a commercial strategy and thereafter commercialize our drug candidates or any future drug candidates in the
United States, and internationally, if approved for marketing, reimbursement, sale and distribution in such countries and territories, whether
alone or in collaboration with others;
the convenience of our treatment or dosing regimen;
acceptance by physicians, payors, and patients of the benefits, safety, and efficacy of our drug candidates or any future drug candidates, if
approved, including relative to alternative and competing treatments;
patient demand for our drug candidates, if approved;
our ability to establish and enforce intellectual property rights in and to our drug candidates or any future drug candidates; and
our ability to avoid third-party patent interference, intellectual property challenges, or intellectual property infringement claims.
These factors, many of which are beyond our control, could cause us to experience significant delays or be unable to obtain regulatory approvals or
commercialize our drug candidates. In addition, disruptions caused by the COVID-19 pandemic may increase the likelihood that we encounter such
difficulties or delays in developing, obtaining regulatory approvals for or commercializing our product candidates. Even if regulatory approvals are
obtained, we may never achieve success in commercializing any of our drug candidates. Accordingly, we cannot provide assurances that we will be able to
generate sufficient revenue through the sale of our drug candidates or any future drug candidates to continue our business or achieve profitability.
Other than UBX1325, all of our other programs are preclinical and face significant development risk.
Other than UBX1325, all of our other programs are in preclinical and early research stage. In addition, we have limited resources for which to develop any
products other than UBX1325. Given the early stage nature of these programs, each of the drug candidates and programs faces substantial development
risk. UBX0101 and UBX1325 are the only drug candidates that we have administered to humans, and as such, we face significant translational risk with
our earlier stage drug candidates. We may also be required by the FDA or similar foreign regulatory agencies to conduct additional preclinical studies
beyond those planned to support the commencement of additional clinical trials. Accordingly, there can be no assurance that we are able to bring any of our
preclinical product candidates or development programs into the clinic or otherwise successfully develop them.
Clinical development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive
of future trial results.
Clinical testing is expensive and can take many years to complete, and its outcome is inherently uncertain. Failure or delay can occur at any time during the
clinical study process. Success in preclinical studies and early clinical studies does not ensure that later clinical studies will be successful. A number of
companies in the biotechnology, and pharmaceutical industries have suffered significant setbacks in clinical studies, even after positive results in earlier
preclinical studies or clinical studies. These setbacks have been caused by, among other things, preclinical findings made while clinical studies were
underway and safety or efficacy observations made in clinical studies, including previously unreported adverse events. The results of our preclinical animal
studies or studies in ex vivo human tissues may not be predictive of the results of outcomes in human clinical studies. For example, our senolytic molecules
may demonstrate different chemical and pharmacological properties in patients than they do in laboratory studies or may interact with human biological
systems in unforeseen or harmful ways.
Drug candidates in later stages of clinical studies may fail to show the desired pharmacological properties or safety and efficacy traits despite having
progressed through preclinical studies and initial clinical studies. Notwithstanding any promising results in earlier studies, we cannot be certain that we will
not face similar setbacks. Even if we are
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able to initiate and complete clinical studies, the results may not be sufficient to obtain regulatory approval for our drug candidates.
We cannot be certain that studies or trials for our drug candidates will begin on time, not require redesign, enroll an adequate number of subjects on time or
be completed on schedule, if at all. The COVID-19 pandemic could cause or exacerbate these factors. For example, for our Phase 1 and Phase 2a or Phase
2 studies for UBX1325, clinical sites may be unable to recruit and retain investigators and study staff, screen and enroll patients, patients may be unable to
adhere to the study visit schedule, and the completion of the study could be delayed. Clinical studies can be prolonged, delayed or terminated for a variety
of reasons, including:
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the FDA or comparable foreign regulatory authorities disagreeing with or requiring changes to the design or implementation of our clinical
studies;
delays in obtaining regulatory approval to commence or continue a trial;
reaching agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical study sites, the terms of which
can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;
obtaining institutional review board, or IRB, approval at each trial site;
recruiting an adequate number of suitable patients to participate in a trial;
having subjects complete a trial or return for post-treatment follow-up;
encountering difficulties in gathering the range of biological data from patients needed to fully assess the impact of our drug candidates;
clinical sites deviating from trial protocol or dropping out of a trial;
addressing subject safety concerns that arise during the course of a trial;
adding a sufficient number of clinical study sites; or
obtaining sufficient product supply of drug candidate for use in preclinical studies or clinical studies from third-party suppliers some of whom
could be adversely impacted by unforeseen events such as pandemics and public health emergencies, such as the COVID-19 pandemic.
We may experience numerous adverse or unforeseen events during, or as a result of, preclinical studies and clinical studies that could delay or prevent our
ability to receive marketing approval or commercialize our drug candidates, including:
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clinical studies of our drug candidates may produce negative or inconclusive results, and we may decide, or regulators may require us, to
modify clinical study design, conduct additional clinical studies or abandon drug development programs, including all of our senolytic
programs;
the number of patients required for clinical studies of our drug candidates may be larger than we anticipate, enrollment in these clinical studies
may be slower than we anticipate, or participants may drop out of these clinical studies at a higher rate than we anticipate;
our third-party contractors may fail to comply with regulatory requirements, fail to maintain adequate quality controls, or be unable to provide
us with sufficient product supply to conduct and complete preclinical studies or clinical studies of our drug candidates in a timely manner, or at
all;
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we or our investigators might have to suspend or terminate clinical studies of our drug candidates for various reasons, including noncompliance
with regulatory requirements, a finding that our drug candidates have undesirable side effects or other unexpected characteristics, a finding that
the participants are being exposed to unacceptable health risks, or due to unforeseen events such as pandemics and public health emergencies,
such as the COVID-19 pandemic;
the cost of clinical studies of our drug candidates may be greater than we anticipate;
the quality of our drug candidates or other materials necessary to conduct preclinical studies or clinical studies of our drug candidates may be
inadequate;
regulators may revise the requirements for approving our drug candidates, or such requirements may not be as we anticipate; and
future collaborators may conduct clinical studies in ways they view as advantageous to them but that are suboptimal for us.
If we are required to conduct additional clinical studies or other testing of our drug candidates beyond those that we currently contemplate, if we are unable
to successfully complete clinical studies of our drug candidates or other testing, if the results of these trials or tests are not positive or are only moderately
positive, or if there are safety concerns, we may:
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incur unplanned costs;
be delayed in obtaining marketing approval for our drug candidates or fail to obtain marketing approval at all;
obtain marketing approval in some countries and not in others;
obtain marketing approval for indications or patient populations that are not as broad as intended or desired;
obtain marketing approval with labeling that includes significant use or distribution restrictions or safety warnings, including boxed warnings;
be subject to additional post-marketing testing requirements; or
have the treatment removed from the market after obtaining marketing approval.
We could also encounter delays if a clinical study is suspended or terminated by us, by the IRBs of the institutions in which such trials are being conducted,
by the Data Safety Monitoring Board, or DSMB, for such trial or by the FDA or other regulatory authorities. Such authorities may suspend or terminate a
clinical study due to a number of factors, including failure to conduct the clinical study in accordance with regulatory requirements or our clinical
protocols, inspection of the clinical study operations or trial site by the FDA or other regulatory authorities resulting in the imposition of a clinical hold,
unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a drug, changes in governmental regulations or administrative
actions or lack of adequate funding to continue the clinical study.
Further, conducting clinical studies in foreign countries, as we may do for certain of our drug candidates, presents additional risks that may delay
completion of our clinical studies. These risks include the failure of enrolled patients in foreign countries to adhere to clinical protocol as a result of
differences in healthcare services or cultural customs, managing additional administrative burdens associated with foreign regulatory schemes, as well as
political and economic risks relevant to such foreign countries, including those caused by unforeseen events such as pandemics and public health
emergencies similar to the COVID-19 pandemic.
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Principal investigators for our clinical studies may serve as scientific advisors or consultants to us from time to time and may receive cash or equity
compensation in connection with such services. If these relationships and any related compensation result in perceived or actual conflicts of interest, or a
regulatory authority concludes that the financial relationship may have affected the interpretation of the trial, the integrity of the data generated at the
applicable clinical study site may be questioned and the utility of the clinical study itself may be jeopardized, which could result in the delay or rejection of
the marketing application we submit. Any such delay or rejection could prevent or delay us from commercializing our current or future drug candidates.
If we experience termination or delays in the completion of any preclinical study or clinical study of our drug candidates, the commercial prospects of our
drug candidates may be harmed, and our ability to generate revenues from any of these drug candidates will be delayed or unrealized. In addition, any
delays in completing our clinical studies may increase our costs, slow down our drug candidate development and approval process and jeopardize our
ability to commence product sales and generate revenues. Any of these occurrences may significantly harm our business, financial condition and prospects.
In addition, many of the factors that cause, or lead to, a delay in the commencement or completion of clinical studies may also ultimately lead to the denial
of regulatory approval of our drug candidates. If one or more of our drug candidates or our senescence technology generally prove to be ineffective, unsafe
or commercially unviable, our platform and pipeline would have significantly diminished value, which would have a material and adverse effect on our
business, financial condition, results of operations and prospects.
The COVID-19 pandemic could adversely impact our business, including our clinical trials, and financial condition.
The COVID-19 pandemic and government measures taken in response have had a significant impact, both direct and indirect, on businesses and commerce,
as worker shortages have occurred, supply chains have been disrupted, facilities and production have been suspended, and demand for certain goods and
services, such as medical services and supplies, has spiked, while demand for other goods and services, such as travel, has fallen. In response to the spread
of COVID-19, as of mid-March 2020, we transitioned to a reduced onsite staffing model and implemented a remote work plan for all of our employees
other than those providing essential services, such as our laboratory staff. In parallel with applicable law and regulations, in June 2021 and again in
February 2022 we began transitioning our staff back to the office but are continuing to monitor and adjust as the COVID-19 pandemic evolves. For onsite
employees, we have implemented heightened safety measures designed to comply with applicable federal, state and local guidelines. We may be required
to take additional actions that could impact our operations if required by applicable laws or regulations or if we determine them to be in the best interests of
our employees.
For the Phase 1 safety and tolerability clinical study and the Phase 2 proof-of-concept clinical studies for UBX1325, we adapted the clinical study protocol
and standard operating procedures to enable a number of adaptations such as: remote data collection for clinical sites if needed; the option for remote data
source verification procedures to limit on-site monitoring; transportation options for patients to utilize for study visit adherence; flexible visit windows to
increase study visit adherence; and geographic distribution of sites to mitigate variation in local restrictions.
These actions enable the collection of all major endpoints if patients adhere with the study visit schedule. Assessments that require an on-site visit may be
missed for some or all patients including laboratory evaluations, clinical examinations, or imaging.
Although one of the manufacturers in our supply chain for UBX0101 experienced a two-week shutdown in April 2020 due to a COVID-19 related incident
and there have been some delays in shipments due to a reduction in overall flights, neither of these factors impacted our supply of UBX0101 prior to our
decision to shut down further clinical advancement of that program. There have been no other disruptions in our supply chain of drug manufacturers
necessary to conduct our ongoing clinical trials, including our Phase 1 and Phase 2 studies in ophthalmology disease.
Several of the contract research organizations, or CROs, that provide preclinical services to us are based in China and India and experienced temporary
shutdowns in February and March due to government mandates. In each case we were able to reassign the balance of activities to other CROs and the
shutdowns did not impact our preclinical timelines. CROs based in the United States that provide preclinical services are experiencing heavy demand,
which
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may impact their ability to start new studies and could lead to delays in the commencement of our preclinical studies. Several of our U.S.-based academic
research partners have also experienced shutdowns which has slowed progress on several early-stage projects, none of which impacted our preclinical
timelines.
As the COVID-19 pandemic continues, we may experience disruptions that could severely impact our business and clinical trials, including:
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delays or difficulties in enrolling patients in our clinical trials;
delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff;
diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites
and hospital staff supporting the conduct of our clinical trials;
interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel imposed or recommended by federal
or state governments, employers and others or interruption of clinical trial subject visits and study procedures, the occurrence of which could
affect the integrity of clinical trial data;
risk that participants enrolled in our clinical trials will contract the COVID-19 coronavirus while the clinical trial is ongoing, which could
impact the results of the clinical trial, including by increasing the number of observed adverse events;
limitations in employee resources that would otherwise be focused on the conduct of our clinical trials, including because of sickness of
employees or their families or the desire of employees to avoid contact with large groups of people;
delays in receiving authorizations from local regulatory authorities to initiate our planned clinical trials;
delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials;
interruption in global shipping that may affect the transport of clinical trial materials, such as investigational drug product used in our clinical
trials;
changes in local regulations as part of a response to the COVID-19 pandemic which may require us to change the ways in which our clinical
trials are conducted, which may result in unexpected costs, or to discontinue such clinical trials altogether;
interruptions, delays, or increased costs in preclinical studies due to restricted or limited operations or supplies at our research and development
laboratory facilities;
delays in necessary interactions with local regulators, ethics committees and other important agencies and contractors due to limitations in
employee resources or forced furlough of government employees; and
refusal of the FDA to accept data from clinical trials in affected geographies outside the United States.
The global pandemic of the COVID-19 coronavirus continues to evolve. The extent to which the COVID-19 pandemic may impact our business, including
our clinical trials, and financial condition will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as
the ultimate geographic spread of the disease, the duration of the pandemic, the adoption and efficacy of vaccines, travel restrictions and social distancing
in the United States and other countries, business closures or business disruptions and the effectiveness of actions taken in the United States and other
countries to contain and treat the disease.
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If we encounter difficulties enrolling patients in our clinical studies, our clinical development activities could be delayed or otherwise adversely
affected.
The timely completion of clinical studies in accordance with their protocols depends, among other things, on our ability to enroll a sufficient number of
patients who remain in the study until its conclusion. We may experience difficulties in patient enrollment in our clinical studies for a variety of reasons.
The enrollment of patients depends on many factors, some of which could be exacerbated by the COVID-19 pandemic, including:
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the patient eligibility criteria defined in the protocol;
the size of the patient population required for analysis of the trial’s primary endpoints;
the proximity of patients to trial sites;
patients’ fear of visiting or traveling to trial sites during the COVID-19 pandemic;
the design of the trial;
our ability to recruit clinical study investigators with the appropriate competencies and experience;
clinicians’ and patients’ perceptions as to the potential advantages of the drug candidate being studied in relation to other available therapies,
including any new drugs that may be approved for the indications we are investigating; and
our ability to obtain and maintain patient consents.
In addition, our clinical studies may compete with other clinical studies for drug candidates that are in the same therapeutic areas as our drug candidates.
This competition will reduce the number and types of patients available to us, because some patients who might have opted to enroll in our trials may
instead opt to enroll in a trial being conducted by one of our competitors. Since the number of qualified clinical investigators is limited, we may conduct
some of our clinical studies at the same clinical study sites that some of our competitors use, which will reduce the number of patients who are available for
our clinical studies in such clinical study site.
Further, the administration of senolytic medicines designed to eliminate or cause the elimination of senescent cells and thereby modulate their associated
SASP may result in unforeseen events, including by harming healthy tissues. As a result, it is possible that safety concerns could negatively affect patient
enrollment among the patient populations that we intend to treat, including among those in indications with a low risk of mortality. Delays in patient
enrollment may result in increased costs or may affect the timing or outcome of the planned clinical studies, which could prevent completion of these trials
and adversely affect our ability to advance the development of our drug candidates.
Interim, “top-line” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data
become available and are subject to audit and verification procedures that could result in material changes in the final data.
From time to time, we may publicly disclose top-line or preliminary data from our clinical trials, which is based on a preliminary analysis of then-available
data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular
study or trial. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had
the opportunity to fully and carefully evaluate all data. As a result, the top-line or preliminary results that we report may differ from future results of the
same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Top-line or
preliminary data also remain subject to audit and verification procedures that may result in the final data being materially different from the top-line or
preliminary data we previously published. As a result, top-line and preliminary data should be viewed with caution until the final data are available.
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From time to time, we may also disclose interim data from our preclinical studies and clinical trials. Interim data from clinical trials that we may conduct
are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become
available. Adverse differences between interim data and final data could significantly harm our business prospects. Further, disclosure of interim data by us
or by our competitors could result in volatility in the price of our common stock.
Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may
interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the
particular product candidate or product, our ability to make certain claims about our products, and our company in general. In addition, the information we
choose to publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree
with what we determine is material or otherwise appropriate information to include in our disclosure.
If the interim, top-line or preliminary data that we report differ from actual results, or if others, including regulatory authorities, disagree with the
conclusions reached, our ability to obtain approval for, and commercialize, our product candidates may be harmed, which could harm our business,
operating results, prospects or financial condition.
Our drug candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the
commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
Undesirable side effects caused by our drug candidates could cause us or regulatory authorities to interrupt, delay or halt clinical studies and could result in
a more restrictive label or the delay or denial of regulatory approval by the FDA or comparable foreign regulatory authorities. Other than our clinical
studies of UBX0101 and UBX1325, senolytic medicines designed to eliminate or cause the elimination of senescent cells have never been tested in
humans. As a result, although UBX1325 has been well tolerated in our Phase 1 and Phase 2 clinical studies with no adversities that would prevent
advancement into later stage clinical trials as of March 2022, UBX1325 could reveal a high and unacceptable severity and prevalence of side effects, and it
is possible that patients enrolled in such clinical studies could respond in unexpected ways. For instance, in preclinical in vivo animal and ex vivo human
tissue studies, our senolytic molecules have exhibited clearance of senescent cells; however, the elimination of accumulated senescent cells may result in
unforeseen events, including harming healthy cells or tissues. In addition, the entry by cells into a senescent state is a natural biological process that we
believe may have protective effects, such as halting the proliferation of damaged cells. The treatment of tissues with senolytic molecules could interfere
with such protective processes.
If unacceptable side effects arise in the development of our drug candidates, we, the FDA, the IRBs at the institutions in which our studies are conducted,
or the DSMB could suspend or terminate our clinical studies, or the FDA or comparable foreign regulatory authorities could order us to cease clinical
studies or deny approval of our drug candidates for any or all targeted indications. Treatment-related side effects could also affect patient recruitment or the
ability of enrolled patients to complete any of our clinical studies or result in potential product liability claims. In addition, these side effects may not be
appropriately recognized or managed by the treating medical staff. We expect to have to train medical personnel using our drug candidates to understand
the side effect profiles for our clinical studies and upon any commercialization of any of our drug candidates. Inadequate training in recognizing or
managing the potential side effects of our drug candidates could result in patient injury or death. Any of these occurrences may harm our business, financial
condition and prospects significantly.
In addition, even if we successfully advance any of our drug candidates into and through clinical studies, such trials will likely only include a limited
number of subjects and limited duration of exposure to our drug candidates. As a result, we cannot be assured that adverse effects of our drug candidates
will not be uncovered when a significantly larger number of patients are exposed to the drug candidate. Further, clinical studies may not be sufficient to
determine the effect and safety consequences of taking our drug candidates over a multi-year period. There can be no assurance that it will demonstrate a
similarly favorable safety profile in subsequent clinical trials.
If any of our drug candidates receives marketing approval, and we or others later identify undesirable side effects caused by such products, a number of
potentially significant negative consequences could result, including:
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regulatory authorities may withdraw their approval of the product;
we may be required to recall a product or change the way such product is administered to patients;
additional restrictions may be imposed on the marketing of the particular product or the manufacturing processes for the product or any
component thereof;
regulatory authorities may require the addition of labeling statements, such as a “black box” warning or a contraindication;
we may be required to implement a Risk Evaluation and Mitigation Strategy, or REMS, or create a Medication Guide outlining the risks of such
side effects for distribution to patients;
we could be sued and held liable for harm caused to patients;
the product may become less competitive; and
our reputation may suffer.
Any of the foregoing events could prevent us from achieving or maintaining market acceptance of the particular drug candidate, if approved, and result in
the loss of significant revenues to us, which would materially and adversely affect our results of operations and business. In addition, if one or more of our
drug candidates or our senescence approach generally prove to be unsafe, our entire platform and pipeline could be affected, which would have a material
and adverse effect on our business, financial condition, results of operations and prospects.
We may not be successful in our efforts to continue to create a pipeline of drug candidates or to develop commercially successful products. If we fail to
successfully identify and develop additional drug candidates, our commercial opportunity may be limited.
We are committed to developing senolytic medicines that slow, halt, or reverse diseases of aging, and we are currently advancing multiple senolytic
molecules to address a variety of diseases of aging, including ophthalmologic disorders. As senolytic medicines are not limited to intervention by a single
mode of action or molecular target, we believe that we can modulate a number of biologic pathways in order to trigger the beneficial elimination of
senescent cells. However, our core therapeutic approach is based on our belief that senescent cells drive diseases of aging, and that hypothesis has not yet
been proven. In addition, we do not know if we will be able to develop medicines that selectively eliminate senescent cells or whether the elimination of
such senescent cells will mitigate the effects of or effectively treat any diseases.
In addition, identifying, developing, obtaining regulatory approval and commercializing drug candidates for the treatment of diseases of aging will require
substantial additional funding and is prone to the risks of failure inherent in drug development. Research programs to identify drug candidates also require
substantial technical, financial and human resources, regardless of whether or not any drug candidates are ultimately identified, and even if our preclinical
research programs initially show promise in identifying potential drug candidates, they may fail to yield drug candidates for clinical development.
While we have a number of ongoing drug discovery programs targeting senescent cells, we do not know whether these will be successful, or whether we
will be able to identify novel senolytic mechanisms to continue to build our pipeline. We also cannot provide any assurance that we will be able to
successfully identify or acquire additional drug candidates, advance any of these additional drug candidates through the development process, successfully
commercialize any such additional drug candidates, if approved, or assemble sufficient resources to identify, acquire, develop or, if approved,
commercialize additional drug candidates. If we are unable to successfully identify, acquire, develop and commercialize additional drug candidates, our
commercial opportunities may be limited.
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We may be unable to obtain regulatory approval for our drug candidates under applicable regulatory requirements. The denial or delay of any such
approval would delay commercialization of our drug candidates and adversely impact our potential to generate revenue, our business and our results of
operations.
To gain approval to market our drug candidates, we must provide the FDA and foreign regulatory authorities with clinical data that adequately demonstrate
the safety and efficacy of the drug candidate for the intended indication applied for in the applicable regulatory filing. For our senolytic medicines, we must
also demonstrate that eliminating or causing the elimination of senescent cells and modulating relevant associated SASP factors will lead to the
improvement of well-defined and measurable endpoints.
We have not previously submitted a new drug application, or NDA, or biologics license application, or BLA, to the FDA, or similar approval filings to
comparable foreign regulatory authorities. An NDA, BLA or other relevant regulatory filing must include extensive preclinical and clinical data and
supporting information to establish that the drug candidate is safe and effective, or that a biological drug candidate is safe, pure and potent for each desired
indication. The NDA, BLA or other relevant regulatory submission must also include significant information regarding the chemistry, manufacturing and
controls for the product.
The research, testing, manufacturing, labeling, approval, sale, marketing, and distribution of drug and biologic products are subject to extensive regulation
by the FDA and other regulatory authorities in the United States and other countries, and such regulations differ from country to country. We are not
permitted to market our drug candidates in the United States or in any foreign countries until they receive the requisite approval from the applicable
regulatory authorities of such jurisdictions.
The FDA or any foreign regulatory bodies can delay, limit or deny approval of our drug candidates for many reasons, including:
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our inability to demonstrate to the satisfaction of the FDA or the applicable foreign regulatory body that any of our drug candidates is safe and
effective for the requested indication;
the FDA’s or the applicable foreign regulatory agency’s disagreement with our trial protocol or the interpretation of data from preclinical
studies or clinical studies;
our inability to demonstrate that the clinical and other benefits of any of our drug candidates outweigh any safety or other perceived risks;
the FDA’s or the applicable foreign regulatory agency’s requirement for additional preclinical studies or clinical studies;
the FDA’s or the applicable foreign regulatory agency’s failure to approve the formulation, labeling or specifications of our current or future
drug candidates, including UBX1325;
the FDA’s or the applicable foreign regulatory agency’s failure to approve the manufacturing processes or facilities of third-party manufacturers
upon which we rely; or
the potential for approval policies or regulations of the FDA or the applicable foreign regulatory agencies to significantly change in a manner
that renders our clinical data insufficient for approval.
Of the large number of biopharmaceutical and pharmaceutical products in development, only a small percentage successfully complete the FDA or other
regulatory approval processes and are commercialized.
Even if we eventually complete clinical testing and receive approval from the FDA or applicable foreign agencies for any of our drug candidates, the FDA
or the applicable foreign regulatory agency may grant approval contingent on the performance of costly additional clinical studies which may be required
after approval. The FDA or the applicable foreign regulatory agency also may approve our current drug candidates for limited indications or narrower
patient populations than we originally requested, and the FDA, or applicable foreign regulatory agency,
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may not approve our drug candidates with the labeling that we believe is necessary or desirable for the successful commercialization of such drug
candidates.
Any delay in obtaining, or inability to obtain, applicable regulatory approval would delay or prevent commercialization of our drug candidates and would
materially adversely impact our business and prospects.
Even if our current drug candidates or any future drug candidates obtain regulatory approval, they may fail to achieve the broad degree of physician
and patient adoption and use necessary for commercial success.
Even if one or more of our drug candidates receive FDA or other regulatory approvals, the commercial success of any of our current or future drug
candidates will depend significantly on the broad adoption and use of the resulting product by physicians and patients for approved indications. Our drug
candidates may not be commercially successful for a variety of reasons, including: competitive factors, pricing or physician preference, reimbursement by
insurers, the degree and rate of physician and patient adoption of our current or future drug candidates. If approved, the commercial success of our drug
candidates will depend on a number of factors, including:
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the clinical indications for which the product is approved and patient demand for approved products that treat those indications;
the safety and efficacy of our product as compared to other available therapies;
the availability of coverage and adequate reimbursement from managed care plans, insurers and other healthcare payors for any of our drug
candidates that may be approved;
acceptance by physicians, operators of clinics, and patients of the product as a safe and effective treatment;
physician and patient willingness to adopt a new therapy over other available therapies to treat approved indications;
overcoming any biases physicians or patients may have toward particular therapies for the treatment of approved indications;
proper training and administration of our drug candidates by physicians and medical staff;
public misperception regarding the use of our therapies, or public bias against “anti-aging” companies;
patient satisfaction with the results and administration of our drug candidates and overall treatment experience, including, for example, the
convenience of any dosing regimen;
the cost of treatment with our drug candidates in relation to alternative treatments and reimbursement levels, if any, and willingness to pay for
the product, if approved, on the part of insurance companies and other third-party payers, physicians and patients;
the willingness of patients to pay for certain of our products, if approved;
the revenue and profitability that our products may offer a physician as compared to alternative therapies;
the prevalence and severity of side effects;
limitations or warnings contained in the FDA-approved labeling for our products;
the willingness of physicians, operators of clinics and patients to utilize or adopt our products as a solution;
any FDA requirement to undertake a REMS;
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the effectiveness of our sales, marketing and distribution efforts;
adverse publicity about our products or favorable publicity about competitive products; and
potential product liability claims.
We cannot assure you that our current or future drug candidates, if approved, will achieve broad market acceptance among physicians and patients. Any
failure by our drug candidates that obtain regulatory approval to achieve market acceptance or commercial success would adversely affect our results of
operations.
We rely on third-party suppliers to manufacture supplies of our drug candidates and we intend to continue to rely on third parties to produce such
preclinical and clinical supplies as well as commercial supplies of any approved product. The loss of these suppliers, or their failure to comply with
applicable regulatory requirements or to provide us with sufficient quantities at acceptable quality levels or prices, or at all, would materially and
adversely affect our business.
We do not have the infrastructure or capability internally to manufacture supplies of our drug candidates or the materials necessary to produce our drug
candidates for use in the conduct of our clinical studies, and we lack the internal resources and the capability to manufacture any of our drug candidates on
a clinical or commercial scale. The facilities used by our contract manufacturers to manufacture our drug candidates are subject to various regulatory
requirements and may be subject to the inspection of the FDA or other regulatory authorities. We do not control the manufacturing process of, and are
completely dependent on, our contract manufacturing partners for compliance with the regulatory requirements, known as cGMPs. If our contract
manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or
comparable regulatory authorities in foreign jurisdictions, we may not be able to rely on their manufacturing facilities for the manufacture or our drug
candidates. In addition, we have limited control over the ability of our contract manufacturers to maintain adequate quality control, quality assurance and
qualified personnel. If the FDA or a comparable foreign regulatory authority finds these facilities inadequate for the manufacture of our drug candidates or
if such facilities are subject to enforcement action in the future or are otherwise inadequate, we may need to find alternative manufacturing facilities, which
would significantly impact our ability to develop, obtain regulatory approval for or market our drug candidates.
We currently intend to supply all of our drug candidates in all territories for our planned clinical development programs. We currently rely on third parties
at key stages in our supply chain. For instance, the supply chains for our current drug candidates involve several manufacturers that specialize in specific
operations of the manufacturing process, specifically, raw materials manufacturing, drug substance manufacturing and drug product manufacturing. As a
result, the supply chain for the manufacturing of our drug candidates is complicated and we expect the logistical challenges associated with our supply
chain to grow more complex as our drug candidates progress through the clinical trial process. Some of these third parties may also be adversely impacted
by COVID-19 or other unforeseen events and public health emergencies. For example, one of the manufacturers in our supply chain for UBX0101
experienced a two-week shutdown in April 2020 due to a COVID-19 related incident. While such incident did not impact our supply of UBX0101 for
clinical studies being conducted in April 2020, there can be no assurance that our supply chain for any of our candidates and clinical trials will not be
disrupted in the future due to the COVID-19 pandemic.
We do not have any control over the process or timing of the acquisition or manufacture of materials by our manufacturers. Further, we have not yet
engaged any manufacturers for the commercial supply of our current drug candidates. Although we intend to enter into such agreements prior to
commercial launch of any of our drug candidates, we may be unable to enter into any such agreement or do so on commercially reasonable terms, which
could have a material adverse impact upon our business. We generally do not begin a preclinical study and we do not intend to initiate any clinical studies
unless we believe we have access to a sufficient supply of a drug candidate to complete such study or trial. In addition, any significant delay in, or quality
control problems with respect to, the supply of a drug candidate, or the raw material components thereof, for an ongoing study or trial could considerably
delay completion of our preclinical studies or future clinical studies, product testing and potential regulatory approval of our drug candidates.
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Moreover, if there is a disruption to one or more of our third-party manufacturers’ or suppliers’ relevant operations, or if we are unable to enter into
arrangements for the commercial supply of our drug candidates, we will have no other means of producing our current drug candidates until they restore
the affected facilities or we or they procure alternative manufacturing facilities or sources of supply. Our ability to progress our preclinical and clinical
programs could be materially and adversely impacted if any of the third-party suppliers upon which we rely were to experience a significant business
challenge, disruption or failure due to issues such as financial difficulties or bankruptcy, issues relating to other customers such as regulatory or quality
compliance issues, or other financial, legal, regulatory or reputational issues.
Additionally, any damage to or destruction of our third-party manufacturers’ or suppliers’ facilities or equipment may significantly impair our ability to
manufacture our drug candidates on a timely basis.
In addition, to manufacture our current drug candidates in the quantities that we believe would be required to meet anticipated market demand, our third-
party manufacturers would likely need to increase manufacturing capacity and, in some cases, we would need to secure alternative sources of commercial
supply, which could involve significant challenges and may require additional regulatory approvals. In addition, the development of commercial-scale
manufacturing capabilities may require us and our third-party manufacturers to invest substantial additional funds and hire and retain the technical
personnel who have the necessary manufacturing experience. Neither we nor our third-party manufacturers may successfully complete any required
increase to existing manufacturing capacity in a timely manner, or at all. If our manufacturers or we are unable to purchase the raw materials necessary for
the manufacture of our drug candidates on acceptable terms, at sufficient quality levels, or in adequate quantities, if at all, the commercial launch of our
current drug candidates or any future drug candidates would be delayed or there would be a shortage in supply, which would impair our ability to generate
revenues from the sale of such drug candidates, if approved.
If we fail to attract and retain key personnel, we may be unable to successfully develop our current drug candidates or any future drug candidates,
conduct our clinical studies and commercialize our current or any future drug candidates.
Our success depends in part on our continued ability to attract, retain and motivate highly qualified management and employees. In February 2022 we
announced a restructuring to advance corporate strategy and focus on key ophthalmology programs. As a result, additional unplanned loss of personnel,
may occur despite our efforts to retain management and employees. Continued disruption caused by the transition or by the loss of ongoing services of any
other members of our management or employees could delay or prevent the successful development of our ongoing programs, initiation or completion of
our planned clinical studies or the commercialization of our current drug candidates or any future drug candidates. Competition for qualified personnel in
the biotechnology and pharmaceuticals field is intense due to the limited number of individuals who possess the skills and experience required by our
industry, and we may not be able to adequately address attrition, including unplanned, attrition, and as a result, the timely completion of our clinical trials
could be jeopardized.
We depend on third-party suppliers for key raw materials used in our manufacturing processes, and the loss of these third-party suppliers or their
inability to supply us with adequate raw materials could harm our business.
We rely on third-party suppliers for the raw materials required for the production of our drug candidates. Our dependence on these third-party suppliers and
the challenges we may face in obtaining adequate supplies of raw materials involve several risks, including limited control over pricing, availability, and
quality and delivery schedules. As a small company, our negotiation leverage is limited, and we are likely to get lower priority than our competitors who
are larger than we are. We cannot be certain that our suppliers will continue to provide us with the quantities of these raw materials that we require or
satisfy our anticipated specifications and quality requirements. Any supply interruption in limited or sole sourced raw materials could materially harm our
ability to manufacture our drug candidates until a new source of supply, if any, could be identified and qualified. We may be unable to find a sufficient
alternative supply channel in a reasonable time or on commercially reasonable terms. Any performance failure on the part of our suppliers could delay the
development and potential commercialization of our drug candidates, including limiting supplies necessary for clinical studies and regulatory approvals,
which would have a material adverse effect on our business.
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We rely on third parties in the conduct of critical portions of our preclinical studies and intend to rely on third parties in the conduct of critical portions of
our future clinical studies. If these third parties do not successfully carry out their contractual duties, fail to comply with applicable regulatory requirements
or meet expected deadlines, we may be unable to obtain regulatory approval for our drug candidates. Some of these third parties may also be adversely
impacted by COVID-19 or other unforeseen events and public health emergencies.
We currently do not have the ability to independently conduct preclinical studies that comply with the regulatory requirements known as good laboratory
practice, or GLP, requirements. We also do not currently have the ability to independently conduct any clinical studies. The FDA and regulatory authorities
in other jurisdictions require us to comply with regulations and standards, commonly referred to as good clinical practice, or GCP, requirements for
conducting, monitoring, recording and reporting the results of clinical studies, in order to ensure that the data and results are scientifically credible and
accurate and that the trial subjects are adequately informed of the potential risks of participating in clinical studies. We rely on medical institutions, clinical
investigators, contract laboratories and other third parties, such as CROs, to conduct GLP-compliant preclinical studies and GCP-compliant clinical studies
on our drug candidates properly and on time. While we have agreements governing their activities, we control only certain aspects of their activities and
have limited influence over their actual performance. The third parties with whom we contract for execution of our GLP-compliant preclinical studies and
our GCP-compliant clinical studies play a significant role in the conduct of these studies and trials and the subsequent collection and analysis of data. These
third parties are not our employees and, except for restrictions imposed by our contracts with such third parties, we have limited ability to control the
amount or timing of resources that they devote to our programs. Although we rely on these third parties to conduct our GLP-compliant preclinical studies
and GCP-compliant clinical studies, we remain responsible for ensuring that each of our GLP preclinical studies and clinical studies is conducted in
accordance with its investigational plan and protocol and applicable laws and regulations, and our reliance on the CROs does not relieve us of our
regulatory responsibilities.
Many of the third parties with whom we contract may also have relationships with other commercial entities, potentially including our competitors, for
whom they may also be conducting clinical studies or other drug development activities that could harm our competitive position. If the third parties
conducting our preclinical studies or our clinical studies do not adequately perform their contractual duties or obligations, experience significant business
challenges, disruptions or failures, do not meet expected deadlines, terminate their agreements with us or need to be replaced, or if the quality or accuracy
of the data they obtain is compromised due to their failure to adhere to our protocols or to GCPs, or for any other reason, we may need to enter into new
arrangements with alternative third parties. This could be difficult, costly or impossible, and our preclinical studies or clinical studies may need to be
extended, delayed, terminated or repeated. As a result, we may not be able to obtain regulatory approval in a timely fashion, or at all, for the applicable
drug candidate, our financial results and the commercial prospects for our drug candidates would be harmed, our costs could increase, and our ability to
generate revenues could be delayed.
We face significant competition in an environment of rapid technological and scientific change, and our drug candidates, if approved, will face
significant competition and our failure to effectively compete may prevent us from achieving significant market penetration. Most of our competitors
have significantly greater resources than we do, and we may not be able to successfully compete.
The biotechnology and pharmaceutical industries in particular are characterized by rapidly advancing technologies, intense competition and a strong
emphasis on developing proprietary therapeutics. Numerous companies are engaged in the development, patenting, manufacturing and marketing of
healthcare products competitive with those that we are developing. We face competition from a number of sources, such as pharmaceutical companies,
generic drug companies, biotechnology companies and academic and research institutions, many of which have greater financial resources, marketing
capabilities, sales forces, manufacturing capabilities, research and development capabilities, clinical study expertise, intellectual property portfolios,
experience in obtaining patents and regulatory approvals for drug candidates and other resources than we do. Some of the companies that offer competing
products also have a broad range of other product offerings, large direct sales forces and long-term customer relationships with our target physicians, which
could inhibit our market penetration efforts. Mergers and acquisitions in the pharmaceutical industry may result in even more resources being concentrated
among a smaller number of our competitors. Smaller or early-stage companies may also prove to be significant competitors, particularly through
collaborative arrangements with large and established companies. These competitors also compete with us in
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recruiting and retaining qualified scientific and management personnel and establishing clinical study sites and patient registration for clinical studies, as
well as in acquiring technologies complementary to, or necessary for, our programs. In addition, certain of our drug candidates, if approved, may compete
with other products that treat diseases of aging, including over the counter, or OTC, treatments, for a share of some patients’ discretionary budgets and for
physicians’ attention within their clinical practices.
We are aware of other companies seeking to develop treatments to prevent or treat diseases of aging through various biological pathways. Within our lead
senolytic program in ophthalmology diseases, our drug candidates would compete against current therapies from a wide range of companies and
technologies, including current standard of care treatments such as anti-VEGF antibodies (bevacizumab, ranibizumab, aflibercept, brolucizumab),
bispecific antibodies (faricimab), intravitreal steroid (dexamethasone), and pan-retinal photocoagulation by laser. There are also potentially disease-
modifying therapeutics being developed by several pharmaceutical and biotechnology companies, including Roche/Genentech and Regeneron.
Further, we believe that potential competitors may be able to develop senolytic medicines utilizing well-established molecules and pathways, which could
enable the development of competitive drug candidates utilizing the same cellular senescence biological theories.
Certain alternative treatments offered by competitors may be available at lower prices and may offer greater efficacy or better safety profiles. Furthermore,
currently approved products could be discovered to have application for treatment of diseases of aging generally, which could give such products
significant regulatory and market timing advantages over any of our drug candidates. Our competitors also may obtain FDA, EMA or other regulatory
approval for their products more rapidly than we may obtain approval for ours and may obtain orphan product exclusivity from the FDA for indications our
drug candidates are targeting, which could result in our competitors establishing a strong market position before we are able to enter the market. Newly
developed systemic or non-systemic treatments that replace existing therapies that currently are only utilized in patients suffering from severe disease may
also have lessened side effects or reduced prices compared to current therapies, which make them more attractive for patients suffering from mild to
moderate disease. Even if a generic or OTC product is less effective than our drug candidates, it may be more quickly adopted by physicians and patients
than our competing drug candidates based upon cost or convenience.
The successful commercialization of our drug candidates will depend in part on the extent to which governmental authorities and health insurers
establish adequate coverage, reimbursement levels and pricing policies. Failure to obtain or maintain coverage and adequate reimbursement for our
drug candidates, if approved, could limit our ability to market those products and decrease our ability to generate revenue.
The availability and adequacy of coverage and reimbursement by governmental healthcare programs such as Medicare and Medicaid, private health
insurers and other third-party payors are essential for most patients to be able to afford prescription medications such as our drug candidates, assuming
FDA approval. Our ability to achieve acceptable levels of coverage and reimbursement for products by governmental authorities, private health insurers
and other organizations will have an effect on our ability to successfully commercialize our drug candidates. Assuming we obtain coverage for our drug
candidates by a third-party payor, the resulting reimbursement payment rates may not be adequate or may require co-payments that patients find
unacceptably high. We cannot be sure that coverage and reimbursement in the United States, the European Union or elsewhere will be available for our
drug candidates or any product that we may develop, and any reimbursement that may become available may be decreased or eliminated in the future.
Third-party payors increasingly are challenging prices charged for pharmaceutical products and services, and many third-party payors may refuse to
provide coverage and reimbursement for particular drugs or biologics when an equivalent generic drug, biosimilar or a less expensive therapy is available.
It is possible that a third-party payor may consider our drug candidates as substitutable and only offer to reimburse patients for the cost of the less
expensive product. Even if we show improved efficacy or improved convenience of administration with our drug candidates, pricing of existing third-party
therapeutics may limit the amount we will be able to charge for our drug candidates. These payors may deny or revoke the reimbursement status of a given
product or establish prices for new or existing marketed products at levels that are too low to enable us to realize an appropriate return on our investment in
our drug candidates. If reimbursement is not available or is available only at limited levels, we may
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not be able to successfully commercialize our drug candidates and may not be able to obtain a satisfactory financial return on our investment in the
development of drug candidates.
There is significant uncertainty related to the insurance coverage and reimbursement of newly approved products. In the United States, third-party payors,
including private and governmental payors, such as the Medicare and Medicaid programs, play an important role in determining the extent to which new
drugs and biologics will be covered. The Medicare and Medicaid programs increasingly are used as models in the United States for how private payors and
other governmental payors develop their coverage and reimbursement policies for drugs and biologics. Some third-party payors may require pre-approval
of coverage for new or innovative devices or drug therapies before they will reimburse healthcare providers who use such therapies. We cannot predict at
this time what third-party payors will decide with respect to the coverage and reimbursement for our drug candidates.
No uniform policy for coverage and reimbursement for products exists among third-party payors in the United States. Therefore, coverage and
reimbursement for products can differ significantly from payor to payor. As a result, the coverage determination process is often a time-consuming and
costly process that will require us to provide scientific and clinical support for the use of our drug candidates to each payor separately, with no assurance
that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Furthermore, rules and regulations regarding
reimbursement change frequently, in some cases on short notice, and we believe that changes in these rules and regulations are likely.
Outside the United States, international operations are generally subject to extensive governmental price controls and other market regulations, and we
believe the increasing emphasis on cost-containment initiatives in Europe and other countries have and will continue to put pressure on the pricing and
usage of our drug candidates. In many countries, the prices of medical products are subject to varying price control mechanisms as part of national health
systems. Other countries allow companies to fix their own prices for medical products but monitor and control company profits.
Additional foreign price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our drug candidates.
Accordingly, in markets outside the United States, the reimbursement for our drug candidates may be reduced compared with the United States and may be
insufficient to generate commercially reasonable revenue and profits.
Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to cap or reduce healthcare costs may cause such
organizations to limit both coverage and the level of reimbursement for newly approved products and, as a result, they may not cover or provide adequate
payment for our drug candidates. We expect to experience pricing pressures in connection with the sale of our drug candidates due to the trend toward
managed health care, the increasing influence of health maintenance organizations and additional legislative changes. The downward pressure on
healthcare costs in general, particularly prescription drugs and biologics and surgical procedures and other treatments, has become intense. As a result,
increasingly high barriers are being erected to the entry of new products.
We currently have no sales organization. If we are unable to establish sales capabilities on our own or through third parties, we may not be able to
market and sell our drug candidates effectively in the U.S. and foreign jurisdictions, if approved, or generate product revenue.
We currently do not have a marketing or sales organization. In order to commercialize our drug candidates in the United States and foreign jurisdictions, we
must build our marketing, sales, distribution, managerial and other non-technical capabilities or make arrangements with third parties to perform these
services, and we may not be successful in doing so. If any of our drug candidates receive regulatory approval, we expect to establish a sales organization
with technical expertise and supporting distribution capabilities to commercialize each such drug candidate, which will be expensive and time consuming.
We have no prior experience in the marketing, sale and distribution of pharmaceutical products and there are significant risks involved in building and
managing a sales organization, including our ability to hire, retain, and incentivize qualified individuals, generate sufficient sales leads, provide adequate
training to sales and marketing personnel, and effectively manage a geographically dispersed sales and marketing team. Any failure or delay in the
development of our internal sales, marketing and distribution capabilities would adversely impact the commercialization of these products. We may choose
to
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collaborate with third parties that have direct sales forces and established distribution systems, either to augment our own sales force and distribution
systems or in lieu of our own sales force and distribution systems. If we are unable to enter into such arrangements on acceptable terms or at all, we may
not be able to successfully commercialize our drug candidates. If we are not successful in commercializing our drug candidates or any future drug
candidates, either on our own or through arrangements with one or more third parties, we may not be able to generate any future product revenue and we
would incur significant additional losses.
If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of our current
or future drug candidates.
We face an inherent risk of product liability as a result of the clinical testing of our drug candidates and will face an even greater risk if we commercialize
any products. For example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during product testing,
manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, and a failure to
warn of dangers inherent in the product, negligence, strict liability, and a breach of warranty. Claims could also be asserted under state consumer protection
acts. If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to limit
commercialization of our drug candidates.
Even a successful defense would require significant financial and management resources. Regardless of the merits or eventual outcome, liability claims
may result in:
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decreased demand for our current or future drug candidates;
injury to our reputation;
withdrawal of clinical study participants;
costs to defend the related litigation;
a diversion of management’s time and our resources;
substantial monetary awards to trial participants or patients;
regulatory investigations, product recalls, withdrawals or labeling, marketing or promotional restrictions;
loss of revenue; and
the inability to commercialize our current or any future drug candidates.
Our inability to obtain and maintain sufficient product liability insurance at an acceptable cost and scope of coverage to protect against potential product
liability claims could prevent or inhibit the commercialization of our current or any future drug candidates we develop. We currently carry product liability
insurance covering our clinical studies. Although we maintain such insurance, any claim that may be brought against us could result in a court judgment or
settlement in an amount that is not covered, in whole or in part, by our insurance or that is in excess of the limits of our insurance coverage. Our insurance
policies also have various exclusions and deductibles, and we may be subject to a product liability claim for which we have no coverage. We will have to
pay any amounts awarded by a court or negotiated in a settlement that exceed our coverage limitations or that are not covered by our insurance, and we
may not have, or be able to obtain, sufficient funds to pay such amounts. Moreover, in the future, we may not be able to maintain insurance coverage at a
reasonable cost or in sufficient amounts to protect us against losses. If and when we obtain approval for marketing any of our drug candidates, we intend to
expand our insurance coverage to include the sale of such drug candidate; however, we may be unable to obtain this liability insurance on commercially
reasonable terms or at all.
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Our existing collaborations as well as additional collaboration arrangements that we may enter into in the future may not be successful, which could
adversely affect our ability to develop and commercialize our drug candidates.
We utilize external collaborations and currently maintain several active early-stage research and discovery focused collaborations. In the future, we may
seek additional collaboration arrangements for the commercialization, or potentially for the development, of certain of our drug candidates depending on
the merits of retaining commercialization rights for ourselves as compared to entering into collaboration arrangements. To the extent that we decide to enter
into additional collaboration agreements in the future, we may face significant competition in seeking appropriate collaborators. Moreover, collaboration
arrangements are complex and time-consuming to negotiate, document, implement and maintain and challenging to manage. We may not be successful in
our efforts to prudently manage our existing collaborations or to enter new ones should we chose to do so. The terms of new collaborations, or other
arrangements that we may establish may not be favorable to us.
The success of our collaboration arrangements will depend heavily on the efforts and activities of our collaborators and partners. Collaborations are subject
to numerous risks, which may include risks that:
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collaborators and partners have significant discretion in determining the efforts and resources that they will apply to collaborations and they
may not devote the level of effort or resources we expect;
collaborators may not pursue development and commercialization of our drug candidates or may elect not to continue or renew development or
commercialization programs based on clinical study results, changes in their strategic focus due to their acquisition of competitive products or
their internal development of competitive products, availability of funding or other external factors, such as a business combination that diverts
resources or creates competing priorities;
collaborators may delay clinical studies, provide insufficient funding for a clinical study program, stop a clinical study, abandon a drug
candidate, repeat or conduct new clinical studies or require a new formulation of a drug candidate for clinical testing;
collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or drug
candidates;
a collaborator with marketing, manufacturing, and distribution rights to one or more products may not commit sufficient resources to or
otherwise not perform satisfactorily in carrying out these activities;
we could grant exclusive rights to our collaborators that would prevent us from collaborating with others;
collaborators may not properly maintain or defend our intellectual property rights or may use our intellectual property or proprietary
information in a way that gives rise to actual or threatened litigation that could jeopardize or invalidate our intellectual property or proprietary
information or expose us to potential liability;
disputes may arise between us and a collaborator that cause the delay or termination of the research, development or commercialization of our
current or future drug candidates or that result in costly litigation or arbitration that diverts management attention and resources;
collaborations may be terminated, resulting in a need for additional capital to pursue further development or commercialization of the
applicable current or future drug candidates;
collaborators may own or co-own intellectual property covering products that results from our collaborating with them, and in such cases, we
would not have the exclusive right to develop or commercialize such intellectual property;
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disputes may arise with respect to the ownership of any intellectual property developed pursuant to our collaborations;
a collaborator’s sales and marketing activities or other operations may not be in compliance with applicable laws resulting in civil or criminal
proceedings; and
collaborators may be adversely impacted by COVID-19 or other unforeseen events and public health emergencies.
Risks Related to Intellectual Property
Our senolytic medicine platform and any future products that we commercialize could be alleged to infringe patent rights and other proprietary rights
of third parties, which may require costly litigation and, if we are not successful, could cause us to pay substantial damages and/or limit our ability to
commercialize our products.
Our commercial success depends on our ability to develop, manufacture and market our senolytic medicines and future drug candidates and use our
proprietary technology without infringing the patents and other proprietary rights of third parties. Intellectual property disputes can be costly to defend and
may cause our business, operating results and financial condition to suffer. We operate in an industry with extensive intellectual property litigation. As the
biopharmaceutical and pharmaceutical industries expand and more patents are issued, the risk increases that there may be patents issued to third parties that
relate to our products and technology of which we are not aware or that we may need to challenge to continue our operations as currently contemplated.
Whether merited or not, we may face allegations that we have infringed the trademarks, copyrights, patents and other intellectual property rights of third
parties, including patents held by our competitors or by non-practicing entities. We may also face allegations that our employees have misappropriated the
intellectual property rights of their former employers or other third parties.
Litigation may make it necessary to defend ourselves by determining the scope, enforceability, and validity of third-party proprietary rights, or to establish
our proprietary rights. Regardless of whether claims that we are infringing patents or other intellectual property rights have merit, the claims can be time
consuming, divert management attention and financial resources and are costly to evaluate and defend. Results of any such litigation are difficult to predict
and may require us to stop treating certain conditions, obtain licenses or modify our products and features while we develop non-infringing substitutes, or
may result in significant settlement costs. For example, litigation can involve substantial damages for infringement (and if the court finds that the
infringement was willful, we could be ordered to pay treble damages and the patent owner’s attorneys’ fees), and the court could prohibit us from selling or
licensing our products unless the third-party licenses rights to us, which it is not required to do at a commercially reasonable price or at all. If a license is
available from a third party, we may have to pay substantial royalties, upfront fees or grant cross-licenses to intellectual property rights for our products.
We may also have to redesign our products so they do not infringe third-party intellectual property rights, which may not be possible at all or may require
substantial monetary expenditures and time, during which our products may not be available for manufacture, use, or sale.
In addition, patent applications in the United States and many international jurisdictions are typically not published until 18 months after the filing of
certain priority documents (or, in some cases, are not published until they issue as patents) and publications in the scientific literature often lag behind
actual discoveries. Thus, we cannot be certain that others have not filed patent applications or made public disclosures relating to our technology or our
contemplated technology. A third party may have filed, and may in the future file, patent applications covering our products or technology similar to ours.
Any such patent application may have priority over our patent applications or patents, which could further require us to obtain rights to issued patents
covering such technologies. If another party has filed a U.S. patent application on inventions similar to ours, depending on whether the timing of the filing
date falls under certain patent laws, we may have to participate in a priority contest (such as an interference proceeding) declared by the U.S. Patent and
Trademark Office, to determine priority of invention in the United States. The costs of patent and other proceedings could be substantial, and it is possible
that such efforts would be unsuccessful if it is
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determined that the other party had independently arrived at the same or similar invention prior to our own invention, resulting in a loss of our U.S. patent
position with respect to such inventions
From time to time, we may be subject to legal proceedings and claims in the ordinary course of business with respect to intellectual property. Although we
are not currently subject to any claims from third parties asserting infringement of their intellectual property rights, in the future, we may receive claims
from third parties asserting infringement of their intellectual property rights. Future litigation may be necessary to establish our intellectual property rights
or to defend ourselves by determining the scope, enforceability and validity of third-party intellectual property rights. There can be no assurance with
respect to the outcome of any current or future litigation brought by or against us, and the outcome of any such litigation could have a material adverse
impact on our business, operating results and financial condition. Litigation is inherently unpredictable and outcomes are uncertain. Further, as the costs
and outcome of these types of claims and proceedings can vary significantly, it is difficult to estimate potential losses that may occur. Accordingly, we are
unable at this time to estimate the effects of these potential future lawsuits on our financial condition, operations or cash flows.
Some of our competitors may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater
resources. Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant
expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements
of the results of hearings, motions or other interim proceedings or developments, and if securities analysts or investors perceive these results to be negative,
it could have a material adverse effect on the price of our common stock. Finally, any uncertainties resulting from the initiation and continuation of any
litigation could have a material adverse effect on our ability to raise the funds necessary to continue our operations.
If we are unable to obtain, maintain and enforce intellectual property protection directed to our senolytic medicine platform and any future
technologies that we develop, others may be able to make, use, or sell products substantially the same as ours, which could adversely affect our ability
to compete in the market.
As of March 1, 2022, we own, co-own, or have an exclusive license in certain fields of use to more than 150 patents and pending applications in the United
States and foreign jurisdictions. This portfolio includes 47 issued and allowed U.S. patents and applications and 38 granted and allowed foreign patents and
applications, respectively. A composition of matter patent filing claiming the specific chemical structure of UBX1325 was issued in the U.S. on April 20,
2021, which will extend our loss of exclusivity on this molecule to 2039, not including any patent term adjustment or patent term extensions to which it
may be entitled.
We have not pursued or maintained, and may not pursue or maintain in the future, patent protection for our products in every country or territory in which
we may sell our products. In addition, we cannot be sure that any of our pending patent applications or pending trademark applications will issue or that, if
issued, they will issue in a form that will be advantageous to us. The U.S. Patent and Trademark Office, or the USPTO, international patent offices or
judicial bodies may deny or significantly narrow claims made under our patent applications and our issued patents may be successfully challenged, may be
designed around, or may otherwise be of insufficient scope to provide us with protection for our commercial products. Further, the USPTO, international
trademark offices or judicial bodies may deny our trademark applications and, even if published or registered, these trademarks may not effectively protect
our brand and goodwill. Like patents, trademarks also may be successfully opposed or challenged.
We cannot be certain that the steps we have taken will prevent unauthorized use or unauthorized reverse engineering of our technology. Moreover, third
parties may independently develop technologies that are competitive with ours and such competitive technologies may or may not infringe our intellectual
property. The enforcement of our intellectual property rights also depends on the success of our legal actions against these infringers in the respective
country or forum, but these actions may not be successful. As with all granted intellectual property, such intellectual property may be challenged,
invalidated or circumvented, may not provide specific protection and/or may not prove to be enforceable in actions against specific alleged infringers.
The market for biopharmaceuticals, pharmaceuticals, and treatments for diseases of aging is highly competitive and subject to rapid technological change.
Our success depends, in part, upon our ability to maintain a competitive position in the development and protection of technologies and products for use in
these fields and upon our ability
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to obtain, maintain and enforce our intellectual property rights in connection therewith. We seek to obtain and maintain patents and other intellectual
property rights to restrict the ability of others to market products that misappropriate our technology and/or infringe our intellectual property to unfairly and
illegally compete with our products. If we are unable to protect our intellectual property and proprietary rights, our competitive position and our business
could be harmed, as third parties may be able to make, use, or sell products that are substantially the same as ours without incurring the sizeable
development and licensing costs that we have incurred, which would adversely affect our ability to compete in the market.
We use a combination of patents, trademarks, know-how, confidentiality procedures, and contractual provisions to protect our proprietary technology.
However, these protections may not be adequate and may not provide us with any competitive advantage. For example, patents may not issue from any of
our currently pending or any future patent applications, and our issued patents and any future patents that may issue may not survive legal challenges to
their scope, validity or enforceability, or provide significant protection for us.
If we or one of our current or future collaborators were to initiate legal proceedings against a third party to enforce a patent covering one of our current
drug candidates or future drug candidates, the defendant could counterclaim that our patent is invalid and/or unenforceable. In patent litigation in the
United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace.
Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, including lack of novelty, obviousness or
nonenablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant
information from the USPTO, or made a misleading statement, during prosecution. Third parties may also raise similar claims before the USPTO, even
outside the context of litigation. The outcome following legal assertions of invalidity and unenforceability is unpredictable.
With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were
unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and
perhaps all, of the patent protection on our drug candidates. Such a loss of patent protection would have a material adverse impact on our business.
Even if our patents are determined by a court to be valid and enforceable, they may not be interpreted sufficiently broadly to prevent others from marketing
products similar to ours or designing around our patents. For example, third parties may be able to make products that are similar to ours but that are not
covered by the claims of our patents. Third parties may assert that we or our licensors were not the first to make the inventions covered by our issued
patents or pending patent applications. The claims of our issued patents or patent applications when issued may not cover our proposed commercial
technologies or the future products that we develop. We may not have freedom to commercialize unimpeded by the patent rights of others. Third parties
may have dominating, blocking, or other patents relevant to our technology of which we are not aware. There may be prior public disclosures or art that
could be deemed to invalidate one or more of our patent claims. Further, we may not develop additional proprietary technologies in the future, and, if we
do, they may not be patentable.
Patent law can be highly uncertain and involve complex legal and factual questions for which important principles remain unresolved. In the United States
and in many international jurisdictions, policy regarding the breadth of claims allowed in patents can be inconsistent. The U.S. Supreme Court and the
Court of Appeals for the Federal Circuit have made, and will likely continue to make, changes in how the patent laws of the United States are interpreted.
Similarly, international courts have made, and will likely continue to make, changes in how the patent laws in their respective jurisdictions are interpreted.
We cannot predict future changes in the interpretation of patent laws or changes to patent laws that might be enacted into law by U.S. and international
legislative bodies. Those changes may materially affect our patents, our ability to obtain patents or the patents and patent applications of our licensors.
Patent reform legislation in the United States could increase the uncertainties and costs surrounding the prosecution of our patent applications and the
enforcement or defense of our issued patents. For example, on September 16, 2011, the Leahy-Smith America Invents Act, or Leahy-Smith Act, was signed
into law. The Leahy-Smith Act included a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications
are prosecuted, redefine prior art, may affect patent litigation, and switch the U.S. patent system from a “first-to-invent” system to a “first-to-file” system.
Under a “first-to-file” system, assuming the other
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requirements for patentability are met, the first inventor to file a patent application generally will be entitled to the patent on an invention regardless of
whether another inventor had made the invention earlier. The U.S. Patent and Trademark Office recently developed new regulations and procedures to
govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law associated with the Leahy-Smith Act, and in particular,
the first-to-file provisions, only became effective on March 16, 2013. The Leahy-Smith Act and its implementation could increase the uncertainties and
costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, which could have a material adverse
effect on our business and financial condition.
In addition, we have a number of international patents and patent applications and expect to continue to pursue patent protection in many of the significant
markets in which we intend to do business. The laws of some international jurisdictions may not protect intellectual property rights to the same extent as
laws in the United States, and many companies have encountered significant difficulties in obtaining, protecting, and defending such rights in international
jurisdictions. If we encounter such difficulties or we are otherwise precluded from effectively protecting our intellectual property rights in international
jurisdictions, our business prospects could be substantially harmed.
Varying filing dates in international countries may also permit intervening third parties to allege priority to certain technology.
Patent terms may be shortened or lengthened by, for example, terminal disclaimers, patent term adjustments, supplemental protection certificates, and
patent term extensions. Patent term extensions and supplemental protection certificates, and the like, may be impacted by the regulatory process and may
not significantly lengthen the patent term. Non-payment or delay in payment of patent fees or annuities, delay in patent filings or delay in extension filing
(including any patent term extension or adjustment filing), whether intentional or unintentional, may also result in the loss of patent rights important to our
business. Certain countries have compulsory licensing laws under which a patent owner may be compelled to grant licenses to other parties. In addition,
many countries limit the enforceability of patents against other parties, including government agencies or government contractors. In these countries, the
patent owner may have limited remedies, which could materially diminish the value of any patents.
In addition to the protection afforded by patents, we rely on confidentiality agreements to protect confidential information and proprietary know-how that is
not patentable or that we elect not to patent, processes for which patents are difficult to enforce and any other elements of our drug candidate discovery and
development processes that involve proprietary know-how, information or technology that is not covered by patents. We seek to protect our proprietary
technology and processes, in part, by entering into confidentiality agreements with our employees, consultants, scientific advisors, and contractors. We
cannot guarantee that we have entered into such agreements with each party that may have or have had access to our confidential information or proprietary
technology and processes. We also seek to preserve the integrity and confidentiality of our data and other confidential information by maintaining physical
security of our premises and physical and electronic security of our information technology systems. While we have confidence in these individuals,
organizations and systems, agreements or security measures may be breached and detecting the disclosure or misappropriation of confidential information
and enforcing a claim that a party illegally disclosed or misappropriated confidential information is difficult, expensive and time-consuming, and the
outcome is unpredictable. Further, we may not be able to obtain adequate remedies for any breach. In addition, our confidential information may otherwise
become known or be independently discovered by competitors, in which case we would have no right to prevent them, or those to whom they communicate
it, from using that technology or information to compete with us. We may in the future rely on trade secret protection, which would be subject to the risks
identified above with respect to confidential information.
Monitoring unauthorized use of our intellectual property is difficult and costly. From time to time, we review our competitors’ products, and may in the
future seek to enforce our patents or other rights against potential infringement. However, the steps we have taken to protect our proprietary rights may not
be adequate to prevent misappropriation of our intellectual property. We may not be able to detect unauthorized use of, or take appropriate steps to enforce,
our intellectual property rights. Our competitors may also independently develop similar technology. Any inability to meaningfully protect our intellectual
property could result in competitors offering products that incorporate our product or service features, which could reduce demand for our products. In
addition, we may need to defend our patents from third-party challenges, such as (but not limited to) interferences, derivation
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proceedings, reexamination proceedings, post-grant review, inter partes review, third-party submissions, oppositions, nullity actions or other patent
proceedings. We may need to initiate infringement claims or litigation.
Adverse proceedings such as litigation can be expensive, time consuming and may divert the efforts of our technical and managerial personnel, which
could in turn harm our business, whether or not we receive a determination favorable to us. In addition, in an infringement proceeding, a court or other
judicial body may decide that the patent we seek to enforce is invalid or unenforceable, or may refuse to stop the other party from using the technology at
issue on the grounds that the patent in question does not cover the technology in question. An adverse result in any litigation could put one or more of our
patents at risk of being invalidated or interpreted narrowly. Some of our competitors may be able to devote significantly more resources to intellectual
property litigation and may have significantly broader patent portfolios to assert against us if we assert our rights against them. Further, because of the
substantial discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be disclosed
or otherwise compromised during litigation.
We may not be able to correctly estimate or control our future operating expenses in relation to obtaining intellectual property, enforcing intellectual
property and/or defending intellectual property, which could affect operating expenses. Our operating expenses may fluctuate significantly in the future as a
result of a variety of factors, including the costs of preparing, filing, prosecuting, defending, and enforcing patent and trademark claims and other
intellectual property-related costs, including adverse proceedings (such as litigation) costs.
Our intellectual property agreements with third parties may be subject to disagreements over contract interpretation, which could narrow the scope of
our rights to the relevant intellectual property or technology or increase our financial or other obligations to our licensors.
Certain provisions in our intellectual property agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation
disagreement that may arise could affect the scope of our rights to the relevant intellectual property or technology, or affect financial or other obligations
under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations and prospects.
In addition, while it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property
to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact
conceives or develops intellectual property that we regard as our own. Our assignment agreements may not be self-executing or may be breached, and we
may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our
intellectual property.
If we are unable to protect the confidentiality of our proprietary information and know-how, the value of our technology and products could be
adversely affected.
We may not be able to protect our proprietary information and technology adequately. Although we use reasonable efforts to protect our proprietary
information, technology, and know-how, our employees, consultants, contractors and outside scientific advisors may unintentionally or willfully disclose
our information to competitors. Enforcing a claim that a third party illegally obtained and is using any of our proprietary information, technology or know-
how is expensive and time consuming, and the outcome is unpredictable. In addition, courts outside the United States are sometimes less willing to protect
proprietary information, technology, and know-how. We rely, in part, on non-disclosure and confidentiality agreements with our employees, consultants and
other parties to protect our proprietary information, technology, and know-how. These agreements may be breached and we may not have adequate
remedies for any breach. Moreover, others may independently develop similar or equivalent proprietary information, and third parties may otherwise gain
access to our proprietary knowledge.
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Risks Related to Government Regulation
Even if we obtain regulatory approval for a drug candidate, our products will remain subject to regulatory scrutiny.
If our drug candidates are approved, they will be subject to ongoing regulatory requirements for manufacturing, labeling, packaging, storage, advertising,
promotion, sampling, record-keeping, conduct of post-marketing studies, and submission of safety, efficacy, and other post-market information, including
both federal and state requirements in the United States and requirements of comparable foreign regulatory authorities.
Manufacturers and manufacturers’ facilities are required to comply with extensive FDA and comparable foreign regulatory authority requirements,
including ensuring that quality control and manufacturing procedures conform to cGMP regulations. As such, we and our contract manufacturers will be
subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any approved marketing application.
Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including
manufacturing, production, and quality control.
We will have to comply with requirements concerning advertising and promotion for our products. Promotional communications with respect to
prescription drugs and biologics are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s
approved label. As such, we may not promote our products for indications or uses for which they do not have approval. The holder of an approved
application must submit new or supplemental applications and obtain approval for certain changes to the approved product, product labeling, or
manufacturing process. We could also be asked to conduct post-marketing clinical studies to verify the safety and efficacy of our products in general or in
specific patient subsets. An unsuccessful post-marketing study or failure to complete such a study could result in the withdrawal of marketing approval.
If a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems
with the facility where the product is manufactured, or disagrees with the promotion, marketing or labeling of a product, such regulatory agency may
impose restrictions on that product or us, including requiring withdrawal of the product from the market. If we fail to comply with applicable regulatory
requirements, a regulatory agency or enforcement authority may, among other things:
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impose civil or criminal penalties;
suspend or withdraw regulatory approval;
suspend any of our clinical studies;
refuse to approve pending applications or supplements to approved applications submitted by us;
impose restrictions on our operations, including closing our contract manufacturers’ facilities; or
seize or detain products or require a product recall.
Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate
negative publicity. Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to commercialize and
generate revenue from our products. If regulatory sanctions are applied or if regulatory approval is withdrawn, the value of our company and our operating
results will be adversely affected.
Moreover, the policies of the FDA and of other regulatory authorities may change and additional government regulations may be enacted that could
prevent, limit or delay regulatory approval of our drug candidates. We cannot
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predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative or executive action, either in the
United States or abroad.
If we are slow or unable to adapt to changes in existing requirements or the adoption of new requirements or policies, or if we are not able to maintain
regulatory compliance, we may be subject to enforcement action, and we may not achieve or sustain profitability.
If any of our small molecule drug candidates obtain regulatory approval, additional competitors could enter the market with generic versions of such
drugs, which may result in a material decline in sales of affected products.
Under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-Waxman Act, a pharmaceutical manufacturer may file an
abbreviated new drug application, or ANDA, seeking approval of a generic version of an approved, small molecule innovator product. Under the Hatch-
Waxman Act, a manufacturer may also submit a new drug application, or NDA, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act that
references the FDA’s prior approval of the small molecule innovator product. A 505(b)(2) NDA product may be for a new or improved version of the
original innovator product. The Hatch-Waxman Act also provides for certain periods of regulatory exclusivity, which preclude FDA approval (or in some
circumstances, FDA filing and review) of an ANDA or 505(b)(2) NDA. In addition to the benefits of regulatory exclusivity, an innovator NDA holder may
have patents claiming the active ingredient, product formulation or an approved use of the drug, which would be listed with the product in the FDA
publication, “Approved Drug Products with Therapeutic Equivalence Evaluations,” known as the Orange Book. If there are patents listed in the Orange
Book for a product, a generic or 505(b)(2) applicant that seeks to market its product before expiration of the patents must include in their applications what
is known as a “Paragraph IV” certification, challenging the validity or enforceability of, or claiming non-infringement of, the listed patent or patents.
Notice of the certification must be given to the patent owner and NDA holder and if, within 45 days of receiving notice, either the patent owner or NDA
holder sues for patent infringement, approval of the ANDA or 505(b)(2) NDA is stayed for up to 30 months.
Accordingly, if any of our small molecule drug candidates, such as UBX1325, are approved, competitors could file ANDAs for generic versions of our
small molecule drug products or 505(b)(2) NDAs that reference our small molecule drug products. If there are patents listed for our small molecule drug
products in the Orange Book, those ANDAs and 505(b)(2) NDAs would be required to include a certification as to each listed patent indicating whether the
ANDA applicant does or does not intend to challenge the patent. We cannot predict which, if any, patents in our current portfolio or patents we may obtain
in the future will be eligible for listing in the Orange Book, how any generic competitor would address such patents, whether we would sue on any such
patents, or the outcome of any such suit.
We may not be successful in securing or maintaining proprietary patent protection for products and technologies we develop or license. Moreover, if any of
our owned or in-licensed patents that are listed in the Orange Book are successfully challenged by way of a Paragraph IV certification and subsequent
litigation, the affected product could immediately face generic competition and its sales would likely decline rapidly and materially.
Any biologic, or large molecule, drug candidates for which we intend to seek approval may face competition sooner than anticipated.
If we are successful in achieving regulatory approval to commercialize any biologic drug candidate faster than our competitors, such drug candidates may
face competition from biosimilar products. In the United States, large molecule drug candidates are regulated by the FDA as biologic products subject to
approval under the biologics license application, or BLA, pathway. The Biologics Price Competition and Innovation Act of 2009, or BPCIA, creates an
abbreviated pathway for the approval of biosimilar and interchangeable biologic products following the approval of an original BLA. The abbreviated
regulatory pathway establishes legal authority for the FDA to review and approve biosimilar biologics, including the possible designation of a biosimilar as
“interchangeable” based on its similarity to an existing brand product. Under the BPCIA, an application for a biosimilar product cannot be approved by the
FDA until 12 years after the original branded product was approved under a BLA. The law is complex and is still being interpreted and implemented by the
FDA. As a result, its ultimate impact, implementation, and meaning are subject to uncertainty.
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Moreover, the extent to which a biosimilar product, once approved, will be substituted for any one of our reference products in a way that is similar to
traditional generic substitution for non-biologic products is not yet clear, and will depend on a number of marketplace and regulatory factors that are still
developing. In addition, a competitor could decide to forego the biosimilar approval path and submit a full BLA after completing its own preclinical studies
and clinical studies. In such cases, any exclusivity to which we may be eligible under the BPCIA would not prevent the competitor from marketing its
product as soon as it is approved.
If competitors are able to obtain marketing approval for biosimilars referencing our large molecule drug candidates, if approved, such products may
become subject to competition from such biosimilars, with the attendant competitive pressure and potential adverse consequences. Such competitive
products may be able to immediately compete with us in each indication for which our drug candidates may have received approval.
Enacted and future healthcare legislation may increase the difficulty and cost for us to obtain marketing approval of and commercialize our drug
candidates and may affect the prices we may set.
In the United States, the European Union and other jurisdictions, there have been, and we expect there will continue to be, a number of legislative and
regulatory changes and proposed changes to the healthcare system that could affect our future results of operations. In particular, there have been and
continue to be a number of initiatives at the U.S. federal and state levels that seek to reduce healthcare costs and improve the quality of healthcare. For
example, in March 2010, the Patient Protection and ACA, as amended by the Health Care and Education Reconciliation Act, or collectively the Affordable
Care Act, was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers. Among the provisions of the
ACA, those of greatest importance to the pharmaceutical and biotechnology industries include the following:
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an annual, non-deductible fee payable by any entity that manufactures or imports certain branded prescription drugs and biologic agents (other
than those designated as orphan drugs), which is apportioned among these entities according to their market share in certain government
healthcare programs;
a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% point-of-sale discounts off negotiated
prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs
to be covered under Medicare Part D;
an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the
average manufacturer price for branded and generic drugs, respectively;
a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled,
infused, instilled, implanted or injected;
extension of a manufacturer’s Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care
organizations;
expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to certain individuals
with income at or below 133% of the federal poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research,
along with funding for such research;
creation of the Independent Payment Advisory Board, which, once empaneled, will have the authority to recommend certain changes to the
Medicare program that could result in reduced payments for prescription drugs and those recommendations could have the effect of law unless
overruled by a supermajority vote of Congress; and
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establishment of a Center for Medicare Innovation at the Centers for Medicare & Medicaid Services, or CMS, to test innovative payment and
service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.
Since its enactment, there have been judicial and Congressional challenges to certain aspects of the Affordable Care Act. For example, the Tax Cuts and
Jobs Act of 2017, or the Tax Act, includes a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment imposed by the
ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual
mandate”. In addition, there may be other efforts to challenge, repeal or replace the ACA that may impact our business or financial condition.
In addition, other legislative changes have been proposed and adopted in the United States since the Affordable Care Act was enacted. In August 2011, the
Budget Control Act of 2011, among other things, led to aggregate reductions of Medicare payments to providers of 2% per fiscal year. These reductions
went into effect in April 2013 and, due to subsequent legislative amendments to the statute, will remain in effect through 2030, with the exception of a
temporary suspension from May 1, 2020 through December 31, 2021, unless additional action is taken by Congress. In addition, in January 2013, the
American Taxpayer Relief Act of 2012 was signed into law, which, among other things, further reduced Medicare payments to several types of providers,
including hospitals, imaging centers and cancer treatment centers, and increased the statute of limitations period for the government to recover
overpayments to providers from three to five years.
Individual states in the United States have also become increasingly aggressive in passing legislation and implementing regulations designed to control
pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and
marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.
Legally mandated price controls on payment amounts by third-party payors or other restrictions could harm our business, results of operations, financial
condition and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what
pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce the ultimate
demand for our drug candidates or put pressure on our product pricing. Moreover, payment methodologies may be subject to changes in healthcare
legislation and regulatory initiatives. For example, CMS may develop new payment and delivery models, such as bundled payment models. In addition,
recently there has been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products.
In the European Union, similar political, economic and regulatory developments may affect our ability to profitably commercialize our drug candidates, if
approved. In addition to continuing pressure on prices and cost containment measures, legislative developments at the EU or member state level may result
in significant additional requirements or obstacles that may increase our operating costs. The delivery of healthcare in the European Union, including the
establishment and operation of health services and the pricing and reimbursement of medicines, is almost exclusively a matter for national, rather than EU,
law and policy. National governments and health service providers have different priorities and approaches to the delivery of health care and the pricing
and reimbursement of products in that context. In general, however, the healthcare budgetary constraints in most European Union member states have
resulted in restrictions on the pricing and reimbursement of medicines by relevant health service providers. Coupled with ever-increasing EU and national
regulatory burdens on those wishing to develop and market products, this could prevent or delay marketing approval of our drug candidates, restrict or
regulate post-approval activities and affect our ability to commercialize our drug candidates, if approved. In markets outside of the United States and
European Union, reimbursement and healthcare payment systems vary significantly by country, and many countries have instituted price ceilings on
specific products and therapies.
We cannot predict the likelihood, nature or extent of government regulation that may arise from future legislation or administrative action in the United
States, the European Union or any other jurisdiction. If we or any third parties we may engage are slow or unable to adapt to changes in existing
requirements or the adoption of new requirements or policies, or if we or such third parties are not able to maintain regulatory compliance, our drug
candidates may lose any regulatory approval that may have been obtained and we may not achieve or sustain profitability.
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Our business operations and current and future relationships with investigators, healthcare professionals, consultants, third-party payors, patient
organizations and customers will be subject to applicable healthcare regulatory laws, which could expose us to penalties.
Our business operations and current and future arrangements with investigators, healthcare professionals, consultants, third-party payors, patient
organizations and customers, may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations. These laws may constrain the
business or financial arrangements and relationships through which we conduct our operations, including how we research, market, sell and distribute our
drug candidates, if approved.
Such laws include:
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the U.S. federal Anti-Kickback Statute, which prohibits, among other things, persons or entities from knowingly and willfully soliciting,
offering, receiving or providing any remuneration (including any kickback, bribe, or certain rebate), directly or indirectly, overtly or covertly, in
cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, lease, order or recommendation of,
any good, facility, item or service, for which payment may be made, in whole or in part, under U.S. federal and state healthcare programs such
as Medicare and Medicaid. A person or entity does not need to have actual knowledge of the statute or specific intent to violate it in order to
have committed a violation;
the U.S. federal false claims and civil monetary penalties laws, including the civil False Claims Act, which, among other things, impose
criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or
causing to be presented, to the U.S. federal government, claims for payment or approval that are false or fraudulent, knowingly making, using or
causing to be made or used, a false record or statement material to a false or fraudulent claim, or from knowingly making a false statement to
avoid, decrease or conceal an obligation to pay money to the U.S. federal government. In addition, the government may assert that a claim
including items and services resulting from a violation of the U.S. federal Anti-Kickback Statute constitutes a false or fraudulent claim for
purposes of the False Claims Act;
the U.S. federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which imposes criminal and civil liability for, among
other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, or knowingly
and willfully falsifying, concealing or covering up a material fact or making any materially false statement, in connection with the delivery of,
or payment for, healthcare benefits, items or services; similar to the U.S. federal Anti-Kickback Statute, a person or entity does not need to have
actual knowledge of the statute or specific intent to violate it in order to have committed a violation;
the FDCA, which prohibits, among other things, the adulteration or misbranding of drugs, biologics and medical devices;
the U.S. Public Health Service Act, which prohibits, among other things, the introduction into interstate commerce of a biological product
unless a biologics license is in effect for that product;
the U.S. Physician Payments Sunshine Act and its implementing regulations, which require certain manufacturers of drugs, devices, biologics
and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to the
government information related to certain payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists,
podiatrists and chiropractors), certain other healthcare providers starting in 2022, and teaching hospitals, as well as ownership and investment
interests held by the physicians described above and their immediate family members;
analogous U.S. state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices,
including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services
reimbursed by any third-party payor,
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including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance
guidelines and the relevant compliance guidance promulgated by the U.S. federal government, or otherwise restrict payments that may be made
to healthcare providers and other potential referral sources; and state laws and regulations that require drug manufacturers to file reports relating
to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare
professionals and entities; and
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similar healthcare laws and regulations in the European Union and other jurisdictions, including reporting requirements detailing interactions
with and payments to healthcare providers.
Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will
involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes,
regulations, agency guidance or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations are found to be in
violation of any of the laws described above or any other governmental laws and regulations that may apply to us, we may be subject to significant
penalties, including civil, criminal and administrative penalties, damages, fines, exclusion from government-funded healthcare programs, such as Medicare
and Medicaid or similar programs in other countries or jurisdictions, disgorgement, individual imprisonment, contractual damages, reputational harm,
diminished profits and the curtailment or restructuring of our operations. Further, defending against any such actions can be costly, time-consuming and
may require significant personnel resources. Therefore, even if we are successful in defending against any such actions that may be brought against us, our
business may be impaired.
U.S. tax legislation and future changes to applicable U.S. tax laws and regulations may have a material adverse effect on our business, financial
condition and results of operations.
New income, sales, use or other tax laws, statutes, rules, regulations or ordinances could be enacted at any time, or interpreted, changed, modified or
applied adversely to us, any of which could adversely affect our business operations and financial performance. We are currently unable to predict whether
such changes will occur and, if so, the ultimate impact on our business. To the extent that such changes have a negative impact on us, our suppliers or our
customers, including as a result of related uncertainty, these changes may materially and adversely impact our business, financial condition, results of
operations and cash flows.
Risks Related to Ownership of Our Common Stock
Our stock price may be volatile and you may not be able to resell shares of our common stock at or above the price you paid.
The trading price of our common stock may be highly volatile and may be subject to wide fluctuations in response to various factors, some of which are
beyond our control.
These factors include those discussed in this “Risk Factors” section of this report and others such as:
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results from, and any delays in, commencing, conducting or completing our clinical studies for our current drug candidates, or any other future
clinical development programs;
announcements by academic or other third parties challenging the fundamental premises underlying our approach to treating diseases of aging
and/or drug development;
announcements of regulatory approval or disapproval of our current or any future drug candidates;
failure or discontinuation of any of our research and development programs;
announcements relating to future licensing, collaboration, or development agreements;
delays in the commercialization of our current or any future drug candidates;
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public misperception regarding the use of our therapies, or public bias of against “anti-aging” companies;
acquisitions and sales of new products, technologies, or businesses;
manufacturing and supply issues related to our drug candidates for clinical studies or future drug candidates for commercialization;
quarterly variations in our results of operations or those of our future competitors;
changes in earnings estimates or recommendations by securities analysts;
announcements by us or our competitors of new products, significant contracts, commercial relationships, acquisitions, or capital commitments;
developments with respect to intellectual property rights;
our commencement of, or involvement in, litigation;
changes in financial estimates or guidance, including our ability to meet our future revenue and operating profit or loss estimates or guidance;
any major changes in our board of directors or management;
new legislation in the United States relating to the sale or pricing of pharmaceuticals;
FDA or other U.S. or foreign regulatory actions affecting us or our industry;
product liability claims or other litigation or public concern about the safety of our drug candidates;
market conditions in the pharmaceutical, biopharmaceutical and biotechnology sectors; and
general economic conditions in the United States and abroad.
In addition, the stock markets in general, and the markets for pharmaceutical, biopharmaceutical, and biotechnology stocks in particular, have experienced
extreme volatility as a result of the COVID-19 pandemic that may be unrelated to the operating performance of the issuer. These broad market fluctuations
may adversely affect the trading price or liquidity of our common stock. In the past, when the market price of a stock has been volatile, holders of that
stock have sometimes instituted securities class action litigation against the issuer. If any of our stockholders were to bring such a lawsuit against us, we
could incur substantial costs defending the lawsuit and the attention of our management would be diverted from the operation of our business.
An active, liquid and orderly market for our common stock may not develop and may not be maintained.
Prior to our initial public offering in May 2018, there was no public market for shares of our common stock. Although our common stock is listed on the
Nasdaq Global Select Market, an active trading market for our common stock may never be sustained on the Nasdaq Global Select Market or any other
exchange in the future. The lack of an active market may impair your ability to sell your shares at the time you wish to sell them or at a price that you
consider reasonable. An inactive market may also impair our ability to raise capital by selling shares and may impair our ability to acquire other businesses,
applications, or technologies using our shares as consideration.
If securities or industry analysts do not publish research or reports about our business, or if they issue an adverse or misleading opinion regarding our
stock, our stock price and trading volume could decline.
The trading market for our common stock is influenced by the research and reports that industry or securities analysts publish about us or our business. In
the event any of the analysts who cover us issue an adverse or
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misleading opinion regarding us, our business model, our intellectual property or our stock performance, or if our clinical studies and operating results fail
to meet the expectations of analysts, our stock price would likely decline. If one or more of these analysts cease coverage of us or fail to publish reports on
us regularly, we could lose visibility in the financial markets, which in turn could cause our stock price or trading volume to decline.
If we sell shares of our common stock in future financings, stockholders may experience immediate dilution and, as a result, our stock price may
decline.
We may from time to time issue additional shares of common stock at a discount from the current trading price of our common stock. As a result, our
stockholders would experience immediate dilution upon the purchase of any shares of our common stock sold at such discount. In addition, as opportunities
present themselves, we may enter into financing or similar arrangements in the future, including the issuance of debt securities, preferred stock or common
stock. For example, on June 3, 2019, we filed a Registration Statement on Form S-3, covering the offering of up to $250.0 million of shares of common
stock, preferred stock, debt securities, warrants and units, and entered into a sales agreement, or the June 2019 Sales Agreement, with Cowen and
Company, LLC, or Cowen, to sell shares of our common stock, from time to time, with aggregate gross sales proceeds of up to $75.0 million, through an
at-the-market equity offering program, or Initial ATM Offering Program, under which Cowen acts as our sales agent. On July 31, 2020, we entered into the
July 2020 Sales Agreement with Cowen to sell shares of our common stock, from time to time, with aggregate gross sales proceeds of up to $50.0 million,
through an additional at-the-market equity offering program, or our Additional ATM Offering Program, under which Cowen acts as our sales agent. During
the year ended December 31, 2020, we issued and sold 5,002,257 shares of our common stock through our Initial ATM Offering Program. During the year
ended December 31, 2021, we issued and sold 1,187,068 shares of the Company’s common stock sold through the Initial ATM Offering Program and
707,459 shares of the Company’s common stock sold through the Additional ATM Offering Program. On September 29, 2021, we entered into a Purchase
Agreement with Lincoln Park Capital Fund, LLC, under which we may at our discretion sell up to $30.0 million shares of our common stock, subject to
certain daily limits, applicable prices, and conditions. As of December 31, 2021, we issued and sold 4,172,855 shares of our common stock under our
Purchase Agreement with Lincoln Park amounting to $8.3 million in gross proceeds. In addition, under the Purchase Agreement, we issued 252,447 shares
of our common stock to Lincoln Park as consideration for its commitment to purchase shares of our common stock under the Purchase Agreement.
We generally have the right to control the timing and amount of any future sales of our common stock to Lincoln Park. Sales of shares of our common
stock, if any, to Lincoln Park will depend upon market conditions and other factors to be determined by us. We may ultimately decide to sell to Lincoln
Park all, some or none of the additional shares of our common stock that may be available for us to sell under the Purchase Agreement. If and when we do
sell shares of our common stock to Lincoln Park, after Lincoln Park has acquired the shares of common stock, Lincoln Park may resell all, some or none of
those shares of common stock at any time or in its discretion. The sale by Lincoln Park of a substantial number of shares of our common stock issued by us
to Lincoln Park under the Purchase Agreement or the anticipation of such sales, could make it more difficult for us to sell equity or equity-related securities
in the future at a time and at a price that we might otherwise wish to effect sales.
In addition, on December 15, 2021 we entered into an amendment to our Loan and Security Agreement dated August 3, 2020 with Hercules Capital, Inc.,
under the terms of Hercules (including any of its assignees) has the option for a period of six (6) months to convert up to $5.0 million of the outstanding
principal under the existing loan into shares of the Company’s common stock. As of December 31, 2021, we issued 1,727,361 shares of our common stock
to Hercules in accordance with this amendment.
Sales of substantial amounts of shares of our common stock or other securities by our stockholders, by us under the Shelf Registration Statement, whether
pursuant to the ATM Offering Program or otherwise or by Lincoln Park or through the Hercules Amendment or through any other means could also lower
the market price of our common stock and impair our ability to raise capital through the sale of equity or equity-related securities.
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Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.
We have incurred substantial losses during our history and may never achieve profitability. To the extent that we continue to generate taxable losses, unused
losses will carry forward to offset a portion of future taxable income, if any, until such unused losses expire, if ever. Under Sections 382 and 383 of the
Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change,” generally defined as a greater than 50 percentage point
change (by value) in its equity ownership by certain stockholders over a three-year period, the corporation’s ability to use its pre-change net operating loss
carryforwards, or NOLs, and other pre-change tax attributes (such as research and development tax credits) to offset its post-change income or taxes may
be limited. We may have experienced ownership changes in the past and may experience ownership changes in the future as a result of subsequent shifts in
our stock ownership (some of which shifts are outside our control). As a result, if we earn net taxable income, our ability to use our pre-change NOLs to
offset such taxable income could be subject to limitations. Similar provisions of state tax law may also apply. As a result, even if we achieve profitability,
we may be unable to use a material portion of our NOLs and other tax attributes.
Provisions in our charter documents and under Delaware law could discourage a takeover that stockholders may consider favorable and may lead to
entrenchment of management.
Our amended and restated certificate of incorporation and amended and restated bylaws contain provisions that could delay or prevent changes in control or
changes in our management without the consent of our board of directors. These provisions include the following:
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a classified board of directors with three-year staggered terms, which may delay the ability of stockholders to change the membership of a
majority of our board of directors;
no cumulative voting in the election of directors, which limits the ability of minority stockholders to elect director candidates;
the exclusive right of our board of directors to elect a director to fill a vacancy created by the expansion of the board of directors or the
resignation, death or removal of a director, which prevents stockholders from being able to fill vacancies on our board of directors;
the ability of our board of directors to authorize the issuance of shares of preferred stock and to determine the price and other terms of those
shares, including preferences and voting rights, without stockholder approval, which could be used to significantly dilute the ownership of a
hostile acquiror;
the ability of our board of directors to alter our amended and restated bylaws without obtaining stockholder approval;
the required approval of at least 66 2/3% of the shares entitled to vote at an election of directors to adopt, amend or repeal our amended and
restated bylaws or repeal the provisions of our amended and restated certificate of incorporation regarding the election and removal of directors;
a prohibition on stockholder action by written consent, which forces stockholder action to be taken at an annual or special meeting of our
stockholders;
the requirement that a special meeting of stockholders may be called only by the chief executive officer or the president or the board of
directors, which may delay the ability of our stockholders to force consideration of a proposal or to take action, including the removal of
directors; and
advance notice procedures that stockholders must comply with in order to nominate candidates to our board of directors or to propose matters to
be acted upon at a stockholders’ meeting, which may discourage or deter a potential acquiror from conducting a solicitation of proxies to elect
the acquiror’s own slate of directors or otherwise attempting to obtain control of us.
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We are also subject to the anti-takeover provisions contained in Section 203 of the Delaware General Corporation Law. Under Section 203, a corporation
may not, in general, engage in a business combination with any holder of 15% or more of its capital stock unless the holder has held the stock for three
years or, among other exceptions, the board of directors has approved the transaction.
Claims for indemnification by our directors and officers may reduce our available funds to satisfy successful third-party claims against us and may
reduce the amount of money available to us.
Our amended and restated certificate of incorporation and amended and restated bylaws provide that we will indemnify our directors and officers, in each
case to the fullest extent permitted by Delaware law.
In addition, as permitted by Section 145 of the Delaware General Corporation Law, our amended and restated bylaws and our indemnification agreements
that we have entered into with our directors and officers provide that:
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We will indemnify our directors and officers for serving us in those capacities or for serving other business enterprises at our request, to the
fullest extent permitted by Delaware law. Delaware law provides that a corporation may indemnify such person if such person acted in good
faith and in a manner such person reasonably believed to be in or not opposed to the best interests of the registrant and, with respect to any
criminal proceeding, had no reasonable cause to believe such person’s conduct was unlawful.
We may, in our discretion, indemnify employees and agents in those circumstances where indemnification is permitted by applicable law.
We are required to advance expenses, as incurred, to our directors and officers in connection with defending a proceeding, except that such
directors or officers shall undertake to repay such advances if it is ultimately determined that such person is not entitled to indemnification. We
will not be obligated pursuant to our amended and restated bylaws to indemnify a person with respect to proceedings initiated by that person
against us or our other indemnitees, except with respect to proceedings authorized by our board of directors or brought to enforce a right to
indemnification.
The rights conferred in our amended and restated bylaws are not exclusive, and we are authorized to enter into indemnification agreements with
our directors, officers, employees and agents and to obtain insurance to indemnify such persons.
We may not retroactively amend our amended and restated bylaw provisions to reduce our indemnification obligations to directors, officers,
employees and agents.
We do not currently intend to pay dividends on our common stock, and, consequently, your ability to achieve a return on your investment will depend
on appreciation in the price of our common stock.
We do not currently intend to pay any cash dividends on our common stock for the foreseeable future. We currently intend to invest our future earnings, if
any, to fund our growth. Therefore, you are not likely to receive any dividends on your common stock for the foreseeable future. Since we do not intend to
pay dividends, your ability to receive a return on your investment will depend on any future appreciation in the market value of our common stock. There is
no guarantee that our common stock will appreciate or even maintain the price at which our holders have purchased it.
General Risk Factors
Unfavorable global economic or political conditions could adversely affect our business, financial condition or results of operations.
Our results of operations could be adversely affected by general conditions in the global economy and in the global financial markets. Furthermore, the
market for products with the potential to treat diseases of aging, particularly those affecting large populations in a wide range of geographic locations, may
be particularly vulnerable to unfavorable economic conditions. A global financial crisis or a global or regional political disruption, including
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most recently as a result of the COVID-19 pandemic, have caused and could continue to cause extreme volatility in the capital and credit markets. A severe
or prolonged economic downturn or political disruption could result in a variety of risks to our business, including weakened demand for our current drug
candidates or any future drug candidates, if approved, and our ability to raise additional capital when needed on acceptable terms, if at all. A weak or
declining economy or political disruption could also strain our manufacturers or suppliers, possibly resulting in supply disruption, or cause our customers to
delay making payments for our services. Weakened or declining economic conditions could be caused by a number of factors. Any of the foregoing could
harm our business and we cannot anticipate all of the ways in which the political or economic climate and financial market conditions could adversely
impact our business.
We or the third parties upon whom we depend may be adversely affected by earthquakes, other natural disasters or unforeseen pandemics and public
health emergencies, such as the COVID-19 pandemic, and our business continuity and disaster recovery plans may not adequately protect us from a
serious disaster.
Our corporate headquarters and other facilities are located in the San Francisco Bay Area, which in the past has experienced both severe earthquakes and
wildfires. Although we carry earthquake insurance, it is limited in scope. Earthquakes, wildfires or other natural disasters could severely disrupt our
operations, and have a material adverse effect on our business, results of operations, financial condition and prospects.
If a natural disaster, power outage or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical
infrastructure, such as our enterprise financial systems or manufacturing resource planning and enterprise quality systems, or that otherwise disrupted
operations, it may be difficult or, in certain cases, impossible, for us to continue our business for a substantial period of time. The disaster recovery and
business continuity plans we have in place currently are limited and are unlikely to prove adequate in the event of a serious disaster or similar event. We
may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which, particularly when taken
together with our lack of earthquake insurance, could have a material adverse effect on our business. Measures taken in response to a pandemic, such as the
COVID-19 pandemic, which causes a public health emergency, could also disrupt our operations, and have a material adverse effect on our business,
results of operations, financial condition and prospects. For example, in mid-March 2020, in alignment with federal, state and local guidance designed to
slow the spread of COVID-19, we transitioned to a remote work plan and reduced onsite staffing model for all employees who cannot perform their work
from home, such as our laboratory, operations, and facilities staff. As the COVID-19 pandemic evolves, we may be required to take additional actions that
could impact our operations if required by applicable laws or regulations or if we determine them to be in the best interests of our employees.
Furthermore, integral parties in our supply chain are similarly vulnerable to natural disasters or other sudden, unforeseen and severe adverse events. If such
an event were to affect our supply chain, it could have a material adverse effect on our business.
Significant disruptions of information technology systems or breaches of data security could materially adversely affect our business, results of
operations and financial condition.
We collect and maintain information in digital form that is necessary to conduct our business, and we are increasingly dependent on information technology
systems and infrastructure to operate our business. In the ordinary course of our business, we collect, store and transmit large amounts of confidential
information, including intellectual property, proprietary business information and personal information. It is critical that we do so in a secure manner to
maintain the confidentiality and integrity of such confidential information. We have established physical, electronic and organizational measures to
safeguard and secure our systems to prevent a data compromise, and rely on commercially available systems, software, tools, and monitoring to provide
security for our information technology systems and the processing, transmission and storage of digital information. We have also outsourced elements of
our information technology infrastructure, and as a result a number of third-party vendors may or could have access to our confidential information. Our
internal information technology systems and infrastructure, and those of our current and any future collaborators, contractors and consultants and other
third parties on which we rely, are vulnerable to damage from computer viruses, malware, natural disasters, terrorism, war, telecommunication and
electrical failures, cyberattacks or cyber-intrusions over the Internet, attachments to emails, persons inside our organization, or persons with access to
systems inside our organization.
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The risk of a security breach or disruption, particularly through cyberattacks or cyber-intrusion, including by computer hackers, “phishing” attacks, foreign
governments and cyber terrorists, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the
world have increased. In addition, the prevalent use of mobile devices that access confidential information increases the risk of data security breaches,
which could lead to the loss of confidential information or other intellectual property. As a result of COVID-19, we may face increased cybersecurity risks
due to our reliance on internet technology and the number of our employees that are working remotely, which may create additional opportunities for
cybercriminals to exploit vulnerabilities. The costs to us to mitigate network security problems, bugs, viruses, worms, malicious software programs and
security vulnerabilities could be significant, and while we have implemented security measures to protect our data security and information technology
systems, our efforts to address these problems may not be successful, and these problems could result in unexpected interruptions, delays, cessation of
service and other harm to our business and our competitive position. If such an event were to occur and cause interruptions in our operations, it could result
in a material disruption of our product development programs. For example, the loss of clinical study data from completed or ongoing or planned clinical
studies could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.
Moreover, if a computer security breach affects our systems, or those of our current and any future collaborators, contractors and consultants and other third
parties on which we rely, or results in the unauthorized release of personally identifiable information, our reputation could be materially damaged. In
addition, such a breach may require notification to governmental agencies, the media or individuals pursuant to various federal and state privacy and
security laws, if applicable, including the Health Insurance Portability and Accountability Act of 1996, as amended by the Health Information Technology
for Economic and Clinical Health Act of 2009, and its implementing rules and regulations, as well as regulations promulgated by the Federal Trade
Commission and state breach notification laws. We would also be exposed to a risk of loss or litigation and potential liability, which could materially
adversely affect our business, results of operations and financial condition.
Our employees and independent contractors, including principal investigators, consultants, commercial collaborators, service providers and other
vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements, which could
have an adverse effect on our results of operations.
We are exposed to the risk that our employees and independent contractors, including principal investigators, consultants, any future commercial
collaborators, service providers and other vendors may engage in misconduct or other illegal activity. Misconduct by these parties could include intentional,
reckless and/or negligent conduct or other unauthorized activities that violate the laws and regulations of the FDA and other similar regulatory bodies,
including those laws that require the reporting of true, complete and accurate information to such regulatory bodies; manufacturing standards; U.S. federal
and state healthcare fraud and abuse, data privacy laws and other similar non-U.S. laws; or laws that require the true, complete and accurate reporting of
financial information or data. Activities subject to these laws also involve the improper use or misrepresentation of information obtained in the course of
clinical studies, the creation of fraudulent data in our preclinical studies or clinical studies, or illegal misappropriation of product, which could result in
regulatory sanctions and cause serious harm to our reputation. It is not always possible to identify and deter misconduct by employees and other third-
parties, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in
protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations. In
addition, we are subject to the risk that a person or government could allege such fraud or other misconduct, even if none occurred. If any such actions are
instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business
and financial results, including, without limitation, the imposition of significant civil, criminal and administrative penalties, damages, monetary fines,
disgorgements, possible exclusion from participation in Medicare, Medicaid and other U.S. healthcare programs, individual imprisonment, other sanctions,
contractual damages, reputational harm, diminished profits and future earnings and curtailment of our operations, any of which could adversely affect our
ability to operate our business and our results of operations.
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Our business involves the use of hazardous materials, and we and our third-party manufacturers and suppliers must comply with environmental laws
and regulations, which can be expensive and restrict how we do business.
Our research and development activities and our third-party manufacturers’ and suppliers’ activities involve the controlled storage, use and disposal of
hazardous materials owned by us, including the components of our product and drug candidates and other hazardous compounds. We and any third-party
manufacturers and suppliers we engage are subject to numerous federal, state and local environmental, health and safety laws, regulations and permitting
requirements, including those governing laboratory procedures; the generation, handling, use, storage, treatment, and disposal of hazardous and regulated
materials and wastes; the emission and discharge of hazardous materials into the ground, air and water; and employee health and safety. Our operations
involve the use of hazardous and flammable materials, including chemicals and biological and radioactive materials. Our operations also produce
hazardous waste. In some cases, these hazardous materials and various wastes resulting from their use are stored at our and our manufacturers’ facilities
pending their use and disposal. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of
contamination, which could cause an interruption of our commercialization efforts, research and development efforts and business operations,
environmental damage resulting in costly clean-up and liabilities under applicable laws and regulations governing the use, storage, handling and disposal of
these materials and specified waste products.
Although we believe that the safety procedures utilized by our third-party manufacturers for handling and disposing of these materials generally comply
with the standards prescribed by these laws and regulations, we cannot guarantee that this is the case or eliminate the risk of accidental contamination or
injury from these materials. Under certain environmental laws, we could be held responsible for costs relating to any contamination at our current or past
facilities and at third-party facilities. In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and
state or federal or other applicable authorities may curtail our use of certain materials and/or interrupt our business operations. Furthermore, environmental
laws and regulations are complex, change frequently and have tended to become more stringent. We cannot predict the impact of such changes and cannot
be certain of our future compliance.
Compliance with applicable environmental laws and regulations may be expensive, and current or future environmental laws and regulations may impair
our research, product development and manufacturing efforts. In addition, we cannot entirely eliminate the risk of accidental injury or contamination from
these materials or wastes. Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our
employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not carry
specific biological or hazardous waste insurance coverage, and our property, casualty, and general liability insurance policies specifically exclude coverage
for damages and fines arising from biological or hazardous waste exposure or contamination. Accordingly, in the event of contamination or injury, we
could be held liable for damages or be penalized with fines in an amount exceeding our resources, and our clinical studies or regulatory approvals could be
suspended, which could have a material adverse effect on our business, results of operations and financial condition.
We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.
We may also be subject to claims that former employees, collaborators or other third parties have an ownership interest in our patents or other intellectual
property. Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail in defending any such
claims, in addition to paying monetary damages, we may lose valuable intellectual property rights. Such an outcome could have a material adverse effect
on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and distraction to management and
other employees.
We may not be able to protect our intellectual property rights throughout the world.
Filing, prosecuting and defending patents on drug candidates in all countries throughout the world would be prohibitively expensive, and our intellectual
property rights in some countries outside the United States can be less extensive than those in the United States. In addition, the laws of some foreign
countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we may not be able to
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prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our
inventions in and into the United States or other jurisdictions. Competitors may use our technologies in jurisdictions where we have not obtained patent
protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but
enforcement is not as strong as that in the United States. These products may compete with our products and our patents or other intellectual property rights
may not be effective or sufficient to prevent them from competing.
Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems
of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly
those relating to biopharmaceuticals, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in
violation of our proprietary rights generally. Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our
efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly and our patent
applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, and the
damages or other remedies awarded, if any, may not be commercially meaningful.
Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from
the intellectual property that we develop or license.
Actual or perceived failures to comply with U.S. and foreign privacy and data protection laws, regulations and standards may adversely affect our
business, operations and financial performance.
We are subject to or affected by numerous federal, state and foreign laws and regulations, as well as regulatory guidance, governing the collection, use,
disclosure, retention, and security of personal information, such as information that we collect about patients and healthcare providers in connection with
clinical trials in the United States and abroad. The global data protection landscape is rapidly evolving, and implementation standards and enforcement
practices are likely to remain uncertain for the foreseeable future. This evolution may create uncertainty in our business, affect our or any service
providers’, contractors’ or future collaborators’ ability to operate in certain jurisdictions or to collect, store, transfer use and share personal information,
necessitate the acceptance of more onerous obligations in our contracts, result in liability or impose additional costs on us. The cost of compliance with
these laws, regulations and standards is high and is likely to increase in the future. Any failure or perceived failure by us or our collaborators, service
providers and contractors to comply with federal, state or foreign laws or regulation, our internal policies and procedures or our contracts governing
processing of personal information could result in negative publicity, diversion of management time and effort and proceedings against us by governmental
entities or others. In many jurisdictions, enforcement actions and consequences for noncompliance are rising.
In the United States, HIPAA imposes privacy, security and breach reporting obligations with respect to individually identifiable health information upon
“covered entities” (health plans, health care clearinghouses and certain health care providers), and their respective business associates, individuals or
entities that create, receive, maintain or transmit protected health information in connection with providing a service for or on behalf of a covered entity.
HIPAA mandates the reporting of certain breaches of health information to the U.S. Department of Health and Human Services, or HHS, affected
individuals and if the breach is large enough, the media. Entities that are found to be in violation of HIPAA as the result of a breach of unsecured protected
health information, a complaint about privacy practices or an audit by HHS, may be subject to significant civil, criminal and administrative fines and
penalties and/or additional reporting and oversight obligations if required to enter into a resolution agreement and corrective action plan with HHS to settle
allegations of HIPAA non-compliance. Even when HIPAA does not apply, according to the Federal Trade Commission, or the FTC, violating consumers’
privacy rights or failing to take appropriate steps to keep consumers’ personal information secure may constitute unfair acts or practices in or affecting
commerce in violation of Section 5(a) of the FTC Act. The FTC expects a company’s data security measures to be reasonable and appropriate in light of the
sensitivity and volume of consumer information it holds, the size and complexity of its business, and the cost of available tools to improve security and
reduce vulnerabilities. Individually identifiable health information is considered sensitive data that merits stronger safeguards.
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In addition, certain state laws govern the privacy and security of personal information, including health-related information, in certain circumstances, some
of which are more stringent than HIPAA and many of which differ from each other in significant ways and may not have the same effect, thus complicating
compliance efforts. Failure to comply with these laws, where applicable, can result in the imposition of significant civil and/or criminal penalties and
private litigation. For example, California enacted the California Consumer Privacy Act, or the CCPA, on June 28, 2018, which went into effect on January
1, 2020. The CCPA gives California residents expanded rights to access and delete their personal information, opt out of certain personal information
sharing, and receive detailed information about how their personal information is used. The CCPA provides for civil penalties for violations, as well as a
private right of action for data breaches that is expected to increase data breach litigation. The CCPA may increase our compliance costs and potential
liability. Some observers have noted that the CCPA could mark the beginning of a trend toward more stringent privacy legislation in the United States,
which could increase our potential liability and adversely affect our business. Further, the California Privacy Rights Act, or the CPRA, recently passed in
California as well. The CPRA will impose additional data protection obligations on covered businesses, including additional consumer rights processes,
limitations on data uses, new audit requirements for higher risk data, and opt outs for certain uses of sensitive data. It will also create a new California data
protection agency authorized to issue substantive regulations and could result in increased privacy and information security enforcement. The majority of
the provisions will go into effect on January 1, 2023, and additional compliance investment and potential business process changes may be required.
Our operations abroad may also be subject to increased scrutiny or attention from data protection authorities. Many countries in these regions have
established or are in the process of establishing privacy and data security legal frameworks with which we, our collaborators, service providers, including
our CRO, and contractors must comply. For example, the European Union General Data Protection Regulation, or GDPR, went into effect in May 2018 and
imposes strict requirements for processing the personal information of subjects within the European Economic Area, or EEA, including clinical trial data.
Further, applicable privacy laws and court decisions could impact our ability to transfer personal data internationally. Recent legal developments in Europe
have created complexity and compliance uncertainty regarding certain transfers of personal data from the EEA. For example, on July 16, 2020, the Court of
Justice of the European Union, or the CJEU, invalidated the EU-U.S. Privacy Shield Framework, or the Privacy Shield, under which personal data could be
transferred from the EEA to United States entities who had self-certified under the Privacy Shield scheme, and imposed further restrictions on use of the
standard contractual clauses, or SCCs. As a result, the Privacy Shield is no longer a valid mechanism for transferring personal data from the EEA to the
United States. The SCC restrictions include a requirement for companies to carry out a transfer impact assessment which, among other things, assesses the
laws governing access to personal data in the recipient country and considers whether supplementary measures that provide privacy protections additional
to those provided under SCCs will need to be implemented to ensure an essentially equivalent level of data protection to that afforded in the EEA. The
European Commission issued revised SCCs on June 4, 2021 to account for the decision of the CJEU and recommendations made by the European Data
Protection Board. The revised SCCs must be used for relevant new data transfers from September 27, 2021; existing standard contractual clauses
arrangements must be migrated to the revised clauses by December 27, 2022. There is some uncertainty around whether the revised clauses can be used for
all types of data transfers, particularly whether they can be relied on for data transfers to non-EEA entities subject to the GDPR. The GDPR has and will
continue to increase compliance burdens on us, including by mandating potentially burdensome documentation requirements and granting certain rights to
individuals to control how we collect, use, disclose, retain and process information about them. The processing of sensitive personal data, such as health
data, may impose heightened compliance burdens under the GDPR and is a topic of active interest among foreign regulators.
In addition, the GDPR provides for more robust regulatory enforcement and fines of up to €20 million or 4% of the annual global revenue of the
noncompliant company, whichever is greater. Further, beginning January 1, 2021, we may have to comply with the GDPR and also the United Kingdom
GDPR, or UK GDPR, which, together with the amended UK Data Protection Act 2018, retains the GDPR in United Kingdom national law. The UK GDPR
mirrors the fines under the GDPR, i.e. fines up to the greater of €20 million (£17.5 million) or 4% of global turnover. The relationship between the United
Kingdom and the European Union in relation to certain aspects of data protection law remains unclear, and it is unclear how United Kingdom data
protection laws and regulations will develop in the medium to longer term. The European Commission has adopted an adequacy decision in favor of the
United Kingdom, enabling data transfers from EU member states to the United Kingdom without additional safeguards.
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However, the UK adequacy decision will automatically expire in June 2025 unless the European Commission re-assesses and renews/ extends that
decision.
We incur increased costs as a result of operating as a public company, and our management devote substantial time to new compliance initiatives. We
may fail to comply with the rules that apply to public companies, including Section 404 of the Sarbanes-Oxley Act of 2002, which could result in
sanctions or other penalties that would harm our business.
We have incurred and will continue to incur significant legal, accounting and other expenses as a public company, including costs resulting from public
company reporting obligations under the Exchange Act and regulations regarding corporate governance practices. The listing requirements of the Nasdaq
Global Select Market and the rules of the Securities and Exchange Commission, or SEC, require that we satisfy certain corporate governance requirements
relating to director independence, filing annual and interim reports, stockholder meetings, approvals and voting, soliciting proxies, conflicts of interest and
a code of conduct. Our management and other personnel have devoted and will need to devote a substantial amount of time to ensure that we comply with
all of these requirements. Moreover, the reporting requirements, rules and regulations will increase our legal and financial compliance costs and will make
some activities more time-consuming and costlier. Any changes we make to comply with these obligations may not be sufficient to allow us to satisfy our
obligations as a public company on a timely basis, or at all. These reporting requirements, rules and regulations, coupled with the increase in potential
litigation exposure associated with being a public company, could also make it more difficult for us to attract and retain qualified persons to serve on our
board of directors or board committees or to serve as executive officers, or to obtain certain types of insurance, including directors’ and officers’ insurance,
on acceptable terms.
We are subject to Section 404 of The Sarbanes-Oxley Act of 2002, or Section 404, and the related rules of the SEC, which generally require our
management and independent registered public accounting firm to report on the effectiveness of our internal control over financial reporting. Section 404
requires an annual management assessment of the effectiveness of our internal control over financial reporting. However, for so long as we remain an
emerging growth company as defined in the JOBS Act, we intend to take advantage of certain exemptions from various reporting requirements that are
applicable to public companies that are not emerging growth companies, including, but not limited to, not being required to comply with the auditor
attestation requirements of Section 404. Once we are no longer an emerging growth company or, if prior to such date, we opt to no longer take advantage of
the applicable exemption, we will be required to include an opinion from our independent registered public accounting firm on the effectiveness of our
internal controls over financial reporting.
During the course of our review of our internal controls we may identify deficiencies in our internal controls that we must remediate. If we identify a
material weakness in our internal controls over financial reporting, we may not detect errors on a timely basis and our financial statements may be
materially misstated. We or our independent registered public accounting firm may not be able to conclude on an ongoing basis that we have effective
internal control over financial reporting, which could harm our operating results, cause investors to lose confidence in our reported financial information
and cause the trading price of our stock to fall. In addition, as a public company we will be required to file accurate and timely quarterly and annual reports
with the SEC under the Exchange Act. In order to report our results of operations and financial statements on an accurate and timely basis, we will depend
in part on CROs to provide timely and accurate notice of their costs to us. Any failure to report our financial results on an accurate and timely basis could
result in sanctions, lawsuits, delisting of our shares from The Nasdaq Global Select Market or other adverse consequences that would materially harm to
our business.
We are an “emerging growth company” and as a result of the reduced disclosure and governance requirements applicable to emerging growth
companies, our common stock may be less attractive to investors.
We are an “emerging growth company,” as defined in the JOBS Act, and we intend to take advantage of certain exemptions from various reporting
requirements that are applicable to other public companies that are not emerging growth companies including, but not limited to, not being required to
comply with the auditor attestation requirements of Section 404, reduced disclosure obligations regarding executive compensation in our periodic reports
and proxy statements, and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval
of any golden parachute payments not previously approved. In addition, as an “emerging growth company” the JOBS Act allows us to delay adoption of
new or revised accounting
77
pronouncements applicable to public companies until such pronouncements are made applicable to private companies. We have elected to use this extended
transition period under the JOBS Act. As a result, our financial statements may not be comparable to the financial statements of issuers who are required to
comply with the effective dates for new or revised accounting standards that are applicable to public companies, which may make comparison of our
financials to those of other public companies more difficult.
We cannot predict if investors will find our common stock less attractive because we will rely on these exemptions. If some investors find our common
stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile. We may take
advantage of these reporting exemptions until we are no longer an emerging growth company. Even after we no longer qualify as an emerging growth
company, we may still qualify as a “smaller reporting company” which may allow us to take advantage of many of the same exemptions from disclosure
requirements including not being required to comply with the auditor attestation requirements of Section 404(b) of the Sarbanes-Oxley Act. We will remain
an emerging growth company until the earlier of (1) the last day of the year following the fifth anniversary of the consummation of our IPO, (2) the last day
of the year in which we have total annual gross revenue of at least $1.07 billion, (3) the last day of the year in which we are deemed to be a “large
accelerated filer” as defined in Rule 12b-2 under the Exchange Act, which would occur if the market value of our common stock held by non-affiliates
exceeded $700.0 million as of the last business day of the second fiscal quarter of such year or (4) the date on which we have issued more than $1.0 billion
in non-convertible debt securities during the prior three-year period.
Item 1B. Unresolved Staff Comments.
None.
Item 2. Properties.
Our corporate headquarters are located in South San Francisco, California, where we currently lease approximately 62,000 square feet of office and
laboratory space pursuant to a lease dated February 28, 2019, of which approximately 23,000 square feet was subleased to Freenome Holdings, Inc. as of
June 2021 through August 31, 2024. The majority of our employees work at our corporate headquarters.
Item 3. Legal Proceedings.
We are not currently a party to any material litigation or other material legal proceedings.
Item 4. Mine Safety Disclosures.
Not applicable.
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Item 5. Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities.
Market Information for Common Stock
PART II
Our common stock has been listed on the Nasdaq Global Select Market under the symbol “UBX” since May 3, 2018. As of March 1, 2022, there were 54
holders of record of our common stock. Because many of our shares of common stock are held by brokers and other institutions on behalf of stockholders,
we are unable to estimate the total number of beneficial owners of our common stock represented by these record holders.
Dividend Policy
We have never declared or paid any cash dividends on our common stock or any other securities. We anticipate that we will retain all available funds and
any future earnings, if any, for use in the operation of our business and do not anticipate paying cash dividends in the foreseeable future. In addition, future
debt instruments may materially restrict our ability to pay dividends on our common stock. Payment of future cash dividends, if any, will be at the
discretion of the board of directors after taking into account various factors, including our financial condition, operating results, current and anticipated
cash needs, the requirements of current or then-existing debt instruments and other factors the board of directors deems relevant.
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Performance Graph
This graph is not “soliciting material” or deemed “filed” with the SEC for purposes of Section 18 of the Exchange Act, or otherwise subject to liabilities
under that Section, and shall not be deemed incorporated by reference into any filing of Unity Biotechnology, Inc. under the Securities Act of 1933, as
amended (the “Securities Act”), whether made before or after the date hereof and irrespective of any general incorporation language in any such filing.
The following graph compares the cumulative total return on our common stock relative to the cumulative total returns of the Nasdaq Composite Index and
the Nasdaq Biotechnology Index. Pursuant to applicable Securities and Exchange Commission rules, all values assume reinvestment of the full amount of
all dividends, however no dividends have been declared on our common stock to date. The stockholder returns shown on the graph below are based on
historical results and are not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns.
Sales of Unregistered Securities
There were no sales of unregistered securities during the year ended December 31, 2021.
Repurchase of Shares or of Company Equity Securities
None.
Item 6. [Reserved]
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Item 7. Management’s Discussion and Analysis of Financial Condition and Results of Operations.
You should read the following discussion and analysis of our financial condition and results of operations together with the section entitled “Selected
Financial Data” and our audited financial statements and related notes included elsewhere in this report. This discussion and other parts of this report
contain forward-looking statements that involve risks and uncertainties, such as our plans, objectives, expectations, intentions and beliefs. Our actual
results could differ materially from those discussed in these forward-looking statements. Factors that could cause or contribute to such differences include,
but are not limited to, those identified below and those discussed in the section entitled “Risk Factors” included elsewhere in this report.
Overview
We are a biotechnology company engaged in researching and developing therapeutics to slow, halt, or reverse diseases of aging. Our initial focus is on
creating senolytic medicines to selectively eliminate senescent cells and thereby treat diseases of aging, such as ophthalmologic diseases.
In July 2020, we filed an Investigational New Drug application, or IND, to commence a Phase 1, first-in-human, open-label, single-ascending dose study of
UBX1325 in patients with advanced diabetic macular edema, or DME, and neovascular age-related macular degeneration, or nAMD. UBX1325 is a potent
small molecule inhibitor of the anti-apoptotic Bcl-2 family member, Bcl-xL, a member of the Bcl-2 family of apoptosis-regulatory proteins. Our goal with
UBX1325 is to transformationally improve real-world outcomes for patients with DME, nAMD, and diabetic retinopathy, or DR. In October 2020, we
dosed our first patient in a Phase 1 clinical study of UBX1325 to evaluate ocular and systemic safety and tolerability of a single intravitreal injection of
UBX1325 by the incidence of dose limiting toxicities and treatment emergent adverse events reported up to 24 weeks after administration. Based on
prospectively determined safety criteria, the Phase 1 study was able to dose-escalate beyond the originally planned 5 mcg dose up to 10 mcg, which
informed the final dose for the Phase 2a study in DME. In July 2021, we announced positive data from this Phase 1 study of UBX1325 in patients with
DME and nAMD for whom anti-VEGF therapy was no longer considered beneficial. On October 5, 2021 we announced 12-week data, on November 9,
2021 we announced 24-week data, and on February 14, 2022 we announced 24-week data from an additionally-enrolled cohort of patients with AMD.
UBX1325 was well-tolerated with no signs of intraocular inflammation or other related ocular adversities, and no dose-limiting toxicities or adversities that
preclude advancing UBX1325 into later stage clinical development. In DME, following a rapid improvement in BCVA, a mean improvement of 9.5
ETDRS letters from baseline at 6 months in the higher dose cohorts (5, 10 mcg) and 6.9 ETDRS letters from baseline at 6 months in all dose cohorts was
observed. In AMD, following a rapid improvement in BCVA, there were improvements or stabilization of both BCVA and CST through 6 months post-
injection. In both diseases, the majority of patients treated with UBX1325 showed durable improvement in vision and did not meet objective rescue criteria
requiring standard of care anti-VEGF treatment. Among patients who received anti-VEGF rescue, there was minimal change in either mean BCVA or CST
following treatment in all but one patient.
In May 2021, we initiated our Phase 2a proof-of-concept study to evaluate the safety, efficacy, and durability of a single intravitreal injection of UBX1325
in a broader population of patients with DME and dosed our first patient in June 2021. Approximately 62 patients will be enrolled, randomized evenly
between UBX1325 and sham-injected patients. An analysis of 12-week safety and efficacy data is expected by mid-2022, and patients will continue to be
followed through 48 weeks post-treatment in a long-term follow-up. Endpoints being explored in the study include safety and tolerability, changes in
BCVA, CST, SRF/IRF, proportion of patients requiring rescue treatment, and durability of effects.
In March 2022 we also enrolled our first patient in our Phase 2 proof-of-concept study in nAMD. This study is expected to randomize 46 patients with wet
AMD who have had at least three intravitreal injections of anti-VEGF therapy in the preceding six months and who have residual sub- or intra-retinal fluid.
Patients will have received their last anti-VEGF treatment approximately 4-8 weeks prior to screening, and all patients will be followed for approximately
24 weeks after dosing with either UBX1325 or aflibercept. We expect to share 16-week data from this Ph2 study in wet AMD in the fourth quarter of 2022.
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In February 2022, we announced a restructuring to align resources to focus on our ongoing clinical programs and deliver on key development milestones.
These actions to prioritize our ophthalmology programs and implement cost saving measures were designed to enable us to achieve multiple key clinical
data readouts for UBX1325 as well as support the Tie2 and Tie2/VEGF bispecific program through advanced candidate nomination, with all other pipeline
programs paused to focus resources on these advanced programs.
Since the commencement of our operations, we have invested a significant portion of our efforts and financial resources in research and development
activities, and we have incurred net losses each year since inception. Our net losses were $60.7 million and $93.8 million for the years ended December 31,
2021 and 2020, respectively. We do not have any products approved for sale, and we have never generated any revenue from contracts with customers. As
of December 31, 2021, we had an accumulated deficit of $400.0 million, and we do not expect positive cash flows from operations in the foreseeable
future.
Substantially all of our net losses have resulted from costs incurred in connection with our research and development programs and from general and
administrative costs associated with our operations. Based on our current operating plans, we expect our existing capital resources will fund our planned
operating expenses into the first quarter of 2023 which is expected to fund key clinical data readouts for UBX1325, but less than 12 months from the date
of this Annual Report. As a result, we will need to raise additional capital. Adequate funding may not be available to us on acceptable terms, or at all,
particularly in light of the current COVID-19 pandemic and associated economic uncertainty and potential for local and/or global economic recession. If
sufficient funds on acceptable terms are not available when needed, we could be required to significantly reduce our operating expenses and delay, reduce
the scope of, or eliminate one or more of our development programs.
We expect to continue to incur net operating losses for at least the next several years as we continue our research and development efforts, advance our
drug candidates through preclinical and clinical development, seek regulatory approval, prepare for and, if approved, proceed to commercialization. We do
not expect to generate revenue from any drug candidates that we develop until we obtain regulatory approval for one or more of such drug candidates and
commercialize our products or enter into collaborative agreements with third parties.
We rely on third parties in the conduct of our preclinical studies and clinical trials and for manufacturing and supply of our drug candidates. We have no
internal manufacturing capabilities, and we will continue to rely on third parties, many of whom are single-source suppliers, for our preclinical and clinical
trial materials, as well as the commercial supply of our products. In addition, we do not yet have a marketing or sales organization or commercial
infrastructure. Accordingly, we will incur significant expenses to develop a marketing and sales organization and commercial infrastructure in advance of
generating any product sales.
COVID-19 Update
The COVID-19 pandemic has placed strains on the providers of healthcare services, including the healthcare institutions, clinical research organizations, or
CROs, and Institutional Review Boards under whose auspices we conduct our clinical trials. These strains have resulted in limits on the initiation of new
clinical trials, slowing or halting enrollment in existing trials and restrictions placed upon on-site monitoring activities of clinical trials. Prior to the
initiation of our Phase 1 and Phase 2 studies of UBX1325, we amended the clinical study protocols to enable remote data collection for clinical sites that
were limited in their ability to conduct study visits in person, for either site or patient safety reasons. We also instituted remote data source verification
procedures to limit the extent that on-site monitoring was required.
Although we rely on third party manufacturers to supply UBX1325, there have been no disruptions in our supply chain of drug manufacturers necessary to
conduct our Phase 1 and Phase 2 studies of UBX1325, and we believe we have sufficient supply of drug inventories to complete our current studies in
ophthalmologic disease.
In late February 2020, we created an internal, cross-functional COVID-19 Response Team to closely monitor the evolving situation and manage our
response in compliance with applicable federal, state, and local guidance. We have implemented protocols designed to reduce onsite staff, increased testing
and monitoring, facilitated remote working and will continue to monitor the situation and plan for re-entry as permitted by applicable laws or regulations
and consistent with the best interests of our employees and business needs.
82
Components of Our Results of Operations
Research and Development Expenses
Research and development expenses consist primarily of costs incurred for the development of our drug candidates, which include:
•
•
•
•
•
•
personnel-related expenses, including salaries, benefits, severance and stock-based compensation for personnel contributing to research
and development activities;
laboratory expenses including supplies and services;
clinical trial expenses;
expenses incurred under agreements with third-party contract manufacturing organizations, contract research organizations, research and
development service providers, academic research institutions, and consultants;
expenses related to license and sponsored research agreements; and
facilities and other allocated expenses, including expenses for rent and facilities maintenance, and depreciation and amortization.
We expect our research and development expenses to increase as we advance our drug candidates into and through preclinical and clinical trials
and pursue regulatory approval of our drug candidates. The process of conducting the clinical trials required to obtain regulatory approval is costly and time
consuming. Clinical trials generally become larger and more costly to conduct as they advance into later stages and we are required to make estimates for
expense accruals related to clinical trial expenses. The actual probability of success for our drug candidates may be affected by a variety of factors
including: the safety and efficacy of our drug candidates, early clinical data, investment in our clinical program, the ability of collaborators, if any, to
successfully develop any drug candidates we license to them, competition, manufacturing capability and commercial viability. We may never succeed in
achieving regulatory approval for any of our drug candidates. Program costs that are direct external expenses are tracked on a program-by-program basis
once they enter clinical studies. As a result of the uncertainties discussed above, we are unable to determine the duration and completion costs of our
research and development projects or when and to what extent we will generate revenue from the commercialization and sale of our drug candidates.
General and Administrative Expenses
Our general and administrative expenses consist primarily of personnel costs, allocated facilities costs and other expenses for outside
professional services, including legal, audit and accounting services, and depreciation and amortization expense related to property and equipment.
Personnel costs consist of salaries, benefits, severance, and stock-based compensation. We expect to continue to incur additional expenses associated with
operating as a public company, including expenses related to compliance with the rules and regulations of the Securities and Exchange Commission and
standards applicable to companies listed on a national securities exchange, additional insurance expenses, investor relations activities, and other
administrative and professional services.
Change Fair Value of Contingent Consideration
Certain of our license agreements include contingent consideration in the form of additional issuances of our common stock based on the
achievement of certain milestones. For asset acquisitions, we assess whether such contingent consideration obligation meets the definition of a derivative
and/or can be equity classified, until such time that the contingency or equity classification criteria is met or expires. We have recorded a liability related to
contingent consideration as the net settlement criteria of the definition of a derivative had been met and equity classification criteria had not been met. The
derivative related to this contingent consideration was measured at fair value as of each balance sheet date with the related change in fair value being
reflected in operating results. Gains or
83
losses on contingent consideration expense is driven by changes in the estimated fair value of the liability, which is determined using a probability-
weighted valuation approach model that reflects the probability and timing of future issuances of our common shares.
Interest Income
Interest income is primarily related to interest earned on our marketable securities for the years ended December 31, 2021, 2020 and 2019.
Interest Expense
Interest expense relates to interest on the Loan Agreement entered into during the year ended December 31, 2020.
Other Income (Expense), Net
We held an equity investment in an entity called Ascentage Pharma Group International, or Ascentage International, an affiliate of a Hong
Kong based clinical-stage biopharmaceutical company called Ascentage Pharma Group Corp. Limited. In October 2019, Ascentage International
completed an initial public offering of shares of its common stock on the Hong Kong Stock Exchange. Following the initial public offering, the underlying
nature of our investment in Ascentage International changed and met the definition of an investment in an equity security with a readily determinable fair
value to be measured at fair value on a recurring basis, based on quoted stock prices available on the Hong Kong Stock Exchange. During the year ended
December 31, 2020, we sold our entire equity investment in Ascentage International. Other expense in 2020 includes the recognized gains and losses
resulting from the sale of the investment in this equity security and the previous changes in fair value, while other expense in 2021 includes the
commitment share expenses related to the equity purchase agreement with Lincoln Park Capital Fund and the debt extinguishment loss from the conversion
of debt to equity.
Results of Operations
Comparison of the Years Ended December 31, 2021 and 2020
The following table sets forth the significant components of our results of operations (in thousands):
Summary of Operations Data:
Licensing revenue – related party
Operating expenses:
Research and development
General and administrative
Change in fair value of contingent consideration
Impairment of long-lived assets
Total operating expenses
Loss from operations
Interest income
Interest expense
Other income (expense), net
Net loss
Year Ended December 31,
2020
2021
Change
$
4,784
$
—
$
4,784
38,393
23,056
—
—
61,449
(56,665)
100
(3,177)
(983)
(60,725) $
67,309
24,025
(33)
2,629
93,930
(93,930)
1,196
(1,292)
182
(93,844) $
(28,916)
(969)
33
(2,629)
(32,481)
37,265
(1,096)
(1,885)
(1,165)
33,119
$
84
Licensing Revenue – Related Party
In December 2021, we entered into a licensing agreement with Jocasta Neuroscience, Inc. (“Jocasta”) pursuant to which we exclusively
licensed all of our rights to UBX2089, our α-Klotho asset. The agreement provided for an upfront fee of $5.0 million. Revenue recognized in the year
ended December 31, 2021 was related to grant of license and delivery of the know-how performance obligation under the License Agreement. We
recognized revenue of $4.8 million and zero for the years ended December 31, 2021 and 2020. Revenue recognized in the year ended December 31, 2021
was related to grant of license and delivery of the know-how performance obligation under the License Agreement entered into with Jocasta in December
2021.
Research and Development
Research and development expenses decreased by $28.9 million, to $38.4 million for the year ended December 31, 2021 from $67.3 million for
the year ended December 31, 2020. The decrease was primarily due to decreases of $11.9 million in direct research and development expenses mainly due
to termination of Osteoarthritis studies and decreased safety studies, $10.2 million in personnel costs due to reduction in force, $3.8 million in facilities-
related costs primarily due to allocation to general and administrative expenses of net expenses on Brisbane and East Grand facilities which have been
subleased, $2.5 million in laboratory supplies and $0.5 million in consultant expenses.
General and Administrative
General and administrative expenses decreased by $1.0 million, to $23.0 million for the year ended December 31, 2021 from $24.0 million for
the year ended December 31, 2020. The decrease was primarily due to decreases of $0.8 million in professional fees, $0.3 million in personnel-related
expenses and $0.1 million in facilities-related costs, offset by $0.2 million increase in insurance-related expense.
Change in Fair Value of Contingent Consideration
There was no contingent consideration liability at December 31, 2021 and 2020. The change in fair value of contingent consideration was
immaterial for the year ended December 31, 2020, and was primarily due to changes in our stock price.
Impairment of Long-Lived Assets
Impairment charges consisted of impairment of long-lived assets. There were no impairment charges during the year ended December 31, 2021.
During the year ended December 31, 2020, we recorded an impairment charge of $2.6 million after evaluating the right-of-use asset and related leasehold
improvements upon exit of our former headquarters located in Brisbane, California.
Interest Income
Our interest income was $0.1 million for the year ended December 31, 2021, as compared to $1.2 million for the year ended December 31,
2020. The decrease is primarily attributable to lower market yields and cash balances on the Company’s cash equivalents and marketable securities.
Interest Expense
Our interest expense of $3.2 million and $1.3 million for the years ended December 31, 2021 and 2020, respectively, is related to the Loan
Agreement.
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Other Income (Expense), Net
Other expense, net, was $1.0 million for the year ended December 31, 2021 which includes $0.8 million commitment share expenses related to
the equity purchase agreement with Lincoln Park Capital Fund and $0.3 million property and other tax expense, offset by $0.2 million gain from the debt
extinguishment from the conversion of debt to equity and the sale of assets. Other income, net, was $0.2 million for the year ended December 31, 2020 and
was primarily due to the change in the fair value of our investment in the common stock of Ascentage International. The entire investment was sold in
2020.
Comparison of the years ended December 31, 2020 and 2019
The following table sets forth the significant components of our results of operations (in thousands):
Summary of Operations Data:
Operating expenses:
Research and development
General and administrative
Change in fair value of contingent consideration
Impairment of long-lived assets
Total operating expenses
Loss from operations
Interest income
Interest expense
Other income (expense), net
Net loss
Year Ended December 31,
2019
2020
Change
$
$
67,309 $
24,025
(33)
2,629
93,930
(93,930)
1,196
(1,292)
182
(93,844) $
70,957 $
20,046
(1,352)
—
89,651
(89,651)
3,289
—
4,185
(82,177) $
(3,648)
3,979
1,319
2,629
4,279
(4,279)
(2,093)
(1,292)
(4,003)
(11,667)
Research and Development
Research and development expenses decreased by $3.6 million, to $67.3 million for the year ended December 31, 2020 from $70.9 million for
the year ended December 31, 2019. The decrease was primarily due to a decrease of $5.3 million in direct research and development expenses mainly due
to lower pre-clinical research and development activities and contract manufacturing costs, partially offset by higher costs from clinical programs started in
late 2019. Laboratory supplies decreased by $1.9 million and facilities-related costs increased by $2.2 million. Personnel-related expenses increased by
$1.4 million, of which $1.6 million was related to non-cash stock compensation expense partially offset by a decrease in payroll due to the corporate
restructuring and other costs such as travel, due to employees working from home.
General and Administrative
General and administrative expenses increased by $4.0 million, to $24.0 million for the year ended December 31, 2020 from $20.0 million for
the year ended December 31, 2019. The increase was primarily due to increases of $2.0 million in personnel-related expenses, of which $1.4 million was
related to non-cash stock compensation expense, $0.8 million in professional fees, $0.7 million in facilities-related costs and $0.5 million in insurance-
related expense.
Change in Fair Value of Contingent Consideration
Change in fair value of contingent consideration reflects a decrease in the contingent consideration liability of $1.3 million for the year ended
December 31, 2020. We issued shares in 2020 as a result of meeting a contractual milestone. The change in the fair value of contingent consideration was
primarily due to changes in assumptions, including probabilities, and our stock price used to calculate the fair value of the liability. Additionally, during the
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third quarter of 2020, we made changes to the related contracts, which resulted in there being no contingent consideration liability at December 31, 2020.
Impairment of Long-Lived Assets
Impairment charges consisted of impairment of long-lived assets. We evaluated the right-of-use asset and related leasehold improvements upon
exit of our former headquarters located in Brisbane, California, and recorded an impairment charge of $2.6 million during the year.
Interest Income
Our interest income was $1.2 million for the year ended December 31, 2020, as compared to $3.3 million for the year ended December 31,
2019. The decrease is primarily attributable to lower market yields and cash balances on the Company’s cash equivalents and marketable securities.
Interest Expense
Our interest expense of $1.3 million for the year ended December 31, 2020 is related to the Loan Agreement.
Other Income (Expense), Net
Other income was $0.2 million for the year ended December 31, 2020, as compared to $4.2 million for the year ended December 31, 2019. The
decrease was primarily due to a change in the fair value of our investment in the common stock of Ascentage International.
Liquidity, Capital Resources and Capital Requirements
Sources of Liquidity
We have incurred net losses each year since inception. We do not have any products approved for sale and have never generated any revenue
from product sales. Historically, we have incurred operating losses as a result of ongoing efforts to develop our drug candidates, including conducting
ongoing research and development, preclinical studies and providing general and administrative support for these operations. Our net losses were $60.7
million and $93.8 million for the years ended December 31, 2021 and 2020, respectively. As of December 31, 2021, we had an accumulated deficit of
$400.0 million, and we do not expect positive cash flows from operations in the foreseeable future. Based on our current operating plans, we expect our
existing capital resources will fund our planned operating expenses into the first quarter of 2023 which is expected to fund key clinical data readouts for
UBX1325, but less than 12 months from the date of this Annual Report. We expect our operating losses and net cash used in operating activities will
increase over at least the next several years as we continue our research and development activities, advance our drug candidates through preclinical and
clinical testing and move into later and more costly stages of drug development, hire personnel and prepare for regulatory submissions and the
commercialization of our drug candidates. As a result, we will need to raise additional capital. Adequate funding may not be available to us on acceptable
terms, or at all, particularly in light of the current COVID-19 pandemic and associated economic uncertainty and potential for local and/or global economic
recession. If sufficient funds on acceptable terms are not available when needed, we could be required to significantly reduce our operating expenses and
delay, reduce the scope of, or eliminate one or more of our development programs.
We have historically financed our operations primarily through private placements of preferred stock and promissory notes, as well as public
equity issuances, such as our initial public offering, or IPO, and more recently through proceeds from our Loan Agreement, the Initial ATM Offering
Program, the Additional ATM Offering Program, the Equity Purchase Agreement and will continue to be dependent upon equity and/or debt financing to
operate our business until we are able to generate positive cash flows from our operations.
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In August 2020, we entered into a Loan Agreement with Hercules Capital, Inc. (“Hercules”) pursuant to a term loan, subject to certain terms
and conditions and $25.0 million dollars was advanced to us on the date of execution of the Loan Agreement. The milestones for the remaining tranches
have not yet been reached and, as of December 31, 2021 will not be reached. We will make interest only payments through September 1, 2022 and will
then repay the principal balance and interest in equal monthly installments through August 1, 2024. In December 2021, we entered into an amendment to
our Loan and Security Agreement under the terms of which, Hercules (including any of its assignees) has the option for a period of six (6) months to
convert up to $5.0 million of the outstanding principal under the existing loan into shares of our common stock. Under the Loan Amendment, the required
cash reserve amount shall be reduced by the principal amount of the converted loan to not less than $10 million. As of December 31, 2021, we issued
1,727,361 shares of our common stock reducing our outstanding loan principal balance by $2.3 million. As of February 14, 2022, the remaining $2.7
million of debt principal was converted to equity, and reducing the required cash reserve to $10 million. In addition, the interest only period may extend by
up to a maximum of 9 months to June 1, 2023 should we meet specific milestones related to our clinical trials and raising additional capital.
In June 2019, we filed a Registration Statement on Form S-3, or the Shelf Registration Statement, covering the offering of up to $250.0 million
of common stock, preferred stock, debt securities, warrants and units. The Shelf Registration Statement included an initial prospectus covering the offering,
issuance and sale of up to $75.0 million of our common stock from time to time through an at-the-market offering, or the Initial ATM Offering Program,
under which Cowen acts as sales agent. In July 2020, we filed an additional prospectus supplement to the Shelf Registration Statement, covering the
offering, issuance and sale of up to an additional $50.0 million of our common stock from time to time through an additional at-the-market offering, or the
Additional ATM Offering Program, under which Cowen acts as sales agent. During the year ended December 31, 2021, we issued and sold 1,187,068
shares of common stock sold through the Initial ATM Offering Program and 707,459 shares of common stock sold through the Additional ATM Offering
Program and received total net proceeds of approximately $10.4 million, after deducting commissions and other offering expenses of $0.3 million. As of
December 31, 2021, no proceeds remained available to be sold under our Initial ATM Offering Program and approximately $48.2 million of Additional
ATM Offering Program proceeds remained available to be sold under our Additional ATM Offering Program.
In September 2021, we entered into a Purchase Agreement with Lincoln Park Capital Fund, LLC, under which we may at our discretion, sell
up to $30.0 million shares of our common stock over a 36-month period, subject to certain daily limits, applicable prices, and conditions. As of December
31, 2021, we had initiated the purchase of 3.9 million shares of our common stock amounting to $8.3 million in gross proceeds. In addition, under the
Purchase Agreement, we issued 252,447 shares of our common stock to Lincoln Park as consideration for its commitment to purchase shares of our
common stock under the Purchase Agreement.
Future Funding Requirements
To date we have not generated any revenue from contracts with customers. We expect to continue to incur significant losses for the foreseeable
future, and we expect the losses to increase as we continue the development of, and seek regulatory approvals for, our drug candidates, and begin to
commercialize any approved products. We are subject to all of the risks typically related to the development of new drug candidates, and we may encounter
unforeseen expenses, difficulties, complications, delays, and other unknown factors that may adversely affect our business. Moreover, since becoming a
public company, we continue to incur additional ongoing costs associated with operating as a public company. We anticipate that we will need substantial
additional funding in connection with our continuing operations.
Until we can generate a sufficient amount of revenue from the commercialization of our drug candidates or from collaborative agreements with
third parties, if ever, we expect to finance our future cash needs through various means. Other than our right to cause Lincoln Park to purchase shares of our
common stock under the LPC Purchase Agreement, which is subject to certain limitations and conditions, we do not have any committed external source of
funds. Additional capital may be raised through the sale of our equity securities, incurring debt, entering into licensing or collaboration agreements with
partners, receiving research contributions, grants or other sources of
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financing to fund our operations. There can be no assurance that sufficient funds will be available to us on attractive terms or at all. If we are unable to
obtain additional funding from these or other sources, it may be necessary to significantly reduce our rate of spending through reductions in staff and
delaying, scaling back, or stopping certain research and development programs. Insufficient liquidity may also require us to relinquish rights to drug
candidates at an earlier stage of development or on less favorable terms than we would otherwise choose.
Based on our current operating plans, we expect our existing capital resources will fund our planned operating expenses into the first quarter of
2023 which is expected to fund key clinical data readouts for UBX1325. We have based our projections of operating capital requirements on assumptions
that may prove to be incorrect and we may use all our available capital resources sooner than we expect. Because of the numerous risks and uncertainties
associated with research, development, and commercialization of biotechnology products, we are unable to estimate the exact amount of our operating
capital requirements. Our future funding requirements will depend on many factors, including, but not limited to:
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the results of our ongoing clinical trials of UBX1325;
the scope, progress, results and costs of researching and developing our drug candidates, and conducting preclinical studies and clinical studies;
potential delays in or an increase in costs associated with our ongoing or planned preclinical studies or clinical trials as a result of the COVID-
19 pandemic;
the timing of, and the costs involved in, obtaining regulatory approvals for our current drug candidates or any future drug candidates;
the number and characteristics of any additional drug candidates we develop or acquire;
the timing and amount of any milestone payments we are required to make pursuant to our license agreements;
the cost of manufacturing our current drug candidates or any future drug candidates and any products we successfully commercialize;
the expenses needed to attract, hire, and retain skilled personnel;
the cost of commercialization activities if our current drug candidates or any future drug candidates are approved for sale, including marketing,
sales and distribution costs;
our ability to maintain existing, and establish new, strategic collaborations, licensing or other arrangements and the financial terms of any such
agreements, including the timing and amount of any future milestone, royalty or other payments due under any such agreement;
any product liability or other lawsuits related to our products;
the costs associated with being a public company;
the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing our intellectual property portfolio; and
the timing, receipt and amount of sales of any future approved products, if any.
Cash Flows
The following table sets forth a summary of the primary sources and uses of cash and restricted cash for each of the periods presented below (in
thousands):
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Cash used in operating activities
Cash provided by (used in) investing activities
Cash provided by financing activities
Net increase (decrease) in cash and
restricted cash
2021
Year Ended December 31,
2020
2019
$
(45,060) $
39,313
20,845
(78,333) $
(5,208)
63,875
(72,421)
67,953
27,438
$
15,098 $
(19,666) $
22,970
Operating Activities
Cash used in operating activities of $45.1 million for the year ended December 31, 2021 consisted primarily of a net loss of $60.7 million
adjusted for net non-cash charges of $16.3 million and net changes to our operating assets and liabilities of $0.6 million. Our non-cash charges consisted
primarily of $11.6 million in stock-based compensation, $2.9 million in depreciation and amortization, $1.5 million in common stock granted to a third
party, $1.0 million in net accretion and amortization of premium and discounts on marketable securities, $0.8 million in amortization of debt issuance costs
and $0.8 million other expenses related to the equity purchase agreement with Lincoln Park Capital Fund, partially offset by a $2.2 million in non-cash rent
expense and $0.1 million debt extinguishment gain from conversion of debt to equity. The net change in our operating assets and liabilities primarily
consisted of decreases of $1.3 million in accrued compensation, $1.1 million in accrued liabilities and other current liabilities, $0.6 million in accounts
payable and increase of $0.1 million in other long-term assets, partially offset by increases of $1.0 million in derivative liability and $0.2 million in
deferred revenue and a decrease of $1.3 million in prepaid expenses and other current assets.
Cash used in operating activities of $78.3 million for the year ended December 31, 2020 consisted primarily of a net loss of $93.8 million
adjusted for net non-cash charges of $20.1 million and net changes to our operating assets and liabilities of $4.6 million. Our non-cash charges consisted
primarily of $13.8 million in stock-based compensation, $3.4 million in depreciation and amortization, $2.6 million in impairment charges pertaining to
leasehold improvements and right of use assets in the Company’s former offices, $1.2 million in common stock granted to a third party, $0.3 million in
amortization of debt issuance costs and $0.3 million in net accretion and amortization of premium and discounts on marketable securities, partially offset
by a $1.1 million in non-cash rent expense and $0.5 million change in fair value of strategic investment. The net change in our operating assets and
liabilities consisted of decreases of $2.6 million in accounts payable, $0.9 million in accrued liabilities and other current liabilities, $0.5 million in accrued
compensation and increase of $1.2 million in prepaid expenses and other current assets, partially offset by a decrease of $0.6 million in other long-term
assets.
Cash used in operating activities of $72.4 million for the year ended December 31, 2019 consisted primarily of a net loss of $82.2 million
adjusted for net non-cash charges of $6.2 million and net changes to our operating assets and liabilities of $3.6 million. Our non-cash charges consisted
primarily of $10.9 million in stock-based compensation, $2.7 million in depreciation and amortization and $1.0 million in common stock granted to a third
party, partially offset by a $1.4 million change in fair value of contingent consideration, $1.3 million in accretion of our tenant improvement allowance and
$1.2 million in net accretion and amortization of premium and discounts on marketable securities. The net change in our operating assets and liabilities
consisted of increases of $2.5 million in deferred rent, net of current portion, and $2.1 million in accrued compensation, partially offset by decreases of $0.6
million in accrued liabilities and other current liabilities, $0.2 million in accounts payable and a $0.2 million increase in prepaid expenses and other current
assets.
Investing Activities
Cash provided by investing activities of $39.3 million for the year ended December 31, 2021 was related to maturities of marketable securities
of $121.0 million which were offset by purchases of marketable securities of $81.5 million and purchases of property and equipment of $0.2 million.
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Cash used in investing activities of $5.2 million for the year ended December 31, 2020 was related to purchases of marketable securities of
$138.5 million and purchases of property and equipment of $0.6 million, which were offset by maturities of marketable securities of $127.9 million and the
sale of our strategic investment of $6.0 million.
Cash provided by investing activities of $68.0 million for the year ended December 31, 2019 was related to maturities of marketable securities
of $188.8 million which were offset by purchases of marketable securities of $119.3 million and purchases of property and equipment of $1.6 million.
Financing Activities
Cash provided by financing activities of $20.8 million for the year ended December 31, 2021 was related to $10.4 million in proceeds from the
sale of common stock through our ATM Offering Program, net of issuance costs, $8.2 million in proceeds from issuance of common stock to Lincoln Park
Capital Fund, net of issuance costs, $1.8 million in proceeds from issuance of common stock upon exercise of stock options, net of repurchases, $0.3
million in proceeds from the issuance of common stock under the 2018 Employee Stock Purchase Plan and $0.2 million in proceeds from the repayment of
employee promissory note, partially offset by $0.1 million current portion of long-term debt arrangement.
Cash provided by financing activities of $63.9 million for the year ended December 31, 2020 was related to $37.3 million in proceeds from the
sale of common stock through our ATM Offering Program, net of issuance costs, $24.2 million in proceeds from long-term debt, net of issuance costs, $1.5
million in proceeds from issuance of common stock upon exercise of stock options, net of repurchases, $0.6 million in proceeds from the issuance of
common stock under the 2018 Employee Stock Purchase Plan, and $0.4 million in proceeds from the repayment of promissory notes from an employee.
Cash provided by financing activities of $27.4 million for the year ended December 31, 2019 was related to $26.1 million in proceeds from the
sale of common stock through our ATM Offering Program, net of issuance costs, $0.8 million in proceeds from the issuance of common stock under the
2018 Employee Stock Purchase Plan and proceeds from issuance of common stock upon exercise of stock options, net of repurchases, of $0.6 million.
Contractual Obligations and Other Commitments
Our contractual obligations and commitments relate primarily to our Loan Agreement, operating leases and non-cancelable purchase
obligations under agreements with various research and development organizations and suppliers in the ordinary course of business. In February 2019, we
entered into a lease agreement for new office and laboratory space in South San Francisco, California. See Note 7, “Commitments and Contingencies” and
Note 8, “Term Loan Facility,” to our financial statements for further information.
We are party to various license agreements pursuant to which we have in-licensed rights to various technologies, including patents, research
“know-how” and proprietary research tools, for the discovery, research, development and commercialization of drug candidates to treat age-related
diseases. The license agreements obligate us to make certain milestone payments related to specified clinical development and sales milestone events, as
well as tiered royalties in the low-single digits based on sales of licensed products. See Note 5 to our financial statements “License Revenue, Agreements
and Strategic Investment” for additional information.
Indemnification
In the normal course of business, we enter into contracts and agreements that contain a variety of representations and warranties and provide for
general indemnifications. Our exposure under these agreements is unknown because it involves claims that may be made against us in the future but have
not yet been made. To date, we have not paid any claims or been required to defend any action related to our indemnification obligations. However, we may
record charges in the future as a result of these indemnification obligations.
In accordance with our certificate of incorporation and bylaws, we have potential indemnification obligations to our officers and directors for
specified events or occurrences, subject to some limits, while they are
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serving at our request in such capacities. There have been no claims to date, and we have director and officer insurance that may enable us to recover a
portion of any amounts paid for future potential claims.
Off-Balance Sheet Arrangements
We have not entered into any off-balance sheet arrangements.
Critical Accounting Policies and Estimates
This discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared
in accordance with accounting principles generally accepted in the United States (“GAAP”). The preparation of these financial statements requires us to
make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of
the financial statements, as well as the reported expenses incurred during the reporting periods. These items are monitored and analyzed by us for changes
in facts and circumstances, and material changes in these estimates could occur in the future. Our estimates are based on our historical experience and on
various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying
value of assets and liabilities that are not readily apparent from other sources. Changes in estimates are reflected in reported results for the period in which
they become known. Actual results may differ from these estimates under different assumptions or conditions.
While our significant accounting policies are described in more detail in the notes to our financial statements included elsewhere in this
prospectus, we believe that the following accounting policies are critical to understanding our historical and future performance, as these policies relate to
the more significant areas involving management’s judgments and estimates.
Research and Development Expenses and Accruals
Costs related to research and development of drug candidates are charged to research and development expense as incurred. Research and
development costs include, but are not limited to, payroll and personnel expenses for personnel contributing to research and development activities,
laboratory supplies, outside services, licenses acquired to be used in research and development, manufacturing of clinical material, pre-clinical testing and
consultants and allocated overhead, including rent, equipment, depreciation and utilities. Research and development costs are expensed as incurred unless
there is an alternative future use in other research and development projects. Payments made prior to the receipt of goods or services to be used in research
and development are deferred and recognized as expense in the period in which the related goods are received or services are rendered. Such payments are
evaluated for current or long-term classification based on when they will be realized.
As part of the process of preparing our financial statements, we are required to estimate expenses resulting from our obligations under contracts
with vendors and consultants and clinical site agreements in connection with conducting clinical trials. The financial terms of these contracts are subject to
negotiations which vary from contract to contract and may result in payment flows that do not match the periods over which materials or services are
provided under such contracts. Our objective is to reflect the appropriate expenses in our financial statements by matching those expenses with the period
in which services and efforts are expended. We account for these expenses according to the progress of the production of clinical trial materials or based on
progression of the clinical trial, as measured by patient progression and the timing of various aspects of the trial. We determine accrual estimates by taking
into account discussion with applicable personnel and outside service providers as to the progress or state of consummation of goods and services, or the
services completed. During the course of a clinical trial, we adjust the rate of expense recognition if actual results differ from our estimates. We make
estimates of accrued expenses as of each balance sheet date in our financial statements based on the facts and circumstances known at that time. Our
clinical trial accrual is dependent in part upon the timely and accurate reporting of contract research organizations, contract manufacturers and other third-
party vendors. 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 our reporting changes in estimates in
any particular period. Adjustments to prior period estimates have not been material for the years ended December 31, 2021 and 2020.
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We have and may continue to enter into license agreements to access and utilize certain technology. We evaluate if the license agreement is an
acquisition of an asset or a business. To date none of our license agreements have been considered to be an acquisition of a business. For asset acquisitions,
the upfront payments to acquire such licenses, as well as any future milestone payments made before product approval, are immediately recognized as
research and development expense when due, provided there is no alternative future use of the rights in other research and development projects. These
license agreements may also include contingent consideration in the form of cash and additional issuances of our common stock.
Stock-Based Compensation
We recognize compensation costs related to stock-based awards granted based on the estimated fair value of the awards on the date of grant,
and we recognize forfeitures as they occur. For awards that vest solely based on service conditions or a combination of service and performance conditions,
we estimate the grant date fair value, and the resulting stock-based compensation expense, using the Black-Scholes option-pricing model. The grant date
fair value of the awards is generally recognized on a straight-line basis over the requisite service period, which is typically their vesting period. We
recognize forfeitures as they occur.
The market traded price of the shares of common stock underlying the stock-based awards is the fair value of our stock as reported on the
Nasdaq Global Select Market on the grant date.
The Black-Scholes option-pricing model requires the use of highly subjective assumptions to determine the fair value of stock-based awards.
These assumptions include:
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Expected term—The expected term represents the period that the stock-based awards are expected to be outstanding. We use, due to
insufficient historical data, the simplified method to determine the expected term, which is based on the average of the time-to-vesting and
the contractual life of the options.
Expected volatility—Due to our limited trading history for our common stock, the expected volatility is estimated based on the average
historical volatilities of common stock of comparable publicly traded entities over a period equal to the expected term of the stock option
grants. The comparable companies are chosen based on their size, stage in the product development cycle or area of specialty. We will
continue to apply this process until a sufficient amount of historical information regarding the volatility of our own stock price becomes
available.
Risk-free interest rate—The risk-free interest rate is based on the U.S. Treasury yield in effect at the time of grant for zero-coupon U.S.
Treasury notes with maturities approximately equal to the expected term of the awards.
Expected dividend—We have never paid dividends on our common stock and have no plans to pay dividends on our common stock.
Therefore, we used an expected dividend yield of zero.
We have also granted stock options to certain key employees that vest in conjunction with certain market conditions. The Company uses the
Monte-Carlo option-pricing model to estimate the fair value of stock option awards that contain only market conditions. The Monte-Carlo option pricing
model uses similar input assumptions as the Black-Scholes model; however, it further incorporates into the fair-value determination the possibility that the
market condition may not be satisfied.
As of December 31, 2021, we had $23.1 million of unrecognized compensation expense related to unvested stock options and restricted stock
units, which is expected to be recognized over an estimated weighted-average period of 3.2 years. For stock-based awards subject to ratable vesting, we
recognize compensation cost on a straight-line basis over the service period for the entire award. In future periods, our stock-based compensation expense
is expected to increase as a result of recognizing our existing unrecognized stock-based compensation for awards that will vest and as we issue additional
stock-based awards to attract and retain our employees.
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JOBS Act Accounting Election
We are an emerging growth company, as defined in the JOBS Act. Under the JOBS Act, emerging growth companies can delay adopting new
or revised accounting standards issued subsequent to the enactment of the JOBS Act until such time as those standards apply to private companies. We
have irrevocably elected to avail ourselves of this exemption from new or revised accounting standards and, therefore, will not be subject to the same new
or revised accounting standards as other public companies that are not emerging growth companies. We also rely on other exemptions provided by the
JOBS Act, including, without limitation, providing an auditor’s attestation report on our system of internal controls over financial reporting pursuant to
Section 404(b) of the Sarbanes-Oxley Act. We will remain an emerging growth company until the earlier of (1) the last day of the year following the fifth
anniversary of the consummation of our IPO, (2) the last day of the year in which we have total annual gross revenue of at least $1.07 billion, (3) the last
day of the year in which we are deemed to be a “large accelerated filer” as defined in Rule 12b-2 under the Exchange Act, which would occur if the market
value of our common stock held by non-affiliates exceeded $700.0 million as of the last business day of the second fiscal quarter of such year or (4) the
date on which we have issued more than $1.0 billion in non-convertible debt securities during the prior three-year period. Even after we no longer qualify
as an emerging growth company, we may still qualify as a “smaller reporting company” which may allow us to take advantage of many of the same
exemptions from disclosure requirements including not being required to comply with the auditor attestation requirements of Section 404(b) of the
Sarbanes-Oxley Act.
Recent Accounting Pronouncements
See Note 2 to our Financial Statements “Summary of Significant Accounting Policies” for information.
Item 7A. Quantitative and Qualitative Disclosures About Market Risk.
Cash, Cash Equivalents and Marketable Securities
We are exposed to market risks in the ordinary course of our business. These risks primarily relate to interest rate sensitivities. We had cash,
cash equivalents, and marketable securities of $90.1 million as of December 31, 2021, which consist of bank deposits, money market funds, and marketable
securities. The primary objective of our investment activities is to preserve capital to fund our operations. We also seek to maximize income from our
investments without assuming significant risk. Because our investments are primarily short-term in duration, we believe that our exposure to interest rate
risk is not significant, and a 1% movement in market interest rates would not have a significant impact on the total value of our portfolio.
Interest Rate Risk
As of December 31, 2021, the outstanding principal amount of the term loan under the Hercules Loan Agreement was $22.7 million. The
interest payments under our term loan may be subject to interest rate risk and our interest expense could increase if market interest rates increase. The
interest on the term loan accrues at a per annum rate of the greater of (i) the Wall Street Journal prime rate plus 6.10% and (ii) 9.35%. Accordingly,
increases in these published rates would increase our interest payments under the term loans. The effective interest rate at December 31, 2021 was 16.69%.
A hypothetical 1% change in interest rates would increase expense by approximately $0.4 million annually and would not have a material impact on our
results of operations.
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Item 8. Financial Statements and Supplementary Data.
UNITY BIOTECHNOLOGY, INC.
Index to Financial Statements
Report of Independent Registered Public Accounting Firm (PCAOB ID 42)
Balance Sheets
Statements of Operations and Comprehensive Loss
Statements of Convertible Preferred Stock and Stockholders’ Equity (Deficit)
Statements of Cash Flows
Notes to the Financial Statements
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100
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Report of Independent Registered Public Accounting Firm
To the Stockholders and the Board of Directors of
Unity Biotechnology, Inc.
Opinion on the Financial Statements
We have audited the accompanying balance sheets of Unity Biotechnology, Inc. (“the Company”) as of December 31, 2021 and 2020, and related
statements of operations and comprehensive loss, and stockholders’ equity and cash flows for each of the three years in the period ended December 31,
2021, and the related notes (collectively referred to as the “financial statements”). In our opinion, the financial statements present fairly, in all material
respects, the financial position of the Company at December 31, 2021 and 2020, and the results of its operations and its cash flows for each of the three
years in the period ended December 31, 2021, in conformity with U.S. generally accepted accounting principles.
The Company's Ability to Continue as a Going Concern
The accompanying financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1 to the
financial statements, the Company has suffered recurring losses from operations, and has stated that substantial doubt exists about the Company’s ability to
continue as a going concern. Management's evaluation of the events and conditions and management’s plans regarding these matters are also described in
Note 1. The financial statements do not include any adjustments that might result from the outcome of this uncertainty.
Basis for Opinion
These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial
statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States)
(PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and
regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable
assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor
were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits, we are required to obtain an understanding of
internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over
financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and
performing procedures that respond to those risks. Such procedures include examining, on a test basis, evidence regarding the amounts and disclosures in
the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as
evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.
/s/ Ernst & Young LLP
We have served as the Company’s auditor since 2017.
Redwood City, California
March 15, 2022
96
UNITY BIOTECHNOLOGY, INC.
Balance Sheets
(in thousands, except for share amounts and par value)
Assets
Current assets:
Cash and cash equivalents
Short-term marketable securities
Prepaid expenses and other current assets
Restricted cash
Total current assets
Property and equipment, net
Operating lease right-of-use assets
Long-term marketable securities
Long-term restricted cash
Other long-term assets
Total assets
Liabilities and Stockholders’ Equity
Current liabilities:
Accounts payable
Accrued compensation
Accrued and other current liabilities
Deferred revenue
Derivative liability related to debt
Current portion of long-term debt
Total current liabilities
Operating lease liability, net of current portion
Long-term debt, net
Other long-term liabilities
Total liabilities
Commitments and contingencies (Note 7)
Stockholders’ equity:
Convertible preferred stock, $0.0001 par value; 10,000,000 shares
authorized; no shares issued and outstanding
Common stock, $0.0001 par value; 300,000,000 shares
authorized as of December 31, 2021 and 2020; 62,991,906
and 53,253,213 shares issued and outstanding as of
December 31, 2021 and 2020, respectively
Additional paid-in capital
Related party promissory notes for purchase of common stock
Accumulated other comprehensive gain
Accumulated deficit
Total stockholders’ equity
Total liabilities and stockholders’ equity
December 31,
2021
2020
32,905 $
55,170
1,879
550
90,504
9,942
21,286
1,993
896
91
124,712 $
1,985 $
4,028
6,370
216
963
3,055
16,617
30,094
18,409
23
65,143
17,807
79,892
3,167
—
100,866
12,627
23,509
17,871
1,446
—
156,319
2,558
5,355
6,550
—
—
—
14,463
34,468
24,508
—
73,439
—
—
6
459,631
—
(44)
(400,024)
59,569
124,712 $
5
422,379
(210)
5
(339,299)
82,880
156,319
$
$
$
$
See accompanying notes to the financial statements.
97
UNITY BIOTECHNOLOGY, INC.
Statements of Operations and Comprehensive Loss
(in thousands, except share and per share amounts)
Licensing revenue – Related Party
Operating expenses:
Research and development
General and administrative
Change in fair value of contingent consideration
Impairment of long-lived assets
Total operating expenses
Loss from operations
Interest income
Interest expense
Other (expense) income, net
Net loss
Other comprehensive loss
Unrealized (loss) gain on marketable debt securities
Comprehensive loss
Net loss per share, basic and diluted
Weighted average number of shares used in computing net loss
per share, basic and diluted
2021
Year ended December 31,
2020
2019
$
4,784 $
— $
—
38,393
23,056
—
—
61,449
(56,665)
100
(3,177)
(983)
(60,725) $
(49)
(60,774) $
(1.09) $
67,309
24,025
(33)
2,629
93,930
(93,930)
1,196
(1,292)
182
(93,844) $
(85)
(93,929) $
(1.84) $
70,957
20,046
(1,352)
—
89,651
(89,651)
3,289
—
4,185
(82,177)
185
(81,992)
(1.88)
55,815,873
50,864,889
43,624,807
$
$
$
See accompanying notes to the financial statements.
98
Balances at December 31, 2018
Issuance of common stock, net of issuance costs, under
at-the-market equity ("ATM") equity offering program
Issuance of common stock upon exercise of stock options
Vesting of early exercised stock options
Stock-based compensation
Common stock issued to third parties
Repurchased shares
Issuance of common stock under employee stock purchase
plan (“2018 ESPP”)
Unrealized gain on available-for-sale marketable securities
Net loss
Balances at December 31, 2019
Issuance of common stock, net of issuance costs, under
ATM equity offering program
Issuance of common stock upon exercise of stock options
Issuance of common stock upon vesting of restricted
stock units
Vesting of early exercised stock options
Stock-based compensation
Common stock issued for services
Common stock issued to third parties for milestone payments
Repayment of promissory note from employee from
purchase of common stock
Repayment of promissory note from employee through
repurchase of early exercise shares
Issuance of common stock under 2018 ESPP
Unrealized loss on available-for-sale marketable securities
Net loss
Balances at December 31, 2020
Issuance of common stock, net of issuance costs, under
ATM equity offering program
Issuance of common stock to Lincoln Park Capital Fund,
net of issuance costs
Issuance of common stock Hercules Capital,
net of issuance costs
Issuance of common stock upon exercise of stock options
Issuance of common stock under 2018 ESPP
Common stock granted to third party
Repurchase of early exercised shares
Vesting of restricted stock units
Stock-based compensation
Repayment of promissory note for purchase of common
stock
Unrealized loss on available-for-sale marketable securities
Net loss
Balances at December 31, 2021
UNITY BIOTECHNOLOGY, INC.
Statements of Stockholders’ Equity
(in thousands, except share amounts)
Common Stock
Shares
42,414,294
$
Amount
Additional
Paid-In
Capital
4
$
324,663
Related Party
Promissory Notes
for Purchase of
Common Stock
$
Employee
Promissory
Notes for
Purchase of
Common Stock
Accumulated
Other
Comprehensive
Gain (Loss)
Accumulated
Deficit
Total
Stockholders’
Equity
(201 ) $
(400 ) $
(95 ) $
(163,278 ) $
160,693
—
—
—
—
—
—
—
185
—
90
—
—
—
—
—
—
—
—
$
26,085
840
647
10,852
3,022
—
586
—
—
366,695
37,270
1,510
—
216
13,746
100
2,310
—
(44 )
576
—
—
422,379
$
$
10,357
9,039
2,704
1,795
347
1,457
—
—
11,553
3,974,908
505,226
—
—
253,334
(4,281 )
83,584
—
—
47,227,065
5,002,257
410,484
$
103,020
—
—
43,550
361,644
—
(12,909 )
118,102
—
—
53,253,213
$
1,894,527
4,172,855
1,727,361
497,538
117,037
400,052
(33,370 )
962,693
—
—
—
—
62,991,906
$
1
—
—
—
—
—
—
—
—
5
—
—
—
—
—
—
—
—
—
—
—
—
5
—
1
—
—
—
—
—
—
—
—
—
6
—
—
—
—
(9 )
—
—
—
—
—
—
—
—
(18 )
—
—
—
—
$
(210 ) $
(418 ) $
—
—
—
—
—
—
—
—
(82,177 )
(245,455 ) $
$
—
—
—
—
—
—
—
—
—
—
—
—
(210 ) $
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
374
44
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
(85 )
—
5
$
$
—
—
—
—
—
—
—
—
—
—
(49 )
—
(44 ) $
$
—
—
—
—
—
—
—
—
—
—
—
(93,844 )
(339,299 ) $
—
—
—
—
—
—
—
—
—
—
—
(60,725 )
(400,024 ) $
—
—
—
459,631
$
$
210
—
—
—
$
See accompanying notes to the financial statements
99
26,086
840
647
10,852
2,995
—
586
185
(82,177 )
120,707
37,270
1,510
—
216
13,746
100
2,310
374
—
576
(85 )
(93,844 )
82,880
10,357
9,040
2,704
1,795
347
1,457
—
—
11,553
210
(49 )
(60,725 )
59,569
UNITY BIOTECHNOLOGY, INC.
Statements of Cash Flows
(in thousands)
Operating activities
Net loss
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization
Amortization of debt issuance costs
Debt extinguishment gain upon conversion to equity
Net accretion and amortization of premium and discounts on marketable securities
Other expense related to the commitment shares issued to Lincoln Park
Capital Fund
Stock-based compensation
Common stock issued to third parties
Non-cash rent expense
Impairment of long-lived assets
Change in fair value of strategic investment
Accretion of tenant improvement allowance
Change in fair value of contingent consideration
Changes in operating assets and liabilities:
Prepaid expenses and other current assets
Other long-term assets
Accounts payable
Accrued compensation
Accrued liabilities and other current liabilities
Other long-term liabilities
Derivative liability related to debt
Deferred revenue
Deferred rent, net of current portion
Net cash used in operating activities
Investing activities
Purchase of marketable securities
Maturities of marketable securities
Sale of strategic investments
Purchase of property and equipment
Net cash provided by (used in) investing activities
Financing activities
Proceeds from issuance of common stock under ATM offering program,
net of issuance costs
Proceeds from issuance of common stock to Lincoln Park Capital Fund,
net of issuance costs
Proceeds from repayment of employee promissory notes
Proceeds from long-term debt, net of issuance costs to lender
Payment of long-term debt non-lender issuance costs
Proceeds from issuance of common stock upon exercise of stock options,
net of repurchases
Proceeds from issuance of common stock under the 2018 ESPP
Current portion of long-term debt arrangement
Payments made on capital lease obligations
Net cash provided by financing activities
Net increase (decrease) in cash, cash equivalents and restricted cash
Cash, cash equivalents and restricted cash at beginning of year
Cash, cash equivalents and restricted cash at end of year
Supplemental Disclosures of Cash Flow Information:
Cash paid for interest
Supplemental Disclosures of Non-Cash Investing and Financing Activities
Issuance of common shares in payment of debt
Property and equipment included in accounts payable
Issuance of common stock in settlement of contingent consideration milestone
Issuance of shares in settlement of share-based liability
Right-of-use assets obtained in exchange for new operating lease liabilities
Lessor funded lease incentives included in property and equipment
Receipt of promissory note from related party for purchase of common stock
2021
Year Ended December 31,
2020
2019
$
(60,725) $
(93,844) $
(82,177)
2,880
813
(123)
1,043
825
11,553
1,457
(2,152)
—
—
—
—
1,288
(91)
(573)
(1,327)
(1,131)
24
963
216
—
(45,060)
(81,492)
121,000
—
(195)
39,313
10,357
8,215
210
—
—
1,784
347
(68)
—
20,845
15,098
19,253
34,351
$
3,449
318
—
256
—
13,813
1,211
(1,076)
2,629
(502)
—
(33)
(1,168)
628
(2,640)
(517)
(857)
—
—
—
—
(78,333)
(138,486)
127,915
6,009
(646)
(5,208)
37,270
—
374
24,550
(360)
1,510
576
—
(45)
63,875
(19,666)
38,919
19,253
$
2,370
$
773
$
2,704
—
—
—
—
—
—
$
$
$
$
$
$
$
—
13
1,098
100
27,714
—
—
$
$
$
$
$
$
$
2,663
—
—
(1,151)
—
10,852
965
—
—
(4,507)
(1,275)
(1,352)
(169)
(31)
(227)
2,114
(587)
—
—
—
2,461
(72,421)
(119,270)
188,809
—
(1,586)
67,953
26,085
—
—
—
—
840
586
—
(73)
27,438
22,970
15,949
38,919
—
—
565
—
—
—
10,651
27
$
$
$
$
$
$
$
$
$
See accompanying notes to the financial statements.
100
UNITY BIOTECHNOLOGY, INC.
NOTES TO THE FINANCIAL STATEMENTS
1. Organization
Description of Business
Unity Biotechnology, Inc. (the “Company”) is a biotechnology company engaged in the research and development of therapeutics to slow, halt, or reverse
diseases of aging. The Company devotes substantially all of its time and efforts to performing research and development, raising capital, and recruiting
personnel. The Company’s headquarters are located in South San Francisco, California. The Company was incorporated in the State of Delaware in 2009.
Liquidity
In accordance with Accounting Standards Update (“ASU”) No. 2014-15, Disclosures of Uncertainties about an Entity’s Ability to Continue as a Going
Concern (Subtopic 205-40) (“ASU No. 2014-15”), management must evaluate whether there are conditions or events, considered in the aggregate, that
raise substantial doubt about the Company’s ability to continue as a going concern within one year after the date that the financial statements are issued.
This evaluation initially does not take into consideration the potential mitigating effect of management’s plans that have not been fully implemented as of
the date the financial statements are issued. When substantial doubt exists under this methodology, management evaluates whether the mitigating effect of
its plans sufficiently alleviates substantial doubt about the Company’s ability to continue as a going concern. The mitigating effect of management’s plans,
however, is only considered if both (1) it is probable that the plans will be effectively implemented within one year after the date that the financial
statements are issued and (2) it is probable that the plans, when implemented, will mitigate the relevant conditions or events that raise substantial doubt
about the entity’s ability to continue as a going concern within one year after the date that the financial statements are issued. Generally, to be considered
probable of being effectively implemented, the plans must have been approved before the date that the financial statements are issued.
The Company’s Financial Statements have been prepared on a going concern basis, which contemplates the continuity of operations, realization of assets
and the satisfaction of liabilities and commitments in the ordinary course of business. The Company has incurred operating losses and has an accumulated
deficit as a result of ongoing efforts to develop drug product candidates, including conducting preclinical and clinical trials and providing general and
administrative support for these operations. The Company had an accumulated deficit of $400.0 million as of December 31, 2021. During the year ended
December 31, 2021, the Company incurred a net loss of $60.7 million and used $45.1 million of cash in operating activities. To date, none of the
Company’s drug candidates have been approved for sale, and therefore, the Company has not generated any revenue from contracts with customers and
does not expect positive cash flows from operations in the foreseeable future. The Company has financed its operations primarily through private
placements of preferred stock and promissory notes, public equity issuances and more recently, from its ATM Offering Program (as defined in Note 10), the
Term Loan Facility (as defined in Note 8) and an Equity Purchase Agreement (as defined in Note 10), and will continue to be dependent upon equity and/or
debt financing until the Company is able to generate positive cash flows from its operations.
The Company had cash, cash equivalents and marketable securities of $90.1 million as of December 31, 2021. As of March 15, 2022, the date of issuance
of these Financial Statements, the Company expects that its cash and cash equivalents as of December 31, 2021 will not be sufficient to fund its current
business plan including related operating expenses and capital expenditure requirements through at least 12 months from the date of issuance of these
Financial Statements. These conditions raise substantial doubt about the Company’s ability to continue as a going concern. The Company plans to seek to
address this condition by raising additional capital to finance its operations. The future viability of the Company is dependent on its ability to raise
additional capital to finance its operations. Although the Company has been successful in raising capital in the past, there is no assurance that it will be
successful in obtaining such additional financing. Therefore, it is not considered probable, as defined in ASU No. 2014-15, that the Company’s plans to
raise additional capital will alleviate the substantial doubt regarding its ability to continue as a going concern.
Management expects operating losses to continue for the foreseeable future. As a result, the Company will need to raise additional capital. If sufficient
funds on acceptable terms are not available when needed, the Company could be required to significantly reduce its operating expenses and delay, reduce
the scope of, or eliminate one or more of its development programs. Failure to manage discretionary spending or raise additional financing, as needed, may
adversely impact the Company’s ability to achieve its intended business objectives.
101
2. Summary of Significant Accounting Policies
Basis of Presentation
These financial statements have been prepared in accordance with accounting principles generally accepted in the United States of America (“GAAP”) and
the rules and regulations of Securities and Exchange Commission (“SEC”) for reporting.
Use of Estimates
The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the amounts
reported in the financial statements and accompanying notes. The Company bases its estimates on historical experience and market-specific or other
relevant assumptions that it believes are reasonable under the circumstances. The amounts of assets and liabilities reported in the Company’s balance sheets
and the amount of expenses and income reported for each of the periods presented are affected by estimates and assumptions, which are used for, but are
not limited to, determining the fair value of assets and liabilities, contingent consideration liability, the fair value of right-of-use assets and lease liabilities,
embedded derivatives and stock-based compensation. Actual results could differ from such estimates or assumptions.
Segments
The Company has one operating segment. The Company’s chief operating decision maker, its Chief Executive Officer, manages the Company’s operations
on a consolidated basis for the purposes of allocating resources.
Cash, Cash Equivalents, and Restricted Cash
The Company considers all highly liquid investments with original maturities of 90 days or less from the date of purchase to be cash equivalents. Cash
equivalents primarily include money market funds that invest in U.S. Treasury obligations which are stated at fair value.
The Company has issued letters of credit under its lease agreements which have been collateralized. This cash is classified as noncurrent restricted cash on
the balance sheet based on the term of the underlying lease.
The following table provides a reconciliation of cash, cash equivalents, and restricted cash reported within the balance sheets that sum to the total of the
same amounts shown in the statements of cash flows (in thousands).
Cash and cash equivalents
Restricted cash
Total cash, cash equivalents, and restricted cash
Marketable Securities
$
$
2021
32,905
1,446
34,351
$
$
December 31,
2020
17,807
1,446
19,253
$
$
2019
37,473
1,446
38,919
The Company generally invests its excess cash in investment grade, short to intermediate-term, fixed income securities. Such investments are considered
available-for-sale debt securities and reported at fair value with unrealized gains and losses included as a component of stockholders’ equity. Marketable
securities with original maturities of greater than 90 days from the date of purchase but less than one year from the balance sheet date that are available to
be converted into cash to fund current operations are classified as short-term, while marketable securities with maturities in one year or beyond one year
from the balance sheet date are classified as long-term. The amortized cost of debt securities is adjusted for amortization of premiums and accretion of
discounts to maturity, which is included in interest income on the statements of operations and comprehensive loss. Realized gains and losses and declines
in value judged to be other-than-temporary, if any, on marketable securities are included in other expense. The cost of securities sold is determined using
the specific identification method.
The Company periodically evaluates whether declines in fair values of its marketable securities below their book value are other-than-temporary. This
evaluation consists of several qualitative and quantitative factors regarding the severity and duration of the unrealized loss as well as the Company’s ability
and intent to hold the marketable security until a forecasted recovery occurs. Additionally, the Company assesses whether it has plans to sell the security or
it is more likely than not it will be required to sell any marketable securities before recovery of its
102
amortized cost basis. Factors considered include quoted market prices, recent financial results and operating trends, implied values from any recent
transactions or offers of investee securities, credit quality of debt instrument issuers, other publicly available information that may affect the value of the
marketable security, duration and severity of the decline in value, and management’s strategy and intentions for holding the marketable security. To date,
the Company has not recorded any impairment charges on its marketable securities related to other-than-temporary declines in market value.
Strategic Investments
The Company has previously made investments in strategic partners and may do so again in the future. The Company does not intend to have a controlling
interest or significant influence when it makes these strategic investments. Investments in equity securities of strategic partners with readily determinable
fair values are measured using quoted market prices, with changes recorded through other income (expense), net in the statement of operations and
comprehensive loss.
Fair Value Measurements
The Company’s financial instruments during the periods presented consist of cash and cash equivalents, restricted cash, marketable securities, strategic
investments, prepaid expenses and other current assets, accounts payable, accrued compensation, accrued and other current liabilities, contingent
consideration liabilities, derivative liabilities related to debt and long-term debt. Fair value estimates of these instruments are made at a specific point in
time, based on relevant market information. Level 3 instruments incorporate certain unobservable inputs such as the selected discount rate of the related
loan. These estimates may be subjective in nature and involve uncertainties and matters of judgment.
Revenue Recognition
The Company recognizes revenue in accordance with the provisions of Accounting Standards Codification Topic 606, Revenue from Contracts with
Customers, or Topic 606. In determining the appropriate amount and timing of revenue to be recognized under this guidance, the Company performs the
following five steps: (i) identifies the contract(s) with our customer; (ii) identifies the promised goods or services in the agreement and determine whether
they are performance obligations, including whether they are distinct in the context of the agreement; (iii) measures the transaction price, including the
constraint on variable consideration; (iv) allocates the transaction price to the performance obligations based on stand-alone selling prices; and (v)
recognizes revenue when (or as) the Company satisfies each performance obligation.
A performance obligation is a promise in an agreement to transfer a distinct good or service to the customer and is the unit of account in Topic 606.
Significant management judgment is required to determine the level of effort required and the period over which completion of the performance obligations
is expected under an agreement. If reasonable estimates regarding when performance obligations are either complete or substantially complete cannot be
made, then revenue recognition is deferred until a reasonable estimate can be made. Revenue is then recognized over the remaining estimated period of
performance using the cumulative catch-up method.
The Company allocates the total transaction price to each performance obligation based on the estimated relative stand-alone selling prices of the promised
goods or services underlying each performance obligation. The total consideration which the Company expects to collect in exchange for the Company’s
products is an estimate and may be fixed or variable. The Company constrains the estimated variable consideration when it assesses it is probable that a
significant reversal in the amount of cumulative revenue recognized may occur in future periods. The transaction price is re-evaluated, including the
estimated variable consideration included in the transaction price and all constrained amounts, in each reporting period and as uncertain events are resolved
or other changes in circumstances occur. The allocation of the transaction price is performed based on standalone selling prices, which are based on
estimated amounts that the Company would charge for a performance obligation if it were sold separately. Revenue is recognized when, or as, performance
obligations in the contracts are satisfied, in the amount reflecting the expected consideration to be received from the goods or services transferred to the
customers. Consideration received in advance are recorded as deferred revenue and are recognized as the related performance obligation is satisfied.
Following is a description of the principal activities from which the Company generates revenue. License revenue primarily represent amounts earned
under agreements that license our intellectual property to other companies. See Note 5, “License Revenue, Agreements and Strategic Investment” for
further detail. Consideration under these
103
contracts generally includes a nonrefundable upfront payment, development, regulatory and commercial milestones and royalties based on net sales of
approved products.
Licenses of Intellectual Property.
If the Company determines the license to intellectual property is distinct from the other performance obligations identified in the agreement and the
licensee can use and benefit from the license, the Company recognizes revenue from the estimated transaction price that is allocated to the license.
Licensing arrangements are analyzed to determine whether the promised goods or services, which may include licenses, transfer of know-how, transfer of
materials, research and development services and governance committee services, are distinct or whether they must be accounted for as part of a combined
performance obligation. If the license is considered not to be distinct, the license would then be combined with other promised goods or services as a
combined performance obligation. If the Company is involved in a governance committee, it assesses whether its involvement constitutes a separate
performance obligation. When governance committee services are determined to be separate performance obligations, the Company determines the fair
value to be allocated to this promised service.
Milestone Payments: At the inception of each agreement that includes milestone payments, the Company evaluates whether the milestones are considered
probable of being achieved and estimate the amount to be included in the transaction price using the most likely amount method. If it is probable that a
significant revenue reversal would not occur, the value of the associated milestone is included in the transaction price. For milestones that the Company do
not deem to be probable of being achieved, the associated milestone payments are fully constrained and the value of the milestone is excluded from the
transaction price with no revenue being recognized. For example, milestone payments that are not within our control, such as regulatory-related
accomplishments, are not considered probable of being achieved until those accomplishments have been communicated by the relevant regulatory
authority. Once the assessment of probability of achievement becomes probable, the Company recognizes revenue for the milestone payment. At each
reporting date, the Company assesses the probability of achievement of each milestone under our current agreements
Royalties. For agreements with sales-based royalties, including milestone payments based on the level of sales, where the license is deemed to be the
predominant item to which the royalties relate, the Company recognizes revenue at the later of (a) when the related sales occur, or (b) when the
performance obligation, to which some or all of the royalty has been allocated, has been satisfied (or partially satisfied). At each reporting date, the
Company estimates the sales incurred by each licensee during the reporting period based on historical experience and accrues the associated royalty
amount.
Concentrations of Risk
Financial instruments that potentially subject the Company to significant concentrations of credit risk consist primarily of cash, cash equivalents, restricted
cash, and marketable securities. Substantially all of the Company’s cash and cash equivalents and restricted cash is deposited in accounts with financial
institutions that management believes are of high credit quality. Such deposits have and will continue to exceed federally insured limits. The Company
maintains its cash with accredited financial institutions and accordingly, such funds are subject to minimal credit risk. The Company has not experienced
any losses on its cash deposits.
The Company’s investment policy limits investments in marketable securities to certain types of securities issued by the U.S. government, its agencies and
institutions with investment-grade credit ratings and places restrictions on maturities and concentration by type and issuer. The Company is exposed to
credit risk in the event of a default by the financial institutions holding its cash, cash equivalents, restricted cash and marketable securities and issuers of
marketable securities to the extent recorded on the balance sheets. As of December 31, 2021 and 2020, the Company had no off-balance sheet
concentrations of credit risk.
The Company depends on third-party suppliers for key raw materials used in its manufacturing processes and is subject to certain risks related to the loss of
these third-party suppliers or their inability to supply the Company with adequate raw materials.
In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic. To date, the Company’s operations have not been materially
impacted by the COVID-19 pandemic. However, the Company cannot at this time predict the specific extent, duration, or full impact that the COVID-19
pandemic will have on its financial condition and results of operations, including ongoing and planned clinical studies. The impact of the COVID-19
pandemic on the financial performance of the Company will depend on future developments. These developments and the impact of the COVID-19
pandemic on the financial markets and the overall economy are highly uncertain. The Company continues to monitor the impact the COVID-19 pandemic
may have on the clinical
104
development of its product candidates, including potential delays or modifications to its ongoing and planned studies.
Research and Development Expenses and Accruals
Costs related to research, design, and development of drug candidates are charged to research and development expense as incurred. Research and
development costs include, but are not limited to, payroll and personnel expenses for personnel contributing to research and development activities,
laboratory supplies, outside services, licenses acquired to be used in research and development, manufacturing of clinical material, pre-clinical testing and
consultants and allocated overhead, including rent, equipment, depreciation, and utilities. Research and development costs are expensed as incurred unless
there is an alternative future use in other research and development projects. Payments made prior to the receipt of goods or services to be used in research
and development are deferred and recognized as expense in the period in which the related goods are received or services are rendered. Such payments are
evaluated for current or long-term classification based on when they will be realized.
As part of the process of preparing its financial statements, the Company is required to estimate expenses resulting from its obligations under contracts with
vendors and consultants and clinical site agreements in connection with conducting clinical trials. The financial terms of these contracts are subject to
negotiations which vary from contract to contract and may result in payment flows that do not match the periods over which materials or services are
provided under such contracts. The Company’s objective is to reflect the appropriate expenses in its financial statements by matching those expenses with
the period in which services and efforts are expended. The Company accounts for these expenses according to the progress of the production of clinical
trial materials or based on progression of the clinical trial, as measured by patient progression and the timing of various aspects of the trial. The Company
determines accrual estimates by taking into account discussion with applicable personnel and outside service providers as to the progress or state of
consummation of goods and services, or the services completed.
During the course of a clinical trial, the rate of expense recognition is adjusted if actual results differ from the Company’s estimates. The Company makes
estimates of accrued expenses as of each balance sheet date in its financial statements based on the facts and circumstances known at that time. The clinical
trial accrual is dependent in part upon the timely and accurate reporting of contract research organizations, contract manufacturers, and other third-party
vendors. Although the Company does not expect its estimates to be materially different from amounts actually incurred, its 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 reporting changes in estimates in any
particular period. Adjustments to prior period estimates have not been material for the years ended December 31, 2021 and 2020.
Contingent Consideration Liability
The Company has entered into and may continue to enter into, license agreements to access and utilize certain technology. In each case, the Company
evaluates whether the license agreement results in the acquisition of an asset or a business. To date, all of the Company’s license agreements have been
considered acquisitions of assets and none have been considered acquisitions of a business. For license agreements that are considered to be acquisitions of
assets, the upfront payments for such license, as well as any future milestone payments made before product approval, are immediately recognized as
research and development expense when due, provided there is no alternative future use of the rights in other research and development projects. Some of
the Company’s license agreements also include contingent consideration in the form of an obligation to issue additional shares of the Company’s common
stock based on the achievement of certain milestones. The Company assesses on a continuous basis whether (i) such contingent consideration meets the
definition of a derivative, and (ii) whether it can be classified within stockholders’ equity. Until such time when equity classification criteria are met or the
milestones expire, the contingent consideration is classified as a liability. The derivative related to this contingent consideration is measured at fair value as
of each balance sheet date with the related change in fair value being reflected in operating expenses. Upon a reassessment event that results in the
contingent consideration no longer meeting the definition of a derivative and/or meeting equity classification criteria, the final change in fair value of the
instrument is recorded within operating expenses and the liability is reclassified into stockholders’ equity.
Property and Equipment, Net
Property and equipment are stated at cost, less accumulated depreciation. Depreciation is calculated using the straight-line method over the estimated useful
lives of the respective assets, generally three years. Leasehold improvements are amortized on a straight-line basis over the shorter of their estimated useful
lives or the term of the lease. Depreciation and amortization begin at the time the asset is placed in service. Maintenance and repairs are charged to expense
as incurred and costs of improvement are capitalized.
105
Leases
Prior to January 1, 2020, the Company accounted for its leases of office space and laboratory facilities under non-cancelable operating lease agreements
and recognized related rent expense on a straight-line basis over the term of the lease. Incentives granted under the Company’s facilities lease, including
allowances to fund leasehold improvements and rent holidays, were recognized as reductions to rental expense on a straight-line basis over the term of the
lease. Lessor funded leasehold improvement incentives not yet received were recorded in prepaid expenses and other current assets on the balance sheets.
The Company did not assume renewals in its determination of the lease term unless they were deemed to be reasonably assured at the inception of the lease
and began recognizing rent expense on the date that it obtained the legal right to use and control the leased space. Deferred rent consisted of the difference
between cash payments and the rent expense recognized. The Company recognized a liability for costs that would continue to be incurred under a lease
contract for its remaining term without economic benefit at its fair value when the entity ceased using the right conveyed by the contract, which was when
the space was completely vacated.
Subsequent to January 1, 2020, the Company determines whether the arrangement is or contains a lease at the inception of the arrangement and if so,
whether such a lease is classified as a financing lease or an operating lease. Operating leases are included in operating lease right-of-use assets, (“ROU
assets”), operating lease liabilities, net of current portion, and accrued and other current liabilities on the Company’s balance sheets. The Company has
elected not to recognize on the balance sheets leases with terms of one year or less. Operating lease ROU assets represent the Company’s right to use an
underlying asset for the lease term and are considered long-lived assets for purposes of identifying, recognizing and measuring impairment. Operating lease
liabilities represent the Company’s obligation to make lease payments arising from the lease. Operating lease ROU assets and operating lease liabilities are
recognized based on the present value of lease payments over the expected lease term. As the Company’s leases do not provide an implicit rate, the
Company uses its incremental borrowing rate, which is the rate incurred to borrow on a collateralized basis over a similar term an amount equal to the lease
payments in a similar economic environment, in determining the present value of lease payments. The operating lease ROU asset also includes any lease
payments made or incentives received and impairment charges if the Company determines the ROU asset is impaired and excludes lease incentives. The
Company’s lease terms may include options to extend or terminate the lease when it is reasonably certain that the Company will exercise such options to
extend or terminate the lease. Lease expense for lease payments is recognized on a straight-line basis over the lease term.
The Company has elected to not separate lease and non-lease components for its leased assets and accounts for all lease and non-lease components of its
agreements as a single lease component. The lease components resulting in a ROU asset have been recorded on the balance sheets and are amortized as
lease expense on a straight-line basis over the lease term.
The Company has subleased all of its Brisbane, California facility and a portion of its South San Francisco, California facility under agreements considered
to be operating leases according to ASC 842. The Company has not been legally released from its primary obligations under the original leases and
therefore it continues to account for the original leases as it did before commencement of the subleases. The Company records both fixed and variable
payments received from the sublessee in its statements of operations on a straight-line basis as an offset to rent expense.
The Company does not have any material financing leases.
Impairment of Long-Lived Assets
The Company evaluates long-lived assets for impairment whenever events or changes in circumstances indicate that the carrying value of an asset may not
be fully recoverable. If indicators of impairment exist and the undiscounted future cash flows that the assets are expected to generate are less than the
carrying value of the assets, the Company reduces the carrying amount of the assets through an impairment charge, to their estimated fair value based on a
discounted cash flow approach or, when available and appropriate, to comparable market values. During the year ended December 31, 2020, the Company
evaluated indicators of impairment for the ROU asset and related leasehold improvements considering the current economic environment and COVID-19
outbreak, its impact on subleasing activity and the exit of its previous headquarters located in Brisbane, California. The Company concluded the carrying
value of these assets were not fully recoverable and recorded an impairment charge of $2.6 million. See Note 7, “Commitments and Contingencies”.
Determining estimated discounted cash flows for purposes of an impairment analysis requires the Company to make estimates and assumptions regarding
the amount and timing of sublease income. There are often risks and uncertainties associated with the intent to sublease offices and laboratory space.
Consequently, the eventual realized sublease revenues may vary from estimates as of the impairment testing date and adjustments may occur in future
106
periods. Furthermore, the Company’s sublease assumptions could be further impacted by the uncertainties caused by the COVID-19 outbreak.
Stock-Based Compensation
The Company measures compensation expense for all stock-based awards based on their grant date fair value. For stock-based awards with service
conditions only, stock-based compensation expense is recognized over the requisite service period using the straight-line method. For awards with
performance conditions, the Company evaluates the probability of achieving performance condition at each reporting date. The Company begins to
recognize stock-based compensation expense using an accelerated attribution method when it is deemed probable that the performance condition will be
met. Forfeitures are recognized as they occur.
The Company uses the Black-Scholes option-pricing model to estimate the fair value of stock option awards that do not contain market conditions. The
Black-Scholes option-pricing model requires assumptions to be made related to the expected term of an award, expected dividends, expected volatility and
risk-free rate.
The Company has used the Monte-Carlo option-pricing model to estimate the fair value of stock option awards that contain only market conditions. The
Monte-Carlo option pricing model uses similar input assumptions as the Black-Scholes model; however, it further incorporates into the fair-value
determination the possibility that the market condition may not be satisfied.
Embedded Derivatives of the Loan Agreement
The Company measures derivative liability related to debt at fair value. Estimated fair value of the derivative liability related to debt, initially measured and
recorded on the date of the amendment of the loan and security agreement, is considered to be a Level 3 instrument. The fair value of the derivative liability
related to debt is based on the term loan principal, the date of maturity, the contractual term loan interest rate, the convertible discount factor, and the
selected discount rate of the loan. The derivative liability related to debt is recorded at fair value at the end of each reporting period with changes in
estimated fair values recognized as a component of other income (expense), net in the statements of operations and comprehensive loss.
Restructuring
The Company recognizes restructuring charges related to reorganization plans that have been committed to by management and when liabilities have been
incurred. In connection with these activities, the Company records restructuring charges at fair value for a) contractual employee termination benefits when
obligations are associated to services already rendered, rights to such benefits have vested, and payment of benefits is probable and can be reasonably
estimated, and b) one-time employee termination benefits when management has committed to a plan of termination, the plan identifies the employees and
their expected termination dates, the details of termination benefits are complete, it is unlikely changes to the plan will be made or the plan will be
withdrawn and communication to such employees has occurred.
One-time employee termination benefits are recognized in their entirety when communication has occurred, and future services are not required. Contract
termination costs to be incurred over the remaining contract term without economic benefit are recorded in their entirety when the contract is canceled.
The recognition of restructuring charges requires the Company to make certain judgments and estimates regarding the nature, timing and amount of costs
associated with the planned reorganization plan. At the end of each reporting period, the Company evaluates the remaining accrued restructuring balances
to ensure that no excess accruals are retained, and the utilization of the provisions are for their intended purpose in accordance with developed restructuring
plans.
Income Taxes
The Company uses the asset and liability method of accounting for income taxes, in which deferred tax assets and liabilities are recognized for future tax
consequences attributable to the differences between the financial statement carrying amounts of existing assets and liabilities and their respective tax
bases. Deferred tax assets and liabilities are measured using the enacted tax rates expected to apply to taxable income in the years in which those temporary
differences are expected to be reversed. The effect on deferred tax assets and liabilities of a change in tax rates is recognized as income in the period that
includes the enactment date. A valuation allowance is established if it is more likely than not that all or a portion of the deferred tax asset will not be
realized.
107
The Company’s tax positions are subject to income tax audits. The Company recognizes the tax benefit of an uncertain tax position only if it is more likely
than not that the position is sustainable upon examination by the taxing authority, based on the technical merits. The tax benefit recognized is measured as
the largest amount of benefit which is more likely than not to be realized upon settlement with the taxing authority. The Company recognizes interest
accrued and penalties related to unrecognized tax benefits in its tax provision. The Company evaluates uncertain tax positions on a regular basis. The
evaluations are based on a number of factors, including changes in facts and circumstances, changes in tax law, correspondence with tax authorities during
the course of the audit, and effective settlement of audit issues. The provision for income taxes includes the effects of any accruals that the Company
believes are appropriate, as well as the related net interest and penalties.
On March 18, 2020, the Families First Coronavirus Response Act (“FFCR Act”), and on March 27, 2020, the Coronavirus Aid, Relief, and Economic
Security Act (“CARES Act”) were each enacted in response to the COVID-19 pandemic. The FFCR Act and the CARES Act contain numerous tax-related
provisions relating to refundable payroll tax credits, deferment of employer side social security payments, net operating loss carryback periods, alternative
minimum tax credit refunds, modifications to the net interest deduction limitations and technical corrections to tax depreciation methods for qualified
improvement property.
On June 29, 2020 California State Assembly Bill 85 (the “Trailer Bill”) was enacted which suspends the use of California net operating loss (“NOL”)
deductions and certain tax credits, including research and development tax credits, for the 2020, 2021, and 2022 tax years.
In December 2020, the Consolidated Appropriations Act, 2021 (the “CAA” ) was signed into law. The CAA included additional funding through tax credits
as part of its economic package for 2021.
The FFCR Act, CARES Act, Trailer Bill and CAA did not have a material impact on the Company’s financial statements as of December 31, 2020;
however, the Company continues to examine the impacts the FFCR Act, CARES Act and Trailer Bill may have on its business, results of operations,
financial condition and liquidity.
On March 10, 2021, Congress passed the American Rescue Plan Act (“ARP Act”) of 2021. On March 11, 2021, President Biden signed the bill into law.
The ARP contains employment-related provisions. The ARP is a follow-up to the CARES Act, and that part of the CAA Act of 2021 devoted to COVID-19
relief. The ARP includes Paycheck Protection Program (PPP) funding changes and expanded the Employee Retention Credit (ERC) provisions under the
CAA. The Company did not apply for a PPP loan. Regarding the ERC, management has calculated that a total ERC of $535,504 for 2020 and $957,839 for
2021 are available. The Company does not expect the ARP to have a material impact on the Company’s financial statements. Any change to the deferred
taxes as a result of the enactment of the ARP is expected to be fully offset to the valuation allowance.
Net Loss per Common Share
Basic net loss per share is calculated by dividing net loss by the weighted average number of shares outstanding for the period. Diluted net loss per share is
calculated by dividing net loss by the weighted average number of shares of common stock and potential dilutive common stock equivalents outstanding
during the period if the effect is dilutive. Since the Company was in a loss position for all periods presented, basic net loss per share is the same as diluted
net loss per share as the effects of potentially dilutive securities are antidilutive. The calculation of diluted loss per share also requires that, to the extent the
presumed issuance of additional shares as contingent consideration is dilutive to loss per share for the period, adjustments to net loss used in the calculation
are required to remove the change in fair value of the contingent consideration liability for the period. Likewise, adjustments to the denominator are
required to reflect the related dilutive shares. In all periods presented, the Company’s outstanding stock options, convertible preferred stock, early exercised
common stock subject to future vesting, restricted stock accounted for as options common and preferred stock warrants and presumed issuance of
additional shares as contingent consideration were excluded from the calculation of diluted net loss per share because their effects were antidilutive.
Comprehensive Loss
Comprehensive loss includes net loss and certain changes in stockholders’ equity that are excluded from net loss, primarily unrealized losses on the
Company’s marketable securities.
108
Recently Issued Accounting Pronouncements Not Yet Adopted
In October 2020, the FASB issued ASU 2020-10, Codification Improvements. The ASU contains improvements to the Codification by ensuring that all
guidance that requires or provides an option for an entity to provide information in the notes to financial statements is codified in the disclosure section of
the Codification. The ASU also improves various topics in the Codification so that entities can apply guidance more consistently on codifications that are
varied in nature where the original guidance may have been unclear. The amendments in ASU 2020-10 are effective for the Company for fiscal years
beginning after December 15, 2021, and interim periods within fiscal years beginning after December 15, 2022. Early adoption is permitted. The Company
does not expect the adoption of ASU 2020-10 to have a material impact on its financial statements and related disclosures.
In August 2020, the FASB issued ASU No. 2020-06, Debt—Debt with Conversion and Other Options (Subtopic 470-20) and Derivatives and Hedging—
Contracts in Entity’s Own Equity. ASU 2020-06 eliminates the beneficial conversion and cash conversion accounting models for convertible instruments. It
also amends the accounting for certain contracts in an entity’s own equity that are currently accounted for as derivatives because of specific settlement
provisions. In addition, ASU 2020-06 modifies how particular convertible instruments and certain contracts that may be settled in cash or shares impact the
diluted EPS computation. The amendments in ASU 2020-06 are effective for smaller reporting companies as defined by the SEC for fiscal years beginning
after December 15, 2023, including interim periods within those fiscal years. Early adoption is permitted, but no earlier than fiscal years beginning after
December 15, 2020. The Company is currently evaluating the impact of ASU 2020-06 on its financial statements.
In June 2016, the FASB issued ASU No. 2016-13, Financial Instruments—Credit Losses (Topic 326), Measurement of Credit Losses on Financial
Instruments, as clarified in subsequent amendments. ASU 2016-13 changes the impairment model for certain financial instruments. The new model is a
forward-looking expected loss model and will apply to financial assets subject to credit losses and measured at amortized cost and certain off-balance sheet
credit exposures. This includes loans, held-to-maturity debt securities, loan commitments, financial guarantees and net investments in leases, as well as
trade receivables. For available-for-sale debt securities with unrealized losses, credit losses will be measured in a manner similar to today, except that the
losses will be recognized as allowances rather than reductions in the amortized cost of the securities. In October 2019, the FASB voted to delay the
effective date of this standard. Topic 326 will be effective for the Company for fiscal years beginning after December 15, 2022. Early adoption is permitted.
The Company is currently assessing the effect that this ASU will have on its financial position, results of operations, and disclosures.
3. Fair Value Measurements
The Company determines the fair value of financial and non-financial assets and liabilities based on the assumptions that market participants would use in
pricing the asset or liability in an orderly transaction between market participants at the measurement date. The identification of market participant
assumptions provides a basis for determining what inputs are to be used for pricing each asset or liability. A fair value hierarchy has been established which
gives precedence to fair value measurements calculated using observable inputs over those using unobservable inputs. This hierarchy prioritized the inputs
into three broad levels as follows:
•
•
•
Level 1: Quoted prices in active markets for identical instruments
Level 2: Other significant observable inputs (including quoted prices in active markets for similar instruments)
Level 3: Significant unobservable inputs (including assumptions in determining the fair value of certain investments)
The carrying amounts of financial instruments such as cash and cash equivalents, restricted cash, prepaid expenses and other current assets, accounts
payable, accrued compensation, accrued and other current liabilities approximate the related fair values due to the short maturities of these instruments. As
the long-term debt is subject to variable interest rates that are based on market rates which are regularly reset, considering level 2 inputs, the Company
believes the carrying value of the long-term debt approximates its fair value.
109
Assets:
Cash equivalents:
Money market funds
Total cash equivalents
Short-term marketable securities:
U.S. treasuries
U.S. government debt securities
Total short-term marketable securities
Long-term marketable securities:
U.S. treasuries
Total long-term marketable securities
Total assets subject to fair value measurements
on a recurring basis
Assets:
Cash equivalents:
Money market funds
Total cash equivalents
Short-term marketable securities:
U.S. treasuries
U.S. and foreign commercial paper
U.S. and foreign corporate debt securities
U.S. government debt securities
Total short-term marketable securities
Long-term marketable securities
U.S. treasuries
U.S. government debt securities
Total long-term marketable securities
Total assets subject to fair value measurements
on a recurring basis
Total
Level 1
Level 2
Level 3
December 31, 2021
$
21,421 $
21,421
21,421 $
21,421
— $
—
52,146
3,024
55,170
1,993
1,993
—
—
—
—
—
52,146
3,024
55,170
1,993
1,993
$
78,584 $
21,421 $
57,163 $
Total
Level 1
Level 2
Level 3
December 31, 2020
$
13,686 $
13,686
13,686 $
13,686
— $
—
55,349
11,999
1,001
11,543
79,892
7,370
10,501
17,871
—
—
—
—
—
—
—
—
55,349
11,999
1,001
11,543
79,892
7,370
10,501
17,871
$
111,449 $
13,686 $
97,763 $
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
The Company estimates the fair value of its money market funds, U.S. and foreign commercial paper, U.S. and foreign corporate debt securities, U.S.
treasuries, and U.S. government debt securities by taking into consideration valuations obtained from third-party pricing services. The pricing services
utilize industry standard valuation models, including both income and market-based approaches, for which all significant inputs are observable, either
directly or indirectly, to estimate fair value. These inputs include reported trades of and broker/dealer quotes on the same or similar securities, issuer credit
spreads; benchmark securities; prepayment/default projections based on historical data; and other observable inputs. See Note 4, “Marketable Securities,”
for further information regarding the carrying value of the Company's financial instruments.
The Company had previously recorded a contingent consideration liability related to three agreements (the “Commercial Agreements”) with Ascentage
Pharma Group Corp. Limited, a clinical-stage biopharmaceutical company based in Hong Kong China (“Ascentage Pharma”). See Note 5, “License
Revenue, Agreements and Strategic Investment”. The fair value of the contingent consideration liability at December 31, 2019 included inputs not
observable in the market and thus represented a Level 3 measurement. The probability of achieving the defined milestone events under the Commercial
Agreements was estimated on a quarterly basis by the Company’s management using a probability-weighted valuation approach model which utilized
current stock price and reflected the probability and timing of future issuances of shares. As a result of settlements and changes made to the Commercial
Agreements, there was no contingent consideration liability at December 31, 2021 and 2020.
110
The following table provides a reconciliation of contingent consideration liabilities measured at fair value on a recurring basis using significant
unobservable inputs (Level 3) (in thousands):
Balance at December 31, 2019
Additions
Settlements
Change in fair value
Balance at December 31, 2020
Contingent Consideration
Liability Amount
1,131
—
(1,098)
(33)
—
$
In December 2021, the Company recorded a derivative liability relating to an amendment to its loan and security agreement. It comprised of a redemption
conversion feature which met the definition of a derivative instrument, which terms are included in the amended loan and security agreement. See Note 8,
“Term Loan Facility”. The Company classified this instrument as a liability on the balance sheet because the feature was not clearly and closely related to
its host instrument and met the definition of a derivative. The derivative liability was initially recorded at fair value upon issuance of the loan amendment
and is being subsequently remeasured to fair value at each reporting date. Changes in the fair value of the derivative liability are recognized as a component
of other income (expense), net in the statements of operations. There were no adjustments to the fair value of the derivative as of December 31, 2021.
The following table provides a reconciliation of the derivative liability related to debt measured at fair value on a recurring basis using significant
unobservable inputs (Level 3) (in thousands):
Balance at December 31, 2020
Additions
Conversion
Change in fair value
Balance at December 31, 2021
Derivative Liability related to
Debt Conversion Feature(1)
$
$
—
1,782
(819)
—
963
(1)
Transfers into Level 3 during the year ended December 31, 2021 relate to the call option with Hercules Capital, Inc, where the lender can convert principal debt into
common stock. Transfers out of Level 3 during the year relate to the conversions calls of this option made by Hercules Capitals, Inc.
4. Marketable Securities
Marketable securities, which are classified as available-for-sale, consisted of the following (in thousands):
Cash equivalents:
Money market funds
Total cash equivalents
Short-term marketable securities:
U.S. government debt securities
U.S. treasuries
Total short-term marketable securities
Long-term marketable securities:
U.S. treasuries
Total long-term marketable securities
Total marketable securities
Amortized
Cost Basis
Unrealized
Gains
Unrealized
Losses
Fair
Value
December 31, 2021
$
21,421 $
21,421
3,026
52,186
55,212
1,995
1,995
78,628 $
$
111
— $
—
—
—
—
—
—
— $
— $
—
(2)
(40)
(42)
(2)
(2)
(44) $
21,421
21,421
3,024
52,146
55,170
1,993
1,993
78,584
Cash equivalents:
Money market funds
Total cash equivalents
Short-term marketable securities:
U.S. and foreign commercial paper
U.S. and foreign corporate debt securities
U.S. government debt securities
U.S. treasuries
Total short-term marketable securities
Long-term marketable securities
U.S. treasuries
U.S. government debt securities
Total long-term marketable securities
Total marketable securities
Amortized
Cost Basis
Unrealized
Gains
Unrealized
Losses
Fair
Value
December 31, 2020
$
13,686 $
13,686
11,998
1,001
11,541
55,350
79,890
7,369
10,498
17,867
111,443 $
$
— $
—
1
—
2
2
5
1
3
4
9 $
— $
—
—
—
—
(3)
(3)
—
—
—
(3) $
13,686
13,686
11,999
1,001
11,543
55,349
79,892
7,370
10,501
17,871
111,449
At December 31, 2021, the remaining contractual maturities of available-for-sale debt securities were less than two years. There have been no significant
realized gains or losses on available-for-sale debt securities for the periods presented. Available-for-sale debt securities that were in a continuous loss
position but were not deemed to be other than temporarily impaired were immaterial at both December 31, 2021 and 2020. The Company does not intend
to and believes it is not more likely than not that it will be required to sell these debt securities before their maturities.
See Note 3, “Fair Value Measurements,” for further information regarding the fair value of the Company's financial instruments.
5. License Revenue, Agreements and Strategic Investment
The Company has entered into license agreements with other pharmaceutical and biotechnology companies. The Company’s accounts receivable balances
may contain billed and unbilled amounts from milestones and other contingent payments. The Company performs a regular review of its customers’ credit
risk and payment histories, including payments made after period end. Historically, the Company has not experienced credit loss from its accounts
receivable and, therefore, has not recorded a reserve for estimated credit losses as of December 31, 2021.
In accordance with the license agreements, the Company recognized revenue as follows:
Jocasta Neuroscience, Inc. (1)
2021
Twelve Months Ended December 31,
2020
2019
$
$
4,784
4,784
$
$
— $
— $
—
—
(1)
Jocasta Neuroscience, Inc. was deemed a related party at the effective time the agreement was made on December 17, 2021.
There have been no material changes to the Company’s license agreements in the three and twelve months ended December 31, 2021, except as described
below.
112
License Agreement with Jocasta Neuroscience, Inc.
In December 2021, the Company signed a License Agreement with Jocasta Neuroscience, Inc. (“the Jocasta Agreement”) to exclusively license its rights in
the α-Klotho asset for development and commercialization, and included a sublicense agreement under the original license agreement with the University
of California, San Francisco. Under the Jocasta Agreement, the Company received a $5.0 million upfront cash payment from Jocasta Neuroscience, Inc.
The Company may also receive additional payments based on development milestones, approval milestones, and sales-based royalties, per indication. The
Jocasta agreement is recognized in accordance with ASC 606, Revenue from Contracts with Customers, and is classified under License Revenue.
Promises that the Company concluded were distinct performance obligations in the License Agreement included: (1) the license of intellectual property and
delivery of know-how, and (2) the transfer of licensed compounds and materials.
In order to determine the transaction price, the Company evaluated all the payments to be received during the duration of the contract. Fixed consideration
exists in the form of the upfront payment. Regulatory milestones and royalties were considered variable consideration. The estimated variable consideration
is constrained until the Company determines it is probable that a significant reversal in the amount of cumulative revenue recognized will not occur in
future periods. Milestone payments are constrained and not included in the transaction price due to the uncertainties of research and development. The
Company will re-evaluate the transaction price, including the estimated variable consideration included in the transaction price and all constrained
amounts, in each reporting period and as uncertain events are resolved or other changes in circumstances occur. The Company determined that the initial
transaction price consists of the upfront payment of $5.0 million. The allocation of the transaction price is performed based on standalone selling prices,
which are based on estimated amounts that the Company would charge for a performance obligation if it were sold separately. The transaction price
allocated to the license of intellectual property and delivery of know-how was recognized upon grant of license and delivery of know-how. The transaction
price allocated the transfer of licensed compounds and materials, will be recognized over time as the materials are delivered. Consideration received in
advance are recorded as deferred revenue and will be recognized as the performance obligations are satisfied.
For the years ended December 31, 2021 and 2020, the Company recognized $4.8 million and zero, respectively, of license revenue, primarily related to the
delivery of a performance obligation consisting of a license of intellectual property and related know-how which was delivered in 2021. For the year ended
December 31, 2021, the Company recorded the $0.2 million as deferred revenue.
License Agreements with Research Institutions
In May 2019, the Company entered into a license agreement with The Regents of the University of California on behalf its San Francisco campus
(collectively, “UCSF”) which provides the Company the rights to certain patents and related know-how to make, use, sell, offer for sale and import certain
products and practice certain methods for use in the development of human therapeutics, which excludes the provision of services to third parties for
consideration of any kind. The license to the Company is subject to UCSF’s reserved rights under the licensed intellectual property for educational and
non-commercial research purposes and a requirement to substantially manufacture any licensed products in the United States. The Company is obligated to
use diligent efforts to develop and obtain regulatory approval for at least one product commercialized pursuant to the agreement, and must meet certain
regulatory and development milestones. In June 2019, as part of this license agreement, the Company issued 120,000 shares of its common stock to UCSF.
In addition, the Company is obligated to pay an annual license maintenance fee and may be obligated to make milestone payments or issue up to an
additional 34,000 shares of its common stock upon the occurrence of specified development events, up to aggregate milestone payments of $13.6 million
for each product licensed under the agreement, and upon commercialization, to make royalty payments in the low single digit percentages (subject to a
specified minimum annual royalty) based on net sales of products commercialized pursuant to the agreement. None of these events had occurred and no
milestone payments or royalty payments had been recognized as of December 31, 2021. The upfront issuance of 120,000 shares of the Company’s common
stock was valued at $1.0 million and recorded as additional paid-in capital upon issuance in June 2019. In December 2021, the Company entered an
agreement to exclusively license its rights in the α-Klotho asset to Jocasta Neuroscience, Inc. for development and commercialization. Under the license
agreement, Jocasta Neuroscience, Inc. is, in addition to the payments due to the Company, required to make all payments due to UCSF from the Company
under the UCSF License. See above, “License Agreement with Jocasta Neuroscience, Inc.” for additional information on the Jocasta Agreement.
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The Company has also entered into license agreements with various research institutions which have provided the Company with rights to patents, and in
certain cases, research “know-how” and proprietary research tools to research, develop and commercialize drug candidates. In addition to upfront
consideration paid to these various research institutions in either cash or shares of the Company’s common stock, the Company may be obligated to make
milestone payments, payable in cash and/or the issuance of shares of the Company’s common stock upon achievement of certain specified clinical
development and/or sales events. The contingent consideration liability considered to be a derivative associated with the potential issuance of common
stock related to these license agreements was not significant at December 31, 2021 and 2020. To date, none of these events has occurred and no contingent
consideration, milestone or royalty payments have been recognized.
License and Compound Library and Option Agreement
The Company is a party to three agreements, two active and one terminated, with Ascentage Pharma: (a) a compound library and option agreement
executed in February 2016 granting the Company the right to identify and take licenses to research, develop, and seek and obtain marketing approval for
library compounds for the treatment of indications outside of oncology (the “Library Agreement”), (b) an initial license agreement executed in February
2016 granting the Company rights to an initial Ascentage Pharma compound known as APG1252 (the “APG1252 License Agreement”), and (c) a second
license agreement executed in January 2019 granting the Company rights to a second licensed compound (this second license agreement, the “Bcl License
Agreement” and collectively with the Library Agreement and APG1252 License Agreement, the “Commercial Agreements”). On July 30, 2020, the
Company notified Ascentage Pharma of its termination of the APG1252 License Agreement due to the Company’s decision to prioritize the progression of
other compounds from Ascentage International’s library of Bcl-2 inhibitors, such as UBX1325, a Bcl-xL inhibitor.
The Commercial Agreements referenced above include cash payments of up to $70.3 million as well as the equity payments of up to an aggregate of (a)
933,337 shares of common stock in the event there is only one licensed product, and (b) 1,333,338 shares of common stock in the event there are two or
more licensed products, in each case to be issued based on the Company’s achievement of certain preclinical and clinical development and sales milestone
events. The Company is required to make 80% of all equity payments to Ascentage Pharma and the remaining 20% to an academic institution from whom
Ascentage Pharma had previously licensed the technology. The milestones include the advancement of additional compounds into Investigational New
Drug application (“IND”) enabling studies, the filing of an IND, the commencement of clinical studies, Food and Drug Administration (“FDA”) and/or
European Medicines Agency approval, and a net sales threshold. The Bcl License Agreement also includes tiered royalties in the low-single digits based on
sales of licensed products.
As of December 31, 2021, pursuant to these agreements, the Company had issued 1,269,755 shares of common stock to Ascentage Pharma and 291,944
shares of common stock to the academic institution from whom Ascentage Pharma had previously licensed the technology. In May 2021, the Company
initiated a Phase 2a proof-of-concept study of UBX1325 in patients with diabetic macular edema. As a result of the first patient dosed in the Phase 2a
UBX1325 study in June 2021, the Company triggered a milestone payment of $2.0 million for Ascentage Pharma, which the Company elected to settle in
shares of the Company’s common stock. At the instruction of Ascentage Pharma, the Company issued 294,775 shares of its common stock to Ascentage
Pharma as of August 2021 with a fair market value of $1.1 million net of withholding taxes, and 105,277 shares of its common stock to the academic
institution with a fair market value of $0.4 million at settlement date. The milestone payment was recognized as research and development expense in the
statement of operations and comprehensive loss during the year ended December 31, 2021. The Company had previously issued 361,664 shares of its
common stock with a value of $2.3 million to Ascentage Pharma as of December 31, 2020.
The Commercial Agreements included contingent consideration in the form of additional issuances of shares of the Company’s common stock based on the
achievement of the specified milestones. Upon the July 2020 termination of the license to APG1252, the Company determined that the contingency no
longer applied and adjusted the fair value of the contingent consideration liability to zero. To date, no royalties were due from the sales of licensed
products.
Strategic Investment
The Company previously held an equity investment in Ascentage International, an affiliate of Ascentage Pharma. The equity interest represented an
insignificant level of ownership in the investee and was recorded within strategic investment on the Company’s condensed balance sheets. The fair value of
the Company’s equity investment in Ascentage International was zero as of December 31, 2021 and 2020. The change in fair value of this investment was
zero and $0.5 million for the years ended December 31, 2021 and 2020, respectively, and was recorded in other expense on the statements of operations
and comprehensive loss.
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The Company agreed to provide funding to Ascentage Pharma for research and development work performed at a cost of up to $2.0 million through
February 2020. During the year ended December 31, 2020, the research and development expense under the research services agreement was not material
to the Company’s financial statements.
6. Balance Sheet Components
Property and Equipment, Net
Property and equipment, net, consists of the following (in thousands):
Laboratory equipment
Computer equipment
Furniture and fixtures
Leasehold improvements
Total property and equipment
Less: accumulated depreciation and amortization
Construction-in-progress
Total property and equipment, net
December 31,
2021
2020
$
$
5,718 $
499
818
15,158
22,193
(12,258)
7
9,942 $
5,960
501
825
15,083
22,369
(9,742)
—
12,627
Depreciation and amortization expense related to property and equipment was $2.9 million, $3.4 million and $2.7 million for the years ended December 31,
2021, 2020 and 2019, respectively.
Accrued and Other Current Liabilities
Accrued and other current liabilities consist of the following (in thousands):
Operating lease liability - current portion
Accrued research and development
Liability related to early exercise shares
Accrued other
7. Commitments and Contingencies
Leases
December 31,
2021
2020
$
$
4,378 $
1,390
10
592
6,370 $
4,520
1,638
21
371
6,550
In February 2019, the Company entered into a lease agreement for new office and laboratory space in South San Francisco, California. The term of the
lease agreement commenced in May 2019. The lease has an initial term from occupancy of approximately ten years ending on December 31, 2029 with an
option to extend the term for an additional eight years at then-market rental rates. The total base rent payment escalates annually based on a fixed
percentage beginning from the 13th month of the lease agreement. The Company will also be responsible for the operating expenses and real estate taxes
allocated to the building and common areas. Pursuant to the lease agreement, the landlord provided the Company with a tenant improvement allowance of
$10.7 million, which was included in deferred rent and leasehold improvements on the balance sheet at December 31, 2019. In connection with the
execution of the lease agreement, the Company delivered a letter of credit of approximately $0.9 million to the landlord.
In May 2016, the Company executed a non-cancellable lease agreement for office and laboratory space in Brisbane, California which commenced in May
2016 and continues through October 2022. The lease agreement includes an escalation clause for increased rent and a renewal provision allowing the
Company to extend this lease for an additional four years by giving the landlord written notice of the election to exercise the option at least fifteen months
prior to the original expiration of the lease term. The lease provides for monthly base rent amounts escalating over the term of the lease and the lessor
provided the Company a $3.9 million tenant improvement allowance to complete the laboratory and office renovation which was recorded as deferred rent
liability and
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leasehold improvements within property and equipment, net. In May 2017, the Company entered into an amendment to expand the leased space and
received a three-month rent holiday for the expanded space.
The Company’s operating leases include various covenants, indemnities, defaults, termination rights, security deposits and other provisions customary for
lease transactions of this nature.
The following table summarizes the components of lease expense, which are included in operating expenses in the Company’s statements of operations and
comprehensive loss (in thousands):
Operating lease expense
Variable lease expense
Sublease income
Impairment of operating lease right-of-use asset
Total lease expense
Year Ended December 31,
2021
2020
$
$
$
4,357
1,633
(2,578)
—
3,412 $
4,721
1,168
—
1,409
7,298
Variable lease payments include amounts relating to common area maintenance, real estate taxes and insurance and are recognized in the statements of
operations and comprehensive loss as incurred. Rent expense for the year ended December 31, 2019 was $4.5 million.
The following table summarizes supplemental information related to leases (in thousands):
Cash paid for amounts included in the measurement of lease liabilities
Operating cash flows from operating leases
Weighted-average remaining lease term (years)
Operating leases
Weighted-average discount rate (percentage)
Operating leases
The following table summarizes the maturities of lease liabilities as of December 31, 2021 (in thousands):
2022
2023
2024
2025
2026
Thereafter
Total future minimum lease payments
Less: Amount representing interest
Present value of future minimum lease payments
Less: Current portion of operating lease liability
Noncurrent portion of operating lease liability
Year Ended December 31,
2021
2020
$
6,653
$
5,797
7.7
5.9%
Amount
$
$
8.5
5.8%
6,286
4,810
4,964
5,123
5,287
16,892
43,362
(8,890)
34,472
(4,378)
30,094
In February 2020, the Company completed its move into the new office and laboratory space in South San Francisco, exited its previous offices and
laboratory space in Brisbane, California, and began to actively market this space for sublease. Concurrent with this move and in consideration of real estate
market conditions, in particular due to the COVID-19 pandemic in March 2020, the Company identified indicators of impairment in the related asset group,
which included the leased ROU asset and related leasehold improvements associated with the lease. The Company subsequently evaluated and compared
the net book value of the asset group to the estimated undiscounted future cash flows over the remaining term of the lease and concluded that an
impairment had occurred. The discounted estimated future cash flows included estimates of sublease rentals through the end of the lease term, which ends
on October 31, 2022, utilizing a discount rate of 3.5% based on the Company’s estimated incremental borrowing rate at that time. The estimated discounted
cash flows were compared to the net book value of the ROU asset and leasehold improvements resulting in an impairment loss of $2.6 million during the
year ended December 31, 2020, which was included in operating expense in the statements of operations and comprehensive loss. No impairment loss was
recorded during the year ended December 31, 2021.
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In February 2021, the Company entered into an agreement to sublease the first floor of the Brisbane, California facility, consisting of approximately 27,000
square feet, to Zymergen, Inc., through August 31, 2022. The base sublease rent rate is $3.53 per rental square foot per month and will increase by 3% on
March 1, 2022 through expiration of the agreement. Additionally, the subtenant is required to pay approximately 41% of operating expenses and property
management fees that the Company is required to pay under the lease for the Brisbane, California facility. In May 2021, the Company entered into an
agreement to sublease the second floor of the Brisbane, California facility, consisting of approximately 11,500 square feet, to CareDx, Inc., through
September 30, 2022. The base sublease rent rate is $1.00 per rental square foot per month through expiration of the agreement. Additionally, the subtenant
is required to pay approximately 30% of operating expenses and property management fees that the Company is required to pay under the lease for the
Brisbane, California facility. The Company incurred initial direct costs of $0.1 million in sublease commissions related to entering into the agreements to
sublease the Brisbane, California facility. To account for the commissions, the Company capitalized the total commissions amount and will amortize the
balance over the term of the sublease. Sublease income was $1.5 million and zero for the years ended December 31, 2021 and 2020, respectively, which
was offset against total rent expense.
In June 2021, the Company entered into an agreement to sublease a portion of the first floor of the South San Francisco facility, consisting of
approximately 23,000 square feet, to Freenome Holdings, Inc., through August 31, 2024. The base sublease rent rate is $6.25 per rental square foot per
month and will increase annually by 3.5% through expiration of the agreement. Additionally, the subtenant is required to pay approximately 37% of
operating expenses and property management fees that the Company is required to pay under the lease for the South San Francisco facility. No impairment
loss was recorded during the year ended December 31, 2021. Sublease income was $1.1 million and zero for the years ended December 31, 2021 and 2020,
respectively, which was offset against total rent expense.
Indemnifications
The Company indemnifies each of its officers and directors for certain events or occurrences, subject to certain limits, while the officer or director is or was
serving at the Company’s request in such capacity, as permitted under Delaware law and in accordance with the Company’s amended and restated
certificate of incorporation and bylaws. The term of the indemnification period lasts as long as an officer or director may be subject to any proceeding
arising out of acts or omissions of such officer or director in such capacity.
The maximum amount of potential future indemnification is unlimited; however, the Company currently holds director and officer liability insurance. This
insurance allows the transfer of risk associated with the Company’s exposure and may enable the Company to recover a portion of any future amounts paid.
The Company believes that the fair value of these potential indemnification obligations is minimal. Accordingly, the Company has not recognized any
liabilities relating to these obligations for any period presented.
8. Term Loan Facility
On August 3, 2020, the Company entered into a Loan and Security Agreement (the “Loan Agreement”) with Hercules Capital, Inc. (“Hercules”). Under the
Loan Agreement, Hercules provided the Company with access to a term loan with an aggregate principal amount of up to $80.0 million (the “Term Loan
Facility”), available in four tranches, subject to certain terms and conditions. The first tranche of $25.0 million was advanced to the Company on the date
the Loan Agreement was executed. The milestones for the remaining tranches have not yet been reached and as of December 31, 2021 are not expected to
be reached as they were dependent, in whole or in part, upon continued advancement in the clinical development of UBX0101 in patients with
osteoarthritis of the knee.
On December 15, 2021, the Company entered into an amendment to the Loan and Security Agreement (“the Loan Amendment”). The Loan Amendment
includes a Lender Optional Conversion where after the effective date and until the six-month anniversary of the execution date, the lender may elect to
convert to equity of the Company all or any part of up to twenty percent (20%) of the original principal amount for a maximum amount of $5.0 million. As
of December 31, 2021, the lender had elected to convert $2.3 million of the outstanding principal into equity. The Company incurred approximately $0.1
million in loan issuance costs relating to the amendment, which were offset against the loan proceeds and are accounted for as a loan discount.
The Company expects to make interest only payments through September 1, 2022 and expects to then repay the principal balance and interest in equal
monthly installments through August 1, 2024. Pursuant to the Loan Amendment, the interest only period may extend up to a maximum of 9 months to June
1, 2023 should the company meet specific milestones related to its clinical trials and raising additional capital.
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The Company may prepay advances under the Loan Agreement, in whole or in part, at any time subject to a prepayment charge of up to 1.50% of any
amount prepaid, depending upon when the prepayment occurs. Upon prepayment or repayment of all or any of the term loans under the Term Loan Facility,
the Company is required to pay an end of term fee (“End of Term Fee”) equal to 6.25% of the total aggregate amount of the term loans being prepaid or
repaid, which has been recorded as a discount on the principal balance upon issuance.
Interest on the term loan accrues at a per annum rate equal to the greater of (i) the Wall Street Journal prime rate plus 6.10% and (ii) 9.35%. On December
31, 2021, the rate was 9.35%. Interest expense is calculated using the effective interest method and is inclusive of non-cash amortization of capitalized loan
issuance costs. At December 31, 2021, the effective interest rate was 16.69%.
Under the terms of the Loan Agreement, the Company granted first priority liens and security interests in substantially all of the Company’s assets, other
than intellectual property, as collateral for the obligations thereunder. The Company also granted Hercules the right, at their discretion, to participate in any
closing of any single subsequent financing as defined up to a maximum aggregate amount of $2.0 million. The Loan Agreement also contains
representations and warranties by the Company and Hercules, indemnification provisions in favor of Hercules and customary affirmative and negative
covenants (including a liquidity covenant beginning July 1, 2021, requiring the Company to maintain at least $15.0 million in unrestricted cash), and events
of default, including a material adverse change in the Company’s business, payment defaults, breaches of covenants following any applicable cure period,
and a material impairment in the perfection or priority of Hercules’ security interest in the collateral. The substantial doubt regarding the Company’s ability
to continue as a going concern does not constitute a material adverse event under the terms of the Loan Agreement. In the event of default by the Company
under the Loan Agreement, the Company may be required to repay all amounts then outstanding under the Loan Agreement.
We have determined that the risk of subjective acceleration under the material adverse events clause included in the Loan Agreement is remote and,
therefore, have classified the outstanding principal amount in current and long-term liabilities based on the timing of scheduled principal payments. As of
December 31, 2021, and as of the date of the issuance of these financial statements, the Company was in compliance with all covenants and has not been
notified of an event of default by the lender under the Loan Agreement.
As of December 31, 2021, the carrying value of the term loan consists of $22.7 million principal outstanding less the debt discount and issuance costs of
approximately $2.8 million. The end of term fee of $1.6 million is recognized over the life of the term loan as interest expense using the effective interest
method. The debt issuance costs have been recorded as a debt discount which are being accreted to interest expense through the maturity date of the term
loan.
Interest expense relating to the term loan, which is included in interest expense in the statements of operations and comprehensive loss, was $3.2 million
and $1.3 million for the years ended December 31, 2021 and 2020, respectively.
Future principal payments for the long-term debt are as follows (in thousands):
2022
2023
2024
Total principal payments
End of term fee due at maturity in 2024
Total principal and end of term fee payments
Unamortized discount and debt issuance costs
Present value of remaining debt payments
Current portion of long-term debt
Long-term debt, net
December 31, 2021
$
118
$
3,485
11,144
8,073
22,702
1,562
24,264
(2,800)
21,464
(3,055)
18,409
9. Related Party Transactions
Licensing Revenue – Related Party
In December 2021, the Company entered into a license agreement with Jocasta Neuroscience, Inc. A member of the Board of Directors of the Company is
also an affiliate of Jocasta Neuroscience, Inc. The agreement provides for an upfront fee of $5.0 million and the opportunity for future research and
development services to be provided. The Company recognized $4.8 million of licensing revenue for the year ended December 31, 2021.
Recourse Notes
In January 2018, the Company issued full-recourse promissory notes to a non-executive officer employee of the Company for an aggregate principal
amount of $0.2 million with an interest rate of 2.5% per annum. All of the principal was used to early exercise options for 59,322 shares of the Company’s
common stock. In December 2019, the full recourse note was deemed satisfied and superseded by a new full recourse promissory note agreement with a
principal amount of $0.2 million and an interest rate of 1.51% per annum. In January 2021, the non-executive officer employee terminated his employment
with the Company. As at March 31, 2021 the Company reclassified the $0.2 million recorded on the balance sheet in stockholders’ equity as ‘Related party
promissory note for purchase of common stock’ to ‘Promissory notes for purchase of common stock’. The balance was repaid in full by June 30, 2021.
10. Equity Financing
The Company has 10,000,000 shares of convertible preferred stock authorized for issuance, par value of $0.0001 per share. As of December 31, 2021 and
2020, no shares of preferred stock were issued and outstanding.
The Company has 300,000,000 shares of common stock authorized for issuance, par value of $0.0001 per share. Holders of the Company’s common stock
are entitled to one vote per share. As of December 31, 2021 and 2020, there were 62,991906 and 53,253,213 shares of common stock issued and
outstanding.
At-the-Market Offering
In June 2019, the Company filed a Registration Statement on Form S-3 (the “Shelf Registration Statement”), covering the offering of up to $250.0 million
of common stock, preferred stock, debt securities, warrants and units. The Shelf Registration Statement included a prospectus covering the offering,
issuance and sale of up to $75.0 million of the Company’s common stock from time to time through an “at-the-market” offering under the Securities Act of
1933, as amended (the “Initial ATM Offering Program”). The SEC declared the Shelf Registration Statement effective on June 6, 2019.
In June 2019, the Company also entered into a sales agreement (the “June 2019 Sales Agreement”) with Cowen and Company, LLC (“Cowen”) to sell
shares of the Company’s common stock, from time to time, with aggregate gross sales proceeds of up to $75.0 million, through the ATM Offering Program
under which Cowen acts as its sales agent. Cowen is entitled to compensation for its services equal to up to 3.0% of the gross proceeds of any shares of
common stock sold through Cowen under the June 2019 Sales Agreement. During the year ended December 31, 2020, the Company issued and sold
5,002,257 shares of its common stock through its ATM Offering Program and received net proceeds of approximately $37.3 million, after deducting
commissions and other offering expenses of $1.3 million.
In July 2020, the Company filed an additional prospectus supplement to the Shelf Registration Statement. This prospectus supplement covers the offering,
issuance and sale of up to an additional $50.0 million of the Company’s common stock from time to time through an additional “at-the-market” offering
under the Securities Act of 1933, as amended (the “Additional ATM Offering Program”). The Initial ATM Offering Program and Additional ATM Offering
Program are collectively called the “ATM Offering Programs”.
In July 2020, the Company entered into a second sales agreement (the “July 2020 Sales Agreement”) with Cowen to sell shares of the Company’s common
stock, from time to time, with aggregate gross sales proceeds of up to $50.0 million, through the Additional ATM Offering Program under which Cowen
will act as its sales agent. The issuance and sale of shares of common stock by the Company pursuant to the July 2020 Sales Agreement are also deemed an
“at-the-market” offering under the Securities Act of 1933, as amended (the “Securities Act”). Cowen is entitled to compensation for its services equal to up
to 3.0% of the gross proceeds of any shares of common stock sold through Cowen under the July 2020 Sales Agreement. During the year ended December
31, 2021, there were 1,187,068 shares of the Company’s common stock sold through the Initial ATM Offering Program and 707,459 shares of the
Company’s common stock sold through the Additional ATM Offering Program and received total net proceeds of approximately $10.4 million, after
deducting commissions and other offering expenses of $0.3 million.
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Equity Purchase Agreement
On September 29, 2021, the Company entered into an equity purchase agreement (the “Purchase Agreement” or “Equity Purchase Agreement”) and a
registration rights agreement with Lincoln Park Capital Fund, LLC (“Lincoln Park” or “Investor”) which provides for the sale to Lincoln Park up to
$30,000,000 of shares (the “Purchase Shares”) of its common stock over the thirty-six (36) month term of the Purchase Agreement. In connection with the
Purchase Agreement, Lincoln Park purchased 1,020,408 Purchase Shares at a purchase price of $2.94 per share, for a total gross purchase price of $3.0
million (the “Initial Purchase”), and the Company issued 252,447 shares of common stock to Lincoln Park as a commitment fee in connection with entering
into the Purchase Agreement. The Company recognized $0.8 million of other expense relating to the commitment fee share issuance. As of December 31,
2021, the Company had initiated the purchase of an additional 2.9 million shares of the Company’s common stock amounting to $5.3 million in gross
proceeds.
Under the Purchase Agreement, the Company has sole discretion, subject to certain conditions, on any business day selected by the Company to require
Lincoln Park to purchase up to 100,000 shares of common stock (the “Regular Purchase Amount”) at the Purchase Price (as defined below) per purchase
notice (each such purchase, a “Regular Purchase”). The Regular Purchase Amount may be increased as follows: to up to 150,000 shares if the closing price
is not below $3.50, up to 200,000 shares if the closing price is not below $5.00, and up to 250,000 shares if the closing price is not below $7.00. Lincoln
Park’s committed obligation under each Regular Purchase is capped at $2,000,000, unless the Parties agree otherwise. The purchase price for Regular
Purchases (the “Purchase Price”) shall be equal to the lesser of: (i) the lowest sale price of the common shares during the Purchase Date, or (ii) the average
of the three (3) lowest closing sale prices of the common shares during the ten (10) business days prior to the Purchase Date.
In addition to Regular Purchases and subject to certain conditions and limitations, the Company in its sole discretion may require Lincoln Park on each
Purchase Date to purchase on the following business day up to the lesser of (i) three (3) times the number of shares purchased pursuant to such Regular
Purchase or (ii) 30% of the trading volume on the Accelerated Purchase Date (the “Accelerated Purchase”) (unless the Parties agree otherwise) at a
purchase price equal to the lesser of 97% of (i) the closing sale price on the Accelerated Purchase Date, or (ii) the Accelerated Purchase Date’s volume
weighted average price (the “Accelerated Purchase Price”). The Company has the sole right to set a minimum price threshold for each Accelerated
Purchase in the notice provided with respect to such Accelerated Purchase and under certain circumstances and in accordance with the Purchase Agreement
the Company may direct multiple Accelerated Purchases in a day.
The aggregate number of shares that the Company can sell to Lincoln Park under the Purchase Agreement may not exceed 11,065,803 shares of the
Common Shares (which is equal to approximately 19.99% of the shares of the Common Shares outstanding immediately prior to the execution of the
Purchase Agreement) (the “Exchange Cap”), unless (i) shareholder approval is obtained to issue Purchase Shares above the Exchange Cap, in which the
Exchange Cap will no longer apply, or (ii) the average price of all applicable sales of Common Shares to Lincoln Park under the Purchase Agreement
equals or exceeds $2.94 per share; provided that at no time may Lincoln Park (together with its affiliates) beneficially own more than 9.99% of the
Company’s issued and outstanding Common Shares.
The Purchase Agreement contains customary representations, warranties, covenants, closing conditions, indemnification and termination provisions. The
Purchase Agreement may be terminated by the Company at any time, at its sole discretion, without any cost or penalty, by giving one business day notice to
Lincoln Park. Further, Lincoln Park has covenanted not to engage in any direct or indirect short selling or hedging of the Common Shares. There are no
limitations on the use of proceeds, financial or business covenants, restrictions on future financings (other than restrictions on the Company’s ability to
enter into a similar type of agreement or Equity Line of Credit during the Term, excluding an At-The-Market transaction with a registered broker-dealer),
rights of first refusal, participation rights, penalties or liquidated damages in the Purchase Agreement.
120
11. Corporate Restructuring
In September 2020, the Company’s board of directors implemented a corporate restructuring to align its resources on cellular senescence programs in
ophthalmology and neurology while further extending operating capital. The restructuring resulted in an elimination of approximately 33 positions, or
approximately 32% of the Company’s workforce, as of September 30, 2020. The Company incurred a one-time employee benefits and severance charge of
approximately $1.8 million in operating expenses during the year ended December 31, 2020. The related accrual is recorded in accrued compensation on
the balance sheet at December 31, 2020. Restructuring charges incurred under this plan primarily consisted of employee termination benefits. Employee
termination benefits include severance costs, employee-related benefits, and supplemental one-time termination payments. Charges and other costs related
to the workforce reduction and structure realignment, and non-cash share-based compensation credits related to the forfeiture of stock options are included
in operating expenses in the statements of operations and comprehensive loss. Of the total charge, $1.5 million was recorded to research and development
expenses and $0.3 million was recorded to general and administrative expenses during the year ended December 31, 2020. Substantially all cash payments
were paid out in the first quarter of 2021. The Company may also incur additional costs not currently contemplated due to events that may occur as a result
of, or that are associated with, the restructuring.
In February 2022, the Company implemented a corporate restructuring to align its resources to focus on its UBX1325 program while further extending
operating capital. The restructuring is expected to result in an elimination of approximately 32 positions and the Company will incur a one-time employee
benefits and severance charge of approximately $1.8 million in operating expenses in the first half of 2022.
12. Stock-Based Compensation
Summary of Equity Incentive Plans
In March 2018, the Company’s board of directors adopted the Company’s 2018 Incentive Award Plan (the “2018 Plan”). The 2018 Plan was approved by
the Company’s stockholders in April 2018 and became effective in May 2018. The 2018 Plan initially reserved 4,289,936 shares for the issuance of stock
options as well as any automatic annual increases in the number of shares of common stock reserved for future issuance under the 2018 Plan. Awards
granted under the 2018 Plan expire no later than ten years from the date of grant. For stock options, the option price shall not be less than 100% of the
estimated fair value on the day of grant. Options granted typically vest over a four-year period but may be granted with different vesting terms. Unvested
options not exercised at the time of an employee’s termination of employment are added back to the 2018 Plan.
Following the Company’s IPO and in connection with the effectiveness of the 2018 Plan, the 2013 Equity Incentive Plan (the “2013 Plan”) terminated and
no further awards will be granted under that plan. All outstanding awards under the 2013 Plan will continue to be governed by their existing terms and the
shares that remained outstanding for issuance under the 2013 Plan were transferred into the 2018 Plan. As of December 31, 2021, there were in aggregate
13,271,831 shares of common stock authorized for issuance under the 2018 Plan.
Prior to its termination, the 2013 Plan provided for the granting of incentive stock options (“ISOs”), non-statutory stock options (“NSOs”) and restricted
shares to employees, directors, and consultants at the discretion of management and the board of directors. The exercise price of an ISO and NSO shall not
be less than 100% of the estimated fair value of the shares on the date of grant, and the exercise price of an ISO and NSO granted to a 10% stockholder
shall not be less than 110% of the estimated fair value of the shares on the date of grant. For awards granted between September 2017 and February 2018
with an exercise price of $3.42, a deemed fair value ranging from $3.95 to $8.47 per share was used in calculating stock-based compensation expense,
which was determined using management hindsight. Options granted under the 2013 Plan expire no later than ten years from the date of grant and generally
vest over a four-year period but may be granted with different vesting terms. Unvested options not exercised at the time of an employee’s termination of
employment are added back to the 2018 Plan.
Under the 2013 Plan, the Company permitted early exercise of certain stock options prior to vesting. These unvested shares are subject to repurchase by the
Company at the original issuance price in the event the optionee’s employment is terminated either voluntarily or involuntarily. The amounts paid for
shares purchased under an early exercise of stock options and subject to repurchase by the Company are reported as a liability and reclassified into
additional paid-in capital as the shares vest.
In March 2020, the Company’s board of directors approved the Company’s 2020 Employment Inducement Incentive Plan (“the 2020 Plan”), to provide for
grants to newly hired employees as a material inducement for them to commence employment with the Company. The 2020 Plan initially reserved
1,100,000 shares for the issuance of
121
stock options, and in November 2020, the Company reserved an additional 1,500,000 shares of common stock for future issuance under the 2020 Plan.
Awards granted under the 2020 Plan expire no later than ten years from the date of grant. For stock options, the option price shall not be less than 100% of
the estimated fair value on the day of grant. Options granted typically vest over a four-year period but may be granted with different vesting terms.
Unvested options not exercised at the time of an employee’s termination of employment are added back to the 2020 Plan. As of December 31, 2021, there
were in aggregate 2,530,000 shares of common stock authorized for issuance under the 2020 Plan.
Equity Incentive Plan Activity
The following sections summarize activity under the Company’s equity incentive plans.
Stock Options, Restricted Stock Units (RSUs) and Performance Stock Units (“PSUs”) Activity
A summary of the Company’s stock option activity under the 2013 Plan, 2018 Plan and 2020 Plan for the year ended December 31, 2021 is as follows:
Balance at December 31, 2020
Shares added
Granted
Exercised
Canceled
Balance at December 31, 2021
Vested and exercisable at December 31, 2021
Vested and expected to vest at December 31, 2021
Shares
Available
for Grant
Outstanding
Options
Weighted-
Average
Exercise
Price
4,270,764
2,942,007
(3,629,461)
—
1,730,141
5,313,451
7,475,472 $
—
3,062,738
(430,047)
(1,441,208)
8,666,955 $
4,204,083 $
8,666,955 $
6.88
—
4.92
3.64
8.70
6.05
6.55
6.05
Weighted-
Average
Remaining
Contract
Term
(in Years)
Aggregate
Intrinsic
Value
(in thousands)
7.7 $
6.4 $
7.7 $
—
—
—
The total intrinsic value of options exercised was $1.1 million and $1.5 million for the years ended December 31, 2021 and 2020, respectively. The
weighted-average estimated fair value of stock options granted was $4.88 and $4.83 for the years ended December 31, 2021 and 2020, respectively.
The aggregate intrinsic value of options exercisable was zero and $4.1 million as of December 31, 2021 and 2020, respectively.
In September 2020, the board of directors granted retention stock-based awards to employees covering an aggregate of 3.2 million shares of common stock,
including options to purchase an aggregate of 250,000 shares of common stock and 2,959,850 of restricted stock units. The awards are all time-based
vesting and vest over three to four years.
During the year ended December 31, 2020 the Company issued 13,550 shares in settlement of stock-based compensation awards accounted for as liability
awards. During the year ended December 31, 2021, there were no shares issued in settlement of stock-based compensation awards accounted for as liability
awards.
The following table summarizes the Company’s RSU, RSA and PSU activity for the year ended December 31, 2021:
Unvested at December 31, 2020
Granted
Released
Canceled
Unvested at December 31, 2021
122
Shares
2,922,077 $
566,723 $
(962,693) $
(535,170) $
1,990,937 $
Weighted-
Average
Grant Date
Fair Value
3.44
4.88
3.36
3.33
3.92
As of December 31, 2021, the total stock-based compensation cost related to options, RSAs, RSUs and PSUs granted but not yet amortized was $23.1
million and will be recognized over a weighted-average period of approximately 3.2 years. The total grant date fair value of RSUs and RSAs vested during
the years ended December 31, 2021 and 2020 was approximately $3.1 million and $1.2 million, respectively.
In March 2020, the board of directors granted the Company’s newly hired Chief Executive Officer stock-based awards covering an aggregate of 1.1 million
shares of common stock, including options to purchase an aggregate of 800,000 shares of common stock, 120,000 RSUs, 150,000 PSUs and 30,000 shares
of common stock. The stock-based awards were granted pursuant to the 2020 Plan.
The 30,000 shares of common stock were fully vested on the date of grant and thus, the related compensation expense of $0.2 million was recognized on
the grant date. The stock options and RSUs will vest subject to continued service through the applicable vesting date.
Valuation of Stock Options
The Company uses the Black-Scholes option-pricing model for determining the estimated fair value and stock-based compensation related to stock options
and ESPP awards. The fair value of stock options granted to employees was estimated on the date of grant using the Black-Scholes option pricing model
using the following assumptions:
Expected term of options (in years)
Expected stock price volatility
Risk-free interest rate
Expected dividend yield
The valuation assumptions were determined as follows:
2021
6.0
85.7%-88.5%
1.08%-1.35%
—
Year Ended December 31,
2020
6.1
92.6%-107.9%
0.29%-0.52%
—
2019
6.1
99.4%-111.3%
1.59%-2.27%
—
Expected Term—The expected term represents the period that the options granted are expected to be outstanding and is determined using the simplified
method (based on the mid-point between the vesting date and the end of the contractual term).
Expected Volatility—The Company used an average historical stock price volatility based on a combined weighted average of the Company’s historical
average volatility and that of a selected peer group of comparable public companies within the biotechnology and pharmaceutical industry that were
deemed to be representative of future stock price trends as the Company does not have a sufficient historical trading history of its own common stock. The
Company will continue to apply this process until a sufficient amount of historical information regarding the volatility of its own stock price becomes
available.
Risk-Free Interest Rate—The Company based the risk-free interest rate over the expected term of the options based on the constant maturity rate of U.S.
Treasury securities with similar maturities as of the date of the grant.
Expected Dividend Yield—The Company has never paid any dividends and does not plan to pay dividends in the foreseeable future. Therefore, the
expected dividend yield is zero.
The fair value of ESPP awards was not material for all periods presented.
Performance Stock Units
The PSUs were originally scheduled to vest as to 50,000 PSUs upon the attainment of (a) a volume-weighted average per share closing trading price of the
Company’s common stock of at least $36.875 over a trailing 30-day period or (b) a change in control transaction in which the price per share to the holders
of the Company’s common stock is at least $36.875 and as to 100,000 PSUs (x) at such time as the Company’s market capitalization reaches at least $2.5
billion, as measured based on the volume weighted-average closing trading price over a trailing 30 day period or (y) a change in control transaction in
which the consideration paid to the Company’s stockholders is equal to at least $2.5 billion, as determined by the Company’s board of directors. In January
2021, the board of directors modified the PSUs to vest as to 50,000 PSUs upon the attainment of (a) a volume-weighted average per share closing trading
price of the Company’s common stock of at least $18 over a trailing 30-day period or (b) a change in
123
control transaction in which the price per share to the holders of the Company’s common stock is at least $18.00 and as to 100,000 PSUs upon the
attainment of (x) a volume-weighted average per share closing trading price of the Company’s common stock of at least $36.00 over a trailing 30-day
period or (y) a change in control transaction in which the price per share to the holders of the Company’s common stock is at least $36.00, as determined by
the Company’s board of directors.
For the PSU awards, the Company used the Monte-Carlo option pricing model to determine the fair value of awards at the date of grant. The Monte-Carlo
option pricing model uses similar input assumptions as the Black-Scholes model; however, it further incorporates into the fair-value determination the
possibility that the market condition may not be satisfied. Compensation costs related to awards with a market-based condition are recognized regardless of
whether the market condition is ultimately satisfied. Compensation cost is not reversed if the achievement of the market condition does not occur. The total
grant date fair value of the PSU awards was determined to be $0.7 million and will be recognized as compensation expense over the weighted-average
derived service period of approximately 4.3 years. The incremental fair value of the PSUs on the modification date of $31,000 are added to the unamortized
value of the original grant of $569,000 and will be amortized to expense over the new implied service periods of 1.63 years to 2.79 years.
Performance and Market Contingent Stock Options
As of December 31, 2020, there were 87,521 performance and market contingent stock option awards outstanding with a grant date total fair value of $0.3
million. As of December 31, 2020 the Company determined that the achievement of the requisite performance conditions was not probable and, as a
result, no compensation cost was recognized for these awards.
In January 2021, the board of directors modified 17,479 performance and market contingent stock options with vesting conditions that required the
combination of a liquidity event, change of control or IPO with a market condition at prescribed levels. The modification removed the performance
condition and lowered the market conditions to a volume-weighted average per share closing trading price of the Company’s common stock of at least
$18.00 over a trailing 30-day period for one tranche and at least $36.00 over a trailing 30-day period for the second tranche. The fair value of the options on
the modification date of $81,000 will be amortized to expense over the implied service periods of 1.46 years to 2.52 years.
In June 2021, the board of directors modified 33,370 performance and market contingent stock options with vesting conditions that required the
combination of a liquidity event, change of control or IPO with a market condition at prescribed levels. The modification removed the performance
condition and adjusted the market conditions to a date on which the Company attains a valuation of at least one billion dollars measured by the volume-
weighted average per share closing trading price of the Company’s common stock over a trailing 30-day period. The fair value of the options on the
modification date of $102,000 will be amortized to expense over the implied service periods of 1.85 years.
As of December 31, 2021, there were 50,849 market contingent stock option awards outstanding with a modification date total fair value of $0.2 million.
2018 Employee Stock Purchase Plan
In March 2018, the Company’s board of directors adopted the Company’s 2018 Employee Stock Purchase Plan (the “2018 ESPP”). The 2018 ESPP was
approved by the Company’s stockholders in April 2018 and became effective on May 2, 2018. The 2018 ESPP reserved 536,242 shares of common stock
for issuance pursuant to future awards, as well as any automatic increases in the number of shares of the Company’s common stock reserved for future
issuance under this plan.
Under the 2018 ESPP, employees are offered the option to purchase the Company’s common stock at a discount during the offering periods, at semi-annual
intervals, with their accumulated payroll deductions. The option purchase price will be 85% of the lower of the closing trading price per share at the
beginning of the offering period or at the purchase date. The 2018 ESPP provides for consecutive offering periods and eligible employees may elect to
withhold up to 15% of their compensation through payroll deductions during the offering period for the purchase of stock. The maximum number of shares
that may be purchased by any one participant is limited to 15,000 shares in each offering period and $25,000 in fair market value during any calendar year
per the Internal Revenue Code limits. The first offering period commenced on September 16, 2018.
124
Stock-Based Compensation Expense
The following table sets forth the total stock-based compensation expense for all options granted to employees and nonemployees, including shares sold
through the issuance of non-recourse promissory notes which are considered to be options for accounting purposes, and costs associated with the 2018
ESPP included in the Company’s statement of operations (in thousands):
Research and development
General and administrative
Total
2021
Year Ended December 31,
2020
2019
$
$
4,809 $
6,744
11,553 $
6,563 $
7,250
13,813 $
4,979
5,873
10,852
Stock-based compensation for the year ended December 31, 2020 includes $0.1 million of expense related to awards accounted for as liability awards.
There was no expense related to awards accounted for as liability awards included in stock-based compensation for the year ended December 31, 2021.
During the years ended December 31, 2021 and 2020, stock-based compensation expense recognized related to nonemployee options was $0.4 million and
$0.3 million, respectively.
13. Net Loss per Common Share
Basic net loss per share is calculated by dividing net loss by the weighted-average number of shares outstanding for the period. Diluted net loss per share is
calculated by dividing net loss by the weighted-average number of shares of common stock and potential dilutive common stock equivalents outstanding
during the period if the effect is dilutive.
The calculation of diluted earnings (loss) per share also requires that, to the extent contingencies are satisfied during the period and the presumed issuance
of additional shares as contingent consideration is dilutive to earnings (loss) per share for the period, adjustments to net income or net loss used in the
calculation are required to remove the change in fair value of the contingent consideration liability for the period. Likewise, adjustments to the denominator
are required to reflect the related dilutive shares. In all periods presented, the Company’s outstanding stock options, RSAs, RSUs (including PSUs), early
exercised common stock subject to future vesting, restricted stock accounted for as options, shares subject to the 2018 ESPP and presumed issuance of
additional shares as contingent consideration were excluded from the calculation of diluted net loss per share because their effects were antidilutive.
A reconciliation of the numerators and denominators used in computing net loss from continuing operations per share is as follows (in thousands, except
per share amounts):
2021
December 31,
2020
(in thousands, except share and per share amounts)
2019
Numerator:
Net loss
Denominator:
Weighted average number of shares outstanding—basic
and diluted
Net loss per share—basic and diluted
$
(60,725)
$
(93,844)
$
(82,177)
55,815,873
(1.09)
$
50,864,889
(1.84)
$
43,624,807
(1.88)
$
125
Since the Company was in a net loss position for all periods presented, basic net loss per common share is the same as diluted net loss per common share as
the inclusion of all potential common shares outstanding would have been anti-dilutive.
Potentially dilutive securities that were not included in the diluted per share calculations because they would be anti-dilutive were as follows:
Options to purchase common stock
Early exercised common stock subject to future vesting
RSUs
PSUs
Shares subject to the 2018 ESPP
Total
2021
8,666,955
33,370
1,990,937
—
147,741
10,839,003
Year Ended December 31,
2020
7,540,472
66,741
2,832,077
150,000
111,383
10,700,673
2019
6,906,898
146,915
325,887
—
47,597
7,427,297
Up to 55,900 shares may be contingently issued, if certain performance conditions are met under the Company’s in-licensing agreements. See Note 5,
“License Revenue, Agreements and Strategic Investment,” to the Company’s financial statements for additional information.
14. Defined Contribution Plan
The Company sponsors a 401(k) Plan that stipulates that eligible employees can elect to contribute to the 401(k) Plan, subject to certain limitations, on a
pretax basis. In January 2019, the Company began to match 4% of employees’ salary. During the years ended December 31, 2021 and 2020, the Company
recorded matching contributions of $0.5 million and $0.6 million, respectively.
15. Income Taxes
The Company has incurred net operating losses for all the periods presented. The Company has not reflected the benefit of any such net operating loss
carryforwards in the accompanying financial statements. The Company has established a full valuation allowance against its deferred tax assets due to the
uncertainty surrounding the realization of such assets. All losses to date have been incurred domestically as the Company has no international operations or
subsidiaries.
No provision for U.S. income taxes exists due to tax losses incurred in all periods presented. All losses incurred were U.S. based.
The effective tax rate for the years ended December 31, 2021, 2020 and 2019 is different from the federal statutory rate primarily due to the valuation
allowance against deferred tax assets as a result of insufficient sources of income. The effective tax rate of the Company’s provision for income taxes
differs from the federal statutory rate as follows:
Taxes at the U.S. statutory income tax rate
State tax, net of federal benefit
Other
Stock-based compensation
Research and development tax credits
Rate change
ASC 740-10
Change in valuation allowance
Total provision for income taxes
2021
Year Ended December 31,
2020
2019
21.0 %
0.9
(0.4)
(1.6)
3.2
7.3
(4.2)
(26.2)
— %
21.0 %
—
1.8
(1.6)
2.2
0.1
—
(23.5)
— %
21.0 %
(2.2)
(0.9)
(0.5)
(0.2)
(3.9)
—
(13.3)
— %
Deferred income taxes reflect the net tax effects of (a) temporary differences between the carrying amounts of assets and liabilities for financial reporting
purposes and the amounts used for income tax purposes, and (b) operating losses and tax credit carryforwards.
126
The tax effects of significant items comprising the Company’s deferred income taxes are as follows:
Deferred tax assets:
Federal and state operating loss carryforwards
Research and development tax credits
Stock-based compensation
Accruals and other
Intangibles
Charitable contributions
Operating lease liabilities
Total deferred tax assets
Deferred tax liabilities:
Operating lease right-of-use assets
Fixed assets
Unrealized gain on equity investment
Total deferred tax liabilities
Valuation allowance
Net deferred tax assets
2021
December 31,
(in thousands)
2020
$
68,216 $
7,356
5,232
837
3,581
266
7,608
93,096
(4,698)
(1,500)
—
(6,198)
(86,898)
$
— $
57,126
5,411
4,326
1,145
1,181
254
8,203
77,646
(4,946)
(1,750)
—
(6,696)
(70,950)
—
The tax benefit of net operating losses, temporary differences and credit carryforwards should be recorded as an asset to the extent that management
assesses that their realization is "more likely than not." Realization of the future tax benefits is dependent on the Company's ability to generate sufficient
taxable income within the carryforward period. Because of the Company's recent history of operating losses, management believes that recognition of the
deferred tax assets arising from the above-mentioned future tax benefits is currently not likely to be realized and, accordingly, has provided a valuation
allowance.
Realization of the net deferred tax assets is dependent upon future taxable income, if any, the amount and timing of which is uncertain. Based on the weight
of available positive and negative objective evidence, management believes it more likely than not that the Company’s deferred tax assets are not
realizable. Accordingly, the net deferred tax assets have been fully offset by a valuation allowance. The valuation allowance increased by $15.9 million and
$22.1 million during the years ended December 31, 2021 and 2020, respectively.
Net operating losses and tax credit carryforwards as of December 31, 2021 are as follows:
Net operating losses, federal (post December 31, 2017)
Net operating losses, federal (pre January 1, 2018)
Net operating losses, state
Research and development tax credits, federal
Research and development tax credits, California
$
Amount
(in thousands)
260,405
64,136
93,166
7,173
6,040
Expiration Years
Do Not Expire
2029-2037
2029-2036
2034-2041
Indefinite
Federal and state laws impose restrictions on the utilization of net operating loss carryforwards and R&D credit carryforwards in the event of a change in
ownership of the Company, which constitutes an 'ownership change' as defined by Internal Revenue Code Section 382 and 383. The Company experienced
an ownership change in the past that impacts the availability of its net operating losses and tax credits. The amounts indicated in the above tables reflect the
reduction of net operating losses and credit carryforwards as a result of previous ownership changes that the Company experienced. Should there be
additional ownership changes in the future, the Company's ability to utilize existing carryforwards could be substantially restricted.
The Company determines its uncertain tax positions based on a determination of whether and how much of a tax benefit taken by the Company in its tax
filings is more likely than not to be sustained upon examination by the relevant income tax authorities.
127
The following table summarizes the activity related to the Company’s unrecognized tax benefits:
Gross unrecognized tax benefits at January 1
Additions for tax positions taken in the current year
Reductions for tax positions taken in the prior year
Gross unrecognized tax benefits at December 31
2021
December 31,
2020
(in thousands)
2019
$
$
7,142 $
3,457
2,622
13,221 $
9,762 $
255
(2,875)
7,142 $
3,714
6,221
(173)
9,762
If recognized, none of the unrecognized tax benefits as of December 31, 2021 and 2020 would reduce the annual effective tax rate, primarily due to
corresponding adjustments to the valuation allowance. The Company will recognize both accrued interest and penalties related to unrecognized benefits in
income tax expense. As of December 31, 2021 and 2020, no liability has been recorded for potential interest or penalties. The Company does not expect the
unrecognized tax benefits to change significantly over the next 12 months.
The Company files income tax returns in the U.S. federal jurisdiction and California, Colorado, Delaware, Florida and Massachusetts. The Company is not
currently under audit by the Internal Revenue Service or other similar state or local authorities. All tax years remain open to examination by major taxing
jurisdictions to which the Company is subject.
16. Subsequent Events
In February 2022, the Company implemented a corporate restructuring to align its resources to focus on its UBX1325 program while further extending
operating capital. The restructuring is expected to result in an elimination of approximately 32 positions, or approximately 50% of the Company’s
workforce, by the first half of 2022. The Company will incur a one-time employee benefits and severance charge of approximately $1.8 million in
operating expenses in the first half of 2022.
During the first quarter of 2022, Hercules Capital, Inc. gave notice to convert the remaining convertible debt option into equity of the Company’s common
stock. This resulted in the conversion of $2.7 million of principal debt into common stock, and reducing the outstanding principal under the first tranche to
$20.0 million.
In February 2022, the Company’s Board of Directors approved the granting of retention awards to critical and important Company personnel. The awards
consisted of 1,893,335 stock options and 463,328 restricted stock units with a grant date total fair value of $2.0 million and $0.5 million, respectively.
128
Item 9. Changes in and Disagreements With Accountants on Accounting and Financial Disclosure.
None.
Item 9A. Controls and Procedures.
Evaluation of Disclosure Controls and Procedures
Our management, with the participation of our chief executive and financial officers, evaluated the effectiveness of our disclosures controls and procedures,
as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, as of December 31, 2021. The term “disclosure controls and procedures,” as defined
in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, means controls and other procedures of a company that are designed to ensure that information
required to be disclosed by a company in the reports that it files or submits under the Exchange Act is recorded, processed, summarized, and reported
within the time periods specified in the SEC’s rules and forms. Disclosure controls and procedures include, without limitation, controls and procedures
designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act is accumulated and
communicated to the company’s management, including its principal executive and principal financial officers, as appropriate, to allow timely decisions
regarding required disclosure. Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only
reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible
controls and procedures. Based on the evaluation of our disclosure controls and procedures as of December 31, 2021, our chief executive officer and chief
financial officer concluded that, as of such date, our disclosure controls and procedures were effective at a reasonable assurance level.
Management’s Annual Report on Internal Control over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as such term is defined in Rule 13a-
15(f) under the Securities Exchange Act of 1934. Our internal control over financial reporting is designed to provide reasonable assurance regarding the
reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally accepted accounting
principles in the United States and includes those policies and procedures that:
•
•
•
Pertain to the maintenance of records that accurately and fairly reflect in reasonable detail the transactions and dispositions of the assets of our
company;
Provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with
generally accepted accounting principles, and that our receipts and expenditures are being made only in accordance with authorizations of our
management and directors; and
Provide reasonable assurances regarding prevention or timely detection of unauthorized acquisition, use or disposition of our assets that could
have a material adverse effect on our financial statements.
Our management assessed the effectiveness of our internal control over financial reporting as of December 31, 2021. In making this assessment,
management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission (COSO) in Internal Control-Integrated
Framework (2013 framework). Based on our assessment, management concluded our internal control over financial reporting was effective as of December
31, 2021, based on the COSO criteria.
Attestation Report of the Registered Public Accounting Firm
This Annual Report on Form 10-K does not include an attestation report of our registered public accounting firm due to an exemption established by the
JOBS Act for “emerging growth companies.”
Inherent Limitations on Effectiveness of Controls and Procedures
In designing and evaluating the disclosure controls and procedures, management recognizes that any controls and procedures, no matter how well designed
and operated, can provide only reasonable assurance of achieving the desired control objectives. In addition, the design of disclosure controls and
procedures must reflect the fact that there are resource constraints and that management is required to apply judgment in evaluating the benefits of possible
controls and procedures relative to their costs.
129
Changes in Internal Control over Financial Reporting
Management determined that, as of December 31, 2021, there were no changes in our internal control over financial reporting that occurred during the
fiscal quarter then ended that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
Item 9B. Other Information.
None.
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections.
Not Applicable.
130
Item 10. Directors, Executive Officers and Corporate Governance.
PART III
Information required by this Item is incorporated herein by reference to the sections titled “Executive Officers,” “Election of Directors,” “Corporate
Governance” and “Section 16(a) Beneficial Ownership and Reporting Compliance” in our Definitive Proxy Statement with respect to our 2022 Annual
Meeting of Stockholders to be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K.
Item 11. Executive Compensation.
Information required by this Item is incorporated herein by reference to the section titled “Executive Compensation,” “Director Compensation” and
“Corporate Governance” in our Definitive Proxy Statement with respect to our 2022 Annual Meeting of Stockholders to be filed with the SEC within 120
days after the end of the fiscal year covered by this Annual Report on Form 10-K.
Item 12. Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters.
Information required by this Item is incorporated herein by reference to the section titled “Security Ownership of Certain Beneficial Owners and
Management” and “Equity Compensation Plan Information” in our Definitive Proxy Statement with respect to our 2022 Annual Meeting of Stockholders to
be filed with the SEC within 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K.
Item 13. Certain Relationships and Related Transactions, and Director Independence.
Information required by this Item is incorporated herein by reference to the section titled “Certain Relationships and Related Party Transactions” and
“Corporate Governance” in our Definitive Proxy Statement with respect to our 2022 Annual Meeting of Stockholders to be filed with the SEC within 120
days after the end of the fiscal year covered by this Annual Report on Form 10-K.
Item 14. Principal Accounting Fees and Services.
Information required by this Item is incorporated herein by reference to the section titled “Ratification of Selection of Independent Registered Public
Accounting Firm” in our Definitive Proxy Statement with respect to our 2022 Annual Meeting of Stockholders to be filed with the SEC within 120 days
after the end of the fiscal year covered by this Annual Report on Form 10-K.
131
Item 15. Exhibits, Financial Statement Schedules.
(a) The following documents are filed as part of this report:
1. Financial Statements
PART IV
See Index to Financial Statements in Part II Item 8 of this Annual Report on Form 10-K.
2. Financial Statement Schedules
All schedules are omitted because they are not applicable or the required information is shown in the financial statements or notes
thereto.
3. Exhibits
132
Exhibit Index
Incorporated by Reference
Exhibit
Number
1.1
3.1
3.2
4.1
4.2
4.3
4.4
10.1(a)
10.1(b)
10.2(a)
10.2(b)
10.2(c)
10.3(a)#
10.3(b)#
10.4(a)#
10.4(b)#
10.4(c)#
10.4(d)#
10.5#
10.6#
10.7#
10.8#
10.9+
10.10+
10.11†
Description
Sales Agreement, dated July 31, 2020, by and between Unity Biotechnology, Inc.
and Cowen and Company, LLC.
Amended and Restated Certificate of Incorporation of Unity Biotechnology, Inc.
Amended and Restated Bylaws of Unity Biotechnology, Inc.
Reference is made to exhibits 3.1 through 3.2.
Form of Common Stock Certificate.
Amended and Restated Investors’ Rights Agreement, dated as of March 15, 2018,
by and among Unity Biotechnology, Inc. and the investors party thereto.
Description of Unity’s Securities Registered Pursuant to Section 12 of the
Securities Exchange Act of 1934.
Lease Agreement, dated as of May 13, 2016, by and between Unity
Biotechnology, Inc. and BMR-Bayshore Boulevard L.P.
First Amendment to Lease Agreement, dated as of May 23, 2017, by and between
Unity Biotechnology, Inc. and BMR-Bayshore Boulevard L.P.
Space License Agreement, dated as of October 20, 2016, by and between Unity
Biotechnology, Inc. and BMR-Bayshore Boulevard L.P.
First Amendment to Space License Agreement, dated as of December 5, 2016, by
and between Unity Biotechnology, Inc. and BMR-Bayshore Boulevard L.P.
Second Amendment to Space License Agreement, dated as of January 30, 2017, by
and between Unity Biotechnology, Inc. and BMR-Bayshore Boulevard L.P.
2013 Equity Incentive Plan.
Form of Stock Option Agreement under 2013 Equity Incentive Plan.
2018 Incentive Award Plan.
Form of Stock Option Grant Notice and Stock Option Agreement under the 2018
Incentive Award Plan.
Form of Restricted Stock Award Grant Notice and Restricted Stock Award
Agreement under the 2018 Incentive Award Plan.
Form of Restricted Stock Unit Award Grant Notice and Restricted Stock Unit
Award Agreement under the 2018 Incentive Award Plan.
2018 Employee Stock Purchase Plan.
Amended and Restated Non-Employee Director Compensation Program (Effective
January 1, 2019)
Form of Indemnification Agreement for directors and officers.
Employment Agreement, dated January 29, 2018, by and between Unity
Biotechnology, Inc. and Jamie Dananberg.
Compound Library and Option Agreement, dated as of February 2, 2016, by and
between Ascentage Pharma Group Corp. Ltd. and Unity Biotechnology, Inc.
APG1252 License Agreement, dated as of February 2, 2016, by and between
Ascentage Pharma Group Corp. Ltd. and Unity Biotechnology, Inc.
Research Services Agreement, dated as of February 2, 2016, by and between
Ascentage Pharma Group Corp. Ltd. and Unity Biotechnology, Inc.
133
Number
Form
10-Q
Filed
Herewith
Filing Date
7-31-20
5-7-18
5-7-18
4-23-18
4-5-18
1.1
3.1
3.2
4.2
4.3
8-K
8-K
S-1
S-1
10-K
4.4
3-11-20
S-1
10.1(a)
4-5-18
S-1
10.1(b)
4-5-18
S-1
10.2(a)
4-5-18
S-1
10.2(b)
4-5-18
S-1
10.2(c)
4-5-18
S-1
S-1
S-1
S-1
10.3(a)
10.3(b)
10.4(a)
10.4(b)
4-5-18
4-5-18
4-23-18
4-5-18
S-1
10.4(c)
4-5-18
S-1
10.4(d)
4-5-18
S-1
10-K
10.5
10.6
4-23-18
3-6-19
S-1
S-1
10.7
10.11
4-5-18
4-5-18
10-K
10.14
3-23-21
10-K
10.15
3-23-21
S-1
10.16
4-5-18
10.12+
10.13+
10.14(a)+
10.14(b)+
10.14(c)†
10.14(d)+
10.14(e)+
10.14(f)+
10.14(g)+
10.15+
10.16+
10.17††
10.18
10.19††††
10.20†††
10.21††††
10.22#
Amendment to APG1252 License Agreement, dated as of February 2, 2016, by
and between Ascentage Pharma Group Corp. Ltd.
Amendment to Compound Library and Option Agreement, dated as of February 2,
2016, by and between Ascentage Pharma Group Corp. Ltd. and Unity
Biotechnology, Inc.
Exclusive License Agreement, dated as of June 28, 2013, by and between the
Mayo Foundation for Medical Education and Research and Unity Biotechnology,
Inc.
Amendment No. 1 to Exclusive License Agreement, dated as of September 10,
2014, by and between the Mayo Foundation for Medical Education and Research
and Unity Biotechnology, Inc.
Amendment No. 2 to Exclusive License Agreement, dated as of November 17,
2014, by and between the Mayo Foundation for Medical Education and Research
and Unity Biotechnology, Inc.
Amendment No. 3 to Exclusive License Agreement, dated as of May 5, 2015, by
and between the Mayo Foundation for Medical Education and Research and Unity
Biotechnology, Inc.
Amendment No. 4 to Exclusive License Agreement, dated as of September 15,
2016, by and between the Mayo Foundation for Medical Education and Research
and Unity Biotechnology, Inc.
Addendum to Amendment No. 4 to Exclusive License Agreement, dated as of
September 15, 2016, by and between the Mayo Foundation for Medical Education
and Research and Unity Biotechnology, Inc.
Amendment No. 5 to Exclusive License Agreement, dated as of October 17, 2016,
by and between the Mayo Foundation for Medical Education and Research and
Unity Biotechnology, Inc.
Amended and Restated License Agreement, dated as of January 27, 2017, by and
between the Buck Institute for Research on Aging and Unity Biotechnology, Inc.
License Agreement, dated as of November 3, 2016, by and between The Johns
Hopkins University and Unity Biotechnology, Inc.
License Agreement for APG1197, dated as of January 2, 2019, by and between
Ascentage Pharma Group Corp. Ltd. And Unity Biotechnology, Inc.
Lease Agreement, dated as of February 28, 2019, by and between Unity
Biotechnology, Inc. and Bayside Area Development, LLC
First Amendment to Compound License Agreement for APG1197, dated as of
November 19, 2019, by and between Ascentage Pharma Group Corp. Ltd. and
Unity Biotechnology, Inc.
Second Amendment to APG1252 License Agreement, dated as of November 19,
2019, by and between Ascentage Pharma Group Corp. Ltd. and Unity
Biotechnology, Inc.
Second Amendment to Compound Library and Option Agreement, dated as of
January 8, 2020, by and between Ascentage Pharma Group Corp. Ltd. and Unity
Biotechnology, Inc.
Amendment to Employment Agreement, dated March 9, 2020, by and between
Unity Biotechnology, Inc. and Nathaniel E. David.
134
10-K
10.17
3-23-21
10-K
10.18
3-23-21
10-K 10.19(a)
3-23-21
10-K 10.19(b)
3-23-21
S-1
10.19(c)
4-23-18
10-K 10.19(d)
3-23-21
10-K 10.19(e)
3-23-21
10-K 10.19(f)
3-23-21
10-K 10.19(g)
3-23-21
10-K
10.20
3-23-21
10-K
10.21
3-23-21
10-K
10.22
3-6-19
10-K
10.23
3-6-19
8-K
10.1
11-25-19
10-K
10.25
3-11-20
10-K
10.26
3-11-20
10-K
10.27
3-11-20
10-K
10.29
3-11-20
8-K
10.1
3-30-20
10-Q
10.2
5-7-20
8-K
10.1
7-1-20
10-Q
10.2
11-4-20
10-Q
10.3
11-4-20
8-K
8-K
8-K
10.1
8-4-20
10.1
12-15-21
10.1
9-29-21
8-K
10.2
9-29-21
10.23#
10.24#
10.25#
10.26†††
10.27#
10.2/#
10.29†††
10.30
10.31
10.32
23.1
24.1
31.1
31.2
32.1**
101.INS
101.SCH
101.CAL
101.DEF
101.LAB
101.PRE
104
Amendment to Employment Agreement, dated March 9, 2020, by and between
Unity Biotechnology, Inc. and Jamie Dananberg.
Employment Agreement, dated March 30, 2020, by and between Unity
Biotechnology, Inc. and Anirvan Ghosh.
Amended and Restated Non-Employee Director Compensation Program (effective
as of March 30, 2020)
Third Amendment to Compound License Agreement for APG-1197, dated June
29, 2020, by and between Ascentage Pharma Group Corp. Ltd. and Unity
Biotechnology, Inc.
Employment Agreement, dated August 1, 2020, by and between Unity
Biotechnology, Inc. and Lynne Sullivan.
Amendment to Employment Agreement, dated September 1, 2020, by and between
Unity Biotechnology, Inc. and Lynne Sullivan.
Loan and Security Agreement, dated August 3, 2020, between Unity
Biotechnology, Inc. and Hercules Capital. Inc.
Amendment No. 1 to Loan and Security Agreement, dated December 15, 2021, by
and between the Company and Hercules Capital, Inc.
Purchase Agreement, dated September 29, 2021, by and between the Unity
Biotechnology, Inc. and Lincoln Park Capital Fund, LLC.
Registration Rights Agreement, dated September 29, 2021, by and between Unity
Biotechnology and Lincoln Park Capital Fund, LLC.
Consent of Independent Registered Public Accounting Firm
Power of Attorney. Reference is made to the signature page.
Certification of Principal Executive Officer Pursuant to Rules 13a-14(a) and 15d-
14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section
302 of the Sarbanes-Oxley Act of 2002.
Certification of Principal Financial Officer Pursuant to Rules 13a-14(a) and 15d-
14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section
302 of the Sarbanes-Oxley Act of 2002.
Certification of Principal Executive Officer and Principal Financial Officer
Pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the
Sarbanes-Oxley Act of 2002.
Inline XBRL Instance Document – the instance document does not appear in the
Interactive Data File because its XBRL tags are embedded within the Inline XBRL
document.
Inline XBRL Taxonomy Extension Schema Document
Inline XBRL Taxonomy Extension Calculation Linkbase Document
Inline XBRL Taxonomy Extension Definition Linkbase Document
Inline XBRL Taxonomy Extension Label Linkbase Document
Inline XBRL Taxonomy Extension Presentation Linkbase Document
Cover Page Interactive Data File (formatted as inline XBRL and contained in
Exhibit 101)
X
X
X
X
X
X
X
X
X
X
X
X
†
††
Confidential treatment has been granted for certain information contained in this exhibit. Such information has been omitted and filed separately
with the Securities and Exchange Commission.
Portions of this exhibit (indicated by asterisks) have been omitted pursuant to a request for confidential treatment filed separately with the Securities
and Exchange Commission.
135
†††
Portions of this exhibit (indicated by asterisks) have been omitted pursuant to Regulation S-K, Item 601(b)(10). Such omitted information is not
material and would likely cause competitive harm to the registrant if publicly disclosed.
+
†††† Portions of this exhibit (indicated by asterisks) have been omitted pursuant to Regulation S-K, Item 601(b)(10). Such omitted information is not
material and would likely cause competitive harm to the registrant if publicly disclosed. Additionally, schedules and attachments to this exhibit have
been omitted pursuant to Regulation S-K, Item 601(a)(5).
Certain confidential portions of this exhibit have been omitted from this exhibit in accordance with Regulation S-K 601(b)(10). Exhibit being
refiled upon expiration of confidential treatment previously granted by the SEC.
Indicates management contract or compensatory plan.
The certification attached as Exhibit 32.1 that accompanies this Annual Report on Form 10-K is not deemed filed with the Securities and Exchange
Commission and is not to be incorporated by reference into any filing of Unity Biotechnology, Inc. under the Securities Act of 1933, as amended, or
the Securities Exchange Act of 1934, as amended, whether made before or after the date of this Annual Report on Form 10-K, irrespective of any
general incorporation language contained in such filing.
#
**
Item 16. Form 10-K Summary.
None.
136
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, as amended, the Registrant has duly caused this
Annual Report on Form 10-K to be signed on its behalf by the undersigned, thereunto duly authorized.
SIGNATURES
Date: March 15, 2022
Unity Biotechnology, Inc.
By:
/s/ Anirvan Ghosh
Anirvan Ghosh, Ph.D.
Chief Executive Officer
POWER OF ATTORNEY
KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints each of Anirvan
Ghosh, Alexander Nguyen, and Lynne Sullivan his or her true and lawful attorney-in-fact and agent, with full power of substitution, for him or her and in
his or her name, place and stead, in any and all capacities, to sign any and all amendments to this Annual Report on Form 10-K, and to file the same, with
all exhibits thereto, and other documents in connection therewith, with the U.S. Securities and Exchange Commission, granting unto said attorneys-in-fact
and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection
therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming that all said attorneys-in-fact and
agents, or their, his or her substitutes or substitutes, may lawfully do or cause to be done by virtue hereof.
137
Pursuant to the requirements of the Securities Exchange Act of 1934, this Annual Report on Form 10-K has been signed by the following
persons on behalf of the Registrant in the capacities and on the dates indicated.
Name
Title
Date
/s/ Anirvan Ghosh
Anirvan Ghosh, Ph.D.
/s/ Lynne Sullivan
Lynne Sullivan
/s/ Keith R. Leonard Jr.
Keith R. Leonard Jr.
/s/ Paul L. Berns
Paul L. Berns
/s/ Kristina M. Burow
Kristina M. Burow
/s/ Graham K. Cooper
Graham K. Cooper
/s/ Nathaniel E. David
Nathaniel E. David, Ph.D.
/s/ Gilmore O’Neill
Gilmore O’Neill, M.B.
/s/ Margo Roberts
Margo Roberts, Ph.D.
/s/ Camille D. Samuels
Camille D. Samuels
Chief Executive Officer and Director
(Principal Executive Officer)
Chief Financial Officer
(Principal Financial and Accounting Officer)
Chairman
Director
Director
Director
Director
Director
Director
Director
138
March 15, 2022
March 15, 2022
March 15, 2022
March 15, 2022
March 15, 2022
March 15, 2022
March 15, 2022
March 15, 2022
March 15, 2022
March 15, 2022
Exhibit 23.1
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We consent to the incorporation by reference in the following Registration Statements:
(1) Registration Statement (Form S-3 No. 333-231893) and related Prospectus of Unity Biotechnology, Inc.,
(2) Registration Statement (Form S-8 No. 333- 254619) pertaining to the 2018 Incentive Award Plan and, 2018 Employee Stock Purchase Plan of
Unity Biotechnology, Inc.;
(3) Registration Statement (Form S-8 No. 333- 250926) pertaining to the 2020 Employment Inducement Incentive Award Plan, as amended of
Unity Biotechnology, Inc.;
(4) Registration Statement (Form S-8 No. 333-237474) pertaining to the 2020 Employment Inducement Incentive Plan of Unity Biotechnology,
Inc.;
(5) Registration Statement (Form S-8 No. 333- 237088) pertaining to the 2018 Incentive Award Plan and 2018 Employee Stock Purchase Plan of
Unity Biotechnology, Inc.;
(6) Registration Statement (Form S-8 No. 333-230086) pertaining to the 2018 Incentive Award Plan and 2018 Employee Stock Purchase Plan of
Unity Biotechnology, Inc.; and
(7) Registration Statement (Form S-8 No. 333-224726) pertaining to the 2013 Equity Incentive Plan, 2018 Incentive Award Plan, and 2018
Employee Stock Purchase Plan of Unity Biotechnology, Inc.
of our report dated March 15, 2022, with respect to the financial statements of Unity Biotechnology, Inc. included in this Annual Report (Form 10-K) of
Unity Biotechnology, Inc. for the year ended December 31, 2021.
/s/ Ernst & Young LLP
Redwood City, California
March 15, 2022
Exhibit 31.1
CERTIFICATION PURSUANT TO
RULES 13a-14(a) AND 15d-14(a) UNDER THE SECURITIES EXCHANGE ACT OF 1934,
AS ADOPTED PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002
I, Anirvan Ghosh, certify that:
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Unity Biotechnology, Inc. for the year ended December 31, 2021;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the
statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this
report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the
financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
The registrant's other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in
Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-
15(f)) for the registrant and have:
(a)
(b)
(c)
(d)
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to
ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those
entities, particularly during the period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our
supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for
external purposes in accordance with generally accepted accounting principles;
Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
Disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent
fiscal quarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to
materially affect, the registrant's internal control over financial reporting; and
5.
The registrant's other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to
the registrant's auditors and the audit committee of the registrant's board of directors (or persons performing the equivalent functions):
(a)
(b)
All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are
reasonably likely to adversely affect the registrant's ability to record, process, summarize and report financial information; and
Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal
control over financial reporting.
Date: March 15, 2022
By:
/s/ Anirvan Ghosh
Anirvan Ghosh, Ph.D.
Chief Executive Officer
(Principal Executive Officer)
Exhibit 31.2
CERTIFICATION PURSUANT TO
RULES 13a-14(a) AND 15d-14(a) UNDER THE SECURITIES EXCHANGE ACT OF 1934,
AS ADOPTED PURSUANT TO SECTION 302 OF THE SARBANES-OXLEY ACT OF 2002
I, Lynne Sullivan, certify that:
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Unity Biotechnology, Inc. for the year ended December 31, 2021;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the
statements made, in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this
report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the
financial condition, results of operations and cash flows of the registrant as of, and for, the periods presented in this report;
The registrant's other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in
Exchange Act Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-
15(f)) for the registrant and have:
(a)
(b)
(c)
(d)
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our supervision, to
ensure that material information relating to the registrant, including its consolidated subsidiaries, is made known to us by others within those
entities, particularly during the period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under our
supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for
external purposes in accordance with generally accepted accounting principles;
Evaluated the effectiveness of the registrant's disclosure controls and procedures and presented in this report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
Disclosed in this report any change in the registrant's internal control over financial reporting that occurred during the registrant's most recent
fiscal quarter (the registrant's fourth fiscal quarter in the case of an annual report) that has materially affected, or is reasonably likely to
materially affect, the registrant's internal control over financial reporting; and
5.
The registrant's other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to
the registrant's auditors and the audit committee of the registrant's board of directors (or persons performing the equivalent functions):
(a)
(b)
All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are
reasonably likely to adversely affect the registrant's ability to record, process, summarize and report financial information; and
Any fraud, whether or not material, that involves management or other employees who have a significant role in the registrant's internal
control over financial reporting.
Date: March 15, 2022
By:
/s/ Lynne Sullivan
Lynne Sullivan
Chief Financial Officer
(Principal Financial and Accounting Officer)
CERTIFICATION PURSUANT TO
18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32.1
In connection with the Annual Report of Unity Biotechnology, Inc. (the “Company”) on Form 10-K for the year ending December 31, 2021 as filed
with the Securities and Exchange Commission on the date hereof (the “Report”), I, Anirvan Ghosh, Chief Executive Officer of the Company, and Lynne
Sullivan, Chief Financial Officer of the Company, do each hereby certify, pursuant to 18 U.S.C. § 1350, as adopted pursuant to § 906 of the Sarbanes-
Oxley Act of 2002, that:
(1)
The Report fully complies with the requirements of section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
(2)
The information contained in the Report fairly presents, in all material respects, the financial condition and result of operations of the
Company.
Date: March 15, 2022
Date: March 15, 2022
By:
By:
/s/ Anirvan Ghosh
Anirvan Ghosh, Ph.D.
Chief Executive Officer
(Principal Executive Officer)
/s/ Lynne Sullivan
Lynne Sullivan
Chief Financial Officer
(Principal Financial and Accounting Officer)