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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
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(D) OF THE SECURITIES EXCHANGE ACT
OF 1934
For the fiscal year ended December 31, 2022
or
Commission File Number 000-15006
CELLDEX THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
Delaware
State or other jurisdiction of
incorporation or organization
13-3191702
(I.R.S. Employer
Identification No.)
Perryville III Building, 53 Frontage Road, Suite 220, Hampton, New Jersey 08827
(Address of principal executive offices) (Zip Code)
Registrant’s telephone number, including area code: (908) 200-7500
Securities registered pursuant to Section 12(b) of the Act:
Title of Each Class:
Common Stock, par value $.001
Trading Symbol(s)
CLDX
Name of Each Exchange Where Registered:
NASDAQ Capital 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 ☐
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒
Securities registered pursuant to Section 12(g) of the Act: None
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 and post such files). Yes ☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, 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. (Check one):
Large accelerated filer ☒
Accelerated filer ☐
Non-accelerated filer ☐
Smaller reporting company ☐
Emerging growth company ☐
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’s 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. ☒
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect
the correction of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any of
the registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒
The aggregate market value of the registrant’s common stock held by non-affiliates as of June 30, 2022 was $1.3 billion. Exclusion of shares held by any person
should not be construed to indicate that such person possesses the power, direct or indirect, to direct or cause the actions of the management or policies of the registrant, or
that such person is controlled by or under common control with the registrant.
The number of shares of common stock outstanding at February 13, 2023 was 47,207,189 shares.
DOCUMENTS INCORPORATED BY REFERENCE
Portions of the definitive Proxy Statement for our 2023 Annual Meeting of Stockholders are incorporated by reference into Part III of this Report.
Auditor Firm ID: 238
Auditor Name: PricewaterhouseCoopers LLP
Auditor Location: Boston, Massachusetts
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CELLDEX THERAPEUTICS, INC.
ANNUAL REPORT ON FORM 10-K
FOR THE FISCAL YEAR ENDED DECEMBER 31, 2022
TABLE OF CONTENTS
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.
Signatures
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 Accountant Fees and Services
Exhibits, Financial Statement Schedules
Form 10-K Summary
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Safe Harbor Statement under the Private Securities Litigation Reform Act of 1995: This Annual Report on Form 10-K contains
forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 under
Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-
looking statements include statements with respect to our beliefs, plans, objectives, goals, expectations, anticipations, assumptions,
estimates, intentions and future performance, and involve known and unknown risks, uncertainties and other factors, which may be
beyond our control and which may cause our actual results, performance or achievements to be materially different from future results,
performance or achievements expressed or implied by such forward-looking statements. All statements other than statements of historical
fact are statements that could be forward-looking statements. You can identify these forward-looking statements through our use of
words such as “may,” “will,” “can,” “anticipate,” “assume,” “should,” “indicate,” “would,” “believe,” “contemplate,” “expect,” “seek,”
“estimate,” “continue,” “plan,” “point to,” “project,” “predict,” “could,” “intend,” “target,” “potential” and other similar words and
expressions of the future.
There are a number of important factors that could cause the actual results to differ materially from those expressed in any forward-
looking statement made by us. These factors include, but are not limited to:
● our dependence on product candidates that are still in an early development stage;
● our ability to successfully complete research and further development, including preclinical and clinical studies;
● our anticipated timing for preclinical development, regulatory submissions, commencement and completion of clinical trials
and product approvals;
● our ability to negotiate strategic partnerships, where appropriate, for our drug candidates;
● our ability to manage multiple clinical trials for a variety of drug candidates at different stages of development;
● the cost, timing, scope and results of ongoing preclinical and clinical testing;
● our expectations of the attributes of our product and development candidates, including pharmaceutical properties, efficacy,
safety and dosing regimens;
● the cost, timing and uncertainty of obtaining regulatory approvals for our drug candidates;
● the availability, cost, delivery and quality of clinical management services provided by our clinical research organization
partners;
● the availability, cost, delivery and quality of clinical and commercial-grade materials produced by our own manufacturing
facility or supplied by contract manufacturers, suppliers and partners;
● our ability to commercialize our drug candidates and the growth of the markets for those drug candidates;
● our ability to develop and commercialize products before competitors that are superior to the alternatives developed by such
competitors;
● our ability to develop technological capabilities, including identification of novel and clinically important targets, exploiting our
existing technology platforms to develop new drug candidates and expand our focus to broader markets for our existing targeted
therapeutics;
● the cost of paying development, regulatory approval and sales-based milestones under the merger agreement by which we
acquired Kolltan Pharmaceuticals, Inc. (“Kolltan”) and our related settlement agreement with Kolltan;
● our ability to raise sufficient capital to fund our preclinical and clinical studies and to meet our long-term liquidity needs, on
terms acceptable to us, or at all. If we are unable to raise the funds necessary to meet our long-term liquidity needs, we may
have to delay or discontinue the development of one or more programs, discontinue or delay ongoing or anticipated clinical
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trials, discontinue or delay our commercial manufacturing efforts, discontinue or delay our efforts to expand into additional
indications for our drug product candidates, license out programs earlier than expected, raise funds at significant discount or on
other unfavorable terms, if at all, or sell all or part of our business;
● our ability to protect our intellectual property rights and our ability to avoid intellectual property litigation, which can be costly
and divert management time and attention;
● our ability to develop and commercialize products without infringing the intellectual property rights of third parties;
● the impact of the COVID-19 pandemic on our business or on the economy generally; and
● the factors listed under “Risk Factors” in this Annual Report on Form 10-K.
All forward-looking statements are expressly qualified in their entirety by this cautionary notice. You are cautioned not to place
undue reliance on any forward-looking statements, which speak only as of the date of this report or the date of the document incorporated
by reference into this report. We have no obligation, and expressly disclaim any obligation, to update, revise or correct any of the
forward-looking statements, whether as a result of new information, future events or otherwise. We have expressed our expectations,
beliefs and projections in good faith, and we believe they have a reasonable basis. However, we cannot assure you that our expectations,
beliefs or projections will result or be achieved or accomplished.
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Item 1. BUSINESS
Overview
PART I
Celldex Therapeutics, Inc., which we refer to as “Celldex,” “we,” “us,” “our” or the “Company,” is a biopharmaceutical company
dedicated to developing therapeutic monoclonal and bispecific antibodies that address diseases for which available treatments are
inadequate. Our drug candidates include antibody- based therapeutics which have the ability to engage the human immune system and/or
directly affect critical pathways to improve the lives of patients with inflammatory diseases and many forms of cancer.
We are focusing our efforts and resources on the continued research and development of
● Barzolvolimab (also referred to as CDX-0159), a monoclonal antibody that specifically binds the KIT receptor and potently
inhibits its activity, which is currently being studied across multiple mast cell driven diseases including
-
-
-
Chronic Urticarias: In June and July 2022 respectively, we announced that enrollment had opened and the first patients
had been dosed in Phase 2 studies in chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU).
Positive interim data from the ongoing Phase 1b study in CSU were reported in February 2023. Positive interim data
from the Phase 1b study in CIndU were reported in July and September 2021 and in December 2022 in patients with
cold urticaria and symptomatic dermographism;
Prurigo Nodularis (PN): In December 2021 we announced that the first patient had been dosed in a Phase 1b study in
PN; enrollment was closed in February 2023 and we plan to present data from the study in the second half of 2023;
Eosinophilic Esophagitis (EoE): We plan to initiate a Phase 2 study in EoE in the first half of 2023.
● Our next generation bispecific antibody platform to support pipeline expansion with additional candidates for inflammatory
diseases and oncology. Targets are being selected based on new science as well as their compatibility to be used in bispecific
antibody formats with Celldex’s existing antibody programs. Development is focused on emerging, important pathways
controlling inflammatory diseases or immunity to tumors.
Our goal is to build a fully integrated, commercial-stage biopharmaceutical company that develops important therapies for patients
with unmet medical needs. We believe our program assets provide us with the strategic options to either retain full economic rights to our
innovative therapies or seek favorable economic terms through advantageous commercial partnerships. This approach allows us to
maximize the overall value of our technology and product portfolio while best ensuring the expeditious development of each individual
product.
Our future success depends upon many factors, including our ability, and that of any licensees and collaborators that we may have,
to successfully develop, obtain regulatory approval for and commercialize our drug candidates. We have had no commercial revenues
from sales of our drug candidates, and we have had a history of operating losses. It is possible that we may not be able to successfully
develop, obtain regulatory approval for, or commercialize, our drug candidates, and we are subject to a number of risks that you should
be aware of before investing in us. These risks are described more fully in “Item 1A. Risk Factors.”
Clinical Development Programs
Barzolvolimab (also referred to as CDX-0159)
Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT and potently inhibits its
activity. KIT is expressed in a variety of cells, including mast cells, and its activation by its ligand SCF regulates mast cell growth,
differentiation, survival, chemotaxis and degranulation. Barzolvolimab is designed to block KIT activation by disrupting both SCF
binding and KIT dimerization. We believe that by targeting KIT, barzolvolimab may be able to inhibit mast cell activity and decrease
mast cell numbers to provide potential clinical benefit in mast cell related diseases.
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In certain inflammatory diseases, such as chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria (CIU), and
chronic inducible urticaria (CIndU), mast cell degranulation plays a central role in the onset and progression of the disease. In June 2020,
we completed a randomized, double-blind, placebo-controlled, single ascending dose escalation Phase 1a study of barzolvolimab in
healthy subjects (n = 32; 8 subjects per cohort, 6 barzolvolimab; 2 placebo). Subjects received a single intravenous infusion of
barzolvolimab at 0.3, 1.0, 3.0, or 9.0 mg/kg or placebo. The objectives of the study included safety and tolerability, pharmacokinetics
(PK) and pharmacodynamics (tryptase and stem cell factor) and immunogenicity. Tryptase is an enzyme synthesized and secreted almost
exclusively by mast cells and decreases in plasma tryptase levels are believed to reflect a systemic reduction in mast cell burden in both
healthy volunteers and in disease. Data from the study were featured in a late breaking presentation at the European Academy of Allergy
and Clinical Immunology (EAACI) Annual Congress 2020 in June. Barzolvolimab demonstrated a favorable safety profile as well as
profound and durable reductions of plasma tryptase, consistent with systemic mast cell suppression.
These data supported expansion of the barzolvolimab program into mast cell driven diseases, including initially in CSU and CIndU,
diseases where mast cell degranulation plays a central role in the onset and progression of the disease. Phase 1 studies in CSU and CIndU
are completing and Phase 2 studies are ongoing. We continue to assess potential opportunities for barzolvolimab in other diseases where
mast cells play an important role, such as dermatologic, respiratory, allergic, gastrointestinal and ophthalmic conditions and to this end,
are conducting an ongoing Phase 1 study in prurigo nodularis and plan to initiate a Phase 2 study in eosinophilic esophagitis in the first
half of 2023. Phase 1 studies of barzolvolimab have been conducted with an intravenous formulation; a subcutaneous formulation has
been successfully developed and is being used in Phase 2 studies.
Chronic Spontaneous Urticaria (CSU)
CSU presents as itchy hives, angioedema or both for at least six weeks without a specific trigger; multiple episodes can play out over
years or even decades. CSU is one of the most frequent dermatologic diseases with a prevalence of 0.5-1.0% of the total population or up
to approximately 1 to 3 million patients in the United States (Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org).
Approximately 50% of patients with CSU achieve symptomatic control with antihistamines. Omalizumab, an IgE inhibitor, provides
relief for roughly half of the remaining antihistamine refractory patients. Consequently, there is a need for additional therapies.
In October 2020, we announced that enrollment had opened and the first patient had been dosed in a Phase 1b multi-center study of
barzolvolimab in CSU. This study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the safety of
multiple ascending doses of barzolvolimab in up to 40 patients with CSU who remain symptomatic despite treatment with
antihistamines. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments, including
measurement of tryptase and stem cell factor levels and clinical activity outcomes (impact on urticaria symptoms, disease control,
clinical response) as well as quality of life assessments. Barzolvolimab is administered intravenously (0.5, 1.5, 3 and 4.5 mg/kg at
varying dosing schedules) as add on treatment to H1-antihistamines, either alone or in combination with H2-antihistamines and/or
leukotriene receptor agonists.
In February 2023, we reported positive interim data from the CSU study. As of the data cut-off date on November 29, 2022,
enrollment was complete with 45 patients with moderate to severe CSU refractory to antihistamines enrolled and treated [35
barzolvolimab (n=9 in 0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg; n=9 in 4.5 mg/kg) and 10 placebo]. The 0.5 mg/kg, 1.5 mg/kg
and 3.0 mg/kg cohorts had completed study participation through 24 weeks; 6 of 9 patients in the 4.5 mg/kg cohort had completed
through the week 20 visit. Complete data were included for all patients in dose levels through 3.0 mg/kg through 24 weeks. All available
data for the 4.5 mg/kg and placebo dose levels were presented for adverse events. Activity data for the 4.5 mg/kg dose level were
reported through week 20. Activity data for the 0.5 mg/kg and placebo group were only included through week 12 because, as expected,
most patients from these groups had significant symptoms ahead of week 24 and discontinued follow up. Two patients did not receive all
doses of study treatment [4.5 mg/kg (1), placebo (1)].
● Barzolvolimab resulted in rapid, marked and durable responses in patients with moderate to severe CSU refractory to
antihistamines, including patients with prior omalizumab treatment.
● The 1.5 mg/kg, 3.0 mg/kg and 4.5 mg/kg dose groups showed similar markedly improved urticaria symptoms and disease
control with sustained durability up to 24 weeks.
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● Mean reduction from baseline in urticaria activity (UAS7) at week 12 of 67% in the 1.5 mg/kg dose group (n=8), 67% in the
3.0 mg/kg dose group (n=9) and 82% in the 4.5 mg/kg dose group (n=9).
● Complete response (UAS7=0) at week 12 of 57% in the 1.5 mg/kg dose group, 44% in the 3.0 mg/kg dose group and 67% in
the 4.5 mg/kg dose group.
● Well-controlled disease (UCT≥ 12) at week 12 of 75% in the 1.5 mg/kg dose group, 63% in the 3.0 mg/kg dose group and 89%
in the 4.5 mg/kg dose group.
● During post-treatment follow up, 7 of 8 (88%) patients who had been treated with barzolvolimab 1.5 mg/kg or 3.0 mg/kg and
had a complete response (UAS7=0) at week 12 maintained their complete response through 24 weeks. Two additional patients
treated with these doses who were not a complete response at week 12 had a complete response at week 24. 6 of 6 (100%)
patients treated with barzolvolimab 4.5 mg/kg maintained their complete response through their last assessment with additional
follow up ongoing.
● Patients with prior omalizumab therapy had similar symptom improvement as all patients.
● Rapid onset of responses after initial dosing and sustained durability were observed; onset as early as 1 week after the first dose
and prolonged symptom control in some patients for up to 24 weeks.
● Tryptase suppression, indicative of mast cell depletion, paralleled symptom improvement, demonstrating the impact of mast
cell depletion on CSU disease activity.
● Barzolvolimab was well tolerated with a favorable safety profile; effects of multiple dose administration were consistent with
observations in single dose studies. Most AEs were mild or moderate in severity and resolved while on study. The most
common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract
infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment. There was one serious adverse event of
salmonella gastroenteritis which was also not related to study therapy. Changes in hematologic parameters were consistent with
observations in single dose studies, with no pattern of further decreases with multiple doses; hematologic values generally
remained within the normal range and returned to baseline levels during the follow up period. Five patients had decreases in
neutrophil counts reported as AEs; four of which were previously reported in the EAACI 2022 data presentation. The pattern
observed in the neutrophil changes for these patients was similar to the pattern seen in patients across the barzolvolimab
program to date—generally transient, asymptomatic, and mild and typically occurring in patients with screening and baseline
neutrophil counts at the lower end of the normal range on study initiation.
In June 2022, we announced that the first patient has been dosed in a Phase 2 study in patients with CSU who remain symptomatic
despite antihistamine therapy. The study is being conducted at approximately 75 sites across 9 countries. The study is a randomized,
double-blind, placebo-controlled, parallel group Phase 2 study evaluating the efficacy and safety profile of multiple dose regimens of
barzolvolimab to determine the optimal dosing strategy. Approximately 168 patients will be randomly assigned on a 1:1:1:1 ratio to
receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo
during a 16-week placebo-controlled treatment phase. Patients will then enter a 36-week active treatment phase, in which patients not
already randomized to barzolvolimab at 150 mg every 4 weeks or 300 mg every 8 weeks will be randomized 1:1 to receive one of these
two dose regimens; patients already randomized to these treatment arms will remain on the same regimen as during the placebo-
controlled treatment phase. Following the treatment period, patients will enter a 24-week follow up phase. The primary endpoint of the
study is mean change in baseline to week 12 in UAS7 (Urticaria Activity Score over 7 days). Secondary endpoints include safety and
other assessments of clinical activity including ISS7 (Itch Severity Score over 7 days), HSS7 (Hive Severity Score over 7 days) and
AAS7 (Angioedema Activity Score over 7 days). Based on current enrollment projections, we anticipate that enrollment to this study will
be completed by the end of the third quarter of 2023 and we plan to report topline data either late this year or in the first quarter of 2024.
Chronic Inducible Urticaria (CIndU)
CIndUs are forms of urticaria that have an attributable cause or trigger associated with them, typically resulting in hives or wheals.
The prevalence of CIndU is estimated at 0.5% of the total population and is reported to overlap in up to 36% of CSU patients
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(Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org). There are currently no approved therapies for chronic inducible
urticarias other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers.
We are exploring cold-induced, dermographism (scratch-induced) and cholinergic (exercise-induced) urticarias.
In December 2020, we announced that enrollment had opened and the first patient had been dosed in a Phase 1b study in CIndU
being conducted in Germany in patients who are refractory to antihistamines. This study is an open label clinical trial designed to
evaluate the safety of a single dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism
(SD). In March and June 2021, respectively, we added a third cohort (single dose, 3 mg/kg) in patients with cholinergic urticaria and a
fourth cohort at a lower dose (single dose, 1.5 mg/kg) in ColdU. Patient’s symptoms are induced via provocation testing that resembles
real life triggering situations. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments,
including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes
(impact on urticaria symptoms, disease control, clinical response), quality of life assessments and measurement of tissue mast cells
through skin biopsies. Barzolvolimab is administered intravenously on Day 1 as add on treatment to H1-antihistamines.
In November 2022, data from the ColdU and SD cohorts treated with a single intravenous infusion of barzolvolimab at 3 mg/kg
were published in Allergy (Terhorst-Molawi et al Allergy. 2022 Nov 16. doi: 10.1111/all.15585). Safety results were reported for 21
patients; activity results were reported for the 20 patients who received a full dose of barzolvolimab. Patients had high disease activity.
At baseline, patients’ mean scores (range) for Dermatology Life Quality Index (DLQI) [10.8 (2–21)] and Urticaria Control Test (UCT)
[6.0 (0–13)] indicated marked impairment of quality of life (QoL) and poorly controlled disease, respectively. Three patients (1 with
ColdU and 2 with SD) were previously treated with omalizumab and chose to discontinue that treatment because they remained
symptomatic. At baseline, provocation thresholds, on average (range), were 18.9°C or 66°F (5–27°C or 41–80.6°F) for patients with
ColdU and 3.5 (2–4) pins for patients with SD.
● Rapid (as early as 1 week) and durable responses were observed in all patients as assessed by provocation testing. A complete
response was achieved in 95% (n = 19/20) of patients (n = 10/10 ColdU; n = 9/10 SD). The median duration (range) of
complete response through the 12-week observation period was 77+ days (29–86; n = 10) for patients with ColdU and 57+ days
(16–70; n = 9) for patients with SD. All three patients who experienced insufficient response to omalizumab treatment had a
complete response after treatment with barzolvolimab.
● Following a single dose of barzolvolimab rapid improvements in urticaria control was observed. A UCT score of ≥12 (well
controlled) was achieved by 80% (n = 16/20) of the patients within week 4 post-treatment. By week 8, all patients (100%; n =
20/20) achieved well-controlled urticaria, which was sustained to week 12 post-dose by 80% (n = 16/20) of patients. Complete
urticaria control (UCT = 16) was achieved by 35% (n = 7/20), 65% (n = 13/20), and 40% (n = 8/20) at weeks 4, 8, and 12,
respectively.
● At baseline, patients in both treatment groups reported disease impact on their QoL. Disease impact significantly decreased
after dosing; a score of 0–1 (minimal/none) was achieved by 80% (n = 16/20) for all patients who completed the DLQI during
the study. Additionally, clinically meaningful improvements in QoL were attained and sustained to week 12.
● A single dose of barzolvolimab led to marked decreases in tryptase and in skin mast cells. The kinetics correlated with
improvements in provocation testing and clinical activity, consistent with a central role for mast cells in the pathogenesis of
ColdU and SD. This confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden
and clinical activity in inducible urticaria and potentially in other diseases with mast cell driven involvement.
● Barzolvolimab was well tolerated. Most adverse events were mild, and the most common (≥3 patients) were hair color changes
(76%; n = 16/21), infusion reactions (43%; n = 9/21), taste changes (38%; n = 8/21), nasopharyngitis (24%; n = 5/21), malaise
(24%; n = 5/21), and headache (19%; n = 4/21). Hair color changes (generally small areas of hair color lightening) and taste
disorders (generally partial changes of ability to taste salt or umami) are consistent with inhibiting KIT signaling in other cell
types and completely resolved over time during follow-up. Infusion reactions, which manifested as localized hives and itching
as well as erythema and feeling hot, resolved spontaneously. One patient with a history of fainting experienced loss of
consciousness during infusion. The patient rapidly recovered. Importantly, no evidence of mast cell activation as measured by
serum tryptase monitoring was observed in this patient. Overall, mean hematology parameters remained within the normal
ranges—an important finding for a KIT inhibitor. Mild, transient, and asymptomatic decreases in hemoglobin and white blood
cell parameters occurred for some patients.
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In December 2022, we presented long term follow up data from the 3.0 mg/kg cohorts in cold urticaria and symptomatic
dermographism at the GA²LEN Global Urticaria Forum (GUF) 2022. 14 patients consented to the optional long term follow up
evaluation (6 cold, 8 symptomatic dermographism); 10 of the 14 still had complete control of their disease as assessed by provocation
testing at week 12. Data were collected at one or more timepoints beyond week 12 through week 36.
● Most patients had return of symptoms and/or loss of urticaria control between 12 and 36 weeks. Remarkably, two patients
remained provocation negative at 36 weeks, and four had well controlled disease (UCT ≥12) 36 weeks post dosing.
● Serum tryptase exhibits a similar rate of recovery as clinical symptoms, while skin mast cells return at a slower rate. Tissue KIT
signaling, as approximated by SCF levels, was rapidly inhibited after dose administration and fully reactivated approximately
18 weeks after dosing.
● Tryptase levels return to pretreatment levels during follow up, while mast cells continue to recover. Drug related adverse events
noted during the study all resolved.
In December 2022, we also presented 12 week treatment results for the 1.5 mg/kg cohort in cold urticaria at the GA²LEN Global
Urticaria Forum (GUF) 2022. 10 patients received a single intravenous infusion of barzolvolimab at 1.5 mg/kg. Patients had high disease
activity as assessed by provocation threshold testing with a mean baseline critical temperature threshold of 18.4°C or 65°F with a range
from 6 to 27°C or 43 to 81°F. All patients had disease refractory to antihistamines and five patients had disease refractory to
omalizumab. Safety results were reported for all 10 patients; activity results were reported for the 9 patients who received a full dose of
barzolvolimab, including four patients with omalizumab refractory disease.
● All 9 of 9 (100%) patients evaluable for activity treated at 1.5 mg/kg experienced a complete response as assessed by
provocation threshold testing, including 4 patients with disease refractory to omalizumab. Rapid onset of responses after dosing
and sustained durability were observed in the 1.5 mg/kg cohort. 6 of 9 patients treated achieved a complete response within a
week of dosing. The median duration of response was 51+ days (7+ weeks).
● Improvements in disease activity as reported by Urticaria Control Test (UCT) were consistent with the complete responses as
measured by provocation testing. All patients entered the study with poorly controlled disease (mean UCT score at baseline of
5.9 and a range of 1-11). Following barzolvolimab administration, all patients achieved well controlled disease (UCT>12) with
7 of 9 achieving complete control (UCT = 16).
● A single 1.5 mg/kg dose of barzolvolimab resulted in rapid, marked and durable suppression of serum tryptase; the kinetics of
tryptase depletion mirrored changes in provocation threshold and UCT. Barzolvolimab was generally well tolerated and the
safety profile at 1.5mg/kg was similar to the profile observed with 3.0 mg/kg.
● No new treatment emergent AEs of concern were noted. While mild, transient and asymptomatic decreases in hemoglobin and
white blood cell (WBC) parameters were noted, consistent with prior studies, the hematology parameters generally remained
within the normal range.
To date, 19 of 19 (100%) patients with cold urticaria treated with either a single dose of barzolvolimab at 1.5 or 3.0 mg/kg in this
Phase 1b study have experienced a complete response by provocation testing, including 5 patients with omalizumab refractory disease.
In July 2022 we announced that the first patient has been dosed in a Phase 2 study in patients with CIndU who remain symptomatic
despite antihistamine therapy. The study will be conducted at approximately 85 sites across approximately 12 countries. The randomized,
double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of
barzolvolimab in patients with CIndU to determine the optimal dosing strategy. Approximately 180 patients in 2 cohorts (differentiated
by CIndU subtype) including 90 patients with cold urticaria and 90 patients with symptomatic dermographism will be randomly assigned
on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a
20-week treatment phase. Patients will then enter a follow-up phase for an additional 24 weeks. In addition, the study includes the option
for patients who have symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label
extension where all patients receive 300 mg every 9 weeks of barzolvolimab. The primary endpoint of the study is the percentage of
patients with a negative provocation test at week 12 (using TempTest(R) and FricTest(R)). Secondary endpoints include safety and other
assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst
itch numeric rating scale).
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Prurigo Nodularis (PN)
We have expanded clinical development of barzolvolimab into prurigo nodularis (PN). PN is a chronic skin disease characterized by
the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and
other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a
hallmark of PN. There is currently only one FDA approved therapy for PN, representing an area of significant unmet need. Industry
sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12
months and, of these, approximately 75,000 would be biologic-eligible. In December 2021, the first patient was dosed in a Phase 1b
multi-center, randomized, double-blind, placebo-controlled intravenous study designed to assess the safety and treatment effects across
multiple dosing cohorts of barzolvolimab in up to 30 patients with PN. Enrolling an intravenous, early stage study in the dermatology
setting has been a challenge and the study has taken longer than expected to complete. In February 2023, we closed enrollment at 24
patients, which we believe will provide sufficient data for analysis to inform future development decisions in PN. Following the
completion of the 24 week follow up period post dosing for patients on study, we plan to present data from the study in the second half of
2023. Potential future development in PN will utilize the subcutaneous formulation of barzolvolimab.
Eosinophilic Esophagitis (EoE)
In February 2022, we announced that we will be expanding clinical development of barzolvolimab into eosinophilic esophagitis
(EoE), the most common type of eosinophilic gastrointestinal disease. EoE is a chronic inflammatory disease of the esophagus
characterized by the infiltration of eosinophils. This chronic inflammation can result in trouble swallowing, chest pain, vomiting and
impaction of food in the esophagus, a medical emergency. Several studies have suggested that mast cells may be an important driver in
the disease, demonstrating that the number and activation state of mast cells are greatly increased in EoE biopsies and that mast cell
signatures correlate with markers of inflammation, fibrosis, pain and disease severity. Currently, there is only one FDA approved therapy
for EoE, representing an area of significant unmet need. Industry sources estimate there are approximately 160,000 patients in the United
States with EoE who have undergone treatment within the last 12 months and, of these, approximately 48,000 would be biologic-eligible.
Given the lack of effective therapies for EoE and barzolvolimab’s potential as a mast cell depleting agent, we believe EoE is an important
indication for future study and plan to initiate a Phase 2 multi-center, randomized, double-blind, placebo-controlled subcutaneous study
designed to assess the treatment effects and safety of barzolvolimab in patients with EoE in the first half of 2023.
Additional Barzolvolimab Development Activities
Manufacturing activities to support the introduction of the barzolvolimab subcutaneous formulation into the clinical program have
been completed and, in September 2021, we initiated dosing in a randomized, double-blind, placebo-controlled, Phase 1 study designed
to evaluate the safety of single ascending doses of the subcutaneous formulation of barzolvolimab in healthy volunteers. In February
2022, we reported that subcutaneous administration of barzolvolimab was well tolerated and that multiple dose levels have been
identified that possess promising pharmacokinetic and pharmacodynamic properties. Importantly, subcutaneous delivery of
barzolvolimab resulted in dose-dependent, rapid and sustained decreases in serum tryptase compared with placebo and achieved
sufficient exposure to produce tryptase suppression levels comparable with the levels that generated impressive clinical activity observed
in the Phase 1 CIndU intravenous study. The Phase 2 multi-dose studies in urticaria are designed to evaluate 75 mg and 150 mg
administered every 4 weeks and 300 mg administered every 8 weeks. These doses support a 0.5 to 2 ml injection volume, allowing for a
single injection as barzolvolimab advances towards potential commercialization. In 2022, we initiated transfer of our current
barzolvolimab manufacturing process to a contract manufacturing organization to support late-stage trials and to prepare for potential
commercialization.
In February 2022, we reported interim data after completing the in-life dosing portion of our six-month chronic toxicology study in
non-human primates. The only clinically adverse finding at the completion of dosing was a profound impact on spermatogenesis, an
expected and well understood effect of KIT inhibition. As a standard part of toxicology studies, some animals from each group continued
to be observed through a recovery period to understand the reversibility of any adverse findings. Due to the very high concentrations of
barzolvolimab at the end of dosing, the recovery period was approximately one year. As we expected, and consistent with previous
findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis
fully recovered in all male animals as measured by both sperm count and motility. We expect the final histologic analysis and study
report in early 2023. We are encouraged with these findings and believe these data strongly support our Phase 2 studies in urticaria and in
future indications.
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Bispecific Platform
Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for
inflammatory diseases and oncology. Targets are being selected based on new science as well as their compatibility to be used in
bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling
inflammatory diseases or immunity to tumors.
CDX-585
CDX-585 combines our proprietary highly active PD-1 blockade and anti-ILT4 blockade to prevent immunosuppressive signals in T
cells and myeloid cells, respectively. ILT4 is emerging as an important immune checkpoint on myeloid cells and is thought to contribute
to resistance to PD-1 blockade. Interactions of PD-1 and ILT4 with their ligands are known to deliver immune suppressive signals that
can attenuate anti-tumor immune responses. The concept behind CDX-585 is to simultaneously inhibit both T cell and myeloid
suppressive signals to potentiate the anti-tumor activity of both cell types, and potentially overcome PD-1 resistance. In preclinical
studies, CDX-585 was demonstrated to be a potent inhibitor of PD-1 signaling in comparison to the approved PD-1 antibody, nivolumab.
In addition, CDX-585 activated and promoted a strong inflammatory phenotype in human macrophage and dendritic cell cultures.
Together these activities of CDX-585 enhanced the response in a mixed lymphocyte reaction assay above that observed for either
parental mAb or the combination of the PD-1 and ILT4 mAbs. The in vivo efficacy of CDX-585 was also demonstrated in a melanoma
humanized mouse model. CDX-585 has successfully completed GMP manufacturing and IND-enabling studies to support clinical
development. CDX-585 will initially be developed for the treatment of solid tumors either as monotherapy or in combination with other
oncologic treatments and is expected to enter the clinic in 2023 in patients with advanced malignancies.
CDX-527
CDX-527 used our proprietary highly active anti-PD-L1 and CD27 human antibodies to couple CD27 co-stimulation with blockade
of the PD-L1/PD-1 pathway to help prime and activate anti-tumor T cell responses through CD27 co-stimulation, while preventing PD-1
inhibitory signals that subvert the immune response. In the summer of 2020, we initiated a Phase 1 dose-escalation study in patients with
advanced or metastatic solid tumors that had progressed during or after standard of care therapy to be followed by tumor-specific
expansion cohorts. Enrollment to the dose escalation portion was successfully completed and an expansion cohort in patients with
checkpoint naïve ovarian cancer was initiated. In November 2022, we provided an update on the study. With multiple clinical trials
actively recruiting in ovarian cancer, enrollment to the expansion cohort did not meet our internal timelines and a review of the results
did not meet internal hurdles for proceeding and we closed enrollment to the study and discontinued the program.
Other programs:
CDX-1140
CDX-1140 is a fully human agonist monoclonal antibody targeted to CD40, a key activator of immune response, which is found on
dendritic cells, macrophages and B cells and is also expressed on many cancer cells. A Phase 1 study was conducted in patients with
recurrent, locally advanced or metastatic solid tumors and B cell lymphomas. An MTD of 1.5 mg/kg was established and clinical activity
was observed both as a monotherapy and in combination with pembrolizumab. Despite evidence of clinical benefit, questions remain to
be answered about CDX-1140, and the broader CD40 agonist class, regarding the best clinical settings, regimens, and possible
combinations before advancing into additional Celldex-sponsored studies. Given our pipeline priorities and resource requirements, in
August of 2022, we announced that we are not progressing further Company-sponsored studies at this time and are exploring these
questions in third-party sponsored studies.
Partnerships
We may enter into co-development and commercialization partnerships for any of our programs where appropriate. In the past, we
have entered into collaborative partnership agreements with pharmaceutical and other companies and organizations that provided
financial and other resources, including capabilities in research, development, manufacturing, and sales and marketing, to support our
research and development programs and may enter into more of them in the future.
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Partnership agreements may terminate without benefit to us if the underlying products are not fully developed. If we fail to meet our
obligations under these agreements, they could terminate, and we might need to enter into relationships with other collaborators and to
spend additional time, money and other valuable resources in the process. We cannot predict whether our collaborators will continue
their development efforts or, if they do, whether their efforts will achieve success. Many of our collaborators face the same kinds of risks
and uncertainties in their businesses that we face. A delay or setback to a partner will, at a minimum, delay the commercialization of any
affected drug candidates, and may ultimately prevent it. Moreover, any partner could breach its agreement with us or otherwise not use
best efforts to promote our products. A partner may choose to pursue alternative technologies or products that compete with our
technologies or drug candidates. In either case, if a partner failed to successfully develop one of our drug candidates, we would need to
find another partner. Our ability to do so would depend upon our legal right to do so at the time and whether the product remained
commercially viable.
Research Collaboration and License Agreements
We have entered into license agreements whereby we have received licenses or options to license technology, specified patents
and/or patent applications. These license and collaboration agreements generally provide for royalty payments equal to specified
percentages of product sales, annual license maintenance fees, continuing patent prosecution costs and potential future milestone
payments to third parties upon the achievement of certain development, regulatory and/or commercial milestones. Summarized below are
our significant research collaboration and license agreements for our current clinical drug candidates.
Yale University (Yale)
Under a license agreement with Yale, we may be required to make a one-time payment to Yale of $3.0 million with respect to
barzolvolimab upon achievement of a specified commercial milestone. In addition, we may be required to pay a low single-digit royalty
on annual worldwide net sales of barzolvolimab. Unless earlier terminated by us or Yale, the Yale license agreement is due to expire no
later than May 2038 but may expire earlier on a country-by-country basis under specified circumstances.
Competition
The biotechnology and pharmaceutical industry is intensely competitive and subject to rapid and significant technological change.
Many of the products that we are attempting to develop and commercialize will be competing with existing therapies. Other companies
are pursuing the development of new therapies that target the same diseases and conditions that we are targeting and may compete
directly with our drug candidates. We face competition from companies, major universities and research institutions in the United States
and abroad, including a number of large pharmaceutical companies, as well as firms specialized in the development and production of
targeted therapies and immune modulators. Some of our competitors possess substantially greater financial, technical and human
resources than we do.
The competitors of which we are aware that have initiated a Phase 3 study or have obtained marketing approval for a potentially
competitive drug to barzolvolimab for treatment of CSU, CIndU, PN and EoE include: Allakos (lirentelimab for EoE), AstraZeneca
(Fasenra for CSU), Galderma/Chugai (nemolizumab for PN), Genentech (fenebrutinib for CSU), Leo Pharma (Adbry for AD), Novartis
(ligelizumab for CSU, CIndU and food allergy; remibrutinib for CSU), Regeneron/Sanofi (Dupixent for CSU, CIndU, PN and EoE), and
Trevi Therapeutics (nalbuphine for PN).
Our competitors may utilize discovery technologies and techniques or partner with collaborators in order to develop products more
rapidly or successfully than us or our collaborators are able to. In addition, some competitors have significantly greater experience than
we have in conducting preclinical and nonclinical testing and human clinical trials of drug candidates, scaling up manufacturing
operations and obtaining regulatory approvals of drugs and manufacturing facilities. Accordingly, our competitors may succeed in
obtaining regulatory approval for drugs more rapidly than we do. If we obtain regulatory approval and commence commercial sales of
our drug candidates, we also will compete with respect to manufacturing efficiency and sales and marketing capabilities, areas in which
we currently have limited experience.
In addition, academic institutions, government agencies and other public and private organizations conducting research may seek
patent protection with respect to potentially competitive products or technologies and may establish exclusive collaborative or licensing
relationships with our competitors. Moreover, technology controlled by third parties that may be advantageous to our business may be
acquired or licensed by our competitors, thereby preventing us from obtaining technology on commercially reasonable terms, if at all. We
will also compete for the services of third parties that may have already developed or acquired internal
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biotechnology capabilities or made commercial arrangements with other biopharmaceutical companies to target the diseases on which we
have focused both in the U.S. and outside of the U.S.
We also face competition in recruiting and retaining highly qualified scientific personnel and consultants and in the development and
acquisition of technologies.
Our competitive position will depend upon our ability to attract and retain qualified personnel, obtain patent protection or otherwise
develop proprietary products or processes and secure sufficient capital resources for the often lengthy period between technological
conception and commercial sales. We will require substantial capital resources to complete development of some or all of our drug
candidates, obtain the necessary regulatory approvals and successfully manufacture and market our drug candidates. In order to secure
capital resources, we anticipate having to sell additional capital stock, which would dilute existing stockholders. We may also attempt to
obtain funds through research grants and agreements with commercial collaborators. However, these types of funding are uncertain
because they are at the discretion of the organizations and companies that control the funds. As a result, we may not receive any funds
from grants or collaborations. Alternatively, we may borrow funds from commercial lenders, likely at high interest rates, which would
increase the risk of any investment in us.
Manufacturing
We are a research and development company and have limited experience in commercial manufacturing. Our ability to conduct late-
stage clinical trials, as well as manufacture and commercialize our drug candidates, depends on the ability of Contract Manufacturing
Organizations (CMOs) to manufacture our drug candidates on a large scale at a competitive cost and in accordance with current Good
Manufacturing Practices (cGMP) and U.S. and foreign regulatory requirements, as applicable. We also rely on CMOs for labeling and
storage for studies inside and outside the US. In order for us to establish our own commercial manufacturing facility, we would require
substantial additional funds and would need to make facility modifications, hire and retain significant additional personnel and comply
with cGMP regulations applicable to such a facility. The commercial manufacturing facility would also need to be licensed for the
production of our drug candidates by the FDA and meet other regulatory standards. We therefore work with CMOs under established
manufacturing arrangements that comply with the FDA’s requirements and other regulatory standards, although there is no assurance that
the manufacturing will be successful.
We operate our own cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for our current and
planned early-stage clinical trials. Our Fall River manufacturing facility has 250L and 1000L bioreactor capacity and is able to
manufacture in compliance with FDA and EU regulations, allowing us to distribute drug candidates to clinical sites in the U.S., EU and
ROW for early-stage clinical trials. We have manufactured barzolvolimab and CDX-585 drug substance in our Fall River facility for our
current and planned Phase 1 and Phase 2 clinical trials. All products are then filled at CMOs. Any manufacturing failures or compliance
issues at contract manufacturers could cause delays in our Phase 1 and Phase 2 clinical studies for these drug candidates.
Our barzolvolimab drug product is currently administered both intravenously and subcutaneously. In 2022, we manufactured
barzolvolimab drug substance at our Fall River facility in subcutaneous form then filled at a CMO to support ongoing and planned
clinical trials. The subcutaneous formulation will allow for a potential self-administration at home setting versus the need for intravenous
dosing in a hospital or clinic setting. The subcutaneous form could improve the patient experience if the product becomes available
commercially. In 2022, we initiated a transfer of our current barzolvolimab manufacturing process to a CMO to allow us to produce
larger batches in support of late-stage trials and to prepare for potential commercialization. We believe that barzolvolimab can be scaled
up to permit manufacturing in commercial quantities. However, there can be no assurance that we will not encounter difficulties in
scaling up the manufacturing processes.
While we believe that there is currently sufficient capacity worldwide for the production of our potential products through CMOs,
establishing long-term relationships with contract manufacturers and securing multiple sources for the necessary quantities of clinical
and commercial materials required can be a challenge due to increasing industry demand for CMO services. Qualifying the initial source
of clinical and ultimately commercial material is a time consuming and expensive process due to the highly regulated nature of the
pharmaceutical/biotech industry. These costs may be mitigated by the economies of scale realized in commercial manufacture and
product sales. The key difficulty in qualifying more than one source for each product is the duplicated time and expense in doing so
without the potential to mitigate these costs if the secondary source is never utilized.
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Use of third-party manufacturers limits our control over and ability to monitor the manufacturing process. As a result, we may not be
able to detect a variety of problems that may arise and may face additional costs in the process of interfacing with and monitoring the
progress of our contract manufacturers. If third-party manufacturers fail to meet our manufacturing needs in an acceptable manner or fail
to comply with regulatory requirements, we would face delays and additional costs while we develop internal manufacturing capabilities
or find alternate third-party manufacturers. It may not be possible to have multiple third-party manufacturers ready to supply us with
needed material at all or without incurring significant costs.
Commercial Organization
We have limited commercial experience in marketing, sales, distribution and product reimbursement. We have the capability to
provide current and future market insights to our research and development organization regarding our potential drug candidates. In the
future, we may choose to expand our commercial team and build a full-scale commercial organization which we believe could provide us
the opportunity to retain marketing rights to our drug candidates and commercialize such products ourselves where we deem appropriate
or pursue strategic partnerships to develop, sell, market and distribute our drug candidates where we deem appropriate.
Patents, Licenses and Proprietary Rights
In general, our intellectual property strategy is to protect our technology by filing patent applications and obtaining patent rights
covering our own technology, both in the United States and in foreign countries that we consider important to our business. In addition,
we have acquired and will seek to acquire as needed or desired, exclusive rights of others through assignment or license to complement
our portfolio of patent rights. We also rely on trade secrets, unpatented know-how and technological expertise and innovation to develop
and maintain our competitive position.
Patents
The successful development and marketing of products by us will depend in part on our ability to create and maintain intellectual
property, including patent rights. We are the owner or exclusive licensee to proprietary patent positions in the areas of immunotherapy
technologies and antibody technologies. Although we continue to pursue patent protection for our products, no assurance can be given
that any pending application will issue as a patent, that any issued patent will have a scope that will be of commercial benefit or that we
will be able to successfully enforce our patent position against infringers. We routinely review our patent portfolio and adjust our
strategies for prosecution and maintenance of individual cases according to a number of factors, including program priorities, stage of
development and patent term.
The key patents and patent applications owned by us or licensed to us that we consider important to our current clinical programs
include the following (except where stated otherwise, the indicated and estimated patent expiry dates are the estimated normal
expirations if all maintenance fees and annuities are paid when due, and do not include any possible additional terms for Patent Term
Adjustments (PTAs), Patent Term Extensions (PTEs), other term extensions or Supplementary Protection Certificates (SPCs), if these
may be secured in due course):
● We own a portfolio of patents and patent applications directed to barzolvolimab and other anti-KIT receptor antibodies. These
patents and patent applications include claims directed to particular anti-KIT antibody compositions of matter, including
barzolvolimab compositions of matter, and methods of using such antibodies. A composition of matter patent has been issued in
the U.S. which would have an estimated patent expiry date in 2034 (this includes additional term due to PTA, but does not
include any PTE if this may be secured in due course) and further U.S. patent applications are pending. Patents have also been
issued in Europe, Japan, Canada, China, Australia, New Zealand, Israel, India,the Republic of Korea, the Russian Federation,
Singapore and certain other countries. Where issued the foregoing would have estimated normal patent expiry dates ranging
from 2032 to 2033. Further international patent applications relating to barzolvolimab are also pending.
● We own a pending international patent application directed to anti-ILT4 antibody sequences used in CDX-585 as compositions
of matter. We also have rights in further pending international patent applications relating to the bispecific antibody CDX-585
and anti-PD-1 antibody sequences used in CDX-585 as compositions of matter. If, when and where issued the foregoing would
have estimated normal patent expiry dates ranging from 2041 to 2042.
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There can be no assurance that patent applications owned by or licensed to us will result in granted patents or that, if granted, the
resultant patents will afford protection against competitors with similar technology. It is also possible that third parties may obtain patents
or other proprietary rights that may be necessary or useful to us. In cases where third parties are first to invent a particular product or
technology, it is possible that those parties will obtain patents that will be sufficiently broad to prevent us from using important
technology or from further developing or commercializing important drug candidates and immunotherapeutic systems. If licenses from
third parties are necessary but cannot be obtained, commercialization of the covered products might be delayed or prevented. Even if
these licenses can be obtained, they would probably require us to pay ongoing royalties and other costs, which could be substantial.
Although a patent has a statutory presumption of validity in the United States, the issuance of a patent is not conclusive as to validity
or as to the enforceable scope of the patent claims. The validity or enforceability of a patent after its issuance by the Patent and
Trademark Office can be challenged in litigation. As a business that uses a substantial amount of intellectual property, we face a
heightened risk of intellectual property litigation. If the outcome of the litigation is adverse to the owner of the patent, third parties may
then be able to use the invention covered by the patent without authorization or payment. There can be no assurance that our issued
patents or any patents subsequently issued to or licensed by us will not be successfully challenged in the future. In addition, there can be
no assurance that our patents will not be infringed or that the coverage of our patents will not be successfully avoided by competitors
through design innovation.
We are aware that others, including universities and companies, have filed patent applications and have been granted patents in the
United States and other countries which claim subject matter potentially useful or necessary to the commercialization of our products.
The ultimate scope and validity of existing or future patents which have been or may be granted to third parties, and the availability and
cost of acquiring rights in those patents necessary to the manufacture, use or sale of our products presently cannot be determined by us.
Third parties may have or may obtain valid and enforceable patents or proprietary rights that could block us from developing
products using our technology, including:
● certain patents and pending patent applications in the United States and foreign countries relating to particular receptors,
antigens and antigenic fragments targeted by our current drug candidates; and
● certain patents and pending patent applications in the United States and foreign countries relating to antibodies targeting certain
receptors and other targets including anti-ILT4 antibodies, anti-PD-1 antibodies, anti-SCF antibodies, anti-TSLP antibodies and
certain other antibodies and their sequences and uses.
In addition to the patents referred to in the previous paragraphs, there may be other patent applications and issued patents belonging
to competitors that may require us to alter our drug candidates and immunotherapeutic delivery systems, pay licensing fees or cease some
of our activities. If our drug candidates conflict with patents that have been or may be granted to competitors, universities or others, the
patent owners could bring legal action against us claiming damages and seeking to enjoin manufacturing and marketing of the patented
products. If any of these actions is successful, in addition to any potential liability for damages, we could be required to obtain a license
in order to continue to manufacture or market the affected products. There can be no assurance that we would prevail in any such action
or that any license required under any such third-party patent would be made available on acceptable terms or at all. We believe that there
may be significant litigation in the biotechnology industry regarding patent and other intellectual property rights. If we become involved
in that litigation, we could consume substantial resources.
Licenses
We have entered into significant license agreements relating to technologies that are being developed by us. Typically, institutions
have granted us an exclusive worldwide license (with right to sublicense) to make, use and sell products embodying the licensed
technology, subject to the reservation by the licensor of a non-exclusive right to use the technologies for non-commercial research
purposes. Generally, the term of each license is through the expiration of the last of the patents issued with respect to the technologies
covered by the license and/or a specified period from first commercial sale on a territory-by- territory basis. We have generally agreed to
use reasonable efforts to develop and commercialize licensed products and to achieve specified milestones and pay license fees,
milestone payments and royalties based on the net sales of the licensed products or to pay a percentage of sublicense income. If we
breach our obligations, the licensor has the right to terminate the license, and, in some cases, convert the license to a non-exclusive
license. Generally, we control and are responsible for the cost of defending the patent rights of the technologies that we license.
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Proprietary Rights
We also rely on unpatented technology, trade secrets and confidential information, and no assurance can be given that others will not
independently develop substantially equivalent information and techniques or otherwise gain access to our know-how and information,
or that we can meaningfully protect our rights in such unpatented technology, trade secrets and information. We require each of our
employees, consultants and advisors to execute a confidentiality agreement at the commencement of an employment or consulting
relationship with us. The agreements generally provide that all inventions conceived by the individual in the course of employment or in
providing services to us and all confidential information developed by, or made known to, the individual during the term of the
relationship shall be the exclusive property of us and shall be kept confidential and not disclosed to third parties except in limited
specified circumstances. There can be no assurance, however, that these agreements will provide meaningful protection for our
information in the event of unauthorized use or disclosure of such confidential information.
Government Regulation
Our activities and products are significantly regulated by a number of governmental entities, including the U.S. Food and Drug
Administration, or FDA, in the United States and by comparable authorities in other countries. These entities regulate, among other
things, the manufacture, testing, safety, effectiveness, labeling, documentation, advertising and sale of our products. We must obtain
regulatory approval from the FDA and comparable authorities in other countries, as applicable, for our drug candidates before we can
commercialize such drugs in the U.S. and foreign jurisdictions. Product development within this regulatory framework takes a number of
years and involves the expenditure of substantial resources. Many drug candidates that initially appear promising ultimately do not reach
the market because they are found to be unsafe or ineffective when tested. Our inability to commercialize a product would impair our
ability to earn future revenues.
FDA Approval Process
In the United States, the FDA regulates drugs and biological products under the Federal Food, Drug, and Cosmetic Act, or FDCA,
the Public Health Service Act, or PHSA, and implementing regulations. The process of obtaining regulatory approvals and the
subsequent compliance with appropriate federal, state, local and foreign statutes and regulations requires the expenditure of substantial
time and financial resources. Failure to comply with the applicable United States requirements at any time during the product
development process, approval process or after approval may subject an applicant to a variety of administrative or judicial sanctions,
such as the FDA’s refusal to approve pending applications, withdrawal of an approval, imposition of a clinical hold, issuance of untitled
or warning letters, product recalls, product seizures, total or partial suspension of production or distribution injunctions, fines, refusals of
government contracts, restitution, disgorgement of profits, civil penalties and criminal prosecution.
The process required by the FDA before a drug or biological product may be marketed in the United States generally involves the
following:
● completion of preclinical studies and formulation studies in compliance with the FDA’s good laboratory practice, or GLP,
regulations;
● submission to the FDA of an investigational new drug, or IND, application which must become effective before human clinical
trials may begin;
● approval by an independent institutional review board, or IRB, at each clinical site before each trial may be initiated;
● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices, or GCP, to
establish the safety and efficacy of the proposed drug or biological product for each indication;
● submission to the FDA of a new drug application, or NDA, or a biologics license application, or BLA, as applicable;
● satisfactory completion of an FDA advisory committee review, if applicable;
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● satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the product is produced to
assess compliance with cGMP requirements and to assure that the facilities, methods and controls are adequate to preserve the
drug’s identity, strength, quality and purity; and
● FDA review and approval of the NDA or BLA.
We expect that all of our clinical drug candidates will be subject to review as biological products under BLA standards.
Data obtained at any stage of testing is susceptible to varying interpretations, which could delay, limit or prevent regulatory
approval. Moreover, during the regulatory process, new or changed drug approval policies may cause unanticipated delays or rejection of
our product. We may not obtain necessary regulatory approvals within a reasonable period of time, if at all, or avoid delays or other
problems in testing our products. Moreover, even if we received regulatory approval for a product, the approval may require limitations
on use, which could restrict the size of the potential market for the product.
Clinical Trials
The FDA provides that human clinical trials may begin 30 days after receipt and review of an IND application, unless the FDA
requests additional information or changes to the study protocol within that period. An IND must be sponsored and filed for each of our
proposed drug candidates. Authorization to conduct clinical trials in no way assures that the FDA will ultimately approve the product.
Clinical trials are generally conducted in three sequential phases. In a Phase 1 trial, the product is given to a small number of patients to
test for safety (adverse effects), determine a recommended Phase 2 dose(s) and evaluate any signals of efficacy. Phase 2 trials are
conducted on a limited group of the target patient population; safety, optimal dosage and efficacy are studied. A Phase 3 trial is
performed in a large patient population, generally over a wide geographic area to provide evidence for the safety and efficacy of the
product. The FDA maintains and exercises oversight authority throughout the clinical trial process.
A product’s safety and effectiveness in one clinical trial is not necessarily indicative of its safety and effectiveness in another clinical
trial. Moreover, we may not discover all potential problems with a product even after completing clinical trials on it. Some of our
products and technologies have undergone only preclinical testing. As a result, we do not know whether they are safe or effective for
humans. Also, regulatory authorities may decide, contrary to our findings, that a product is unsafe or not as effective in actual use as its
clinical trial results indicated. This could prevent the product’s widespread use, require its withdrawal from the market or expose us to
liability. The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the
patients are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its
institution if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the drug has been associated with
unexpected serious harm to patients. Any such action could materially harm us. Clinical trials are critical to the success of our products
but are subject to unforeseen and uncontrollable delay, including delay in enrollment of patients. Any delay in clinical trials could delay
our commercialization of a product.
Marketing Approval
Assuming successful completion of the required clinical testing, the results of the preclinical and clinical studies, together with
detailed information relating to the product’s pharmacology, chemistry, manufacture, controls and proposed labeling, among other things,
are submitted to the FDA as part of an NDA or BLA requesting approval to market the product for one or more indications. FDA
approval of the NDA or BLA is required before marketing of the product may begin in the United States. Under federal law, the
submission of most NDAs and BLAs is additionally subject to a substantial application user fee and the sponsor of an approved NDA or
BLA is also subject to annual prescription drug program fees.
The FDA conducts a preliminary review of all NDAs and BLAs within the first 60 days after receipt before accepting them for filing
based on the agency’s threshold determination that they are sufficiently complete to permit substantive review. The FDA may request
additional information rather than accept an NDA or BLA for filing. In this event, the application must be resubmitted with the additional
information. The resubmitted application is also subject to review before the FDA accepts it for filing. Once the submission is accepted
for filing, the FDA begins an in-depth substantive review. The FDA has agreed to specified performance goals in the review of NDAs
and BLAs. Most such applications for non-priority products are reviewed within ten to twelve months after filing, and most applications
for priority review products, that is, drugs and biologics that the FDA determines represent a significant improvement over existing
therapy, are reviewed in six to eight months after filing. The review process may be extended by the FDA for three additional months to
consider certain late-submitted information or clarification regarding information already provided in
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the submission. The FDA may also refer applications for novel drugs or biological products or products that present difficult questions of
safety or efficacy to an advisory committee, typically a panel that includes clinicians and other experts, for review, evaluation and a
recommendation as to whether the application should be approved. The FDA is not bound by the recommendations of an advisory
committee, but it considers such recommendations carefully when making decisions.
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. In addition, before approving an
NDA or BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP and integrity of the clinical data
submitted.
The testing and approval processes require substantial time, effort and financial resources, and each may take many years to
complete. Data obtained from clinical activities are not always conclusive and may be susceptible to varying interpretations that could
delay, limit or prevent regulatory approval. The FDA may not grant approval on a timely basis, or at all. We may encounter difficulties or
unanticipated costs in our efforts to develop our drug candidates and secure necessary governmental approvals, which could delay or
preclude us from marketing our products.
After the FDA’s evaluation of the NDA or BLA and inspection of the manufacturing facilities, the FDA may issue an approval letter
or a complete response letter. An approval letter authorizes commercial marketing of the drug or biological product with specific
prescribing information for specific indications. A complete response letter generally outlines the deficiencies in the submission and may
require substantial additional testing or information in order for the FDA to reconsider the application. If and when those deficiencies
have been addressed to the FDA’s satisfaction in a resubmission of the NDA or BLA, the FDA will resume review and may subsequently
issue an approval letter. The FDA has committed to reviewing such resubmissions in two or six months depending on the type of
information included. Even with submission of this additional information, the FDA ultimately may decide that the application does not
satisfy the regulatory criteria for approval.
Even if the FDA approves a product, it may limit the approved indications for use for the product, require that contraindications,
warnings or precautions be included in the product labeling, require that post- approval studies, including Phase 4 clinical trials, be
conducted to further assess a drug’s safety after approval, require testing and surveillance programs to monitor the product after
commercialization, or impose other conditions, including distribution restrictions or other risk management mechanisms, which can
materially affect the potential market and profitability of the product. The FDA may prevent or limit further marketing of a product based
on the results of post-market studies or surveillance programs. After approval, many types of changes to the approved product, such as
changes in indications, manufacturing changes and labeling, are subject to further testing requirements and FDA review and approval.
Special Regulatory Procedures
Fast track designation — The FDA is required to facilitate the development and expedite the review of drugs and biologics that are
intended for the treatment of a serious or life-threatening disease or condition and that demonstrate the potential to address unmet
medical needs. Under the fast track program, the sponsor of a new drug or biologic candidate may request the FDA to designate the
product for a specific indication as a fast track product, concurrent with or after the filing of the IND for the drug candidate. A drug that
receives fast track designation is eligible for some or all of the following: (i) more frequent meetings with the FDA to discuss the drug’s
development plan and ensure collection of appropriate data needed to support drug approval; (ii) more frequent written communication
from the FDA about such things as the design of the proposed clinical trials and use of biomarkers; (iii) eligibility for accelerated
approval and priority review, if relevant criteria are met; and (iv) “Rolling Review,” which means that a drug company can submit
completed sections of its BLA or NDA for review by the FDA, rather than waiting until every section of the NDA or BLA is completed
before the entire application can be reviewed. This rolling review is available if the applicant provides and the FDA approves a schedule
for the submission of the remaining information and the applicant pays applicable user fees. However, the FDA’s time period goal for
reviewing a fast track application does not begin until the last section of the NDA or BLA is submitted. In addition, the fast track
designation may be withdrawn by the FDA if it believes that the designation is no longer supported by data emerging in the clinical trial
process.
Priority review — Under FDA policies, a drug candidate may be eligible for priority review. The priority review program provides
for expedited review or an NDA or BLA, typically within a six to eight month time frame from the time a complete application is
accepted for filing. Products regulated by the FDA’s Center for Drug Evaluation and Research, or CDER, are eligible
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for priority review if they provide a significant improvement compared to marketed products in the treatment, diagnosis or prevention of
a disease. Products regulated by the FDA’s Center for Biologics Evaluation and Research, or CBER, are eligible for priority review if
they provide a significant improvement in the safety or effectiveness of the treatment, diagnosis or prevention of a serious or life-
threatening disease. A fast track designated drug candidate could be eligible for priority review if supported by clinical data at the time of
the BLA or NDA submission.
Accelerated approval — Under the law and the FDA’s accelerated approval regulations, the FDA may approve a drug or biologic for
a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based on a surrogate
endpoint that is reasonably likely to predict clinical benefit. Surrogate endpoints can often be measured more easily or more rapidly than
clinical endpoints. A drug candidate approved on this basis is subject to rigorous post-marketing compliance requirements, including the
completion of Phase 4 or post-approval clinical trials to confirm the effect on the clinical endpoint. Failure to conduct required post-
approval studies, or confirm a clinical benefit during post-marketing studies, would allow the FDA to withdraw the drug from the market
on an expedited basis. All promotional materials for drug candidates approved under accelerated regulations are subject to prior review
by the FDA.
Breakthrough therapy designation — The FDA is also required to expedite the development and review of the application for
approval of drugs that are intended to treat a serious or life-threatening disease or condition where preliminary clinical evidence indicates
that the drug candidate may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Under the breakthrough therapy program, the sponsor of a new drug candidate may request that the FDA designate the drug candidate for
a specific indication as a breakthrough therapy concurrent with, or after, the filing of the IND for the drug candidate.
Orphan drug designation — Under the Orphan Drug Act, the FDA may grant orphan drug designation to a drug or biologic intended
to treat a rare disease or condition, which is generally defined as a disease or condition that affects fewer than 200,000 individuals in the
United States. Orphan drug designation does not convey any advantage in, or shorten the duration of, the regulatory review and approval
process. The first NDA or BLA applicant to receive FDA approval for a particular active ingredient to treat a particular disease with
FDA orphan drug designation is entitled to a seven-year exclusive marketing period in the United States for that product, for that
indication. During the seven-year exclusivity period, the FDA may not approve any other applications to market the same drug or
biologic for the same orphan indication, except in limited circumstances. Among the other benefits of orphan drug designation are tax
credits for certain research and a waiver of the NDA or BLA application user fee.
Pediatric Information
Under the Pediatric Research Equity Act of 2003, an NDA, BLA or supplement to an NDA or BLA must contain data that are
adequate to assess the safety and effectiveness of the drug or biological product for the claimed indications in all relevant pediatric
subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product is safe and effective.
The FDA may, on its own initiative or at the request of the applicant, grant deferrals for submission of some or all pediatric data until
after approval of the product for use in adults, or full or partial waivers from the pediatric data requirements. Under the Food and Drug
Administration Safety and Innovation Act, or FDASIA, the FDA has additional authority to take action against manufacturers not
adhering to pediatric study requirements. Unless otherwise required by regulation, the pediatric data requirements do not apply to
products with orphan drug designation.
Post Approval
Any drug or biological products manufactured or distributed by us 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.
The FDA may impose a number of post-approval requirements as a condition of approval of an NDA or BLA. For example, the
FDA may require post-marketing testing, including Phase 4 clinical trials, and surveillance to further assess and monitor the product’s
safety and effectiveness after commercialization. Regulatory approval of oncology products often requires that patients in clinical trials
be followed for long periods to determine the overall survival benefit of the drug or biologic.
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In addition, drug and biologic manufacturers and other entities involved in the manufacture and distribution of approved drugs and
biological products are required to register their establishments with the FDA and state agencies and are subject to periodic unannounced
inspections by the FDA and these state agencies for compliance with cGMP requirements. The FDA was also granted new inspection
authorities under FDASIA. Changes to the manufacturing process are strictly regulated and often 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 areas of production and quality control to maintain cGMP compliance.
Once an approval is granted, the FDA may withdraw the 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 trials to assess new safety risks or imposition of distribution or other restrictions under a Risk Evaluation and Mitigation Strategy
program. Other potential consequences include, among other things:
● restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product
recalls;
● fines, untitled and warning letters or holds on post-approval clinical trials;
● refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of
product license approvals;
● product seizure or detention, or refusal to permit the import or export of products; or
● consent decrees, injunctions or the imposition of civil or criminal prosecution.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on the market. Drugs and
biologics may be promoted only for the approved indications and in accordance with the provisions of the approved label. The FDA, the
Office of the Inspector General of Health and Human Services 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.
Biosimilars Law
The Biologics Price Competition and Innovation Act of 2009, or BPCIA, amended the PHSA to provide for an abbreviated approval
pathway for biological products that demonstrate biosimilarity to a previously-approved biological product. The BPCIA establishes
criteria for determining that a product is biosimilar to an already-licensed biologic, or reference product, and establishes a process by
which an abbreviated BLA for a biosimilar product is submitted, reviewed and approved. The BPCIA provides periods of exclusivity that
protect a reference product from biosimilars competition. Under the BPCIA, the FDA may not accept a biosimilar application for review
until four years after the date of first licensure of the reference product, and the biosimilar may not be licensed until 12 years after the
reference product’s approval. Additionally, the BPCIA establishes procedures by which the biosimilar applicant may provide information
about its application and product to the reference product sponsor, and by which information about potentially relevant patents is shared
and litigation over patents may proceed in advance of approval. The BPCIA also provides a period of exclusivity for the first biosimilar
to be determined by the FDA to be interchangeable with the reference product. The BPCIA applies to our drug candidates and could be
applied to allow approval of biosimilars to our products.
21st Century Cures Act
On December 13, 2016, Congress passed the 21st Century Cures Act, or the Cures Act. The Cures Act is designed to modernize and
personalize health care, spur innovation and research, and streamline the discovery and development of new therapies through increased
federal funding of particular programs. It authorizes increased funding for the FDA to spend on innovation projects, including for certain
oncology- directed research. The new law also amends the Public Health Service Act to reauthorize and expand funding for the National
Institutes of Health.
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The Cures Act also authorizes funding for the “Cancer Moonshot” initiative. The Cancer Moonshot initiative’s strategic goals
encourage inter-agency cooperation and fund research and innovation to catalyze new scientific breakthroughs, bring new therapies to
patients and strengthen prevention and diagnosis. This initiative aims to stimulate drug development through the creation of a public-
private partnership with 20 to 30 pharmaceutical and biotechnology companies to expedite cancer researchers’ access to investigational
agents and approved drugs. This partnership is designed to permit researchers to obtain drugs and other technologies from a preapproved
“formulary” list without having to negotiate with each company for individual research projects. We will continue to monitor these
developments to assess their potential impacts on our business.
Companion Diagnostic Review and Approval
Our drug candidates may rely on the use of a companion diagnostic. Companion diagnostics are subject to regulation by the FDA
and comparable foreign regulatory authorities as medical devices and require separate clearance or approval prior to their
commercialization. Based on recent FDA guidance documents and the FDA’s past treatment of companion diagnostics, we believe that
the FDA will likely require one or more of our in vitro companion diagnostics to obtain Premarket Approval Application, or PMA, in
conjunction with approval of the related drug candidate. The receipt and timing of PMA approval may have a significant effect on the
receipt and timing of commercial approval for such drug candidates.Currently we rely on third-party collaborators to develop companion
diagnostics for our drug candidates.
The PMA process is similar to the NDA and BLA processes and is costly, lengthy and uncertain. PMA applications must be
supported by valid scientific evidence, which typically requires extensive data, including technical, preclinical, clinical and
manufacturing data, to demonstrate to the FDA’s satisfaction the safety and effectiveness of the device. For diagnostic tests, a PMA
application typically includes data regarding analytical and clinical validation studies. As part of its review of the PMA, the FDA will
conduct a pre-approval inspection of the manufacturing facility or facilities to ensure compliance with the Quality System Regulation, or
QSR, which requires manufacturers to follow design, testing, control, documentation and other quality assurance procedures. If the FDA
evaluations of both the PMA application and the manufacturing facilities are favorable, the FDA will either issue an approval letter or an
approvable letter, which usually contains a number of conditions that must be met in order to secure the final approval of the PMA. If the
FDA’s evaluation of the PMA or manufacturing facilities is not favorable, the FDA will deny approval of the PMA or issue a not
approvable letter. A not approvable letter will outline the deficiencies in the application and, where practical, will identify what is
necessary to make the PMA approvable. The FDA may also determine that additional clinical trials are necessary, in which case the
PMA approval may be delayed while the trials are conducted and then the data submitted in an amendment to the PMA.
Furthermore, even after PMA approval is obtained, numerous regulatory requirements apply to the manufacturer of the companion
diagnostic. The FDA enforces these requirements by inspection and market surveillance. These requirements include: the QSR, labeling
regulations, the FDA’s general prohibition against promoting products for unapproved or “off label” uses, the medical device reporting
regulation, and the reports of corrections and removals regulation. If the FDA finds a violation, it can institute a wide variety of
enforcement actions, ranging from a public warning letter to more severe sanctions such as: fines, injunctions and civil penalties; recall
or seizure of products; operating restrictions, partial suspension or total shutdown of production; refusing requests for PMA of new
products; and withdrawing PMAs already granted.
Federal and State Fraud and Abuse, Data Privacy and Security and Transparency Laws
In addition to FDA restrictions on marketing and promotion of pharmaceutical products, several other types of federal and state laws
have been applied to restrict certain marketing business practices in the biopharmaceutical and medical device industries in recent years.
These laws include, without limitation, state and federal anti-kickback statutes and false claims statutes and false claims laws, data
privacy and security laws, as well as transparency laws regarding payments or other items of value provided to health care providers.
Applicable state law may be broader in scope than federal law and may apply regardless of payor, in addition to items and services
reimbursed under Medicaid and other state programs. If our operations are found to be in violation of any of the health regulatory laws
described above or any other laws that apply to us, we may be subject to penalties, including potentially significant criminal and civil
and/or administrative penalties, damages, fines, disgorgement, imprisonment, exclusion from participation in government health care
programs, contractual damages, reputational harm, administrative burdens, diminished profits and future earnings, and the curtailment or
restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations. To
the extent that any of our products are sold in a foreign country, we may be subject to similar foreign laws, which may include, for
instance, applicable post-marketing requirements, including safety surveillance, anti-fraud and abuse laws and implementation of
corporate compliance programs and reporting of payments or transfers of value to health care professionals.
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In addition, the United States Foreign Corrupt Practices Act, or FCPA, prohibits corporations and individuals from engaging in
certain activities to obtain or retain business or to influence a person working in an official capacity. It is illegal to pay, offer to pay or
authorize the payment of anything of value to any official of another country, government staff member, political party or political
candidate in an attempt to obtain or retain business or to otherwise influence a person working in that capacity. In many countries, the
health care professionals we may interact with may meet the FCPA’s definition of a foreign government official.
Foreign Regulation
In order to market any therapeutic or diagnostic product outside of the United States, we need to comply with numerous and varying
regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials, marketing
authorization, commercial sales and distribution of our products. Whether or not we obtain FDA approval for a product, we need to
obtain the necessary approvals by the comparable regulatory authorities of foreign countries before we can commence clinical trials or
marketing of the product in those countries. The approval process varies from country to country and can involve additional product
testing and additional administrative review periods. The time required to obtain approval in other countries might differ from and be
longer than that required to obtain FDA approval. Regulatory approval in one country does not ensure regulatory approval in another, but
a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others.
Under the EU regulatory system, we will submit most of our marketing authorization applications under the centralized procedure.
The centralized procedure is compulsory for medicines produced by biotechnology, or are for the treatment of cancer, or officially
designated as ‘orphan medicines.’ The centralized procedure provides for the grant of a single marketing authorization that is valid for all
EU member states. As in the United States, we may apply for designation of a drug candidate as an orphan drug for the treatment of a
specific indication in the EU before the application for marketing authorization is made. The European Medicines Agency (“EMA”)
grants orphan medicinal product designation to promote the development of products that may offer therapeutic benefits for life-
threatening or chronically debilitating conditions affecting not more than five in 10,000 people in the EU. Orphan drugs in Europe enjoy
economic and marketing benefits, including a 10-year market exclusivity period for the approved indication, but not for the same
product, unless another applicant can show that its product is safer, more effective or otherwise clinically superior to the orphan-
designated product.
Other Regulatory Processes
From time to time, legislation is drafted, introduced and passed in Congress that could significantly change the statutory provisions
governing the testing, approval, manufacturing and marketing of products regulated by the FDA.
In addition to new legislation, FDA regulations and policies are often revised or interpreted by the agency in ways that may
significantly affect our business and our products. It is impossible to predict whether further legislative changes will be enacted or
whether FDA regulations, guidance, policies or interpretations will change or what the effect of such changes, if any, may be.
Third-Party Payor Coverage and Reimbursement
Significant uncertainty exists as to the coverage and reimbursement status of any drug products for which we obtain regulatory
approval. Sales of any of our drug candidates, if approved, will depend, in part, on the extent to which the costs of the drugs will be
covered by third-party payors, including government health programs such as Medicare and Medicaid, as well as commercial health
insurers, such as managed care organizations. The process for determining reimbursement rates is separate from the payor coverage
decision. Therefore, despite obtaining coverage, reimbursement rates may be lower than expected, which can result in larger out-of-
pocket payments for the patient.
In order to secure coverage and reimbursement for any drug that might be approved for sale, we need to conduct analyses and
pharmaco-economic studies in order to demonstrate the incremental medical benefit over and above the generally-accepted standard of
care and cost-effectiveness of the drug. Our drug candidates may not be considered medically necessary, provide insufficient incremental
medical benefit, or may not be deemed cost-effective. A payor’s decision to provide coverage for a drug product does not imply that an
adequate reimbursement rate will be approved.
The containment of health care costs has become a priority of federal, state and foreign governments, and the prices of drugs have
been a focus in this effort. Given that the Inflation Reduction Act is now in place, potential implications for the biopharma industry are
being assessed. In the meantime, third-party payors are increasingly challenging the prices charged for medical products and services
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and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. If
these third-party payors do not consider our drugs to be cost-effective compared to other available therapies, they may not cover our
drugs after approval as a benefit under their plans or, if they do, the level of reimbursement and/or restrictions in formulary placement
may be such that they would significantly limit projected sales volumes. In addition to third-party payors, we will also need to negotiate
formulary placement with hospitals, health systems and certain independent delivery networks. Such negotiations may be more
protracted than anticipated and may be compromised because of similar considerations, relating to insufficient incremental medical
benefit and/or cost-effectiveness.
Pricing and reimbursement schemes vary widely from country to country. For example, certain EU member states may approve a
specific price and volume for a drug product after which incremental revenues or profits need to be paid back by way of rebates. They
may also institutionalize utilization restrictions, curb physicians’ drug budgets, provide conditional reimbursement schemes that require
additional evidence to be generated post-marketing authorization, etc. The downward pressure on health care costs in general, including
prescription drugs, has been evident in EU markets for some time and is now a major focus of federal and state governments in the U.S.
As a result, increasingly high barriers are being erected to the pricing and reimbursement of new drugs, despite regulatory efforts to bring
drugs to market sooner. Cross- border trade has existed for some time in the EU, allowing pharmacies in one country to import, at a
lower price, drug from another country, further exerting pricing pressures across the EU. A proposal to allow importation of less
expensive drugs from Canada to the U.S. has been under consideration in U.S. Congress. There can be no assurance that any country that
has price controls or reimbursement limitations for drug products will allow favorable reimbursement and pricing arrangements for any
of our drugs.
The marketability of any drugs for which we receive regulatory approval for commercial sale may suffer if third-party payors and/or
hospital administrators fail to provide adequate coverage, reimbursement or formulary placement. Coverage policies, third-party
reimbursement rates and drug pricing regulations may change in the future. In addition, the States may continue to consider legislation of
their own which could further restrict the ability to freely price drugs and/or curb utilization in the U.S. Even if favorable coverage and
reimbursement status is attained for one or more drugs for which we receive regulatory approval, less favorable coverage policies and
reimbursement rates may be implemented in the future.
Employees
As a mission driven organization, we believe the engagement and dedication of our employees is central to our success and employ
talented individuals who have the skills and expertise to help us achieve our goals.
As of December 31, 2022, we had 148 full-time employees, 26 of whom have Ph.D. and/or M.D. degrees. Of these employees, 123
were engaged in or directly support research and development activities. We consider our relationship with our employees to be good.
We believe that our success depends in large part on our ability to attract and retain experienced and skilled employees. We endeavor
to provide competitive compensation and benefits packages designed to attract, retain and reward talented individuals who possess the
skills necessary to support our business objectives, assist in the achievement of our strategic goals and increase stockholder value. We
employ a pay for performance philosophy. Annual salary increases, incentive bonuses and stock option grants are available to all
employees and are based on merit and include individual and corporate performance factors.
Much of our success is rooted in the diversity of our teams and our commitment to inclusion. We value diversity at all levels and
continue to focus on extending our diversity and inclusion initiatives across our entire workforce. We believe that our business benefits
from the different perspectives that a diverse workforce brings.
We are committed to the health, safety and well-being of our employees at all times. We follow federal, state and local rules and
guidelines to ensure the safety of our workforce and provide resources to assist our employees in managing their overall physical and
mental health. As a result of the COVID-19 pandemic, we have implemented additional safety procedures to protect our employees.
Research and Development
We have dedicated a significant portion of our resources to our efforts to develop our drug candidates. We incurred research and
development expenses of $82.3 million, $53.3 million and $42.5 million during the years ended December 31, 2022, 2021 and 2020,
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respectively. We anticipate that a significant portion of our operating expenses will continue to be related to research and development in
2023 as we continue to advance our drug candidates through clinical development.
Corporate and Available Information
We are incorporated in Delaware. Our website is located at http://www.celldex.com. On our website, investors can obtain, free of
charge, a copy of our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, our Code of
Conduct and Business Ethics, including disclosure related to any amendments or waivers thereto, other reports and any amendments
thereto filed or furnished pursuant to Section 13(a) or 15(d) of the Exchange Act of 1934, as amended, as soon as reasonably practicable
after we file such material electronically with, or furnish it to, the Securities and Exchange Commission, or the SEC. None of the
information posted on our website is incorporated by reference into this Annual Report. The SEC also maintains a website at
http://www.sec.gov that contains reports, proxy and information statements and other information regarding us and other companies that
file materials with the SEC electronically.
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Item 1A. RISK FACTORS
You should consider carefully these risk factors together with all of the information included or incorporated by reference in this
Annual Report in addition to our financial statements and the notes to our financial statements. This section includes forward-looking
statements.
The following is a discussion of the risk factors that we believe are material to us at this time. These risks and uncertainties are not
the only ones facing us, and there may be additional matters that we are unaware of or that we currently consider immaterial. All of these
could adversely affect our business, results of operations, financial condition and cash flows.
Summary of Risk Factors
Risks Related to Our Financial Condition and Capital Requirements
● Risks related to our need for additional capital to fund our operations.
● Risks related to the Merger Agreement and related Settlement Agreement with Kolltan.
● Risks related to U.S. federal income tax reform.
Risks Related to Development and Regulatory Approval of Drug Candidates
● Risks related to our ability to fund and complete the research and development activities and obtain regulatory approval for our
program assets.
● Risks related to the extensive regulatory scrutiny to which we are subject.
● Risks related to our ability to commence, enroll, manage and complete our clinical trials.
● Risk of serious adverse or unacceptable side effects identified related to our drug candidates.
● We may enter collaboration agreements for our lead drug candidates that may not meet our expectations.
Risks Related to Commercialization of Our Drug Candidates
● Risks related to delays, difficulties or unanticipated costs in establishing sales, marketing and distribution capabilities.
● Risks related to the acceptance of our drug candidates by physicians, patients and third-party payors.
● Risks related to reimbursement decisions by third-party payors.
● Risks, including the terms of FDA approval, that could affect the demand for and sales and profitability of any of our drug
candidates.
● Risks related to the failure to obtain regulatory approvals in foreign jurisdictions and risks related to international operations if
we do obtain regulatory approval in foreign jurisdictions.
Risks Related to Reliance on Third Parties
● Risks related to our reliance on third parties.
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Risks Related to Business Operations
● Risks related to strategic transactions.
● Risks related to managing our growth.
● Risks related to our ability to integrate and modify our technologies to create new drugs.
● Risks related to computer systems that we and third parties use and potential security breaches.
● Risks related to hazardous materials.
● Risks related to product liability claims.
● Risks related to the global economy and supply chain disruptions.
Risks Related to Intellectual Property
● Risks related to intellectual property.
Regulatory Risks
● Risks related to the regulatory approval process for our drugs.
● Risks related to changes in product candidate manufacturing or formulation.
● Risks related to our compliance with laws and regulations.
Risks Related to Our Capital Stock
● Risks related to our history of losses and uncertainty of future profitability.
● Risks relates to the volatility of our common stock.
● Risks related to our use of our net operating loss carryforwards.
General Risk Factors
● Risks related to internal controls over financial reporting.
● Risks that our competitors may develop technologies that make ours obsolete.
● Risks related to health epidemics and outbreaks.
● Risks related to the loss of our key executives and scientists.
● Risks that our employees may engage in misconduct or other improper activities.
● Risks related to our compliance with the Nasdaq Listing Rules.
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Risks Related to Our Financial Condition and Capital Requirements
We currently have no product revenue and will need to raise capital to operate our business.
To date, we have generated no product revenue and cannot predict when and if we will generate product revenue. We had an
accumulated deficit of $1.3 billion as of December 31, 2022. Until, and unless, we complete clinical trials and other development
activity, and receive approval from the FDA and other regulatory authorities, for our drug candidates, we cannot sell our drugs and will
not have product revenue. We expect to spend substantial funds to continue the research, development and testing of our products that are
in the preclinical and clinical testing stages of development and to prepare to commercialize products in anticipation of FDA approval.
Therefore, for the foreseeable future, we will have to fund all of our operations and development expenditures from cash on hand, equity
or debt financings, licensing fees and grants. Additional financing will be required to meet our liquidity needs. If we do not succeed in
raising additional funds on acceptable terms, we might not be able to complete planned preclinical and clinical trials or obtain approval
of any drug candidates from the FDA and other regulatory authorities. In addition, we could be forced to discontinue product
development, reduce or forego sales and marketing efforts, forego attractive business opportunities or curtail operations. Any additional
sources of financing could involve the issuance of our equity securities, which would have a dilutive effect on our stockholders. No
assurance can be given that additional financing will be available to us when needed on acceptable terms, or at all.
We cannot be certain that we will achieve or sustain profitability in the future. Failure to achieve profitability could diminish our
ability to sustain operations, pay dividends on our common stock, obtain additional required funds and make required payments on our
present or future indebtedness.
We expect to incur future losses and we may never become profitable.
We have incurred operating losses of $115.2 million, $71.2 million and $63.4 million during 2022, 2021 and 2020, respectively, and
expect to incur an operating loss in 2023 and beyond. We believe that operating losses will continue in 2023 and beyond because we are
planning to incur significant costs associated with the development of our drug candidates. During the years ended December 31, 2022,
2021 and 2020, we incurred $23.8 million, $8.0 million and $4.9 million in clinical trial expense and $4.5 million, $1.7 million and $1.2
million in contract manufacturing expense. Our net losses have had and will continue to have an adverse effect on, among other things,
our stockholders’ equity, total assets and working capital. We expect that losses will fluctuate from quarter to quarter and year to year,
and that such fluctuations may be substantial. We cannot predict when we will become profitable, if at all.
We will need additional capital to fund our operations, including the development, manufacture and potential commercialization of
our drug candidates. If we do not have or cannot raise additional capital when needed, we may be unable to develop and ultimately
commercialize our drug candidates successfully.
We expect to incur significant costs as we develop our drug candidates. The continuing development and commercialization of our
drug candidates requires additional capital beyond our current resources. As of December 31, 2022, we had cash, cash equivalents and
marketable securities of $305.0 million. During the next twelve months and beyond, we will take further steps to raise additional capital
to fund our long-term liquidity needs. Our capital raising activities may include, but may not be limited to, one or more of the following:
● licensing of drug candidates with existing or new collaborative partners;
● possible business combinations;
● issuance of debt; or
● issuance of common stock or other securities via private placements or public offerings.
While we may seek capital through a number of means, there can be no assurance that additional financing will be available on
acceptable terms, if at all, and our negotiating position in capital-raising efforts may worsen as existing resources are used. There is also
no assurance that we will be able to enter into further collaborative relationships. Additional equity financing may be dilutive to our
stockholders; debt financing, if available, may involve significant cash payment obligations and covenants that restrict our ability to
operate as a business; and licensing or strategic collaborations may result in royalties or other terms which reduce our economic potential
from drug candidates under development. If we are unable to raise the funds necessary to meet our liquidity needs, we may
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have to delay or discontinue the development of one or more programs, discontinue or delay ongoing or anticipated clinical trials,
discontinue or delay our commercial manufacturing efforts, discontinue or delay our efforts to expand into additional indications for our
drug product candidates, license out programs earlier than expected, raise funds at significant discount or on other unfavorable terms, if
at all, or sell all or part of our business.
Our stockholders may be subject to substantial dilution if we elect to pay future milestone consideration to the former Kolltan
stockholders in shares of common stock. If we elect to pay future milestone consideration in cash, we would likely need to raise
additional capital.
In connection with the agreement pursuant to which we acquired Kolltan in 2016 (the “Merger Agreement”) as modified by the
definitive settlement agreement (the “Settlement Agreement”) we entered on July 15, 2022 related to litigation arising from the Kolltan
merger, in the event that certain specified milestones related to the successful completion of a Phase 2 clinical trial of CDX-0159 or
regulatory approval by the United States Food and Drug Administration or European Medicines Agency of certain drug candidates are
achieved, we will be required to pay to the former stockholders of Kolltan milestone payments, which milestone payments may be made,
at our sole election, in cash, in shares of our common stock or a combination of both, subject to provisions of the Merger Agreement.
Pursuant to the Settlement Agreement, as of December 31, 2022 we may be obligated to make milestone payments of up to $65,000,000.
If we elect to issue shares of our common stock to make these milestone payments, you will experience further dilution.
We may require additional capital to fund any milestone payments in cash, depending on the facts and circumstances at the time
such payments become due. The number of shares of our common stock issuable in connection with a milestone payment, if any, will be
determined based on the average closing price per share of our common stock for the five trading day period ending three calendar days
prior to the achievement of such milestone. If we elect to pay the Kolltan Milestones in shares of our common stock, our stockholders
would experience substantial dilution.
U.S. federal income tax reform could adversely affect us.
On March 27, 2020, in response to COVID-19, U.S. Congress enacted the Coronavirus Aid, Relief, and Economic Security Act (the
“CARES Act”). The CARES Act modified the Tax Cuts and Jobs Act (“TCJA”) by, among other things, eliminating the limitation on the
deduction of net operating losses to 80% of current year taxable income for tax years beginning before January 1, 2021, and increasing
the amount of interest expense that may be deducted from 30% to 50% of adjusted taxable income for tax years beginning in 2019 or
2020. We continue to examine the impact of this tax reform legislation, as well as any additional regulatory guidance that may be issued,
may have on our business. For example, change of administration could result in additional tax legislative activity that could have a
material adverse effect on the Company.
Risks Related to Development and Regulatory Approval of Drug Candidates
Our long-term success depends heavily on our ability to fund and complete the research and development activities and obtain
regulatory approval for our program assets.
Only a small minority of all research and development programs ultimately result in commercially successful drugs. Clinical failure
can occur at any stage of clinical development. Clinical and preclinical trials may produce negative or inconclusive results, and we may
decide, or regulators may require us, to conduct additional clinical or preclinical trials. In addition, data obtained from trials are
susceptible to varying interpretations, and regulators may not interpret our data as favorably as we do, which may delay, limit or prevent
regulatory approval. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will generate the same
results or otherwise provide adequate data to demonstrate the efficacy and safety of a drug candidate. As part of development, we also
must show that we can formulate and manufacture our product candidates in compliance with regulatory requirements.
We will need substantial additional financing to complete the development of our drug candidates and comply with the regulatory
requirements governing this process. Further, even if we complete the development of our drug candidates and gain marketing approvals
from the FDA and comparable foreign regulatory authorities in a timely manner, we cannot be sure that such drug candidates will be
commercially successful in the pharmaceutical market. If the results of clinical trials, the anticipated or actual timing of marketing
approvals, or the market acceptance of any of our drug candidates, if approved, do not meet the expectations of investors or public
market analysts, the market price of our common stock would likely decline.
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Our drug candidates are subject to extensive regulatory scrutiny.
All of our drug candidates are at various stages of development, and our activities and drug candidates are significantly regulated by
a number of governmental entities, including the FDA in the United States and by comparable authorities in other countries. These
entities regulate, among other things, the manufacture, testing, safety, effectiveness, labeling, documentation, advertising and sale of
drugs and drug candidates. We or our partners must obtain regulatory approval for a drug candidate in all of these areas before we can
commercialize any of our drug candidates. Product development within this regulatory framework takes a number of years and involves
the expenditure of substantial resources. This process typically requires extensive preclinical and clinical testing, which may take longer
or cost more than we anticipate, and may prove unsuccessful due to numerous factors. Many drug candidates that initially appear
promising ultimately do not reach the market because they are found to be unsafe or ineffective when tested. Companies in the
pharmaceutical, biotechnology and immunotherapeutic drug industries have suffered significant setbacks in advanced clinical trials, even
after obtaining promising results in earlier trials. Our inability to commercialize a drug candidate would impair our ability to earn future
revenues.
If our drug candidates do not pass required tests for safety and effectiveness, we will not be able to obtain regulatory approval and
derive commercial revenue from them.
In order to succeed, we will need to obtain regulatory approval for our drug candidates. The FDA has not approved any of our drug
candidates for sale to date. Our drug candidates are in various stages of preclinical and clinical testing. Preclinical tests are performed at
an early stage of a product’s development and provide information about a drug candidate’s safety and effectiveness before initiating
human clinical trials. Preclinical tests can last years. If a product passes its preclinical tests satisfactorily and we determine that further
development is warranted, we would file an IND application for the product with the FDA, and, if the FDA gives its approval, we would
begin Phase 1 clinical tests. Phase 1 testing generally lasts between 6 and 24 months. If Phase 1 test results are satisfactory and the FDA
gives its approval, we can begin Phase 2 clinical tests. Phase 2 testing generally lasts between 6 and 36 months. If Phase 2 test results are
satisfactory and the FDA gives its approval, we can begin Phase 3 pivotal studies. Phase 3 studies generally last between 12 and 48
months. Once clinical testing is completed and a BLA or NDA is filed with the FDA, it may take more than a year to receive FDA
approval.
In all cases we must show that a drug candidate is both safe and effective before the FDA, or drug approval agencies of other
countries where we intend to sell the product, will approve it for sale. Our research and testing programs must comply with drug
approval requirements both in the United States and in other countries, since we are developing our drug candidates with the intention to,
or could later decide to, commercialize them both in the U.S. and abroad. A product may fail for safety or effectiveness at any stage of
the testing process. A major risk we face is the possibility that none of our products under development will come through the testing
process to final approval for sale, with the result that we cannot derive any commercial revenue from them after investing significant
amounts of capital in multiple stages of preclinical and clinical testing.
Success in early clinical trials does not ensure that later clinical trials will be successful, and we cannot assure you that any of the
clinical trials that we may conduct will demonstrate consistent or adequate efficacy and safety to obtain regulatory approval.
The results of preclinical studies and early clinical trials may not be predictive of the results of later- stage clinical trials, and interim
results of a clinical trial do not necessarily predict final results. Preclinical and clinical data are susceptible to various interpretations and
analyses, and many companies that have believed their drug candidates performed satisfactorily in preclinical studies and early-stage
clinical trials have nonetheless failed to replicate such results in later-stage clinical trials and subsequently failed to obtain marketing
approval. Drug candidates in later-stage clinical trials may fail to show the desired safety and efficacy despite having progressed through
preclinical and initial clinical trials, even if certain analyses of primary or secondary endpoints in those early trials showed trends
towards efficacy. Later-stage clinical trials with larger numbers of patients or longer durations of therapy may also reveal safety concerns
that were not identified in earlier smaller or shorter trials. Our failure to demonstrate efficacy and safety data sufficient to support
marketing approval for any of our other drug candidates would substantially harm our business, prospectus, financial condition and
results of operations.
Product testing is critical to the success of our drug candidates but subject to delay or cancellation if we have difficulty enrolling
patients.
As our portfolio of drug candidates moves from preclinical testing to clinical testing, and then through progressively larger and more
complex clinical trials, we will need to enroll an increasing number of patients with the appropriate characteristics. At times we
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have experienced difficulty enrolling patients, and we may experience more difficulty as the scale of our clinical testing program
increases. The factors that affect our ability to enroll patients are largely uncontrollable and include principally the following:
● the nature of the clinical test;
● the size of the patient population;
● patients’ willingness to receive a placebo or less effective treatment on the control arm of a clinical study;
● the distance between patients and clinical test sites; and
● the eligibility criteria for the trial.
If we cannot enroll patients as needed, our costs may increase, or we may be forced to delay or terminate testing for a product.
We may have delays in commencing, enrolling and completing our clinical trials, and we may not complete them at all.
We have not completed the clinical trials necessary to obtain FDA approval to market any of our drug candidates in development.
Clinical trials for our products in development may be delayed or terminated as a result of many factors, including the following:
● inability to reach agreements on acceptable terms with prospective contract research organizations (CROs) and trial sites, the
terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;
● difficulty in enrolling patients in our clinical trials;
● inability to maintain necessary supplies of study drug and comparator to maintain predicted enrollment rates at clinical trial
sites;
● patients failing to complete clinical trials due to dissatisfaction with the treatment, side effects or other reasons;
● failure by regulators to authorize us to commence a clinical trial;
● suspension or termination by regulators of clinical research for many reasons, including concerns about patient safety, bias or
failure of our contract manufacturers to comply with cGMP requirements;
● delays or failure to obtain clinical supply for our products necessary to conduct clinical trials from contract manufacturers,
including commercial grade-clinical supply for our Phase 3 clinical trials;
● inability to identify and maintain a sufficient number of trial sites, many of which may already be engaged in other clinical trial
programs, including some that may be for the same indication as our product candidates;
● drug candidates demonstrating a lack of efficacy during clinical trials;
● inability to continue to fund clinical trials or to find a partner to fund the clinical trials;
● competition with ongoing clinical trials and scheduling conflicts with participating clinicians; and
● delays in completing data collection and analysis for clinical trials.
Any delay or failure to commence, enroll or complete clinical trials, fulfill regulatory requirements and obtain FDA approval for our
drug candidates could have a material adverse effect on our cost to develop and commercialize, and our ability to generate revenue from,
a particular drug candidate.
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If serious adverse or unacceptable side effects are identified during the development of our drug candidates, such events could
prevent us from obtaining regulatory approval or achieving market acceptance of our drug candidates, and we may need to abandon
or limit our development of some of our drug candidates.
If our drug candidates are associated with serious adverse events or undesirable side effects in clinical trials or have characteristics
that are unexpected, such events could prevent us from obtaining regulatory approval or achieving market acceptance of our drug
candidates, and we may need to abandon their development or limit development to more narrow uses or subpopulations in which the
serious adverse events, undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-
benefit perspective. In pharmaceutical development, many drugs that initially show promise in early-stage testing are later found to cause
side effects that prevent further development of the drug. Currently marketed therapies for the treatment of cancer and inflammatory
diseases are generally limited to some extent by their toxicity. In addition, some of our drug candidates would be chronic therapies or be
used in pediatric populations, for which safety concerns may be particularly important. Use of our drug candidates as monotherapies may
also result in adverse events consistent in nature with those associated with other marketed therapies. In addition, when used in
combination with other marketed therapies, our drug candidates may exacerbate adverse events associated with the marketed therapy.
Our drug candidates, including barzolvolimab, are monoclonal antibodies, which are biologics. Side effects from biologics may
include hypersensitivity; severe reactions such as anaphylaxis or cytokine release syndrome; immune-mediated adverse reactions that
may occur in any organ system or tissue, such as pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, and dermatologic reactions;
as well as infusion-related reactions, cellulitis, sepsis, pneumonia, urinary tract infection, fatigue, rash, and diarrhea.
Most biologics, including some of our drug candidates, are injected, either subcutaneously or intravenously. There are risks inherent
in subcutaneous injections, such as injection-site reactions (including redness, itching, swelling, pain, and tenderness) and other side
effects. In addition, there are risks inherent in intravenous administration such as infusion-related reactions (including nausea, pyrexia,
rash, and dyspnea). These and other complications or side effects could harm further development and/or commercialization of our
antibody-based products and product candidates utilizing this method of administration.
In addition to the safety, efficacy, manufacturing, and regulatory hurdles faced by our product candidates, the administration of
biologics frequently causes an immune response, sometimes resulting in the creation of antibodies against the drug candidate which can
impact the safety and/or efficacy associated with the treatment.
We may expend our resources to pursue a particular drug candidate or indication and forgo the opportunity to capitalize on drug
candidates or indications that may ultimately be more profitable or for which there is a greater likelihood of success.
Because we have limited financial and managerial resources, we intend to focus on developing drug candidates for specific
indications that we identify as most likely to succeed, in terms of both their potential for regulatory approval and commercialization. As a
result, we may forego or delay pursuit of opportunities with other drug candidates or for other indications that may prove to have greater
commercial potential.
Our resource allocation decisions may cause us to fail to capitalize on viable commercial drugs or profitable market opportunities.
Our spending on current and future research and development programs and drug candidates for specific indications may not yield any
commercially viable drug candidates. If we do not accurately evaluate the commercial potential or target market for a particular drug
candidate, we may relinquish valuable rights to that drug candidate through collaboration, licensing or other royalty arrangements in
cases in which it would have been more advantageous for us to retain sole development and commercialization rights to the drug
candidate.
We may be unable to manage multiple late-stage clinical trials for a variety of drug candidates simultaneously.
As our current clinical trials progress, we may need to manage multiple late-stage clinical trials simultaneously in order to continue
developing all of our current products. The management of late-stage clinical trials is more complex and time consuming than early-stage
trials. Typically, early-stage trials involve several hundred patients in no more than 10 to 30 clinical sites. Late-stage (Phase 3) trials may
involve up to several thousand patients in up to several hundred clinical sites and may require facilities in several countries. Therefore,
the project management required to supervise and control such an extensive program in a compliant manner is substantially larger than
early-stage programs. As the need for these resources is not known until some months before the trials begin, it is necessary to recruit
large numbers of experienced and talented individuals very quickly. If the labor market does not allow this
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team to be recruited quickly, the sponsor is faced with a decision to delay the program or to initiate it with inadequate management
resources. This may result in recruitment of inappropriate patients, inadequate monitoring of clinical investigators and inappropriate
handling of data or data analysis. Consequently, it is possible that conclusions of efficacy or safety may not be acceptable to permit filing
of a BLA or NDA for any one of the above reasons or a combination of several.
Failure to successfully validate, develop and obtain regulatory approval for companion diagnostics for our drug candidates, if
needed, could harm our drug development strategy and operational results.
As an element of our clinical development approach, we may seek to screen and identify subsets of patients that express a certain
biomarker or that have a certain genetic alteration who may derive meaningful benefit from our development drug candidates. To achieve
this, one or more of our drug development programs may be dependent on the development and commercialization of a companion
diagnostic by us or by third-party collaborators. Companion diagnostics are developed in conjunction with clinical programs for the
associated drug candidate. Companion diagnostics are subject to regulation as medical devices and must themselves be approved for
marketing by the FDA or certain other foreign regulatory agencies before the related drug candidate may be commercialized. The
approval of a companion diagnostic as part of the product label will limit the use of the drug candidate to only those patients who express
the specific biomarker it was developed to detect. We or our third-party collaborators may also experience delays in developing a
sustainable, reproducible and scalable manufacturing process or transferring that process to commercial partners or negotiating insurance
reimbursement for such companion diagnostic, all of which may prevent us from completing our clinical trials or commercializing our
drugs on a timely or profitable basis, if at all.
We and our third-party collaborators may encounter difficulties in developing and obtaining approval for these companion
diagnostics. Any delay or failure by us or third-party collaborators to develop or obtain regulatory approval of a companion diagnostic
could delay or prevent approval of our related drug candidates or, if regulatory approval is obtained, delay or limit our ability to
commercialize our related drug candidates.
Any delay in obtaining regulatory approval would have an adverse impact on our ability to earn future revenues.
It is possible that none of the drug candidates that we develop will obtain the regulatory approvals necessary for us to begin
commercializing them. The time required to obtain FDA and other approvals is unpredictable but in general takes years following the
commencement of clinical trials, depending upon the nature of the drug candidate. Any analysis we perform of data from clinical
activities is subject to confirmation and interpretation by regulatory authorities, which could delay, limit or prevent regulatory approval.
Any delay or failure in obtaining required approvals could have a material adverse effect on our ability to generate revenues from the
particular drug candidate including, but not limited to, loss of patent term during the approval period. Furthermore, if we, or our partners,
do not reach the market with our products before our competitors offer products for the same or similar uses, or if we, or our partners, are
not effective in marketing our products, our revenues from product sales, if any, will be reduced.
We face intense competition in our development activities. We face competition from many companies in the United States and
abroad, including a number of large pharmaceutical companies, firms specialized in the development and production of vaccines,
adjuvants and vaccine and immunotherapeutic delivery systems and major universities and research institutions. Most of our competitors
have substantially greater resources, more extensive experience in conducting preclinical studies and clinical testing and obtaining
regulatory approvals for their products, greater operating experience, greater research and development and marketing capabilities and
greater production capabilities than those of ours. These companies might succeed in obtaining regulatory approval for competitive
products more rapidly than we can for our products, especially if we experience any delay in obtaining required regulatory approvals.
We may enter into collaboration agreements for the licensing, development and ultimate commercialization of some of our drug
candidates including, where appropriate, for our lead drug candidates. In such cases, we will depend greatly on our third-party
collaborators to license, develop and commercialize such drug candidates, and they may not meet our expectations.
We may enter into co-development and commercialization partnerships for our drug candidates where appropriate. The process of
identifying collaborators and negotiating collaboration agreements for the licensing, development and ultimate commercialization of
some of our drug candidates may cause delays and increased costs. We may not be able to enter into collaboration agreements on terms
favorable to us or at all. Furthermore, some of those agreements may give substantial responsibility over our drug candidates to the
collaborator. Some collaborators may be unable or unwilling to devote sufficient resources to develop our drug candidates as their
agreements require. They often face business risks similar to ours, and this could interfere with their efforts. Also, collaborators may
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choose to devote their resources to products that compete with ours. If a collaborator does not successfully develop any one of our
products, we will need to find another collaborator to do so. The success of our search for a new collaborator will depend on our legal
right to do so at the time and whether the product remains commercially viable.
If we enter into collaboration agreements for one or more of our lead drug candidates, the success of such drug candidates will
depend in great part upon our and our collaborators’ success in promoting them as superior to other treatment alternatives. We believe
that our drug candidates can be proven to offer disease treatment with notable advantages over drugs in terms of patient compliance and
effectiveness. However, there can be no assurance that we will be able to prove these advantages or that the advantages will be sufficient
to support the successful commercialization of our drug candidates.
Risks Related to Commercialization of Our Drug Candidates
We may face delays, difficulties or unanticipated costs in establishing sales, marketing and distribution capabilities or seeking a
partnership for the commercialization of our drug candidates, even if regulatory approval is obtained.
We may retain full economic rights to our drug candidates or seek favorable economic terms through advantageous commercial
partnerships. As a result, we may have full responsibility for commercialization of one or more of our drug candidates if and when they
are approved for sale. We currently lack sufficient marketing, sales and distribution capabilities to carry out this strategy. If any of our
drug candidates are approved by the FDA, we will need a drug sales force with technical expertise prior to the commercialization of any
of our drug candidates. We may not succeed in developing such sales and distribution capabilities, the cost of establishing such sales and
distribution capabilities may exceed any product revenue, or our direct marketing and sales efforts may be unsuccessful. We may find it
necessary to enter into strategic partnerships, co-promotion or other licensing arrangements. To the extent we enter into such strategic
partnerships, co- promotion or other licensing arrangements, our product revenues are likely to be lower than if we directly marketed and
sold such drugs, and some or all of the revenues we receive will depend upon the efforts of third parties, which may not be successful
and may not be within our control. If we are unable to enter into such strategic partnerships, co-promotion or other licensing
arrangements on acceptable terms or at all, we may not be able to successfully commercialize our existing and future drug candidates. If
we are not successful in commercializing any drug candidates for which we obtain regulatory approval, either on our own or through
collaborations with one or more third parties, our future product revenue will suffer, and we may never achieve profitability or become
unable to continue the operation of our business.
If our drug candidates for which we obtain regulatory approval do not achieve broad acceptance from physicians, patients and third-
party payors, we may be unable to generate significant revenues, if any.
Even if we obtain regulatory approval for our drug candidates, our approved drugs may not gain market acceptance among
physicians and patients. We believe that effectively marketing our drug candidates, if any of them are approved, will require substantial
efforts, both prior to commercial launch and after approval. Physicians may elect not to prescribe our drugs, and patients may elect not to
request or take them, for a variety of reasons, including:
● limitations or warnings contained in a drug’s FDA-approved labeling;
● changes in the standard of care or the availability of alternative drugs for the targeted indications for any of our drug candidates;
● limitations in the approved indications for our drug candidates;
● the approval, availability, market acceptance and reimbursement for the companion diagnostic, where applicable;
● demonstrated clinical safety and efficacy compared to other drugs;
● significant adverse side effects;
● effectiveness of education, sales, marketing and distribution support;
● timing of market introduction and perceived effectiveness of competitive drugs;
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● cost-effectiveness;
● adverse publicity about our drug candidates or favorable publicity about competitive drugs;
● convenience and ease of administration of our drug candidates; and
● willingness of third-party payors to reimburse for the cost of our drug candidates.
If our future drugs fail to achieve market acceptance, we will not be able to generate significant revenues and may never achieve
profitability.
Even if any of our drug candidates receive FDA approval, the terms of the approval may limit such drug’s commercial potential.
Additionally, even after receipt of FDA approval, such drug would be subject to substantial, ongoing regulatory requirements.
The FDA has complete discretion over the approval of our drug candidates. If the FDA grants approval, the scope of the approval
may limit our ability to commercialize such drug, and in turn, limit our ability to generate substantial product revenue. For example, the
FDA may grant approval contingent on the performance of costly post-approval clinical trials or subject to warnings or contraindications
or under a Risk Evaluation and Mitigation Strategy (REMS) drug safety program. Additionally, even after granting approval, the
manufacturing processes, labeling, packaging, distribution, adverse event reporting, storage, advertising, promotion and recordkeeping
for such drug will be subject to extensive and ongoing regulatory requirements. In addition, manufacturers of our drug candidates are
required to comply with cGMP regulations, which include requirements related to quality control and quality assurance as well as the
corresponding maintenance of records and documentation. Further, regulatory authorities must inspect and approve these manufacturing
facilities before they can be used to manufacture our drug candidates, and these facilities are subject to continual review and periodic
inspections by the FDA and other regulatory authorities for compliance with cGMP regulations. If we or a third party discover previously
unknown problems with a drug, such as adverse events of unanticipated severity or frequency, or problems with the facility where the
drug is manufactured, a regulatory authority may impose restrictions on that product, the manufacturer or us, including requiring
withdrawal of the drug from the market or suspension of manufacturing. If we, our drug candidates or the manufacturing facilities for our
drug candidates fail to comply with regulatory requirements of the FDA and/or other non-U.S. regulatory authorities, we could be subject
to administrative or judicially imposed sanctions, including the following:
● warning letters;
● civil or criminal penalties and fines;
● injunctions;
● consent decrees;
● suspension or withdrawal of regulatory approval;
● suspension of any ongoing clinical studies;
● voluntary or mandatory product recalls and publicity requirements;
● refusal to accept or approve applications for marketing approval of new drugs;
● restrictions on operations, including costly new manufacturing requirements; or
● seizure or detention of drugs or import bans.
The regulatory requirements and policies may change, and additional government regulations may be enacted with which we may
also be required to comply. We cannot predict the likelihood, nature or extent of government regulation that may arise from future
legislation or administrative action, either in the United States or in other countries. If we are not able to maintain regulatory compliance,
we may not be permitted to market our future products and our business may suffer.
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Reimbursement decisions by third-party payors may have an adverse effect on pricing and market acceptance of any of our drug
candidates. If there is not sufficient reimbursement for our future drugs, it is less likely that such drugs will be widely used.
Market acceptance and sales of any of our drug candidates for which we obtain regulatory approval will depend on reimbursement
policies and may be affected by future health care reform measures in both the United States and foreign jurisdictions. Government
authorities and third-party payors, such as private health insurers and health maintenance organizations, decide which drugs they will
cover and establish payment levels. In addition, government authorities and these third-party payors are increasingly attempting to
contain health care costs by demanding price discounts or rebates and limiting both the types and variety of drugs that they will cover
and the amounts that they will pay for these drugs. In addition, we might need to conduct post-marketing studies in order to demonstrate
the cost-effectiveness of any future drugs to such payors’ satisfaction. Such studies might require us to commit a significant amount of
management time and financial and other resources.
Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on
payments allowed for lower-cost products that are already reimbursed, may be incorporated into existing payments for other products or
services and may reflect budgetary constraints and/or imperfections in Medicare or Medicaid data used to calculate these rates. Net
prices for drugs may be reduced by mandatory discounts or rebates required by government health care programs. Such programs, or
regulatory changes or relaxation of laws that restrict imports of drugs from other countries, could reduce the net price we receive for any
future marketed drugs. In addition, our future drugs might not ultimately be considered cost-effective.
We cannot be certain that reimbursement will be available for any drug candidates that we develop.Also, we cannot be certain that
reimbursement policies will not reduce the demand for, or the price paid for, any future drugs. If reimbursement is not available or is
available on a limited basis, we may not be able to successfully commercialize any drug candidates that we develop.
Other factors could affect the demand for and sales and profitability of any drug candidates that we may commercialize in the future.
In general, other factors that could affect the demand for and sales and profitability of our future drugs include, but are not limited
to:
● the timing of regulatory approval, if any, of competitive drugs;
● our or any other of our partners’ pricing decisions, as applicable, including a decision to increase or decrease the price of a
drug, and the pricing decisions of our competitors;
● government and third-party payor reimbursement and coverage decisions that affect the utilization of our future drugs and
competing drugs;
● negative safety or efficacy data from new clinical studies conducted either in the U.S. or internationally by any party, which
could cause the sales of our future drugs to decrease or a future drug to be recalled;
● the degree of patent protection afforded our future drugs by patents granted to or licensed by us and by the outcome of litigation
involving our or any of our licensor’s patents;
● marketing exclusivity, if any, awarded by the FDA to our drugs;
● the outcome of litigation involving patents of other companies concerning our future drugs or processes related to production
and formulation of those drugs or uses of those drugs;
● the increasing use and development of alternate therapies;
● the rate of market penetration by competing drugs; and
● the termination of, or change in, existing arrangements with our partners.
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Any of these factors could have a material adverse effect on the sales of any drug candidates that we may commercialize in the
future.
Failure to obtain regulatory approvals in foreign jurisdictions will prevent us from marketing our products internationally.
We may seek approval for our drug candidates outside the United States and may market future products in international markets. In
order to market our future products in the European Economic Area, or EEA, and many other foreign jurisdictions, we must obtain
separate regulatory approvals. Specifically, in the EEA, medicinal products can only be commercialized after obtaining a Marketing
Authorization, or MA.
Before granting the MA, the European Medicines Agency or the competent authorities of the member states of the EEA make an
assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.
The approval procedures vary among countries and can involve additional clinical testing, and the time required to obtain approval
may differ from that required to obtain FDA approval. Clinical studies conducted in one country may not be accepted by regulatory
authorities in other countries. Approval by the FDA does not ensure approval by regulatory authorities in other countries, and approval
by one or more foreign regulatory authorities does not ensure approval by regulatory authorities in other foreign countries or by the FDA.
However, a failure or delay in obtaining regulatory approval in one country may have a negative effect on the regulatory process in
others. The foreign regulatory approval process may include all of the risks associated with obtaining FDA approval. We may not obtain
foreign regulatory approvals on a timely basis, if at all. We may not be able to file for regulatory approvals, and even if we file, we may
not receive necessary approvals to commercialize our products in any market.
If we obtain approval to commercialize any approved products outside of the United States, a variety of risks associated with
international operations could materially adversely affect our business.
If our drug candidates are approved for commercialization outside of the United States, we expect that we will be subject to
additional risks related to international operations and entering into international business relationships, including:
● different regulatory requirements for drug approvals;
● reduced protection for intellectual property rights, including trade secret and patent rights;
● unexpected changes in tariffs, trade barriers and regulatory requirements;
● economic weakness, including inflation, rising interest rates or political instability in particular foreign economies and markets;
● compliance with tax, employment, immigration and labor laws for employees living or traveling abroad;
● foreign taxes, including withholding of payroll taxes;
● foreign currency fluctuations, which could result in increased operating expenses and reduced revenues, and other obligations
incident to doing business in another country;
● workforce uncertainty in countries where employment regulations are different than, and labor unrest is more common than, in
the United States;
● production shortages resulting from any events affecting raw material supply or manufacturing capabilities abroad;
● business interruptions resulting from geopolitical actions, including war and terrorism, or natural disasters, including
earthquakes, hurricanes, floods and fires; and
● difficulty in importing and exporting clinical trial materials and study samples.
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Risks Related to Reliance on Third Parties
We rely on third parties to plan, conduct and monitor our clinical tests, and their failure to perform as required would interfere with
our product development.
We rely on third parties to conduct a significant portion of our clinical development activities. These activities include clinical
patient recruitment and observation, clinical trial monitoring, clinical data management and analysis, safety monitoring and project
management. We conduct project management and medical and safety monitoring in-house for some of our programs and rely on third
parties for the remainder of our clinical development activities. If any of these third parties is unable to perform in a quality and timely
manner, and at a feasible cost, our clinical studies will face delays. Further, if any of these third parties fails to perform as we expect or if
their work fails to meet regulatory standards, our testing could be delayed, cancelled or rendered ineffective.
We rely on contract manufacturers over whom we have limited control. Should the cost, delivery and quality of clinical materials
manufactured by us in our Fall River facility or supplied by contract manufacturers vary to our disadvantage, our business
operations could suffer significant harm.
We have limited experience in commercial manufacturing. We rely on CMOs to manufacture drug substance and drug product for
any late-stage clinical studies of our drug candidates as well as for future commercial supplies. Our ability to conduct late-stage clinical
trials, manufacture and commercialize our drug candidates, if regulatory approval is obtained, depends on the ability of such third parties
to manufacture our drug candidates on a large scale at a competitive cost and in accordance with cGMP and foreign regulatory
requirements, if applicable. We also rely on CMOs for labeling and storage for studies inside and outside the US. In order for us to
establish our own commercial manufacturing facility, we would require substantial additional funds and would need to make facility
modifications, hire and retain significant additional personnel and comply with extensive cGMP regulations applicable to such a facility.
The commercial manufacturing facility would also need to be licensed for the production of our drug candidates by the FDA and meet
other regulatory standards.
Prior to approval of any drug candidate, the FDA must review and approve validation studies for both drug substance and drug
product. The manufacturing processes for our drug candidates and immunotherapeutic delivery systems utilize known technologies. We
believe that the products we currently have under development can be scaled up to permit manufacture in commercial quantities.
However, there can be no assurance that we will not encounter difficulties in scaling up the manufacturing processes. Significant scale-up
of manufacturing may result in unanticipated technical challenges and may require additional validation studies that the FDA must
review and approve. CMOs may encounter difficulties in scaling up production, including problems involving supply chain, raw material
suppliers, production yields, technical difficulties, scaled-up product characteristics, quality control and assurance, shortage of qualified
personnel, capacity constraints, changing priorities within the CMOs, compliance with FDA and foreign regulations, environmental
compliance, production costs and development of advanced manufacturing techniques and process controls. Any of these difficulties, if
they occur and are not overcome to the satisfaction of the FDA or other regulatory agency, could lead to significant delays and possibly
the termination of the development program for such drug candidate. These risks become more acute as we scale up for commercial
quantities, where reliable sources of drug substance and drug product become critical to commercial success. The commercial viability of
any of our drug candidates, if approved, will depend on the ability of our contract manufacturers to produce drug substance and drug
product on a large scale. Failure to achieve this level of supply can jeopardize and prevent the successful commercialization of the drug.
We operate our own cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for our current and
planned early-stage clinical trials. Our Fall River manufacturing facility has 250L and 1000L bioreactor capacity and is able to
manufacture in compliance with FDA and EU regulations, allowing us to distribute potential products to clinical sites in the U.S., EU and
ROW for early-stage clinical trials. We have manufactured barzolvolimab and CDX-585 drug substance in our Fall River facility for our
current and planned Phase 1 and Phase 2 clinical trials. All products are then filled at CMOs. Any manufacturing failures, supply chain
delays or compliance issues at our Fall River facility or at our CMOs could cause delays in our Phase 1 and Phase 2 clinical studies for
these drug candidates.
Our barzolvolimab drug product is currently administered both intravenously and subcutaneously. In 2022, we manufactured
barzolvolimab drug substance at our Fall River facility in subcutaneous form then filled at a CMO to support ongoing and planned
clinical trials. The subcutaneous formulation will allow for a potential self-administration at home setting versus the need for intravenous
dosing in a hospital or clinic setting. The subcutaneous form could improve the patient experience if the product becomes available
commercially. In 2022, we initiated a transfer of our current barzolvolimab manufacturing process to a CMO to allow us to
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produce larger batches in support of late-stage trials and to prepare for potential commercialization. We believe that barzolvolimab can
be scaled up to permit manufacturing in commercial quantities. However, there can be no assurance that we will not encounter
difficulties in scaling up the manufacturing processes.
Our leading drug candidates require specialized manufacturing capabilities and processes. We may face difficulty in securing
commitments from U.S. and foreign contract manufacturers as these manufacturers could be unwilling or unable to accommodate our
needs. Relying on foreign manufacturers involves peculiar and increased risks, including the risk relating to the difficulty foreign
manufacturers may face in complying with cGMP requirements as a result of language barriers, lack of familiarity with cGMP or the
FDA regulatory process, supply chain issues or other causes, economic or political instability in or affecting the home countries of our
foreign manufacturers, shipping delays, potential changes in foreign regulatory laws governing the sales of our product supplies,
fluctuations in foreign currency exchange rates and the imposition or application of trade restrictions.
There can be no assurances that contract manufacturers will be able to meet our timetable and requirements. Further, contract
manufacturers must operate in compliance with cGMP and failure to do so could result in, among other things, the disruption of product
supplies. As noted above, non-U.S. contract manufacturers may face special challenges in complying with cGMP requirements, and
although we are not currently dependent on non-U.S. collaborators or contract manufacturers, we may choose or be required to rely on
non-U.S. sources in the future as we seek to develop stable supplies of increasing quantities of materials for ongoing clinical trials of
larger scale. Our dependence upon third parties for the manufacture of our products may adversely affect our profit margins and our
ability to develop, manufacture, sell and deliver products on a timely and competitive basis.
We may need to rely on third-party collaborators to develop and commercialize companion diagnostic tests for our drug candidates.
We do not have experience or capabilities in developing, administering, obtaining regulatory approval for, or commercializing
companion diagnostic tests and will need to rely in large part on third-party collaborators to perform these functions. Companion
diagnostic tests are subject to regulation by the FDA and similar regulatory authorities outside of the United States as medical devices
and require separate regulatory approval prior to commercialization. We may need to rely on such third-party collaborators to obtain
regulatory approval and commercialize such companion diagnostic tests. Such third-party collaborators:
● may not perform its obligations as expected or as required under our collaboration agreement;
● may encounter production difficulties that could constrain the supply of the companion diagnostic test;
● may have difficulties gaining acceptance of the use of the companion diagnostic test in the clinical community;
● may not pursue commercialization of the companion diagnostic test even if they receive any required regulatory approvals;
● may elect not to continue the development or commercialization of the companion diagnostic test based on changes in the third
parties’ strategic focus or available funding, or external factors such as an acquisition, that divert resources or create competing
priorities;
● may be susceptible to third party cyber-attacks on our and their information security systems;
● may not commit sufficient resources to the marketing and distribution of the companion diagnostic test; and
● may terminate their relationship with us.
If such third-party collaborators fail to develop, obtain regulatory approval or commercialize the companion diagnostic test, we may
not be able to enter into arrangements with another diagnostic company to obtain supplies of an alternative diagnostic test for use in
connection with the development and commercialization of our drug candidates or do so on commercially reasonable terms, which could
adversely affect and/or delay the development or commercialization of our drug candidates.
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Our reliance on third parties requires us to share our trade secrets, which increases the possibility that a competitor will discover
them.
Because we rely on third parties to develop our drug candidates, we must share trade secrets with them.We seek to protect our
proprietary technology in part by entering into confidentiality agreements and, if applicable, material transfer agreements, collaborative
research agreements, consulting agreements or other similar agreements with our collaborators, advisors, employees and consultants
prior to beginning research or disclosing proprietary information. These agreements typically restrict the ability of our collaborators,
advisors, employees and consultants to publish data potentially relating to our trade secrets. Our academic collaborators typically have
rights to publish data, provided that we are notified in advance and may delay publication for a specified time in order to secure our
intellectual property rights arising from the collaboration. In other cases, publication rights are controlled exclusively by us, although in
some cases we may share these rights with other parties. We also conduct joint research and development programs which may require us
to share trade secrets under the terms of research and development partnership or similar agreements. Despite our efforts to protect our
trade secrets, our competitors may discover our trade secrets, either through breach of these agreements, independent development or
publication of information including our trade secrets in cases where we do not have proprietary or otherwise protected rights at the time
of publication. A competitor’s discovery of our trade secrets would impair our competitive position.
We or the third parties upon whom we depend may be adversely affected by natural disasters and our business continuity and disaster
recovery plans may not adequately protect us from a serious disaster.
Any unplanned event, such as flood, fire, explosion, earthquake, extreme weather condition, medical epidemic, including the
COVID-19 pandemic, power shortage, telecommunication failure or other natural or manmade accidents or incidents that result in us
being unable to fully utilize our facilities, or the manufacturing facilities of our third-party CMOs, could severely disrupt our operations
and have a material adverse effect on our business, results of operations, financial condition and prospects. For example, our operations
are located primarily on the east coast of the United States, and any adverse weather event or natural disaster, such as a hurricane or
heavy snowstorm, could have a material adverse effect on a substantial portion of our operations. If any event occurred that prevented us
from using all or a significant portion of our manufacturing and lab facilities, that damaged critical infrastructure, such as third-party
manufacturing facilities, or that otherwise disrupted operations and travel, 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 may prove
inadequate 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 could have a material adverse effect on our business.
Risks Related to Business Operations
We may engage in strategic transactions that could impact our liquidity, increase our expenses and present significant distractions to
our management.
From time to time we may consider strategic transactions, including acquisitions of companies, asset purchases and out-licensing or
in-licensing of products, drug candidates or technologies. Additional potential transactions that we may consider include a variety of
different business arrangements, including spin-offs, strategic partnerships, joint ventures, restructurings, divestitures, business
combinations, acquisitions of assets and investments. Any such transaction may require us to incur non-recurring or other charges, may
increase our near and long-term expenditures and may pose significant integration challenges or disrupt our management or business,
which could adversely affect our operations and financial results. For example, these transactions may entail numerous operational and
financial risks, including:
● exposure to unknown liabilities;
● disruption of our business and diversion of our management’s time and attention in order to develop acquired products, drug
candidates or technologies;
● incurrence of substantial debt or dilutive issuances of equity securities to pay for acquisitions;
● higher than expected acquisition and integration costs;
● write-downs of assets or impairment charges;
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● increased amortization expenses;
● difficulty and cost in combining the operations and personnel of any acquired businesses with our operations and personnel;
● impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and
ownership; and
● inability to retain key employees of any acquired businesses.
Accordingly, although there can be no assurance that we will undertake or successfully complete any transactions of the nature
described above, any transactions that we do complete could have a material adverse effect on our business, results of operations,
financial condition and prospects.
We may expand our clinical development, regulatory and sales and marketing capabilities, and as a result, we may encounter
difficulties in managing our growth, which could disrupt our operations.
We expect that if our drug candidates continue to progress in development, we may require significant additional investment in
personnel, management systems and resources, particularly in the build out of our commercial capabilities. To date we have hired a core
commercial team to plan for potential commercial launches if any of our drug candidates are approved. Over the next several years, we
may experience significant growth in the number of our employees and the scope of our operations, particularly in the areas of drug
development, regulatory affairs and sales and marketing. To manage this potential future growth, we may continue to implement and
improve our managerial, operational and financial systems, expand our facilities and continue to recruit and train additional qualified
personnel. Due to our limited financial resources and the limited experience of our management team in managing a company with such
anticipated growth, we may not be able to effectively manage the expansion of our operations or recruit and train additional qualified
personnel. The physical expansion of our operations may lead to significant costs and may divert our management and business
development resources. Any inability to manage growth could delay the execution of our business plans or disrupt our operations.
We may not be able to successfully integrate our existing technology or to modify our technologies to create new immunotherapeutic
drugs.
If we are able to integrate our acquired assets and licensed assets with our immunotherapy technologies, we believe these assets will
give our immunotherapeutic drugs a competitive advantage. However, if we are unable to successfully integrate licensed assets, or other
technologies which we have acquired or may acquire in the future, with our existing technologies and potential products currently under
development, we may be unable to realize any benefit from our acquisition of these assets, or other technologies which we have acquired
or may acquire in the future, and we may face the loss of our investment of financial resources and time in the integration process.
We believe that our immunotherapy technology portfolio may offer opportunities to develop immunotherapeutic drugs that treat a
variety of cancers and inflammatory and infectious diseases by stimulating a patient’s immune system against those diseases. If our
immunotherapy technology portfolio cannot be used to create effective immunotherapeutic drugs against a variety of diseases, we may
lose all or portions of our investment in development efforts for new drug candidates.
Our internal computer systems, or those of our CROs, CMOs, or other contractors or consultants, may fail or suffer security
breaches, which could result in a material disruption of our drug development programs.
Despite the implementation of security measures, our internal computer systems and those of our CROs, CMOs, and other
contractors and consultants are vulnerable to damage from cyberattacks, malicious intrusion, computer viruses, unauthorized access, loss
of data privacy, natural disasters, terrorism, war and telecommunication, electrical failures or other significant disruption. If such an
event were to occur and cause interruptions in our operations, it could result in a material disruption of our drug development programs
and commercialization efforts. For example, the loss of clinical study data from completed or ongoing clinical studies for any of our drug
candidates could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data.
Further, the risk of cyber-attacks or other privacy or data security incidents may be heightened due to common, external attempts to
attack our information technology systems and data using means such as phishing. To the extent that any disruption or security breach
were to result in a loss of or damage to our data or applications or inappropriate disclosure of confidential
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or proprietary information, we could incur liability and the further development or commercialization of our drug candidates could be
delayed.
While we have not experienced any such event to date, if such an event were to occur and cause interruptions in our operations, it
could result in a material disruption of our independent drug development programs. For example, the loss of clinical trial data from
ongoing or future clinical trials for any of our product candidates could result in delays in regulatory approval efforts and significantly
increase costs to recover or reproduce the data. Our information security systems are also subject to laws and regulations requiring that
we take measures to protect the privacy and security of certain information we gather and use in our business. For example, HIPAA and
its implementing regulations impose, among other requirements, certain regulatory and contractual requirements regarding the privacy
and security of personal health information. In the European Union the General Data Protection Regulation, or GDPR, is even more
restrictive with respect to all personal information, including information masked by a coding system. In addition to HIPAA and GDPR,
numerous other federal and state laws, including, without limitation, state security breach notification laws, state health information
privacy laws and federal and state consumer protection laws, govern the collection, use, disclosure and storage of personal information.
To the extent that any disruption or security breach of our information technology systems were to result in a loss of or damage to data or
applications, or inappropriate disclosure of confidential or proprietary information or personal health information, we could incur
substantial liability under laws that protect the privacy of personal information, our reputation would be damaged, and the further
development of our product candidates could be delayed, any of which could adversely affect our business.
Our business requires us to use hazardous materials, which increases our exposure to dangerous and costly accidents.
Our research and development activities involve the use of biological materials and small amounts of hazardous chemicals. The
company has internal policies and procedures for the safe handling and disposal of these materials, in full compliance with applicable
laws and regulations, including applicable OSHA, EPA, state and local regulations, and utilizing EPA licensed disposal companies and
facilities. Although we believe we have reduced our risk and impacts from these materials through our safety procedures, we cannot
completely eliminate the risk of accidental contamination or injury from these materials. The ongoing cost of complying with
environmental laws and regulations is significant and may increase in the future. All risks of environmental damage inherent to our
operations cannot be mitigated and failure to comply with applicable government regulations could result in the imposition of fines,
restrictions, or increased operational costs, which could impact our ability to carry on with our operations.
We face the risk of product liability claims, which could exceed our insurance coverage, and product recalls, each of which could
deplete our cash resources.
As a participant in the pharmaceutical, biotechnology and immunotherapeutic drug industries, we are exposed to the risk of product
liability claims alleging that use of our drug candidates caused an injury or harm. These claims can arise at any point in the development,
testing, manufacture, marketing or sale of our drug candidates and may be made directly by patients involved in clinical trials of our
products, by consumers or health care providers or by individuals, organizations or companies selling our products.Product liability
claims can be expensive to defend, even if the drug or drug candidate did not actually cause the alleged injury or harm.
Insurance covering product liability claims becomes increasingly expensive as a drug candidate moves through the development
pipeline to commercialization. However, there can be no assurance that such insurance coverage is or will continue to be adequate or
available to us at a cost acceptable to us or at all. We may choose or find it necessary under our collaborative agreements to increase our
insurance coverage in the future. We may not be able to secure greater or broader product liability insurance coverage on acceptable
terms or at reasonable costs when needed. Any liability for damages resulting from a product liability claim could exceed the amount of
our coverage, require us to pay a substantial monetary award from our own cash resources and have a material adverse effect on our
business, financial condition and results of operations. Moreover, a product recall, if required, could generate substantial negative
publicity about our products and business and inhibit or prevent development of our drug candidates and, if approval is obtained,
commercialization of our future drugs.
Disruptions in the global economy and supply chains may have a material adverse effect on our business, financial condition and
results of operations.
The disruptions to the global economy since 2020 have impeded global supply chains, resulting in longer lead times and also
increased critical component costs and freight expenses. We have taken steps to minimize the impact of these increased costs by working
closely with our suppliers. Despite the actions we have undertaken to minimize the impacts from disruptions to the global
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economy, there can be no assurances that unforeseen future events in the global supply chain, and inflationary pressures, will not have a
material adverse effect on our business, financial condition and results of operations.
Risks Related to Intellectual Property
We license technology from other companies to develop products, and those companies could influence research and development or
restrict our use of it. In addition, if we fail to comply with our obligations in our intellectual property licenses with third parties, we
could lose license rights that are important to our business.
Companies that license technologies to us that we use in our research and development programs may require us to achieve
milestones or devote minimum amounts of resources to develop products using those technologies. They may also require us to make
significant royalty and milestone payments, including a percentage of any sublicensing income, as well as payments to reimburse them
for patent costs. The number and variety of our research and development programs require us to establish priorities and to allocate
available resources among competing programs. From time to time, we may choose to slow down or cease our efforts on particular
products. If in doing so we fail to fully perform our obligations under a license, the licensor can terminate the license or permit our
competitors to use the technology. Termination of these licenses or reduction or elimination of our licensed rights may result in our
having to negotiate new or reinstated licenses with less favorable terms. Moreover, we may lose our right to market and sell any products
based on the licensed technology. The occurrence of such events could materially harm our business.
Our ability to successfully develop and, if regulatory approval is obtained, commercialize our drug candidates may be materially
adversely affected if we are unable to obtain and maintain effective intellectual property rights for our drug candidates and
technologies.
Our success depends in part on our ability to obtain and maintain patent protection and other intellectual property protection for our
drug candidates and proprietary technology. We have sought to protect our proprietary position by filing patent applications in the United
States and abroad related to our drug candidates and technology that are important to our business. This process is expensive and time-
consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely
manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to
obtain patent protection. Our existing patents and any future patents we obtain may not be sufficiently broad to prevent others from using
our technologies or from developing competing drugs and technologies. We may also be unable to obtain patent term adjustments or
extensions (or similar rights, such as Supplementary Protection Certificates, in foreign countries) at the relevant times, or the duration of
any such adjustments, extensions or the like may be less than requested.
Biotechnology patents involve complex legal, scientific and factual questions and are highly uncertain and may also result in
different outcomes in different territories. To date, there is no consistent policy regarding the breadth of claims allowed in biotechnology
patents, particularly in regard to patents for technologies for human uses like those we use in our business. We cannot predict whether the
patents we or our licensors seek will issue. If such patents are issued, a competitor may challenge them and may potentially have them
revoked or limit their scope, for example based on existing or newly identified prior art or other issues of validity. Moreover, our patents
may not afford effective protection against competitors with similar technology. A successful challenge to any one of our patents could
result in a third party’s ability to use the technology covered by the patent. We also face the risk that others will infringe, avoid or
circumvent our patents. Technology that we license from others is subject to similar risks and this could harm our ability to use that
technology. If we, or a company that licenses technology to us, were not the first creator of an invention that we use, and/or if
inventorship were to be decided against us (or our licensor) in any relevant litigation, our use of the underlying product or technology
will face restrictions, including elimination, and our ability to defend and/or enforce any affected patent rights could also be materially
harmed.
If we must defend against suits brought against us or prosecute suits against others involving intellectual property rights, we will
incur substantial costs. In addition to any potential liability for significant monetary damages, a decision against us may require us to
obtain licenses to patents or other intellectual property rights of others on potentially unfavorable terms. If those licenses from third
parties are necessary but we cannot acquire them, we would attempt to design around the relevant technology, which would cause higher
development costs and delays and may ultimately prove impracticable.
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We may need to license intellectual property from third parties, and such licenses may not be available or may not be available on
commercially reasonable terms.
A third party may hold intellectual property, including patent rights, that are important or necessary to the development of our drug
candidates. It may be necessary for us to use the patented or proprietary technology of a third party to commercialize our own technology
or drug candidates, in which case we would be required to obtain a license from such third party. A license to such intellectual property
may not be available or may not be available on commercially reasonable terms, which could have a material adverse effect on our
business and financial condition.
We may be unable to protect the confidentiality of our trade secrets, thus harming our business and competitive position.
We rely upon trade secrets, including unpatented know-how, technology and other proprietary information to develop and maintain
our competitive position, which we seek to protect, in part, by confidentiality agreements with our employees and our collaborators and
consultants. We also have agreements with our employees that obligate them to assign their inventions to us. However, it is possible that
technology relevant to our business will be independently developed by a person that is not a party to such an agreement. Furthermore, if
the employees, consultants or collaborators that are parties to these agreements breach or violate the terms of these agreements, we may
not have adequate remedies for any such breach or violation, and we could lose our trade secrets through such breaches or violations.
Further, our trade secrets could be disclosed, misappropriated or otherwise become known or be independently discovered by our
competitors. In addition, intellectual property laws in foreign countries may not protect our intellectual property to the same extent as the
laws of the United States. If our trade secrets are disclosed or misappropriated, it would harm our ability to protect our rights and have a
material adverse effect on our business.
We may become involved in lawsuits to protect or enforce our patents, which could be expensive, time- consuming and unsuccessful.
Competitors may infringe our patents. To counter infringement or unauthorized use, we may be required to file infringement claims,
which can be expensive and time-consuming. In addition, in an infringement proceeding, a court may decide that a patent of ours is
invalid or unenforceable or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not
cover the technology in question. An adverse result in any litigation proceeding could put one or more of our patents at risk of being
invalidated or interpreted narrowly. Furthermore, because of the substantial amount of discovery required in connection with intellectual
property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of
litigation.
Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the outcome of which
would be uncertain and could have a material adverse effect on the success of our business.
Our commercial success depends upon our ability and the ability of our collaborators to develop, manufacture, market and sell our
drug candidates and use our proprietary technologies without infringing, misappropriating or otherwise violating the proprietary rights or
intellectual property of third parties. We may become party to, or be threatened with, future adversarial proceedings or litigation
regarding intellectual property rights with respect to our drug candidates and technology. Third parties may assert infringement claims
against us based on existing patents or patents that may be granted in the future. If we are found to infringe a third-party’s intellectual
property rights, we could be required to obtain a license from such third-party to continue developing our drug candidates and
technology. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were
able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. We
could be forced, including by court order, to cease developing the infringing technology or product. In addition, we could be found liable
for monetary damages. Claims that we have misappropriated the confidential information or trade secrets of third parties can have a
similar negative impact on our business.
Third parties may assert that our employees or consultants have wrongfully used or disclosed confidential information or
misappropriated trade secrets.
We employ individuals who were previously employed at universities or other diagnostic or biopharmaceutical companies, including
our competitors or potential competitors. Although we try to ensure that our employees and consultants do not use the proprietary
information or know-how of others in their work for us, we may be subject to claims that we or our employees, consultants or
independent contractors have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other
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proprietary information, of a former employer or other third parties. Litigation may be necessary to defend against these claims. If we fail
in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.
Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management
and other employees.
Regulatory Risks
We may not be able to obtain or maintain orphan drug designation or exclusivity for our product candidates.
We may seek orphan drug designation for some of our product candidates in the United States.Regulatory authorities in some
jurisdictions, including the United States and Europe, may designate drugs for relatively small patient populations as orphan drugs.
Under the Orphan Drug Act, the FDA may designate a product as an orphan drug if it is a drug intended to treat a rare disease or
condition, which is generally defined as a patient population of fewer than 200,000 individuals in the United States.
Generally, if a product with an orphan drug designation subsequently receives the first marketing approval for the indication for
which it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the FDA or the EMA from
approving another marketing application for the same indication for that drug during that time period. The applicable period is seven
years in the United States and ten years in Europe. The European exclusivity period can be reduced to six years if a drug no longer meets
the criteria for orphan drug designation or if the drug is sufficiently profitable so that market exclusivity is no longer justified. Orphan
drug exclusivity may be lost if the FDA or the EMA determines that the request for designation was materially defective or if the
manufacturer is unable to assure sufficient quantity of the drug to meet the needs of patients with the rare disease or condition.
We cannot assure you that any future application for orphan drug designation with respect to any product candidate will be granted.
If we are unable to obtain orphan drug designation in the United States, we will not be eligible to obtain the period of market exclusivity
that could result from orphan drug designation or be afforded the financial incentives associated with orphan drug designation. Even if
we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because
different drugs can be approved for the same condition. Even after an orphan drug is approved, the FDA can subsequently approve the
same drug for the same condition if the FDA concludes that the later drug is clinically superior in that it is shown to be safer, more
effective or makes a major contribution to patient care.
Any fast track designation or grant of priority review status by the FDA may not actually lead to a faster development or regulatory
review or approval process, nor will it assure FDA approval of our product candidates. Additionally, our product candidates may treat
indications that do not qualify for priority review vouchers.
We may seek fast track designation for some of our product candidates or priority review of applications for approval of our product
candidates. If a drug is intended for the treatment of a serious or life- threatening condition and the drug demonstrates the potential to
address unmet medical needs for this condition, the drug sponsor may apply for FDA fast track designation. If a product candidate offers
major advances in treatment, the FDA may designate it eligible for priority review. The FDA has broad discretion whether or not to grant
these designations, so even if we believe a particular product candidate is eligible for these designations, we cannot assure you that the
FDA would decide to grant them. Even if we do receive fast track designation or priority review, we may not experience a faster
development process, review or approval compared to conventional FDA procedures. The FDA may withdraw fast track designation if it
believes that the designation is no longer supported by data from our clinical development program.
Any breakthrough therapy designation granted by the FDA for our product candidates may not lead to a faster development or
regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing
approval.
We may seek a breakthrough therapy designation for some of our product candidates. A breakthrough therapy is defined as a drug
that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and
preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more
clinically significant endpoints, such as substantial treatment effects observed early in clinical development. For drugs and biologics that
have been designated as breakthrough therapies, interaction and communication between the FDA and the sponsor of the trial can help to
identify the most efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens.
Drugs designated as breakthrough therapies by the FDA may also be eligible for accelerated approval if the relevant criteria are met.
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Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product
candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead determine not to make such
designation. In any event, the receipt of a breakthrough therapy designation for a product candidate may not result in a faster
development process, review or approval compared to drugs considered for approval under conventional FDA procedures and does not
assure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the
FDA may later decide that the products no longer meet the conditions for qualification or decide that the time period for FDA review or
approval will not be shortened.
If our processes and systems are not compliant with regulatory requirements, we could be subject to delays in submitting BLAs,
NDAs or restrictions on marketing of drugs after they have been approved.
We currently are developing drug candidates for regulatory approval and are in the process of implementing regulated processes and
systems required to obtain and maintain regulatory approval for our drug candidates. Certain of these processes and systems for
conducting clinical trials and manufacturing material must be compliant with regulatory requirements before we can apply for regulatory
approval for our drug candidates. These processes and systems will be subject to continual review and periodic inspection by the FDA
and other regulatory bodies. If we are unable to achieve compliance in a timely fashion or if compliance issues are identified at any point
in the development and approval process, we may experience delays in filing for regulatory approval for our drug candidates or delays in
obtaining regulatory approval after filing. In addition, any later discovery of previously unknown problems or safety issues with
approved drugs or manufacturing processes, or failure to comply with regulatory requirements may result in restrictions on such drugs or
manufacturing processes, withdrawal of drugs from the market, the imposition of civil or criminal penalties or a refusal by the FDA
and/or other regulatory bodies to approve pending applications for marketing approval of new drugs or supplements to approved
applications, any of which could have a material adverse effect on our business. In addition, we are a party to agreements that transfer
responsibility for complying with specified regulatory requirements, such as filing and maintenance of marketing authorizations and
safety reporting or compliance with manufacturing requirements, to our collaborators and third-party manufacturers. If our collaborators
or third-party manufacturers do not fulfill these regulatory obligations, any drugs for which we or they obtain approval may be subject to
later restrictions on manufacturing or sale or may even risk withdrawal, which could have a material adverse effect on our business.
We have conducted and are conducting clinical trials outside the United States and anticipate conducting additional clinical trials
outside the United States, and the FDA may not accept data from such trials.
We are currently conducting clinical trials for our product candidates in countries outside of the United States and we anticipate that
we will conduct additional clinical trials in countries outside the United States. Although the FDA may accept data from clinical trials
conducted outside the United States, acceptance of such study data by the FDA is subject to certain conditions. For example, the clinical
trial must be conducted in accordance with GCP requirements and the FDA must be able to validate the data from the clinical trial
through an onsite inspection if it deems such inspection necessary. Where data from foreign clinical trials are intended to serve as the
sole basis for marketing approval in the United States, the FDA will not approve the application on the basis of foreign data alone unless
those data are considered applicable to the U.S. patient population and U.S. medical practice, the clinical trials were performed by
clinical investigators of recognized competence, and the data is considered valid without the need for an on-site inspection by the FDA
or, if the FDA considers such an inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other
appropriate means. In addition, such clinical trials would be subject to the applicable local laws of the foreign jurisdictions where the
clinical trials are conducted. A description of any studies related to overdosage is also required, including information on dialysis,
antidotes, or other treatments, if known. There can be no assurance the FDA will accept data from clinical trials conducted outside of the
United States. If the FDA does not accept any such data, it would likely result in the need for additional clinical trials, which would be
costly and time-consuming and delay aspects of our development plan.
Risks inherent in conducting international clinical trials include, but are not limited to:
● foreign regulatory requirements that could burden or limit our ability to conduct our clinical trials;
● administrative burdens of conducting clinical trials under multiple foreign regulatory schema;
● foreign currency fluctuations which could negatively impact our financial condition since certain payments are paid in local
currencies;
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● manufacturing, customs, shipment and storage requirements;
● cultural differences in medical practice and clinical research; and
● diminished protection of intellectual property in some countries.
Changes in product candidate manufacturing or formulation may result in additional costs or delay.
As product candidates are developed through preclinical studies to late-stage clinical trials towards approval and commercialization,
it is common that various aspects of the development program, such as manufacturing methods and formulation, are altered along the
way in an effort to optimize processes and results. During the course of a development program, sponsors may also change the contract
manufacturers used to produce the product candidates. Such changes carry the risk that they will not achieve these intended objectives.
Any of these changes could cause our product candidates to perform differently and affect the results of clinical trials. Such changes may
also require additional testing, notification or approval by the FDA, EMA or other regulatory authorities. This could delay completion of
clinical trials; require the conduct of bridging clinical trials or studies, or the repetition of one or more clinical trials; increase clinical trial
costs; delay approval of our product candidates and jeopardize our ability to commence product sales and generate revenue.
Even if we receive regulatory approval for a drug candidate, we will be subject to ongoing regulatory obligations and continued
regulatory review, which may result in significant additional expense and subject us to penalties if we fail to comply with applicable
regulatory requirements.
Once regulatory approval has been granted, the approved product and its manufacturer are subject to continual review by the FDA
and/or non-U.S. regulatory authorities. Any regulatory approval that we or our collaboration partners receive for our drug candidates may
be subject to limitations on the indicated uses for which the product may be marketed or contain requirements for potentially costly post-
marketing follow-up studies to monitor the safety and efficacy of the product. In addition, if the FDA and/or non-U.S. regulatory
authorities approve any of our drug candidates, we will be subject to extensive and ongoing regulatory requirements by the FDA and
other regulatory authorities with regard to the labeling, packaging, adverse event reporting, storage, advertising, promotion and
recordkeeping for our products. In addition, manufacturers of our drug products are required to comply with cGMP regulations, which
include requirements related to quality control and quality assurance as well as the corresponding maintenance of records and
documentation. Further, regulatory authorities must inspect and approve these manufacturing facilities before they can be used to
manufacture our drug products, and these facilities are subject to continual review and periodic inspections by the FDA and other
regulatory authorities for compliance with cGMP regulations. If we or a third party discover 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, a
regulatory authority may impose restrictions on that product, the manufacturer or us, including requiring withdrawal of the product from
the market or suspension of manufacturing. If we, our drug candidates or the manufacturing facilities for our drug candidates fail to
comply with regulatory requirements of the FDA and/or other non-U.S. regulatory authorities, we could be subject to administrative or
judicially imposed sanctions, including the following:
● warning letters;
● civil or criminal penalties and fines;
● injunctions;
● consent decrees;
● suspension or withdrawal of regulatory approval;
● suspension of any ongoing clinical studies;
● voluntary or mandatory product recalls and publicity requirements;
● refusal to accept or approve applications for marketing approval of new drugs;
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● restrictions on operations, including costly new manufacturing requirements; or
● seizure or detention of drugs or import bans.
The regulatory requirements and policies may change and additional government regulations may be enacted with which we may
also be required to comply. We cannot predict the likelihood, nature or extent of government regulation that may arise from future
legislation or administrative action, either in the United States or in other countries. If we are not able to maintain regulatory compliance,
we may not be permitted to market our future products, and our business may suffer.
We may be subject, directly or indirectly, to federal and state health care fraud and abuse laws, false claims laws, transparency and
pricing laws and health information privacy and security laws. If we are unable to comply, or have not fully complied, with such laws,
we could face substantial penalties.
If we obtain FDA approval for any of our drug candidates and begin commercializing those products in the United States, our
operations will be directly, or indirectly through our customers, subject to various federal and state fraud and abuse laws, including,
without limitation, the federal Anti-Kickback Statute and the federal False Claims Act. These laws may affect, among other things, our
proposed sales, marketing and education programs. In addition, we may be subject to patient privacy regulation by both the federal
government and the states in which we conduct our business. The laws that may affect our ability to operate include:
● the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting,
receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of
an item or service reimbursable under a federal health care program, such as the Medicare and Medicaid programs;
● federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or
entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid or other third-
party payors that are false or fraudulent;
● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, as amended by the Health Information
Technology for Economic and Clinical Health Act of 2009, or HITECH, and its implementing regulations, which impose
certain requirements relating to the privacy, security and transmission of individually identifiable health information;
● the federal transparency requirements under the Patient Protection and Affordable Care Act of 2010 (“ACA”) requires
manufacturers of drugs, devices, biologics and medical supplies to report to the Department of Health and Human Services
information related to physician payments and other transfers of value and physician ownership and investment interests;
● state law and foreign law equivalents of each of the above federal laws, such as anti-kickback and false claims laws which may
apply to items or services reimbursed by any third-party payor, including commercial insurers, and state laws governing the
privacy and security of health information in certain circumstances, many of which differ from each other in significant ways
and may not have the same effect, thus complicating compliance efforts; and
● state and federal laws, such as the Physician Sunshine Act, directed at generating transparency on financial issues, including
drug prices and payments made by drug companies to various entities and individuals involved in healthcare.
Although compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, the risks cannot be
entirely eliminated. If our operations are found to be in violation of any of the laws described above or any other governmental
regulations that apply to us, we may be subject to penalties, including exclusion from payment by federal health care programs, civil and
criminal penalties, damages, fines and the curtailment or restructuring of our operations, any of which could adversely affect our ability
to operate our business and our results of operations. Moreover, achieving and sustaining compliance with applicable federal and state
privacy, security and fraud laws may prove costly.
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Compliance with laws and regulations pertaining to the privacy and security of health information may be time consuming, difficult
and costly, particularly in light of increased focus on privacy issues in countries around the world, including the U.S. and the EU.
We are subject to various domestic and international privacy and security regulations related to personal information, including
health information, that are appliable to our business and associated data processing activities. The confidentiality, collection, use and
disclosure of personal data, including clinical trial patient-specific information, are subject to governmental regulation generally in the
country that the personal data were collected or used. In the United States, we are subject to various state and federal privacy and data
security regulations, including but not limited to HIPAA and as amended by the HITECH Act. HIPAA imposes specified requirements
relating to the privacy, security and transmission of individually identifiable health information, and mandates, among other things, the
adoption of uniform standards for the electronic exchange of information in common health care transactions, as well as standards
relating to the privacy and security of individually identifiable health information, which require the adoption of administrative, physical
and technical safeguards to protect such information. We may also be subject to state security breach notification laws, state laws
protecting the privacy and security of health and personal information, and federal and state consumer protections laws which regulate
the collection, use, disclosure and transmission of personal information. These laws may overlap and conflict with each other, and each
of these laws is subject to varying interpretations by courts and government agencies, creating complex compliance issues for us. In the
EU, personal data includes any information that relates to an identified or identifiable natural person with health information carrying
additional obligations, including obtaining the explicit consent from the individual for collection, use or disclosure of the information.
We are also subject to the EU General Data Protection Regulation 2016/679 (“GDPR”). Violations of the GDPR can carry hefty fines. In
addition, we may be subject to additional national laws and regulations that govern the privacy and security of health information in
certain circumstances, many of which differ from each other in significant ways, thus complicating compliance efforts. If we fail to
comply with applicable data protection laws and regulations, we could be subject to penalties or sanctions, including criminal penalties.
Furthermore, the legislative and regulatory landscape for privacy and data protection continues to evolve, and there has been an
increasing amount of focus on privacy and data protection issues.
Compliance with these laws may be time-consuming, difficult and costly. If we fail to comply with applicable laws, regulations or
duties relating to the use, privacy or security of personal data we could be subject to the imposition of significant civil and criminal
penalties, be forced to alter our business practices and suffer reputational harm.
Changes in health care law and implementing regulations, including government restrictions on pricing and reimbursement, as well
as health care policy and other health care payor cost-containment initiatives, may have a material adverse effect on us.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory changes and proposed
changes regarding the regulatory system, health care system and efforts to control health care costs, including drug prices, that could
have a significant negative impact on our business, including preventing, limiting or delay regulatory approval of our drug candidates
and reducing the sales and profits derived from our products once they are approved. For example, in the United States, the ACA
substantially changed the way health care is financed by both governmental and private insurers and significantly affects the
pharmaceutical industry. Many provisions of ACA impact the biopharmaceutical industry, including that in order for a biopharmaceutical
product to receive federal reimbursement under the Medicare Part B and Medicaid programs or to be sold directly to U.S. government
agencies, the manufacturer must extend discounts to entities eligible to participate in the drug pricing program under the Public Health
Services Act, or PHS. Since its enactment, there have been judicial and Congressional challenges and amendments to certain aspects of
ACA. There is continued uncertainty about the implementation of ACA, including the potential for further amendments to the ACA and
legal challenges to or efforts to repeal the ACA.
In addition, the Inflation Reduction Act of 2022, enacted in August 2022, empowers the Centers for Medicare and Medicaid
Services to negotiate directly with pharmaceutical companies to set the prices for a limited set of high-cost drugs covered by Medicare,
and puts penalties in place for drug manufacturers who increase their Medicare prices by more than the rate of inflation.
Other examples of proposed changes include, but are not limited to, expanding post-approval requirements, changing the Orphan
Drug Act, and restricting sales and promotional activities for pharmaceutical products.
We cannot be sure whether additional legislative changes will be enacted, or whether government regulations, guidance or
interpretations will be changed, or what the impact of such changes would be on the marketing approvals, sales, pricing, or
reimbursement of our drug candidates or products, if any, may be.
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Risks Related to Our Capital Stock
Our history of losses and uncertainty of future profitability make our common stock a highly speculative investment.
We have had no commercial revenue to date from sales of our drug candidates. We had an accumulated deficit of $1.3 billion as of
December 31, 2022. We expect to spend substantial funds to continue the research and development testing of our drug candidates.
In anticipation of FDA approval of these products, we will need to make substantial investments to establish sales, marketing,
quality control, regulatory compliance capabilities and commercial manufacturing alliances. These investments will increase if and when
any of these drug candidates receive FDA approval. We cannot predict how quickly our lead drug candidates will progress through the
regulatory approval process. As a result, we may continue to lose money for several years.
We cannot be certain that we will achieve or sustain profitability in the future. Failure to achieve profitability could diminish our
ability to sustain operations, pay dividends on our common stock, obtain additional required funds and make required payments on our
present or future indebtedness.
Our share price has been and could remain volatile.
The market price of our common stock has historically experienced and may continue to experience significant volatility. From
January 2021 through December 2022, the market price of our common stock has fluctuated from a high of $57.20 per share in the fourth
quarter of 2021, to a low of $15.37 per share in the first quarter of 2021. Our progress in developing and commercializing our products,
the impact of government regulations on our products and industry, the potential sale of a large volume of our common stock by
stockholders, our quarterly operating results, changes in general conditions in the economy or the financial markets and other
developments affecting us or our competitors could cause the market price of our common stock to fluctuate substantially with
significant market losses. If our stockholders sell a substantial number of shares of common stock, especially if those sales are made
during a short period of time, those sales could adversely affect the market price of our common stock and could impair our ability to
raise capital. In addition, in recent years, the stock market has experienced significant price and volume fluctuations. This volatility has
affected the market prices of securities issued by many companies for reasons unrelated to their operating performance and may
adversely affect the price of our common stock. In addition, we could be subject to a securities class action litigation as a result of
volatility in the price of our stock, which could result in substantial costs and diversion of management’s attention and resources and
could harm our stock price, business, prospects, results of operations and financial condition.
Our ability to use our net operating loss carryforwards will be subject to limitation and, under certain circumstances, may be
eliminated.
As of December 31, 2022, we had net operating loss carryforwards, or NOLs, of approximately $623.1 million for federal income
tax purposes, and $879.9 million for state income tax purposes. Utilization of these NOLs depends on many factors, including our future
income, which cannot be assured. In addition, utilization of our net operating loss and research and development credit carryforwards
may be subject to substantial annual limitation due to ownership change limitations that have occurred previously or that could occur in
the future provided by Section 382 of the Internal Revenue Code of 1986, or Section 382, as well as similar state provisions. In general,
an ownership change, as defined by Section 382, results from transactions increasing the ownership of certain shareholders or public
groups in the stock of a corporation by more than 50 percentage points over a three-year period.
In October 2007, June 2009, December 2009 and December 2013, we experienced a change in ownership as defined by Section 382.
Historically, we have raised capital through the issuance of capital stock on several occasions which, combined with shareholders’
subsequent disposition of those shares, has resulted in three changes of control, as defined by Section 382. As a result of these ownership
changes, utilization of at least some of our federal NOL carryforwards is subject to an annual limitation. We have not undertaken a study
to assess whether an ownership change or multiple ownership changes have occurred for (i) acquired businesses with NOLs prior to
being acquired by the Company, (ii) the Company on the state level, (iii) the Company since March 2015 or (iv) research and
development credits. If, based on such a study, we were to determine that there has been an ownership change at any time, utilization of
net operating loss or tax credit carryforwards would be subject to an annual limitation under Section 382 (or similar state provisions).
Any unused annual limitation may be carried over to later years, and the amount of the limitation may, under certain circumstances,
be subject to adjustment if the fair value of our net assets is determined to be below or in excess of the tax basis of such
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assets at the time of the ownership change, and such unrealized loss or gain is recognized during the five-year period after the ownership
change. Subsequent ownership changes, as defined in Section 382, could further limit the amount of net operating loss carryforwards and
research and development credits that can be utilized annually to offset future taxable income. Additionally, the Tax Cuts and Jobs Act
limited the deduction for net operating losses to 80% of taxable income while providing that net operating loss carryovers for years after
2017 will not expire. The CARES Act provides relief to corporate taxpayers by permitting a five year carryback of 2018 – 2020 NOLs,
removing the 80% limitation on the carryback of those NOLs, and accelerates refunds for minimum tax credit carryforwards, along with
a few other provisions. During the twelve months ended December 31, 2022, no material adjustments were made to provision amounts
recorded as a result of the enactment of the CARES Act.
Refer to Note 15, “Income Taxes,” in the accompanying notes to the financial statements for additional discussion on income taxes.
General Risk Factors
If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately report our
financial results or prevent fraud. As a result, stockholders could lose confidence in our financial and other public reporting, which
would harm our business and the trading price of our common stock.
Effective internal controls over financial reporting are necessary for us to provide reliable financial reports and, together with
adequate disclosure controls and procedures, are designed to prevent fraud. Any failure to implement required or improved controls, or
difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations. We have designed, implemented
and tested the internal control over financial reporting required to comply with this obligation, which was and is time consuming, costly,
and complicated. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that
the control system’s objectives will be met. Because of the inherent limitations in all control systems, no evaluation of controls can
provide absolute assurance that misstatements due to error or fraud will not occur or that all control issues and instances of fraud will be
detected. Any testing by us conducted in connection with Section 404 of the Sarbanes-Oxley Act of 2002, or any subsequent testing by
our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are
deemed to be material weaknesses or that may require prospective or retroactive changes to our financial statements or identify other
areas for further attention or improvement. Inferior internal controls could also cause investors to lose confidence in our reported
financial information, which could have a negative effect on the trading price of our common stock.
We have many competitors in our field, and they may develop technologies that make ours obsolete.
Biotechnology, pharmaceuticals and therapeutics are rapidly evolving fields in which scientific and technological developments are
expected to continue at a rapid pace. We have many competitors in the U.S. and abroad. The competitors of which we are aware that
have initiated a Phase 3 study or have obtained marketing approval for a potentially competitive drug to barzolvolimab for treatment of
CSU, CIndU, PN and EoE include: Allakos (lirentelimab for EoE), AstraZeneca (Fasenra for CSU), Galderma/Chugai (nemolizumab for
PN), Genentech (fenebrutinib for CSU), Leo Pharma (Adbry for AD), Novartis (ligelizumab for CSU, CIndU and food allergy;
remibrutinib for CSU), Regeneron/Sanofi (Dupixent for CSU, CIndU, PN and EoE), and Trevi Therapeutics (nalbuphine for PN). Our
success depends upon our ability to develop and maintain a competitive position in the product categories and technologies on which we
focus. Many of our competitors have greater capabilities, experience and financial resources than we do. Competition is intense and is
expected to increase as new products enter the market and new technologies become available. Our competitors may:
● develop technologies and products that are more effective than ours, making ours obsolete or otherwise noncompetitive;
● obtain regulatory approval for products more rapidly or effectively than us; and
● obtain patent protection or other intellectual property rights that would block our ability to develop competitive products.
We face risks related to health epidemics and outbreaks, including COVID-19, which could significantly disrupt our preclinical
studies and clinical trials.
The future progression of the COVID-19 pandemic and its effects on our business and operations are uncertain. The duration and the
geographic impact of the business disruption and related financial impact resulting from the COVID-19 pandemic cannot be
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reasonably estimated at this time and our business could be adversely impacted by its effects. In an effort to halt or slow the outbreak of
COVID-19, many governments have, at times, placed significant restrictions on travel and many businesses have, at times, announced
closures for extended periods which could adversely impact our operations. Enrollment of patients in our clinical trials and our planned
and ongoing preclinical and clinical trials may be delayed due to COVID-19. The impact of the COVID-19 pandemic on the operations
of the FDA and other health authorities may delay potential approvals of our clinical trial protocols. In addition, we rely on independent
clinical investigators, contract research organizations and other third-party service providers to assist us in managing, monitoring and
otherwise carrying out our preclinical studies and clinical trials, and the pandemic may affect their ability to devote sufficient time and
resources to our programs. We also rely on third party suppliers and contract manufacturers to produce the drug product we utilize in our
clinical trials, and the pandemic may cause delays in the delivery of active pharmaceutical ingredients (“APIs”) and drug product.
Temporary closure of our facilities, or facilities at which our clinical or preclinical trials are conducted, or restrictions on the ability of
our employees, clinicians or patients enrolled in our trials to travel could adversely affect our operations and our ability to conduct and
complete our preclinical and clinical trials. In addition, the COVID-19 pandemic, including insufficient vaccination of the general
population and the emergence of COVID-19 variants, could affect the health and availability of our workforce as well as those of the
third parties on whom we rely. If new, more infectious or severe variants emerge, it is possible that the impact of the pandemic on our
business may increase or lengthen in duration.
As a result of the foregoing factors, the expected timeline for data readouts of our preclinical studies and clinical trials and certain
regulatory filings may be negatively impacted, which would adversely affect our business.
We depend greatly on the intellectual capabilities and experience of our key executives and scientists, and the loss of any of them
could affect our ability to develop our products.
The loss of any of our executive officers could harm us. We entered into employment agreements with each of our executive
officers, although an employment agreement as a practical matter does not guarantee retention of an employee. We also depend on our
scientific and clinical collaborators and advisors, all of whom have outside commitments that may limit their availability to us. In
addition, we believe that our future success will depend in large part upon our ability to attract and retain highly skilled scientific,
managerial and marketing personnel, particularly as we expand our activities in clinical trials, the regulatory approval process and sales
and manufacturing. We routinely enter into consulting agreements with our scientific and clinical collaborators and advisors, key opinion
leaders and heads of academic departments in the ordinary course of our business. We also enter into contractual agreements with
physicians and institutions who recruit patients into our clinical trials on our behalf in the ordinary course of our business.
Notwithstanding these arrangements, we face significant competition for this type of personnel from other companies, research and
academic institutions, government entities and other organizations. We cannot predict our success in hiring or retaining the personnel we
require for continued growth.
Our employees may engage in misconduct or other improper activities, including noncompliance with regulatory standards and
requirements, which could have a material adverse effect on our business.
We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees could include intentional failures to
comply with FDA regulations, provide accurate information to the FDA, comply with applicable privacy laws, comply with
manufacturing standards we have established, comply with federal and state health care fraud and abuse laws and regulations, report
financial information or data accurately or disclose unauthorized activities to us. In particular, sales, marketing and business
arrangements in the health care industry are subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing
and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and
promotion, sales commission, customer incentive programs and other business arrangements. Employee misconduct could also involve
the improper use of information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to
our reputation. We have adopted a Code of Business Conduct and Ethics and launched a Health Care Compliance program, but it is not
always possible to identify and deter employee misconduct. The precautions we take and the investments we make 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. 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
effect on our business and results of operations, including the imposition of significant fines or other sanctions.
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We may not be able to maintain compliance with the Listing Rules of the NASDAQ Stock Exchange.
There can be no assurance that in the future we will be able to maintain compliance with the Nasdaq Listing Rules, including the
minimum bid price requirement and other applicable corporate governance requirements. If we fail to maintain compliance with the
minimum bid requirement or to meet the other applicable continued listing requirements for the NASDAQ Capital Market in the future
and NASDAQ determines to delist our common stock, the delisting could adversely affect the market price and liquidity of our common
stock and reduce our ability to raise additional capital. In addition, if our common stock is delisted from NASDAQ and the trading price
remains below $5.00 per share, trading in our common stock might also become subject to the requirements of certain rules promulgated
under the Exchange Act, which require additional disclosure by broker-dealers in connection with any trade involving a stock defined as
a “penny stock” (generally, any equity security not listed on a national securities exchange or quoted on NASDAQ that has a market
price of less than $5.00 per share, subject to certain exceptions).
Item 1B. UNRESOLVED STAFF COMMENTS
None.
Item 2. PROPERTIES
As of December 31, 2022, our significant leased properties are described below.
Property Location
Hampton, New Jersey
Fall River, Massachusetts
New Haven, Connecticut
Approximate
Square Feet
Use
Lease Expiration Date
33,400 Headquarters, Office and Laboratory July 2025(1)
33,900 Manufacturing, Office and Laboratory July 2025(2)
April 2025
17,700 Office and Laboratory
(1) Lease includes one renewal option of two years followed by one renewal option of three years.
(2) Lease includes one renewal option of two years followed by one renewal option of three years.
Item 3. LEGAL PROCEEDINGS
We are not currently a party to any material legal proceedings.
Item 4. MINE SAFETY DISCLOSURES
Not applicable.
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PART II
Item 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER
PURCHASES OF EQUITY SECURITIES
Our common stock currently trades on the Nasdaq Capital Market (NASDAQ) under the symbol “CLDX.” As of February 13, 2023,
there were approximately 154 shareholders of record of our common stock. On February 13, 2023 the closing price of our common
stock, as reported by NASDAQ, was $42.17 per share. We have not paid any dividends on our common stock since our inception and do
not intend to pay any dividends in the foreseeable future.
CELLDEX THERAPEUTICS, INC., NASDAQ MARKET INDEX — U.S. AND PEER GROUP INDICES
The graph below compares the cumulative total stockholder return on the common stock for the period from December 31, 2017
through December 31, 2022, with the cumulative return on (i) NASDAQ U.S. Benchmark TR Index and (ii) NASDAQ Pharmaceutical
(Subsector) Index. The comparison assumes investment of $100 on December 31, 2017 in our common stock and in each of the indices
and, in each case, assumes reinvestment of all dividends. The points on the graph are as of December 31 of the year indicated.
Celldex Therapeutics, Inc.
NASDAQ U.S. Benchmark TR Index
NASDAQ Pharmaceutical (Subsector) Index
Item 6. [Reserved]
2017
$ 100
$ 100
$ 100
2018
7
$
$
95
$ 108
2019
$
5
$ 124
$ 124
2020
2021
2022
$
$
$
41
150
137
$
$
$
91
189
170
$
$
$
105
152
189
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Item 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS
OVERVIEW
We are a biopharmaceutical company dedicated to developing therapeutic monoclonal and bispecific antibodies that address diseases
for which available treatments are inadequate. Our drug candidates include antibody-based therapeutics which have the ability to engage
the human immune system and/or directly affect critical pathways to improve the lives of patients with inflammatory diseases and many
forms of cancer.
We are focusing our efforts and resources on the continued research and development of
● Barzolvolimab (also referred to as CDX-0159), a monoclonal antibody that specifically binds the KIT receptor and potently
inhibits its activity, which is currently being studied across multiple mast cell driven diseases including
-
-
-
Chronic Urticarias: In June and July 2022 respectively, we announced that enrollment had opened and the first patients
had been dosed in Phase 2 studies in chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU).
Positive interim data from the ongoing Phase 1b study in CSU were reported in February 2023. Positive interim data
from the Phase 1b study in CIndU were reported in July and September 2021 and in December 2022 in patients with
cold urticaria and symptomatic dermographism;
Prurigo Nodularis (PN): In December 2021 we announced that the first patient had been dosed in a Phase 1b study in
PN; enrollment was closed in February 2023 and we plan to present data from the study in the second half of 2023;
Eosinophilic Esophagitis (EoE): We plan to initiate a Phase 2 study in EoE in the first half of 2023.
● Our next generation bispecific antibody platform to support pipeline expansion with additional candidates for inflammatory
diseases and oncology. Targets are being selected based on new science as well as their compatibility to be used in bispecific
antibody formats with Celldex’s existing antibody programs. Development is focused on emerging, important pathways
controlling inflammatory diseases or immunity to tumors.
Our goal is to build a fully integrated, commercial-stage biopharmaceutical company that develops important therapies for patients
with unmet medical needs. We believe our program assets provide us with the strategic options to either retain full economic rights to our
innovative therapies or seek favorable economic terms through advantageous commercial partnerships. This approach allows us to
maximize the overall value of our technology and product portfolio while best ensuring the expeditious development of each individual
product.
The expenditures that will be necessary to execute our business plan are subject to numerous uncertainties. Completion of clinical
trials may take several years or more, and the length of time generally varies substantially according to the type, complexity, novelty and
intended use of a drug candidate. It is not unusual for the clinical development of these types of drug candidates to each take five years or
more, and total development costs could exceed hundreds of millions of dollars for each drug candidate. We estimate that clinical trials
of the type we generally conduct are typically completed over the following timelines:
Clinical Phase
Phase 1
Phase 2
Phase 3
Estimated
Completion
Period
1 – 2 Years
1 – 5 Years
1 – 5 Years
The duration and the cost of clinical trials may vary significantly over the life of a project as a result of differences arising during the
clinical trial protocol, including, among others, the following:
● the number of patients that ultimately participate in the trial;
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● the duration of patient follow-up that seems appropriate in view of results;
● the number of clinical sites included in the trials;
● the length of time required to enroll suitable patient subjects; and
● the efficacy and safety profile of the drug candidate.
We test potential drug candidates in numerous preclinical studies for safety, toxicology and immunogenicity. We may then conduct
multiple clinical trials for each drug candidate. As we obtain results from trials, we may elect to discontinue or delay clinical trials for
certain drug candidates in order to focus our resources on more promising drug candidates.
An element of our business strategy is to pursue the discovery, research and development of a broad portfolio of drug candidates.
This is intended to allow us to diversify the risks associated with our research and development expenditures. To the extent we are unable
to maintain a broad range of drug candidates, our dependence on the success of one or a few drug candidates increases.
Regulatory approval is required before we can market our drug candidates as therapeutic products. In order to proceed to subsequent
clinical trial stages and to ultimately achieve regulatory approval, the regulatory agencies must conclude that our clinical data
demonstrate that our product candidates are safe and effective. Historically, the results from preclinical testing and early clinical trials
(through Phase 2) have often not been predictive of results obtained in later clinical trials. A number of new drugs and biologics have
shown promising results in early clinical trials but subsequently failed to establish sufficient safety and efficacy data to obtain necessary
regulatory approvals.
Furthermore, our business strategy includes the option of entering into collaborative arrangements with third parties to complete the
development and commercialization of our drug candidates. In the event that third parties take over the clinical trial process for one of
our drug candidates, the estimated completion date would largely be under control of that third party rather than us. We cannot forecast
with any degree of certainty which proprietary products, if any, will be subject to future collaborative arrangements, in whole or in part,
and how such arrangements would affect our development plan or capital requirements. Our programs may also benefit from subsidies,
grants, contracts or government or agency-sponsored studies that could reduce our development costs.
As a result of the uncertainties discussed above, among others, it is difficult to accurately estimate the duration and completion costs
of our research and development projects or when, if ever, and to what extent we will receive cash inflows from the commercialization
and sale of a product. Our inability to complete our research and development projects in a timely manner or our failure to enter into
collaborative agreements, when appropriate, could significantly increase our capital requirements and could adversely impact our
liquidity. These uncertainties could force us to seek additional, external sources of financing from time to time in order to continue with
our business strategy. Our inability to raise additional capital, or to do so on terms reasonably acceptable to us, would jeopardize the
future success of our business.
During the past five years through December 31, 2022, we incurred an aggregate of $287.2 million in research and development
expenses. The following table indicates the amount incurred for each of our significant research programs and for other identified
research and development activities during the years ended December 31, 2022, 2021 and 2020. The amounts disclosed in the following
table reflect direct research and development costs, license fees associated with the underlying technology and an allocation of indirect
research and development costs to each program.
Barzolvolimab/Anti-KIT Program
CDX-585
CDX-527
CDX-1140 and CDX-301
Other Programs
Total R&D Expense
Year Ended
Year Ended
Year Ended
December 31, 2022 December 31, 2021 December 31, 2020
51,220
9,793
2,012
3,992
15,241
82,258
(In thousands)
24,395
7,133
3,619
5,439
12,725
53,311
$
$
$
$
8,444
—
8,840
10,948
14,302
42,534
$
$
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Clinical Development Programs
Barzolvolimab (also referred to as CDX-0159)
Barzolvolimab is a humanized monoclonal antibody that specifically binds the receptor tyrosine kinase KIT and potently inhibits its
activity. KIT is expressed in a variety of cells, including mast cells, and its activation by its ligand SCF regulates mast cell growth,
differentiation, survival, chemotaxis and degranulation. Barzolvolimab is designed to block KIT activation by disrupting both SCF
binding and KIT dimerization. We believe that by targeting KIT, barzolvolimab may be able to inhibit mast cell activity and decrease
mast cell numbers to provide potential clinical benefit in mast cell related diseases.
In certain inflammatory diseases, such as chronic spontaneous urticaria (CSU), also known as chronic idiopathic urticaria (CIU), and
chronic inducible urticaria (CIndU), mast cell degranulation plays a central role in the onset and progression of the disease. In June 2020,
we completed a randomized, double-blind, placebo-controlled, single ascending dose escalation Phase 1a study of barzolvolimab in
healthy subjects (n = 32; 8 subjects per cohort, 6 barzolvolimab; 2 placebo). Subjects received a single intravenous infusion of
barzolvolimab at 0.3, 1.0, 3.0, or 9.0 mg/kg or placebo. The objectives of the study included safety and tolerability, pharmacokinetics
(PK) and pharmacodynamics (tryptase and stem cell factor) and immunogenicity. Tryptase is an enzyme synthesized and secreted almost
exclusively by mast cells and decreases in plasma tryptase levels are believed to reflect a systemic reduction in mast cell burden in both
healthy volunteers and in disease. Data from the study were featured in a late breaking presentation at the European Academy of Allergy
and Clinical Immunology (EAACI) Annual Congress 2020 in June. Barzolvolimab demonstrated a favorable safety profile as well as
profound and durable reductions of plasma tryptase, consistent with systemic mast cell suppression.
These data supported expansion of the barzolvolimab program into mast cell driven diseases, including initially in CSU and CIndU,
diseases where mast cell degranulation plays a central role in the onset and progression of the disease. Phase 1 studies in CSU and CIndU
are completing and Phase 2 studies are ongoing. We continue to assess potential opportunities for barzolvolimab in other diseases where
mast cells play an important role, such as dermatologic, respiratory, allergic, gastrointestinal and ophthalmic conditions and to this end,
are conducting an ongoing Phase 1 study in prurigo nodularis and plan to initiate a Phase 2 study in eosinophilic esophagitis in the first
half of 2023. Phase 1 studies of barzolvolimab have been conducted with an intravenous formulation; a subcutaneous formulation has
been successfully developed and is being used in Phase 2 studies.
Chronic Spontaneous Urticaria (CSU)
CSU presents as itchy hives, angioedema or both for at least six weeks without a specific trigger; multiple episodes can play out over
years or even decades. CSU is one of the most frequent dermatologic diseases with a prevalence of 0.5-1.0% of the total population or up
to approximately 1 to 3 million patients in the United States (Weller et al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org).
Approximately 50% of patients with CSU achieve symptomatic control with antihistamines. Omalizumab, an IgE inhibitor, provides
relief for roughly half of the remaining antihistamine refractory patients. Consequently, there is a need for additional therapies.
In October 2020, we announced that enrollment had opened and the first patient had been dosed in a Phase 1b multi-center study of
barzolvolimab in CSU. This study is a randomized, double-blind, placebo- controlled clinical trial designed to assess the safety of
multiple ascending doses of barzolvolimab in up to 40 patients with CSU who remain symptomatic despite treatment with
antihistamines. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments, including
measurement of tryptase and stem cell factor levels and clinical activity outcomes (impact on urticaria symptoms, disease control,
clinical response) as well as quality of life assessments. Barzolvolimab is administered intravenously (0.5, 1.5, 3 and 4.5 mg/kg at
varying dosing schedules) as add on treatment to H1- antihistamines, either alone or in combination with H2-antihistamines and/or
leukotriene receptor agonists.
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In February 2023, we reported positive interim data from the CSU study. As of the data cut-off date on November 29, 2022,
enrollment was complete with 45 patients with moderate to severe CSU refractory to antihistamines enrolled and treated [35
barzolvolimab (n=9 in 0.5 mg/kg; n=8 in 1.5 mg/kg; n=9 in 3.0 mg/kg; n=9 in 4.5 mg/kg) and 10 placebo]. The 0.5 mg/kg, 1.5 mg/kg
and 3.0 mg/kg cohorts had completed study participation through 24 weeks; 6 of 9 patients in the 4.5 mg/kg cohort had completed
through the week 20 visit. Complete data were included for all patients in dose levels through 3.0 mg/kg through 24 weeks. All available
data for the 4.5 mg/kg and placebo dose levels were presented for adverse events. Activity data for the 4.5 mg/kg dose level were
reported through week 20. Activity data for the 0.5 mg/kg and placebo group were only included through week 12 because, as expected,
most patients from these groups had significant symptoms ahead of week 24 and discontinued follow up. Two patients did not receive all
doses of study treatment [4.5 mg/kg (1), placebo (1)].
● Barzolvolimab resulted in rapid, marked and durable responses in patients with moderate to severe CSU refractory to
antihistamines, including patients with prior omalizumab treatment.
● The 1.5 mg/kg, 3.0 mg/kg and 4.5 mg/kg dose groups showed similar markedly improved urticaria symptoms and disease
control with sustained durability up to 24 weeks.
● Mean reduction from baseline in urticaria activity (UAS7) at week 12 of 67% in the 1.5 mg/kg dose group (n=8), 67% in the
3.0 mg/kg dose group (n=9) and 82% in the 4.5 mg/kg dose group (n=9).
● Complete response (UAS7=0) at week 12 of 57% in the 1.5 mg/kg dose group, 44% in the 3.0 mg/kg dose group and 67% in
the 4.5 mg/kg dose group.
● Well-controlled disease (UCT≥ 12) at week 12 of 75% in the 1.5 mg/kg dose group, 63% in the 3.0 mg/kg dose group and 89%
in the 4.5 mg/kg dose group.
● During post-treatment follow up, 7 of 8 (88%) patients who had been treated with barzolvolimab 1.5 mg/kg or 3.0 mg/kg and
had a complete response (UAS7=0) at week 12 maintained their complete response through 24 weeks. Two additional patients
treated with these doses who were not a complete response at week 12 had a complete response at week 24. 6 of 6 (100%)
patients treated with barzolvolimab 4.5 mg/kg maintained their complete response through their last assessment with additional
follow up ongoing.
● Patients with prior omalizumab therapy had similar symptom improvement as all patients.
● Rapid onset of responses after initial dosing and sustained durability were observed; onset as early as 1 week after the first dose
and prolonged symptom control in some patients for up to 24 weeks.
● Tryptase suppression, indicative of mast cell depletion, paralleled symptom improvement, demonstrating the impact of mast
cell depletion on CSU disease activity.
● Barzolvolimab was well tolerated with a favorable safety profile; effects of multiple dose administration were consistent with
observations in single dose studies. Most AEs were mild or moderate in severity and resolved while on study. The most
common treatment emergent adverse events were hair color changes, COVID-19, headache, neutropenia and urinary tract
infections (UTIs). UTIs and COVID-19 were reported as unrelated to treatment. There was one serious adverse event of
salmonella gastroenteritis which was also not related to study therapy. Changes in hematologic parameters were consistent with
observations in single dose studies, with no pattern of further decreases with multiple doses; hematologic values generally
remained within the normal range and returned to baseline levels during the follow up period. Five patients had decreases in
neutrophil counts reported as AEs; four of which were previously reported in the EAACI 2022 data presentation. The pattern
observed in the neutrophil changes for these patients was similar to the pattern seen in patients across the barzolvolimab
program to date—generally transient, asymptomatic, and mild and typically occurring in patients with screening and baseline
neutrophil counts at the lower end of the normal range on study initiation.
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In June 2022, we announced that the first patient has been dosed in a Phase 2 study in patients with CSU who remain symptomatic
despite antihistamine therapy. The study is being conducted at approximately 75 sites across 9 countries. The study is a randomized,
double-blind, placebo-controlled, parallel group Phase 2 study evaluating the efficacy and safety profile of multiple dose regimens of
barzolvolimab to determine the optimal dosing strategy. Approximately 168 patients will be randomly assigned on a 1:1:1:1 ratio to
receive subcutaneous injections of barzolvolimab at 75 mg every 4 weeks, 150 mg every 4 weeks, 300 mg every 8 weeks or placebo
during a 16-week placebo-controlled treatment phase. Patients will then enter a 36-week active treatment phase, in which patients not
already randomized to barzolvolimab at 150 mg every 4 weeks or 300 mg every 8 weeks will be randomized 1:1 to receive one of these
two dose regimens; patients already randomized to these treatment arms will remain on the same regimen as during the placebo-
controlled treatment phase. Following the treatment period, patients will enter a 24-week follow up phase. The primary endpoint of the
study is mean change in baseline to week 12 in UAS7 (Urticaria Activity Score over 7 days). Secondary endpoints include safety and
other assessments of clinical activity including ISS7 (Itch Severity Score over 7 days), HSS7 (Hive Severity Score over 7 days) and
AAS7 (Angioedema Activity Score over 7 days). Based on current enrollment projections, we anticipate that enrollment to this study will
be completed by the end of the third quarter of 2023 and we plan to report topline data either late this year or in the first quarter of 2024.
Chronic Inducible Urticaria (CIndU)
CIndUs are forms of urticaria that have an attributable cause or trigger associated with them, typically resulting in hives or wheals.
The prevalence of CIndU is estimated at 0.5% of the total population and is reported to overlap in up to 36% of CSU patients (Weller et
al. 2010. Hautarzt. 61(8), Bartlett et al. 2018. DermNet.Org). There are currently no approved therapies for chronic inducible urticarias
other than antihistamines and patients attempt to manage symptoms associated with their disease through avoidance of triggers. We are
exploring cold-induced, dermographism (scratch-induced) and cholinergic (exercise-induced) urticarias.
In December 2020, we announced that enrollment had opened and the first patient had been dosed in a Phase 1b study in CIndU
being conducted in Germany in patients who are refractory to antihistamines. This study is an open label clinical trial designed to
evaluate the safety of a single dose (3 mg/kg) of barzolvolimab in patients with cold urticaria (ColdU) or symptomatic dermographism
(SD). In March and June 2021, respectively, we added a third cohort (single dose, 3 mg/kg) in patients with cholinergic urticaria and a
fourth cohort at a lower dose (single dose, 1.5 mg/kg) in ColdU. Patient’s symptoms are induced via provocation testing that resembles
real life triggering situations. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments,
including changes from baseline provocation thresholds, measurement of tryptase and stem cell factor levels, clinical activity outcomes
(impact on urticaria symptoms, disease control, clinical response), quality of life assessments and measurement of tissue mast cells
through skin biopsies. Barzolvolimab is administered intravenously on Day 1 as add on treatment to H1-antihistamines.
In November 2022, data from the ColdU and SD cohorts treated with a single intravenous infusion of barzolvolimab at 3 mg/kg
were published in Allergy (Terhorst-Molawi et al Allergy. 2022 Nov 16. doi: 10.1111/all.15585). Safety results were reported for 21
patients; activity results were reported for the 20 patients who received a full dose of barzolvolimab. Patients had high disease activity.
At baseline, patients’ mean scores (range) for Dermatology Life Quality Index (DLQI) [10.8 (2–21)] and Urticaria Control Test (UCT)
[6.0 (0–13)] indicated marked impairment of quality of life (QoL) and poorly controlled disease, respectively. Three patients (1 with
ColdU and 2 with SD) were previously treated with omalizumab and chose to discontinue that treatment because they remained
symptomatic. At baseline, provocation thresholds, on average (range), were 18.9°C or 66°F (5–27°C or 41–80.6°F) for patients with
ColdU and 3.5 (2–4) pins for patients with SD.
● Rapid (as early as 1 week) and durable responses were observed in all patients as assessed by provocation testing. A complete
response was achieved in 95% (n = 19/20) of patients (n = 10/10 ColdU; n = 9/10 SD). The median duration (range) of
complete response through the 12-week observation period was 77+ days (29–86; n = 10) for patients with ColdU and 57+ days
(16–70; n = 9) for patients with SD. All three patients who experienced insufficient response to omalizumab treatment had a
complete response after treatment with barzolvolimab.
● Following a single dose of barzolvolimab rapid improvements in urticaria control was observed. A UCT score of ≥12 (well
controlled) was achieved by 80% (n = 16/20) of the patients within week 4 post-treatment. By week 8, all patients (100%; n =
20/20) achieved well-controlled urticaria, which was sustained to week 12 post-dose by 80% (n = 16/20) of patients. Complete
urticaria control (UCT = 16) was achieved by 35% (n = 7/20), 65% (n = 13/20), and 40% (n = 8/20) at weeks 4, 8, and 12,
respectively.
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● At baseline, patients in both treatment groups reported disease impact on their QoL. Disease impact significantly decreased
after dosing; a score of 0–1 (minimal/none) was achieved by 80% (n = 16/20) for all patients who completed the DLQI during
the study. Additionally, clinically meaningful improvements in QoL were attained and sustained to week 12.
● A single dose of barzolvolimab led to marked decreases in tryptase and in skin mast cells. The kinetics correlated with
improvements in provocation testing and clinical activity, consistent with a central role for mast cells in the pathogenesis of
ColdU and SD. This confirmed that serum tryptase level is a robust pharmacodynamic biomarker for assessing mast cell burden
and clinical activity in inducible urticaria and potentially in other diseases with mast cell driven involvement.
● Barzolvolimab was well tolerated. Most adverse events were mild, and the most common (≥3 patients) were hair color changes
(76%; n = 16/21), infusion reactions (43%; n = 9/21), taste changes (38%; n = 8/21), nasopharyngitis (24%; n = 5/21), malaise
(24%; n = 5/21), and headache (19%; n = 4/21). Hair color changes (generally small areas of hair color lightening) and taste
disorders (generally partial changes of ability to taste salt or umami) are consistent with inhibiting KIT signaling in other cell
types and completely resolved over time during follow-up. Infusion reactions, which manifested as localized hives and itching
as well as erythema and feeling hot, resolved spontaneously. One patient with a history of fainting experienced loss of
consciousness during infusion. The patient rapidly recovered. Importantly, no evidence of mast cell activation as measured by
serum tryptase monitoring was observed in this patient. Overall, mean hematology parameters remained within the normal
ranges—an important finding for a KIT inhibitor. Mild, transient, and asymptomatic decreases in hemoglobin and white blood
cell parameters occurred for some patients.
In December 2022, we presented long term follow up data from the 3.0 mg/kg cohorts in cold urticaria and symptomatic
dermographism at the GA²LEN Global Urticaria Forum (GUF) 2022. 14 patients consented to the optional long term follow up
evaluation (6 cold, 8 symptomatic dermographism); 10 of the 14 still had complete control of their disease as assessed by provocation
testing at week 12. Data were collected at one or more timepoints beyond week 12 through week 36.
● Most patients had return of symptoms and/or loss of urticaria control between 12 and 36 weeks. Remarkably, two patients
remained provocation negative at 36 weeks, and four had well controlled disease (UCT ≥12) 36 weeks post dosing.
● Serum tryptase exhibits a similar rate of recovery as clinical symptoms, while skin mast cells return at a slower rate. Tissue KIT
signaling, as approximated by SCF levels, was rapidly inhibited after dose administration and fully reactivated approximately
18 weeks after dosing.
● Tryptase levels return to pretreatment levels during follow up, while mast cells continue to recover. Drug related adverse events
noted during the study all resolved.
In December 2022, we also presented 12 week treatment results for the 1.5 mg/kg cohort in cold urticaria at the GA²LEN Global
Urticaria Forum (GUF) 2022. 10 patients received a single intravenous infusion of barzolvolimab at 1.5 mg/kg. Patients had high disease
activity as assessed by provocation threshold testing with a mean baseline critical temperature threshold of 18.4°C or 65°F with a range
from 6 to 27°C or 43 to 81°F. All patients had disease refractory to antihistamines and five patients had disease refractory to
omalizumab. Safety results were reported for all 10 patients; activity results were reported for the 9 patients who received a full dose of
barzolvolimab, including four patients with omalizumab refractory disease.
● All 9 of 9 (100%) patients evaluable for activity treated at 1.5 mg/kg experienced a complete response as assessed by
provocation threshold testing, including 4 patients with disease refractory to omalizumab. Rapid onset of responses after dosing
and sustained durability were observed in the 1.5 mg/kg cohort. 6 of 9 patients treated achieved a complete response within a
week of dosing. The median duration of response was 51+ days (7+ weeks).
● Improvements in disease activity as reported by Urticaria Control Test (UCT) were consistent with the complete responses as
measured by provocation testing. All patients entered the study with poorly controlled disease (mean UCT score at baseline of
5.9 and a range of 1-11). Following barzolvolimab administration, all patients achieved well controlled disease (UCT>12) with
7 of 9 achieving complete control (UCT=16).
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● A single 1.5 mg/kg dose of barzolvolimab resulted in rapid, marked and durable suppression of serum tryptase; the kinetics of
tryptase depletion mirrored changes in provocation threshold and UCT. Barzolvolimab was generally well tolerated and the
safety profile at 1.5mg/kg was similar to the profile observed with 3.0 mg/kg.
● No new treatment emergent AEs of concern were noted. While mild, transient and asymptomatic decreases in hemoglobin and
white blood cell (WBC) parameters were noted, consistent with prior studies, the hematology parameters generally remained
within the normal range.
To date, 19 of 19 (100%) patients with cold urticaria treated with either a single dose of barzolvolimab at 1.5 or 3.0 mg/kg in this
Phase 1b study have experienced a complete response by provocation testing, including 5 patients with omalizumab refractory disease.
In July 2022 we announced that the first patient has been dosed in a Phase 2 study in patients with CIndU who remain symptomatic
despite antihistamine therapy. The study will be conducted at approximately 85 sites across approximately 12 countries. The randomized,
double-blind, placebo-controlled, parallel group Phase 2 study is evaluating the efficacy and safety profile of multiple dose regimens of
barzolvolimab in patients with CIndU to determine the optimal dosing strategy. Approximately 180 patients in 2 cohorts (differentiated
by CIndU subtype) including 90 patients with cold urticaria and 90 patients with symptomatic dermographism will be randomly assigned
on a 1:1:1 ratio to receive subcutaneous injections of barzolvolimab at 150 mg every 4 weeks, 300 mg every 8 weeks or placebo during a
20-week treatment phase. Patients will then enter a follow-up phase for an additional 24 weeks. In addition, the study includes the option
for patients who have symptoms following the treatment phase, including patients who were on placebo, to enroll in an open label
extension where all patients receive 300 mg every 9 weeks of barzolvolimab. The primary endpoint of the study is the percentage of
patients with a negative provocation test at week 12 (using TempTest(R) and FricTest(R)). Secondary endpoints include safety and other
assessments of clinical activity including CTT (Critical Temperature Threshold), CFT (Critical Friction Threshold) and WI-NRS (Worst
itch numeric rating scale).
Prurigo Nodularis (PN)
We have expanded clinical development of barzolvolimab into prurigo nodularis (PN). PN is a chronic skin disease characterized by
the development of hard, intensely itchy (pruritic) nodules on the skin. Mast cells through their interactions with sensory neurons and
other immune cells are believed to play an important role in amplifying chronic itch and neuroinflammation, both of which are a
hallmark of PN. There is currently only one FDA approved therapy for PN, representing an area of significant unmet need. Industry
sources estimate there are approximately 154,000 patients in the United States with PN who have undergone treatment within the last 12
months and, of these, approximately 75,000 would be biologic-eligible. In December 2021, the first patient was dosed in a Phase 1b
multi-center, randomized, double-blind, placebo-controlled intravenous study designed to assess the safety and treatment effects across
multiple dosing cohorts of barzolvolimab in up to 30 patients with PN. Enrolling an intravenous, early stage study in the dermatology
setting has been a challenge and the study has taken longer than expected to complete. In February 2023, we closed enrollment at 24
patients, which we believe will provide sufficient data for analysis to inform future development decisions in PN. Following the
completion of the 24 week follow up period post dosing for patients on study, we plan to present data from the study in the second half of
2023. Potential future development in PN will utilize the subcutaneous formulation of barzolvolimab.
Eosinophilic Esophagitis (EoE)
In February 2022, we announced that we will be expanding clinical development of barzolvolimab into eosinophilic esophagitis
(EoE), the most common type of eosinophilic gastrointestinal disease. EoE is a chronic inflammatory disease of the esophagus
characterized by the infiltration of eosinophils. This chronic inflammation can result in trouble swallowing, chest pain, vomiting and
impaction of food in the esophagus, a medical emergency. Several studies have suggested that mast cells may be an important driver in
the disease, demonstrating that the number and activation state of mast cells are greatly increased in EoE biopsies and that mast cell
signatures correlate with markers of inflammation, fibrosis, pain and disease severity. Currently, there is only one FDA approved therapy
for EoE, representing an area of significant unmet need. Industry sources estimate there are approximately 160,000 patients in the United
States with EoE who have undergone treatment within the last 12 months and, of these, approximately 48,000 would be biologic-eligible.
Given the lack of effective therapies for EoE and barzolvolimab’s potential as a mast cell depleting agent, we believe EoE is an important
indication for future study and plan to initiate a Phase 2 multi-center, randomized, double-blind, placebo-controlled subcutaneous study
designed to assess the treatment effects and safety of barzolvolimab in patients with EoE in the first half of 2023.
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Additional Barzolvolimab Development Activities
Manufacturing activities to support the introduction of the barzolvolimab subcutaneous formulation into the clinical program have
been completed and, in September 2021, we initiated dosing in a randomized, double-blind, placebo-controlled, Phase 1 study designed
to evaluate the safety of single ascending doses of the subcutaneous formulation of barzolvolimab in healthy volunteers. In February
2022, we reported that subcutaneous administration of barzolvolimab was well tolerated and that multiple dose levels have been
identified that possess promising pharmacokinetic and pharmacodynamic properties. Importantly, subcutaneous delivery of
barzolvolimab resulted in dose-dependent, rapid and sustained decreases in serum tryptase compared with placebo and achieved
sufficient exposure to produce tryptase suppression levels comparable with the levels that generated impressive clinical activity observed
in the Phase 1 CIndU intravenous study. The Phase 2 multi-dose studies in urticaria are designed to evaluate 75 mg and 150 mg
administered every 4 weeks and 300 mg administered every 8 weeks. These doses support a 0.5 to 2 ml injection volume, allowing for a
single injection as barzolvolimab advances towards potential commercialization. In 2022, we initiated transfer of our current
barzolvolimab manufacturing process to a contract manufacturing organization to support late-stage trials and to prepare for potential
commercialization.
In February 2022, we reported interim data after completing the in-life dosing portion of our six-month chronic toxicology study in
non-human primates. The only clinically adverse finding at the completion of dosing was a profound impact on spermatogenesis, an
expected and well understood effect of KIT inhibition. As a standard part of toxicology studies, some animals from each group continued
to be observed through a recovery period to understand the reversibility of any adverse findings. Due to the very high concentrations of
barzolvolimab at the end of dosing, the recovery period was approximately one year. As we expected, and consistent with previous
findings with KIT blocking antibodies, we were pleased to report in December 2022, that during this recovery period spermatogenesis
fully recovered in all male animals as measured by both sperm count and motility. We expect the final histologic analysis and study
report in early 2023. We are encouraged with these findings and believe these data strongly support our Phase 2 studies in urticaria and in
future indications.
Bispecific Platform
Our next generation bispecific antibody platform is supporting the expansion of our pipeline with additional candidates for
inflammatory diseases and oncology. Targets are being selected based on new science as well as their compatibility to be used in
bispecific antibody formats with our existing antibody programs. Development is focused on emerging, important pathways controlling
inflammatory diseases or immunity to tumors.
CDX-585
CDX-585 combines our proprietary highly active PD-1 blockade and anti-ILT4 blockade to prevent immunosuppressive signals in T
cells and myeloid cells, respectively. ILT4 is emerging as an important immune checkpoint on myeloid cells and is thought to contribute
to resistance to PD-1 blockade. Interactions of PD-1 and ILT4 with their ligands are known to deliver immune suppressive signals that
can attenuate anti-tumor immune responses. The concept behind CDX-585 is to simultaneously inhibit both T cell and myeloid
suppressive signals to potentiate the anti-tumor activity of both cell types, and potentially overcome PD-1 resistance. In preclinical
studies, CDX-585 was demonstrated to be a potent inhibitor of PD-1 signaling in comparison to the approved PD-1 antibody, nivolumab.
In addition, CDX-585 activated and promoted a strong inflammatory phenotype in human macrophage and dendritic cell cultures.
Together these activities of CDX-585 enhanced the response in a mixed lymphocyte reaction assay above that observed for either
parental mAb or the combination of the PD-1 and ILT4 mAbs. The in vivo efficacy of CDX-585 was also demonstrated in a melanoma
humanized mouse model. CDX-585 has successfully completed GMP manufacturing and IND-enabling studies to support clinical
development. CDX-585 will initially be developed for the treatment of solid tumors either as monotherapy or in combination with other
oncologic treatments and is expected to enter the clinic in 2023 in patients with advanced malignancies.
CDX-527
CDX-527 used our proprietary highly active anti-PD-L1 and CD27 human antibodies to couple CD27 co-stimulation with blockade
of the PD-L1/PD-1 pathway to help prime and activate anti-tumor T cell responses through CD27 co-stimulation, while preventing PD-1
inhibitory signals that subvert the immune response. In the summer of 2020, we initiated a Phase 1 dose-escalation study in patients with
advanced or metastatic solid tumors that had progressed during or after standard of care therapy to be followed by tumor-specific
expansion cohorts. Enrollment to the dose escalation portion was successfully completed and an expansion cohort in patients with
checkpoint naïve ovarian cancer was initiated. In November 2022, we provided an update on the study. With multiple
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clinical trials actively recruiting in ovarian cancer, enrollment to the expansion cohort did not meet our internal timelines and a review of
the results did not meet internal hurdles for proceeding and we closed enrollment to the study and discontinued the program.
Other programs:
CDX-1140
CDX-1140 is a fully human agonist monoclonal antibody targeted to CD40, a key activator of immune response, which is found on
dendritic cells, macrophages and B cells and is also expressed on many cancer cells. A Phase 1 study was conducted in patients with
recurrent, locally advanced or metastatic solid tumors and B cell lymphomas. An MTD of 1.5 mg/kg was established and clinical activity
was observed both as a monotherapy and in combination with pembrolizumab. Despite evidence of clinical benefit, questions remain to
be answered about CDX-1140, and the broader CD40 agonist class, regarding the best clinical settings, regimens, and possible
combinations before advancing into additional Celldex-sponsored studies. Given our pipeline priorities and resource requirements, in
August of 2022, we announced that we are not progressing further Company-sponsored studies at this time and are exploring these
questions in third-party sponsored studies.
CRITICAL ACCOUNTING POLICIES AND ESTIMATES
Our significant accounting policies are described in Note 2 to the financial statements included in Item 8 of this Form 10-K. We
believe our most critical accounting policies include accounting for contingent consideration, revenue recognition, intangible and long-
lived assets, research and development expenses and stock-based compensation expense.
The methods, estimates and judgments we use in applying our most critical accounting policies have a significant impact on the
results we report in our financial statements. We evaluate our estimates and judgments on an ongoing basis. We base our estimates on
historical experience and on assumptions that we believe to be reasonable under the circumstances. Our experience and assumptions
form the basis for our judgments about the carrying value of assets and liabilities that are not readily apparent from other sources. Actual
results may vary from what we anticipate and different assumptions or estimates about the future could materially change our reported
results. We believe the following accounting policies are the most critical to us in that they are important to the portrayal of our financial
statements and they require our most difficult, subjective or complex judgments in the preparation of our financial statements:
Contingent Consideration
We record contingent consideration resulting from a business combination at its fair value on the acquisition date. We determine the
fair value of the contingent consideration based primarily on the following factors:
● timing and probability of success of clinical events or regulatory approvals;
● timing and probability of success of meeting clinical and commercial milestones; and
● discount rates.
Our contingent consideration arose in connection with our acquisition of Kolltan. On a quarterly basis, we revalue these obligations
and record increases or decreases in their fair value as an adjustment to operating earnings. As of December 31, 2022, the fair value of
our contingent consideration was $0.0 million. Changes to contingent consideration obligations can result from adjustments to discount
rates, accretion of the discount rates due to the passage of time, changes in our estimates of the likelihood or timing of achieving
development or commercial milestones, changes in the probability of certain clinical events or changes in the assumed probability
associated with regulatory approval.
The assumptions related to determining the value of contingent consideration include a significant amount of judgment, and any
changes in the underlying estimates could have a material impact on the amount of contingent consideration adjustment recorded in any
given period.
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Revenue Recognition
Revenues are recognized when performance obligations under agreements or contracts are satisfied, in an amount that reflects the
consideration the Company expects to be entitled to in exchange for those services.
The Company determines revenue recognition through the following steps:
● Identification of the contract, or contracts, with a customer;
● Identification of the performance obligations in the contract;
● Determination of the transaction price;
● Allocation of the transaction price to the performance obligations in the contract; and
● Recognition of revenue when, or as, the Company satisfies a performance obligation.
Revenue for the Company is derived from product development agreements with collaborative partners for the research and
development of therapeutic drug candidates. The terms of the agreements may include nonrefundable signing and licensing fees, funding
for research, development and manufacturing, milestone payments and royalties on any product sales derived from collaborations. The
Company assesses the multiple obligations typically within product development contracts to determine the distinct performance
obligations and how to allocate the arrangement consideration to each distinct performance obligation. Under product development
agreements, revenue is generally recognized using a cost-to-cost measure of progress. Revenue is recognized based on the costs incurred
to date as a percentage of the total estimated costs to fulfill the contract. Incurred cost represents work performed, which corresponds
with, and thereby best depicts, the transfer of control to the customer. Due to the nature of the work performed in these arrangements, the
estimation of cost at completion is complex, subject to many variables, such as expected clinical trial costs, and requires significant
judgements. Circumstances can arise that change original estimates of costs or progress toward completion. Any revisions to estimates
are reflected in revenue on a cumulative catch-up basis in the period in which the change in circumstances became known.
Revenue for the Company is also derived from manufacturing and research and development arrangements. The Company owns and
operates a cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for its current and planned early-stage
clinical trials. In order to utilize excess capacity, the Company has, from time to time, entered into contract manufacturing and research
and development arrangements in which services are provided on a time-and-material basis or at a negotiated fixed- price. Revenue from
time-and-material contracts is generally recognized on an output basis as labor hours and/or direct expenses are incurred. Under fixed-
price contracts, revenue is generally recognized on an output basis as progress is made toward completion of the performance obligations
using surveys of performance completed to date.
Intangible and Long-Lived Assets
We evaluate the recoverability of our long-lived assets, including property and equipment when circumstances indicate that an event
of impairment may have occurred. Determination of recoverability is based on an estimate of undiscounted future cash flows resulting
from the use of the asset and its eventual disposition. In the event that such cash flows are not expected to be sufficient to recover the
carrying amount of the assets, the assets are written down to their estimated fair values.
IPR&D assets acquired in a business combination initially are recorded at fair value and accounted for as indefinite-lived intangible
assets. These assets are capitalized on our balance sheets until either the project underlying them is completed or the assets become
impaired. If a project is completed, the carrying value of the related intangible asset is amortized over the remaining estimated life of the
asset beginning in the period in which the project is completed. If a project becomes impaired or is abandoned, the carrying value of the
related intangible asset is written down to its fair value and an impairment charge is taken in the period in which the impairment occurs.
Discounted cash flow models are typically used in these tests, and the models require the use of significant estimates and assumptions
including but not limited to:
● timing and costs to complete the in-process projects;
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● timing and probability of success of clinical events or regulatory approvals;
● estimated future cash flows from product sales resulting from completed products and in-process projects; and
● discount rates
Each IPR&D asset is assessed for impairment at least annually or when impairment indicators are present. The Company has the
option to assess qualitative factors to determine if it is more likely than not that the IPR&D asset is impaired and whether it is necessary
to perform a quantitative impairment test.
Research and Development Expenses
Research and development costs, including internal and contract research costs, are expensed as incurred. Research and development
expenses consist mainly of clinical trial costs, manufacturing of clinical material, toxicology and other preclinical studies, personnel
costs, depreciation, license fees and funding of outside contracted research.
Clinical trial expenses include expenses associated with clinical research organization, or CRO, services. Contract manufacturing
expenses include expenses associated with contract manufacturing organization, or CMO, services. The invoicing from CROs and CMOs
for services rendered can lag several months. We accrue the cost of services rendered in connection with CRO and CMO activities based
on our estimate of costs incurred. We maintain regular communication with our CROs and CMOs to assess the reasonableness of our
estimates. Differences between actual expenses and estimated expenses recorded have not been material and are adjusted for in the
period in which they become known.
Stock-Based Compensation Expense
We record stock-based compensation expense for all stock-based awards made to employees, consultants and non-employee
directors based on the estimated fair values of the stock-based awards expected to vest at the grant date and adjust, if necessary, to reflect
actual forfeitures. Our estimates of employee, consultant, and non-employ director stock option values rely on estimates of future
uncertain events. Significant assumptions include the use of historical volatility to estimate the expected stock price volatility. We also
estimate expected term based on historical exercise patterns. For consultant and non-employee director grants, we may elect to use the
contractual term as the expected term in the option-pricing model. Actual volatility and lives of options may be significantly different
from our estimates. Compensation expense for all stock-based awards is recognized using the straight-line method over the term of
vesting or performance.
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RESULTS OF OPERATIONS
Year Ended December 31, 2022 compared with Year Ended December 31, 2021
Revenues:
Product development and licensing agreements
Contracts and grants
Total revenues
Operating expenses:
Research and development
General and administrative
Intangible asset impairment
Gain on fair value remeasurement of contingent consideration
Litigation settlement related loss
Total operating expenses
Operating loss
Investment and other income, net
Net loss before income tax benefit
Income tax benefit
Net loss
Net Loss
Year Ended
December 31,
Increase/
(Decrease)
Increase/
(Decrease)
2022
2021
$
%
(In thousands)
$
$
56
2,301
2,357
$
$
31
4,620
4,651
$
$
25
(2,319)
(2,294)
82,258
27,195
—
(6,862)
15,000
117,591
(115,234)
2,909
(112,325)
—
$ (112,325)
53,311
20,488
3,500
(1,405)
—
75,894
(71,243)
505
(70,738)
227
$ (70,511)
$
28,947
6,707
(3,500)
5,457
15,000
41,697
43,991
2,404
41,587
(227)
41,814
81 %
(50)%
(49)%
54 %
33 %
(100)%
388 %
n/a
55 %
62 %
476 %
59 %
(100)%
59 %
The $41.8 million increase in net loss for the year ended December 31, 2022, as compared to the year ended December 31, 2021,
was primarily due to the $15.0 million litigation settlement related loss recorded in the second quarter of 2022 and increases in research
and development and general and administrative expenses, partially offset by an increase in the gain on fair value remeasurement of
contingent consideration.
Revenue
Product development and licensing agreements revenue for the year ended December 31, 2022, was relatively consistent with the
year ended December 31, 2021. The $2.3 million decrease in contracts and grants revenue for the year ended December 31, 2022, as
compared to the year ended December 31, 2021, was primarily related to a decrease in services performed under our manufacturing and
research and development agreements with Rockefeller University and Gilead Sciences. We expect revenue to increase over the next
twelve months as a result of an increase in services expected to be performed under our manufacturing and research and development
agreement with Rockefeller University.
Research and Development Expense
Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the
development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as
follows:
Personnel
Laboratory supplies
Facility
Product development
Year Ended
December 31,
2022
2021
(In thousands)
Increase/
(Decrease)
$
%
$ 32,674
6,310
4,764
32,156
$ 26,424
5,981
4,771
12,230
$ 6,250
329
(7)
19,926
24 %
6 %
0 %
163 %
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Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $6.3 million increase in
personnel expenses for the year ended December 31, 2022, as compared to the year ended December 31, 2021, was primarily due to
higher stock-based compensation expense and an increase in employee headcount. We expect personnel expenses to increase over the
next twelve months as a result of additional headcount to support the expanded development of barzolvolimab.
Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the
development of our technology. The $0.3 million increase in laboratory supply expenses for the year ended December 31, 2022, as
compared to the year ended December 31, 2021, was primarily due to higher laboratory services, materials and supplies purchases. We
expect laboratory supplies expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a
quarterly basis.
Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities.
Facility expenses for the year ended December 31, 2022 were relatively consistent with the year ended December 31, 2021. We expect
facility expenses to remain relatively consistent over the next twelve months, although there may be fluctuations on a quarterly basis.
Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs,
contracted research and outside clinical drug product manufacturing. The $19.9 million increase in product development expenses for the
year ended December 31, 2022, as compared to the year ended December 31, 2021, was primarily due to an increase in barzolvolimab
clinical trial and contract manufacturing expenses. We expect product development expenses to increase over the next twelve months as a
result of further increases in barzolvolimab clinical trial and contract manufacturing expenses.
General and Administrative Expense
The $6.7 million increase in general and administrative expenses for the year ended December 31, 2022, as compared to the year
ended December 31, 2021, was primarily due to higher stock-based compensation, legal and barzolvolimab commercial planning
expenses. We expect general and administrative expenses to remain relatively consistent over the next twelve months, although there
may be fluctuations on a quarterly basis.
Intangible Asset Impairment
During the third quarter of 2021, we evaluated the TAM program IPR&D asset for potential impairment as a result of a lack of
interest in the program from third parties. We concluded that the TAM program IPR&D asset was fully impaired, and a non-cash
impairment charge of $3.5 million was recorded in the third quarter of 2021.
Gain on Fair Value Remeasurement of Contingent Consideration
The $6.9 million gain on fair value remeasurement of contingent consideration for the year ended December 31, 2022 was primarily
due to our decision to deprioritize the CDX-1140 program.
Litigation Settlement Related Loss
We recorded a loss of $15.0 million in the second quarter of 2022 related to the Initial Payment due under the binding settlement
term sheet (the “Term Sheet”) entered with SRS.
Investment and Other Income, Net
The $2.4 million increase in investment and other income, net for the year ended December 31, 2022, as compared to the year ended
December 31, 2021, was primarily due to higher interest rates on fixed income investments. We expect investment and other income to
increase over the next twelve months primarily due to higher interest rates and higher other income related to our sale of New Jersey tax
benefits.
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Income Tax Benefit
A $0.2 million non-cash income tax benefit was recorded for the year ended December 31, 2021 related to the impairment of the
TAM program IPR&D asset in the third quarter of 2021.
Year Ended December 31, 2021 compared with Year Ended December 31, 2020
Year Ended
December 31,
2021
2020
Increase/
(Decrease)
$
Increase/
(Decrease)
%
(In thousands)
Revenues:
Product development and licensing agreements
Contracts and grants
Total revenues
Operating expenses:
Research and development
General and administrative
Intangible asset impairment
Gain on fair value remeasurement of contingent consideration
Total operating expenses
Operating loss
Investment and other income, net
Net loss before income tax benefit
Income tax benefit
Net loss
Net Loss
$
$
31
4,620
4,651
$
$
2,301
5,117
7,418
$ (2,270)
(497)
$ (2,767)
53,311
20,488
3,500
(1,405)
75,894
(71,243)
505
(70,738)
227
10,777
6,032
(14,500)
(2,813)
5,122
7,889
(1,902)
9,791
(940)
$ (70,511) $ (59,780) $ 10,731
42,534
14,456
18,000
(4,218)
70,772
(63,354)
2,407
(60,947)
1,167
(99)%
(10)%
(37)%
25 %
42 %
(81)%
(67)%
7 %
12 %
(79)%
16 %
(81)%
18 %
The $10.7 million increase in net loss for the year ended December 31, 2021, as compared to the year ended December 31, 2020,
was primarily the result of an increase in research and development and general and administrative expenses, a decrease in the gain on
fair value remeasurement of contingent consideration and revenue, partially offset by a decrease in non-cash intangible asset impairment
expense.
Revenue
The Company’s agreement with Rockefeller University, as amended, (the “Rockefeller Agreement”) provides for the Company to
perform manufacturing and development services for Rockefeller University for their portfolio of antibodies against HIV. This portfolio
was licensed to Gilead Sciences in January 2020 from Rockefeller University (“Rockefeller Transaction”). The $2.3 million decrease in
revenue from product development and licensing agreements for the year ended December 31, 2021, as compared to the year ended
December 31, 2020, was primarily due to the $1.8 million received from the Rockefeller Transaction in the first quarter of 2020. The
$0.5 million decrease in revenue from contracts and grants for the year ended December 31, 2021, as compared to the year ended
December 31, 2020, was primarily related to a decrease in services performed under our contract manufacturing and research and
development agreements with Rockefeller University and Gilead Sciences.
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Research and Development Expense
Research and development expenses consist primarily of (i) personnel expenses, (ii) laboratory supply expenses relating to the
development of our technology, (iii) facility expenses and (iv) product development expenses associated with our drug candidates as
follows:
Personnel
Laboratory supplies
Facility
Product development
Year Ended
December 31,
2021
2020
(In thousands)
Increase/
(Decrease)
$
%
$ 26,424
5,981
4,771
12,230
$ 21,896
4,393
6,367
6,233
$ 4,528
1,588
(1,596)
5,997
21 %
36 %
(25)%
96 %
Personnel expenses primarily include salary, benefits, stock-based compensation and payroll taxes. The $4.5 million increase in
personnel expenses for the year ended December 31, 2021, as compared to the year ended December 31, 2020, was primarily due to
higher stock-based compensation expense and an increase in employee headcount.
Laboratory supplies expenses include laboratory materials and supplies, services, and other related expenses incurred in the
development of our technology. The $1.6 million increase in laboratory supply expenses for the year ended December 31, 2021, as
compared to the year ended December 31, 2020, was primarily due to higher laboratory materials and supplies purchases.
Facility expenses include depreciation, amortization, utilities, rent, maintenance and other related expenses incurred at our facilities.
The $1.6 million decrease in facility expenses for the year ended December 31, 2021, as compared to the year ended December 31, 2020,
was primarily due to lower rent as a result of the consolidation of our Massachusetts lab and manufacturing facilities in the second
quarter of 2020 and lower depreciation expenses.
Product development expenses include clinical investigator site fees, external trial monitoring costs, data accumulation costs,
contracted research and outside clinical drug product manufacturing. The $6.0 million increase in product development expenses for the
year ended December 31, 2021, as compared to the year ended December 31, 2020, was primarily due to an increase in barzolvolimab
clinical trial and contract research expenses.
General and Administrative Expense
The $6.0 million increase in general and administrative expenses for the year ended December 31, 2021, as compared to the year
ended December 31, 2020, was primarily due to higher stock-based compensation and legal expenses.
Intangible Asset Impairment
We evaluated the TAM program IPR&D asset for potential impairment in the fourth quarter of 2020 as a result of our decision to
focus our efforts on out-licensing opportunities for the program, which caused changes in projected development and regulatory
timelines related to the program. We concluded that the TAM program IPR&D asset was partially impaired, and a non-cash impairment
charge of $14.5 million was recorded in the fourth quarter of 2020. During the third quarter of 2021, we evaluated the TAM program
IPR&D asset for potential impairment as a result of a lack of interest in the program from third parties. We concluded that the TAM
program IPR&D asset was fully impaired, and a non-cash impairment charge of $3.5 million was recorded in the third quarter of 2021.
We evaluated the CDX-3379 IPR&D asset for potential impairment as a result of the discontinuation of the CDX-3379 program in the
second quarter of 2020. We concluded that the CDX-3379 IPR&D asset was fully impaired, and a non-cash impairment charge of $3.5
million was recorded in the second quarter of 2020.
Gain on Fair Value Remeasurement of Contingent Consideration
The $1.4 million gain on fair value remeasurement of contingent consideration for the year ended December 31, 2021 was primarily
due to updated assumptions for the TAM program, partially offset by losses related to changes in discount rates and the passage of time.
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Investment and Other Income, Net
The $1.9 million decrease in investment and other income, net for the year ended December 31, 2021, as compared to the year ended
December 31, 2020, was primarily due to lower other income related to our sale of New Jersey tax benefits.
Income Tax Benefit
A $0.2 million non-cash income tax benefit was recorded for the year ended December 31, 2021 related to the impairment of the
TAM program IPR&D asset in the third quarter of 2021.
LIQUIDITY AND CAPITAL RESOURCES
Our cash equivalents are highly liquid investments with a maturity of three months or less at the date of purchase and consist
primarily of investments in money market mutual funds with commercial banks and financial institutions. We maintain cash balances
with financial institutions in excess of insured limits. We do not anticipate any losses with respect to such cash balances. We invest our
excess cash balances in marketable securities, including municipal bond securities, U.S. government agency securities and high- grade
corporate bonds that meet high credit quality standards, as specified in our investment policy. Our investment policy seeks to manage
these assets to achieve our goals of preserving principal and maintaining adequate liquidity.
The use of our cash flows for operations has primarily consisted of salaries and wages for our employees; facility and facility-related
costs for our offices, laboratories and manufacturing facility; fees paid in connection with preclinical studies, clinical studies, contract
manufacturing, laboratory supplies and services; and consulting, legal and other professional fees. We anticipate that our cash flows from
operations will continue to be focused in these areas as we progress our current drug candidates through the clinical trial process and
develop additional drug candidates. To date, the primary sources of cash flows from operations have been payments received from our
collaborative partners and from government entities and payments received for contract manufacturing and research and development
services provided by us. The timing of any new contract manufacturing and research and development agreements, collaboration
agreements, government contracts or grants and any payments under these agreements, contracts or grants cannot be easily predicted and
may vary significantly from quarter to quarter.
At December 31, 2022, our principal sources of liquidity consisted of cash, cash equivalents and marketable securities of $305.0
million. We have had recurring losses and incurred a loss of $112.3 million for the year ended December 31, 2022. Net cash used in
operations for the year ended December 31, 2022 was $103.7 million. We believe that the cash, cash equivalents and marketable
securities at December 31, 2022 are sufficient to meet estimated working capital requirements and fund planned operations through 2025,
which include our ongoing Phase 1b studies in urticaria and prurigo nodularis and our ongoing and planned Phase 2 studies in CSU,
CIndU and EoE. This could be impacted if we elect to pay the future milestones under the Settlement Agreement with SRS, if any, in
cash.
During the next twelve months, we may take further steps to raise additional capital to meet our long-term liquidity needs including,
but not limited to, one or more of the following: the licensing of drug candidates with existing or new collaborative partners, possible
business combinations, issuance of debt, or the issuance of common stock or other securities via private placements or public offerings.
Although we have been successful in raising capital in the past, there can be no assurance that additional financing will be available on
acceptable terms, if at all, and our negotiating position in capital raising efforts may worsen as existing resources are used. There is also
no assurance that we will be able to enter into further collaborative relationships. Additional equity financings may be dilutive to our
stockholders; debt financing, if available, may involve significant cash payment obligations and covenants that restrict our ability to
operate as a business; and licensing or strategic collaborations may result in royalties or other terms which reduce our economic potential
from products under development. Our ability to continue funding our planned operations into and beyond twelve months from the
issuance date is also dependent on the timing and manner of payment of the future milestones under the Settlement Agreement with SRS,
in the event that we achieve the milestones related to those payments. We may decide to pay those milestone payments in cash, shares of
our common stock or a combination thereof. If we are unable to raise the funds necessary to meet our long-term liquidity needs, we may
have to delay or discontinue the development of one or more programs, discontinue or delay ongoing or anticipated clinical trials,
discontinue or delay our commercial manufacturing efforts, discontinue or delay our efforts to expand into additional indications for our
drug product candidates, license out programs earlier than expected, raise funds at a significant discount or on other unfavorable terms, if
at all, or sell all or a part of our business.
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Operating Activities
Net cash used in operating activities was $103.7 million for the year ended December 31, 2022 compared to $60.9 million for the
year ended December 31, 2021. The increase in net cash used in operating activities was primarily due to increases in research and
development and general and administrative expenses and the $15.0 million Initial Payment made to SRS under the Settlement
Agreement. We expect that cash used in operating activities (not including the $15.0 million Initial Payment made to SRS) will increase
over the next twelve months as a result of the expanded development of barzolvolimab.
Net cash used in operating activities was $60.9 million for the year ended December 31, 2021 compared to $40.4 million for the year
ended December 31, 2020. The increase in net cash used in operating activities was primarily due to increases in research and
development and general and administrative expenses and a decrease in revenue.
We have incurred and will continue to incur significant costs in the area of research and development, including preclinical and
clinical trials and clinical drug product manufacturing as our drug candidates are developed. We plan to spend significant amounts to
progress our current drug candidates through the clinical trial processes as well as to develop additional drug candidates. As our drug
candidates progress through the clinical trial process, we may be obligated to make significant milestone payments, pursuant to our
existing arrangements and arrangements we may enter in the future.
Investing Activities
Net cash provided by investing activities was $89.9 million for the year ended December 31, 2022 compared to net cash used in
investing activities of $216.2 million for the year ended December 31, 2021. The increase in net cash provided by investing activities
was primarily due to net sales and maturities of marketable securities of $91.7 million for the year ended December 31, 2022 as
compared to net purchases of $214.9 million for the year ended December 31, 2021. We expect that cash provided by investing activities
will increase over the next twelve months as we fund our operations through the combination of net proceeds from the sales and
maturities of marketable securities, cash provided by financing activities and/or new partnerships, although there may be significant
fluctuations on a quarterly basis based on the amount of cash provided by financing activities and/or new partnerships.
Net cash used in investing activities was $216.2 million for the year ended December 31, 2021 compared to $98.2 million for the
year ended December 31, 2020. The increase in net cash used in investing activities was primarily due to net purchases of marketable
securities for the year ended December 31, 2021 of $214.9 million as compared to $96.7 million for the year ended December 31, 2020.
Financing Activities
Net cash provided by financing activities was $4.1 million for the year ended December 31, 2022 compared to $272.4 million for the
year ended December 31, 2021. The decrease in net cash provided by financing activities was primarily due to a decrease in net proceeds
from stock issuances.
Net cash provided by financing activities was $272.4 million for the year ended December 31, 2021 compared to $171.2 million for
the year ended December 31, 2020. The increase in net cash provided by financing activities was primarily due to an increase in net
proceeds from stock issuances.
Equity Offerings
In November 2020, we filed an automatic shelf registration statement with the SEC to register for sale any combination of the types
of securities described in the shelf registration statement.
In May 2016, we entered into a controlled equity offering sales agreement with Cantor Fitzgerald & Co. (“Cantor”) to allow us to
issue and sell shares of our common stock from time to time through Cantor, acting as agent. During the year ended December 31, 2020,
we issued 7,125,004 million shares of common stock under the agreement with Cantor resulting in net proceeds of $29.4 million, after
deducting commission and offering expenses. No shares of common stock were sold under the Cantor Agreement during the years ended
December 31, 2021 and December 31, 2022. At December 31, 2022, we had $50.0 million remaining in aggregate gross offering price
available under our November 2020 prospectus supplement.
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During the second quarter of 2020, the Company issued 15,384,614 shares of its common stock in an underwritten public offering
resulting in net proceeds to the Company of $141.4 million, after deducting underwriting fees and offering expenses.
During the third quarter of 2021, we issued 6,845,238 shares of common stock in an underwritten public offering resulting in net
proceeds of $269.9 million, after deducting underwriting fees and offering expenses.
Item 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK
We own financial instruments that are sensitive to market risk as part of our investment portfolio. Our investment portfolio is used to
preserve our capital until it is used to fund operations, including our research and development activities. None of these market-risk
sensitive instruments are held for trading purposes. We invest our cash primarily in money market mutual funds. These investments are
evaluated quarterly to determine the fair value of the portfolio. From time to time, we invest our excess cash balances in marketable
securities, including municipal bond securities, U.S. government agency securities, and high-grade corporate bonds that meet high credit
quality standards, as specified in our investment policy. Our investment policy seeks to manage these assets to achieve our goals of
preserving principal and maintaining adequate liquidity. Because of the short-term nature of these investments, we do not believe we
have material exposure due to market risk. The impact to our financial position and results of operations from changes in interest rates is
not material.
We do not utilize derivative financial instruments. The carrying amounts reflected in the balance sheet of cash and cash equivalents,
accounts receivables and accounts payable approximates fair value at December 31, 2022 due to the short-term maturities of these
instruments.
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Item 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA
Report of Independent Registered Public Accounting Firm
To the Board of Directors and Stockholders of Celldex Therapeutics, Inc.
Opinions on the Financial Statements and Internal Control over Financial Reporting
We have audited the accompanying consolidated balance sheets of Celldex Therapeutics, Inc. and its subsidiary (the “Company”) as
of December 31, 2022 and 2021, and the related consolidated statements of operations and comprehensive loss, of stockholders’ equity
and of cash flows for each of the three years in the period ended December 31, 2022, including the related notes (collectively referred to
as the “consolidated financial statements”). We also have audited the Company’s internal control over financial reporting as of December
31, 2022, based on criteria established in Internal Control - Integrated Framework (2013) issued by the Committee of Sponsoring
Organizations of the Treadway Commission (COSO).
In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position of
the Company as of December 31, 2022 and 2021, and the results of its operations and its cash flows for each of the three years in the
period ended December 31, 2022 in conformity with accounting principles generally accepted in the United States of America. Also in
our opinion, the Company maintained, in all material respects, effective internal control over financial reporting as of December 31,
2022, based on criteria established in Internal Control - Integrated Framework (2013) issued by the COSO.
Basis for Opinions
The Company’s management is responsible for these consolidated financial statements, for maintaining effective internal control
over financial reporting, and for its assessment of the effectiveness of internal control over financial reporting, included in Management’s
Annual Report on Internal Control over Financial Reporting appearing under Item 9A. Our responsibility is to express opinions on the
Company’s consolidated financial statements and on the Company’s internal control over financial reporting 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
audits to obtain reasonable assurance about whether the consolidated financial statements are free of material misstatement, whether due
to error or fraud, and whether effective internal control over financial reporting was maintained in all material respects.
Our audits of the consolidated financial statements included performing procedures to assess the risks of material misstatement of
the consolidated financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such
procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the consolidated 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 consolidated financial statements. Our audit of internal control over financial reporting included obtaining
an understanding of internal control over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating
the design and operating effectiveness of internal control based on the assessed risk. Our audits also included performing such other
procedures as we considered necessary in the circumstances. We believe that our audits provide a reasonable basis for our opinions.
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Definition and Limitations of Internal Control over Financial Reporting
A company’s internal control over financial reporting is a process 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. A company’s internal control over financial reporting includes those policies and procedures that (i) pertain to the
maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the
company; (ii) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in
accordance with generally accepted accounting principles, and that receipts and expenditures of the company are being made only in
accordance with authorizations of management and directors of the company; and (iii) provide reasonable assurance regarding
prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a material effect
on the financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,
projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of
changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
Critical Audit Matters
The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial
statements that was communicated or required to be communicated to the audit committee and that (i) relates to accounts or disclosures
that are material to the consolidated financial statements and (ii) involved our especially challenging, subjective, or complex judgments.
The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements, taken as a
whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on
the accounts or disclosures to which it relates.
Kolltan Settlement - Accounting for Future Milestone Payments
As described in Note 17 to the consolidated financial statements, on November 29, 2016, the Company acquired all of the share and
debt interests of Kolltan, a clinical-stage biopharmaceutical company, in exchange for 1,217,200 shares of the Company’s common stock
plus contingent consideration of up to $172.5 million payable in cash, in shares of Celldex’s common stock or a combination of both, in
the sole discretion of the Company and subject to provisions of the Agreement and Plan of Merger, dated November 1, 2016 (the
“Merger Agreement”) with such contingent consideration based on the achievement of development, regulatory approval or sales-based
milestones (“Kolltan Milestones”). In October 2019, the Company received a letter from Shareholder Representative Services LLC
(“SRS”), the hired representative of the former stockholders of Kolltan, notifying the Company that it objected to the Company’s
characterization of the development, regulatory approval and sales-based Kolltan Milestones relating to CDX-0158 as having been
abandoned and contending instead that the related milestone payments are due from the Company to the Kolltan stockholders. On
August 18, 2020, the Company filed a Verified Complaint in the Court of Chancery of the State of Delaware against SRS (the
“litigation”). On June 20, 2022, the Company entered into a binding settlement term sheet with SRS, related to the litigation, which, upon
execution of a definitive settlement agreement and the initial payment of $15 million would result in the joint dismissal, with prejudice,
of all claims and counterclaims in the litigation. The definitive settlement agreement between the Company and SRS was executed on
July 15, 2022 (the “Settlement Agreement”). The payment obligations under the Settlement Agreement replace, in their entirety, the
contingent consideration in the Merger Agreement. As described by management, future milestone payments related to the CDX-0159
program, which was subject to the litigation, will be recorded when and if payment becomes probable and reasonably estimable in
accordance with the loss contingency model whereas milestones related to the remaining surviving company products are measured at
fair value in accordance with the contingent consideration model.
The principal consideration for our determination that performing procedures relating to the Kolltan settlement - accounting for
future milestone payments is a critical audit matter is the high degree of auditor effort in performing procedures relating to management’s
determination that the future milestone payments required in connection with the Kolltan settlement will be assessed under the loss
contingency model as it relates to the CDX-0159 program, and under the contingent consideration model as it relates to the surviving
company products under the Merger Agreement.
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Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion
on the consolidated financial statements. These procedures included testing the effectiveness of controls relating to management’s
determination of the accounting treatment for the future milestone payments. These procedures also included, among others, reviewing
the Settlement Agreement and evaluating whether the future milestone payments have been properly accounted for and disclosed in
accordance with the relevant accounting standards. /s/ PricewaterhouseCoopers LLP
Boston, Massachusetts
February 28, 2023
We have served as the Company’s auditor since 2008.
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CELLDEX THERAPEUTICS, INC.
CONSOLIDATED BALANCE SHEETS
(In thousands, except share and per share amounts)
Assets
Current assets:
Cash and cash equivalents
Marketable securities
Accounts and other receivables
Prepaid and other current assets
Total current assets
Property and equipment, net
Operating lease right-of-use assets, net
Intangible assets
Other assets
Total assets
Liabilities and stockholders’ equity
Current liabilities:
Accounts payable
Accrued expenses
Current portion of operating lease liabilities
Current portion of long-term liabilities
Total current liabilities
Long-term portion of operating lease liabilities
Other long-term liabilities
Total liabilities
Commitments and contingent liabilities (Note 14)
Stockholders’ equity:
Convertible preferred stock, $.01 par value; 3,000,000 shares authorized; no shares issued and
outstanding at December 31, 2022 and 2021
Common stock, $.001 par value; 297,000,000 shares authorized; 47,200,695 and 46,730,198
shares issued and outstanding at December 31, 2022 and 2021, respectively
Additional paid-in capital
Accumulated other comprehensive income
Accumulated deficit
Total stockholders’ equity
Total liabilities and stockholders’ equity
December 31, 2022 December 31, 2021
$
$
$
$
$
$
$
29,429
275,523
347
12,394
317,693
3,747
4,001
27,190
104
352,735
3,340
12,835
1,445
990
18,610
2,588
5,333
26,531
39,143
369,107
172
2,417
410,839
3,551
2,970
27,190
104
444,654
1,228
12,000
1,746
1,554
16,528
1,296
7,354
25,178
—
—
47
1,580,829
1,260
(1,255,932)
326,204
352,735
$
47
1,561,142
1,894
(1,143,607)
419,476
444,654
The accompanying notes are an integral part of the financial statements.
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CELLDEX THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(In thousands, except per share amounts)
Year Ended
Year Ended
December 31, 2022 December 31, 2021 December 31, 2020
Year Ended
Revenues:
Product development and licensing agreements
Contracts and grants
Total revenues
Operating expenses:
Research and development
General and administrative
Intangible asset impairment
Gain on fair value remeasurement of contingent consideration
Litigation settlement related loss
Total operating expenses
Operating loss
Investment and other income, net
Net loss before income tax benefit
Income tax benefit
Net loss
Basic and diluted net loss per common share
Shares used in calculating basic and diluted net loss per share
Comprehensive loss:
Net loss
Other comprehensive income (loss):
Unrealized loss on marketable securities
Comprehensive loss
$
$
$
$
$
$
$
56
2,301
2,357
82,258
27,195
—
(6,862)
15,000
117,591
(115,234)
2,909
(112,325) $
—
(112,325) $
(2.40) $
46,888
$
31
4,620
4,651
53,311
20,488
3,500
(1,405)
—
75,894
(71,243)
505
(70,738) $
227
(70,511) $
(1.64) $
42,870
2,301
5,117
7,418
42,534
14,456
18,000
(4,218)
—
70,772
(63,354)
2,407
(60,947)
1,167
(59,780)
(2.02)
29,640
(112,325) $
(70,511) $
(59,780)
(634)
(112,959) $
(695)
(71,206) $
(30)
(59,810)
The accompanying notes are an integral part of the financial statements.
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CELLDEX THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF STOCKHOLDERS’ EQUITY
(In thousands, except share amounts)
Balance at December 31, 2019
Shares issued under stock option and employee stock purchase plans
Shares issued in connection with at the market agreement
Shares issued in underwritten offering, net
Stock-based compensation
Unrealized loss on marketable securities
Net loss
Balance at December 31, 2020
Shares issued under stock option and employee stock purchase plans
Shares issued in underwritten offering, net
Stock-based compensation
Unrealized loss on marketable securities
Net loss
Balance at December 31, 2021
Shares issued under stock option and employee stock purchase plans
Stock-based compensation
Unrealized loss on marketable securities
Net loss
Balance at December 31, 2022
Common
Stock
Shares
16,972,077
122,076
7,125,004
15,384,614
—
—
—
39,603,771
281,189
6,845,238
—
—
—
46,730,198
470,497
—
—
—
47,200,695
$
$
$
$
Common
Stock Par
Value
17
—
8
15
—
—
—
40
—
7
—
—
—
47
—
—
—
—
47
Additional
Paid-In
Capital
1,104,706
434
29,423
141,346
3,915
—
—
1,279,824
2,479
269,886
8,953
—
—
1,561,142
4,076
15,611
—
—
1,580,829
$
$
$
$
Accumulated
Other
Comprehensive Accumulated
Income
2,619
—
—
—
—
(30)
—
2,589
—
—
—
(695)
—
1,894
—
—
(634)
—
1,260
Deficit
$ (1,013,316)
—
—
—
—
—
(59,780)
$ (1,073,096)
—
—
—
—
(70,511)
$ (1,143,607)
—
—
—
(112,325)
$ (1,255,932)
$
$
$
$
Total
Stockholders’
Equity
$
$
$
$
94,026
434
29,431
141,361
3,915
(30)
(59,780)
209,357
2,479
269,893
8,953
(695)
(70,511)
419,476
4,076
15,611
(634)
(112,325)
326,204
The accompanying notes are an integral part of the financial statements.
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CELLDEX THERAPEUTICS, INC.
CONSOLIDATED STATEMENTS OF CASH FLOWS
(In thousands)
Cash flows from operating activities:
Net loss
Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization
Amortization and premium of marketable securities, net
Loss (gain) on sale or disposal of assets
Intangible asset impairment
Gain on fair value remeasurement of contingent consideration
Non-cash income tax benefit
Stock-based compensation expense
Changes in operating assets and liabilities:
Accounts and other receivables
Prepaid and other current assets
Other assets
Accounts payable and accrued expenses
Other liabilities
Net cash used in operating activities
Cash flows from investing activities:
Sales and maturities of marketable securities
Purchases of marketable securities
Acquisition of property and equipment
Proceeds from sale or disposal of assets
Net cash provided by (used in) investing activities
Cash flows from financing activities:
Net proceeds from stock issuances
Proceeds from issuance of stock from employee benefit plans
Issuance of term loan
Payment of term loan
Net cash provided by financing activities
Net (decrease) increase in cash and cash equivalents
Cash and cash equivalents at beginning of period
Cash and cash equivalents at end of period
Non-cash investing activities
Accrued construction in progress
Year Ended
December 31, 2022
Year Ended
December 31, 2021
Year Ended
December 31, 2020
$
(112,325)
$
(70,511)
$
(59,780)
2,896
844
2
—
(6,862)
—
15,611
(175)
(9,572)
—
3,123
2,726
(103,732)
280,666
(188,965)
(1,828)
69
89,942
—
4,076
—
—
4,076
(9,714)
39,143
29,429
113
$
$
3,068
(3,209)
(24)
3,500
(1,405)
(227)
8,953
1,574
(1,871)
(5)
3,653
(4,405)
(60,909)
174,947
(389,881)
(1,249)
27
(216,156)
269,893
2,479
—
—
272,372
(4,693)
43,836
39,143
289
$
$
3,929
(729)
(55)
18,000
(4,218)
(1,167)
3,915
(787)
(334)
—
1,638
(816)
(40,404)
123,600
(220,321)
(1,552)
55
(98,218)
170,792
434
2,962
(2,962)
171,226
32,604
11,232
43,836
221
$
$
The accompanying notes are an integral part of the financial statements.
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CELLDEX THERAPEUTICS, INC.
NOTES TO FINANCIAL STATEMENTS
(1) Nature of Business and Overview
Celldex Therapeutics, Inc. (the “Company” or “Celldex”) is a biopharmaceutical company dedicated to developing therapeutic
monoclonal and bispecific antibodies that address diseases for which available treatments are inadequate. The Company is primarily
focusing its efforts and resources on the continued research and development of barzolvolimab (also referred to as CDX-0159) and CDX-
585.
At December 31, 2022, the Company had cash, cash equivalents and marketable securities of $305.0 million. The Company has had
recurring losses and incurred a loss of $112.3 million for the year ended December 31, 2022. Net cash used in operations for the year
ended December 31, 2022 was $103.7 million. The Company believes that the cash, cash equivalents and marketable securities at the
filing date of this Form 10-K will be sufficient to meet estimated working capital requirements and fund planned operations for at least
the next twelve months from the date of issuance of these financial statements.
During the next twelve months and beyond, the Company may take further steps to raise additional capital to meet its long-term
liquidity needs including, but not limited to, one or more of the following: the licensing of drug candidates with existing or new
collaborative partners, possible business combinations, issuance of debt, or the issuance of common stock or other securities via private
placements or public offerings. Although the Company has been successful in raising capital in the past, there can be no assurance that
additional financing will be available on acceptable terms, if at all, and the Company’s negotiating position in capital-raising efforts may
worsen as existing resources are used. There is also no assurance that the Company will be able to enter into further collaborative
relationships. Additional equity financings may be dilutive to the Company’s stockholders; debt financing, if available, may involve
significant cash payment obligations and covenants that restrict the Company’s ability to operate as a business; and licensing or strategic
collaborations may result in royalties or other terms which reduce the Company’s economic potential from products under development.
The Company’s ability to continue funding its planned operations beyond twelve months from the issuance date is also dependent on the
timing and manner of payment of amounts due under the Settlement Agreement with Shareholder Representative Services LLC (“SRS”)
(refer to Note 17), in the event that the Company achieves the milestones related to those payments. The Company, at its option, may
decide to pay those milestone payments in cash, shares of its common stock or a combination thereof. If the Company is unable to raise
the funds necessary to meet its long-term liquidity needs, it may have to delay or discontinue the development of one or more programs,
discontinue or delay ongoing or anticipated clinical trials, discontinue or delay our commercial manufacturing efforts, discontinue or
delay our efforts to expand into additional indications for our drug product candidates, license out programs earlier than expected, raise
funds at a significant discount or on other unfavorable terms, if at all, or sell all or a part of the Company.
(2) Summary of Significant Accounting Policies
Basis of Presentation
The balance sheets and statements of operations and comprehensive loss, stockholders’ equity, and cash flows, are consolidated for
the years ended December 31, 2022, 2021 and 2020. These consolidated financial statements reflect the operations of the Company and
its wholly-owned subsidiary. All intercompany balances and transactions have been eliminated in consolidation. The Company operates
in one segment, which is the business of development, manufacturing and commercialization of novel therapeutics for human health
care.
Use of Estimates
The preparation of the financial statements in conformity with accounting principles generally accepted in the United States of
America (U.S. GAAP) requires management to make estimates and use assumptions that affect the reported amounts of assets and
liabilities, the disclosure of contingent assets and liabilities at the dates of the financial statements and the reported amounts of revenues
and expenses during the reporting period. Actual results could differ from those estimates.
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Cash and Cash Equivalents
The Company considers all highly liquid investments purchased with a maturity date of 90 days or less at the date of purchase to be
cash equivalents. Cash equivalents consist principally of money market funds and debt securities.
Marketable Securities
The Company invests its excess cash balances in marketable securities, including municipal bond securities, U.S. government
agency securities, and highly rated corporate bonds. The Company classifies all of its marketable securities as current assets on the
balance sheets because they are available-for-sale and available to fund current operations. Marketable securities are stated at fair value
with unrealized gains and losses included as a component of accumulated other comprehensive income (loss), which is a separate
component of stockholders’ equity, until such gains and losses are realized. If a decline in the fair value is considered other-than-
temporary, based on available evidence, the unrealized loss is reclassified from accumulated other comprehensive income (loss) to the
statements of operations. Realized gains and losses are determined on the specific identification method and are included in investment
and other income, net.
Concentration of Credit Risk and of Significant Customers and Suppliers
Financial instruments that potentially subject the Company to concentrations of credit risk primarily consist of cash, cash
equivalents, marketable securities and accounts receivable. The Company invests its cash, cash equivalents and marketable securities in
debt instruments and interest-bearing accounts at major financial institutions in excess of insured limits. The Company mitigates credit
risk by limiting the investment type and maturity to securities that preserve capital, maintain liquidity and have a high credit quality. The
Company has not historically experienced credit losses from its accounts receivable and therefore has not established an allowance for
doubtful accounts.
Revenue from Rockefeller University represented 75% of total Company revenue for the year ended December 31, 2022. Revenue
from Rockefeller University and Gilead Sciences represented 88% and 85% of total Company revenue for the years ended December 31,
2021 and 2020, respectively.
The Company relies on contract manufacturing organizations (CMO) to manufacture drug substance and drug product as well as for
future commercial supplies. The Company also relies on CMOs for supply of raw materials as well as filling, packaging, storing and
shipping our drug products.
Fair Value Measurements
The Company has certain assets and liabilities that are measured at fair value in the financial statements. The Company seeks to
maximize the use of observable inputs (market data obtained from sources independent from the Company) and to minimize the use of
unobservable inputs (the Company’s assumptions about how market participants would price assets and liabilities) when measuring the
fair value of its assets and liabilities. These assets and liabilities are classified into one of three levels of the following fair value
hierarchy as defined by U.S. GAAP:
Level 1: Observable inputs such as quoted prices in active markets for identical assets or liabilities. An active market for an asset or
liability is a market in which transactions for the asset or liability occur with sufficient frequency and volume to provide pricing
information on an ongoing basis.
Level 2: Observable inputs other than Level 1 prices, such as quoted prices in active markets for similar assets or liabilities and
quoted prices for identical assets or liabilities in markets that are not active.
Level 3: Unobservable inputs based on the Company’s assessment of the assumptions that market participants would use in pricing
the asset or liability.
Property and Equipment
Property and equipment are stated at cost and depreciated over the estimated useful lives of the related assets using the straight-line
method. Laboratory equipment and office furniture and equipment are depreciated over five years, and computer equipment is
depreciated over three years. Manufacturing equipment is depreciated over seven to ten years. Leasehold improvements
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are amortized over the shorter of the estimated useful life or the non-cancelable term of the related lease, including any renewals that are
reasonably assured of occurring. Property and equipment under construction is classified as construction in progress and is depreciated or
amortized only after the asset is placed in service. Expenditures for maintenance and repairs are charged to expense whereas the costs of
significant improvements which extend the life of the underlying asset are capitalized. Upon retirement or sale, the cost of assets
disposed of and the related accumulated depreciation are eliminated and any resulting gain or loss is reflected in the Company’s
statements of operations and comprehensive loss.
The treatment of costs to construct property and equipment depends on the nature of the costs and the stage of construction. Costs
incurred in the project planning, design, construction and installation phases are capitalized as part of the cost of the asset. The Company
stops capitalizing these costs when the asset is substantially complete and ready for its intended use. For manufacturing property and
equipment, the Company also capitalizes the cost of validating these assets for the underlying manufacturing process. The Company
completes the capitalization of validation costs when the asset is substantially complete and ready for its intended use. Costs capitalized
include incremental labor and fringe benefits, and direct consultancy services.
Leases
The Company has operating leases of office, manufacturing and laboratory space, which have remaining lease terms of one to three
years and may include one or more options to renew or terminate early.
The Company determines if an arrangement contains a lease at inception. Operating lease right-of-use assets and lease liabilities are
recognized based on the present value of the future minimum lease payments over the lease term at commencement date. Certain
adjustments to the right-of-use asset may be required for items such as prepaid or accrued lease payments, initial direct costs paid or
incentives received. The Company’s leases do not contain an implicit rate, and therefore the Company uses an estimated incremental
borrowing rate based on the information available at the lease commencement date in determining the present value of lease payments.
Options to extend or terminate the lease are reflected in the calculation when it is reasonably certain that the option will be exercised.
The Company has elected to account for lease and non-lease components as a single lease component, however non-lease components
that are variable, such as common area maintenance and utilities, are generally paid separately from rent based on actual costs incurred
and therefore are not included in the right-of-use asset and operating lease liability and are reflected as an expense in the period incurred.
Leases with an initial term of 12 months or less are not recorded on the balance sheet.
Contingent Consideration
The Company records contingent consideration resulting from a business combination at its fair value on the acquisition date. The
Company determines the fair value of the contingent consideration based primarily on the (i) timing and probability of success of clinical
events or regulatory approvals; (ii) timing and probability of success of meeting clinical and commercial milestones; and (iii) discount
rates. The Company’s contingent consideration liabilities arose in connection with its acquisition of Kolltan. On a quarterly basis, the
Company revalues these obligations and records increases or decreases in their fair value as an adjustment to operating earnings.
Changes to contingent consideration obligations can result from adjustments to discount rates, accretion of the discount rates due to the
passage of time, changes in the Company’s estimates of the likelihood or timing of achieving development or commercial milestones,
changes in the probability of certain clinical events or changes in the assumed probability associated with regulatory approval. The
assumptions related to determining the value of contingent consideration include a significant amount of judgment, and any changes in
the underlying estimates could have a material impact on the amount of contingent consideration adjustment recorded in any given
period.
Intangible Assets
IPR&D assets acquired in a business combination initially are recorded at fair value and accounted for as indefinite-lived intangible
assets. The valuation model used to measure the fair value of the Company’s IPR&D assets was primarily a discounted cash flow
approach. The assumptions used in determining the fair value of the Company’s IPR&D assets include (i) probability of success; (ii)
probability of partnership; (iii) partnership milestones; and (iv) discount rate. These assets are capitalized on the Company’s balance
sheets until either the project underlying them is completed or the assets become impaired. If a project is completed, the carrying value of
the related intangible asset is amortized over the remaining estimated life of the asset beginning in the period in which the project is
completed. If a project becomes impaired or is abandoned, the carrying value of the related intangible asset is written down to its fair
value and an impairment charge is taken in the period in which the impairment occurs.
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Each IPR&D asset is assessed for impairment at least annually or when impairment indicators are present. The Company has the
option to assess qualitative factors to determine if it is more likely than not that the IPR&D asset is impaired and whether it is necessary
to perform a quantitative impairment test.
Impairment of Intangible and Long-Lived Assets
The Company evaluates the recoverability of its long-lived assets, including property and equipment, right-of-use assets, and
intangible assets when circumstances indicate that an event of impairment may have occurred. Determination of recoverability is based
on an estimate of undiscounted future cash flows resulting from the use of the asset and its eventual disposition. In the event that such
cash flows are not expected to be sufficient to recover the carrying amount of the assets, the assets are written-down to their estimated
fair values.
Revenue Recognition
Revenues are recognized when performance obligations under agreements or contracts are satisfied, in an amount that reflects the
consideration the Company expects to be entitled to in exchange for those services.
The Company determines revenue recognition through the following steps:
● Identification of the contract, or contracts, with a customer;
● Identification of the performance obligations in the contract;
● Determination of the transaction price;
● Allocation of the transaction price to the performance obligations in the contract; and
● Recognition of revenue when, or as, the Company satisfies a performance obligation.
Revenue for the Company is derived from product development agreements with collaborative partners for the research and
development of therapeutic drug candidates. The terms of the agreements may include nonrefundable signing and licensing fees, funding
for research, development and manufacturing, milestone payments and royalties on any product sales derived from collaborations. The
Company assesses the multiple obligations typically within product development contracts to determine the distinct performance
obligations and how to allocate the arrangement consideration to each distinct performance obligation. Under product development
agreements, revenue is generally recognized using a cost-to-cost measure of progress. Revenue is recognized based on the costs incurred
to date as a percentage of the total estimated costs to fulfill the contract. Incurred cost represents work performed, which corresponds
with, and thereby best depicts, the transfer of control to the customer. Due to the nature of the work performed in these arrangements, the
estimation of cost at completion is complex, subject to many variables, such as expected clinical trial costs, and requires significant
judgements. Circumstances can arise that change original estimates of costs or progress toward completion. Any revisions to estimates
are reflected in revenue on a cumulative catch-up basis in the period in which the change in circumstances became known.
Revenue for the Company is also derived from manufacturing and research and development arrangements. The Company owns and
operates a cGMP manufacturing facility in Fall River, Massachusetts, to produce drug substance for its current and planned early-stage
clinical trials. In order to utilize excess capacity, the Company has, from time to time, entered into contract manufacturing and research
and development arrangements in which services are provided on a time-and-material basis or at a negotiated fixed price. Revenue from
time-and-material contracts is generally recognized on an output basis as labor hours and/or direct expenses are incurred. Under fixed-
price contracts, revenue is generally recognized on an output basis as progress is made toward completion of the performance obligations
using surveys of performance completed to date.
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Contract Assets and Liabilities
The Company classifies the right to consideration in exchange for products or services transferred to a client as either a receivable or
a contract asset. A receivable is a right to consideration that is unconditional as compared to a contract asset which is a right to
consideration that is conditional upon factors other than the passage of time.
The Company’s contract liabilities result from arrangements where the Company has received payment in advance of performance
under the contract. These amounts are included as deferred revenue within current portion of long-term liabilities on the consolidated
balance sheets.
Research and Development Expenses
Research and development costs, including internal and contract research costs, are expensed as incurred. Research and development
expenses consist mainly of clinical trial costs, manufacturing of clinical material, toxicology and other preclinical studies, personnel
costs, depreciation, license fees and funding of outside contracted research.
Clinical trial expenses include expenses associated with clinical research organization, or CRO, services. Contract manufacturing
expenses include expenses associated with contract manufacturing organization, or CMO, services. The invoicing from CROs and CMOs
for services rendered can lag several months. The Company accrues the cost of services rendered in connection with CRO and CMO
activities based on our estimate of costs incurred. The Company maintains regular communication with our CROs and CMOs to assess
the reasonableness of its estimates. Differences between actual expenses and estimated expenses recorded have not been material and are
adjusted for in the period in which they become known.
Patent Costs
Patent costs are expensed to general and administrative expense as incurred. Certain patent costs are reimbursed by the Company’s
product development and licensing partners. Any reimbursed patent costs are recorded as product development and licensing agreement
revenues in the Company’s consolidated financial statements.
Stock-Based Compensation
The Company records stock-based compensation expense for all stock-based awards made to employees, consultants and non-
employee directors based on the estimated fair values of the stock-based awards expected to vest at the grant date and adjusts, if
necessary, to reflect actual forfeitures. Compensation expense for all stock-based awards is recognized using the straight-line method
over the term of vesting or performance.
Foreign Currency Translation
Net unrealized gains and losses resulting from foreign currency translation are included in accumulated other comprehensive
income. At December 31, 2022 and 2021, accumulated other comprehensive income includes a net unrealized gain related to foreign
currency translation of $2.6 million.
Income Taxes
The Company uses the asset and liability method to account for income taxes, including the recognition of deferred tax assets and
deferred tax liabilities for the anticipated future tax consequences attributable to differences between financial statement amounts and
their respective tax basis. Quarterly, the Company reviews its deferred tax assets for recovery. A valuation allowance is established when
the Company believes that it is more likely than not that its deferred tax assets will not be realized. Changes in valuation allowances from
period to period are included in the Company’s tax provision in the period of change.
The Company records uncertain tax positions in the financial statements only if it is more likely than not that the uncertain tax
position will be sustained upon examination by the taxing authorities. The Company records interest and penalties related to uncertain
tax positions in income tax expense.
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Comprehensive Loss
Comprehensive loss is comprised of net loss and certain changes in stockholders’ equity that are excluded from net loss. The
Company includes foreign currency translation adjustments and unrealized gains and losses on marketable securities in other
comprehensive loss. The statements of operations and comprehensive loss reflect total comprehensive loss for the years ended December
31, 2022, 2021 and 2020.
Net Loss Per Share
Basic net loss per common share is based upon the weighted-average number of common shares outstanding during the period,
excluding restricted stock that has been issued but is not yet vested. Diluted net loss per common share is based upon the weighted-
average number of common shares outstanding during the period plus additional weighted-average potentially dilutive common shares
outstanding during the period when the effect is dilutive. In periods in which the Company reports a net loss, there is no difference
between basic and diluted net loss per share because dilutive shares of common stock are not assumed to have been issued as their effect
is anti-dilutive. The potentially dilutive common shares that have not been included in the net loss per common share calculations
because the effect would have been anti-dilutive are as follows:
Stock options
Recent Accounting Pronouncements
2022
5,085,662
Year Ended December 31,
2021
4,077,667
2020
3,042,229
From time to time, new accounting pronouncements are issued by the Financial Accounting Standards Board (“FASB”) or other
standard setting bodies that are adopted by the Company as of the specified effective date. Unless otherwise discussed, the Company
believes that the impact of recently issued standards that are not yet effective will not have a material impact on the Company’s
consolidated financial statements upon adoption.
In June 2016, the FASB issued guidance on the Measurement of Credit Losses on Financial Instruments. The guidance requires that
credit losses be reported using an expected losses model rather than the incurred losses model that is currently used, and establishes
additional disclosures related to credit risks. For available-for-sale debt securities with unrealized losses, the standard now requires
allowances to be recorded instead of reducing the amortized cost of the investment. This standard will be effective for the Company on
January 1, 2023. The adoption of this new guidance is not expected to have a material impact on the Company’s consolidated financial
statements and related disclosures.
(3) Accumulated Other Comprehensive Income
The changes in accumulated other comprehensive income, which is reported as a component of stockholders’ equity, for the year
ended December 31, 2022 are summarized below:
Balance at December 31, 2021
Other comprehensive loss
Balance at December 31, 2022
Unrealized
Gain (Loss) on
Marketable
Securities
$
$
(702)
(634)
(1,336)
Foreign
Currency Items
(In thousands)
2,596
$
—
2,596
$
$
$
Total
1,894
(634)
1,260
No amounts were reclassified out of accumulated other comprehensive income during the years ended December 31, 2022, 2021 and
2020.
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(4) Fair Value Measurements
The following tables set forth the Company’s financial assets and liabilities subject to fair value measurements:
Assets:
Money market funds and cash equivalents
Marketable securities
Liabilities:
Kolltan acquisition contingent consideration
Assets:
Money market funds and cash equivalents
Marketable securities
Liabilities:
Kolltan acquisition contingent consideration
As of
December 31, 2022
Level 1
Level 2
(In thousands)
Level 3
$
$
$
$
16,813
275,523
292,336
— $
—
— $
16,813
275,523
292,336
—
—
—
—
— $
— $
As of
December 31, 2021
$
$
$
$
26,220
369,107
395,327
6,862
6,862
Level 1
Level 2
(In thousands)
Level 3
— $
—
— $
26,220
369,107
395,327
—
—
— $
— $
6,862
6,862
—
—
—
—
—
—
—
—
The Company’s financial assets consist mainly of cash equivalents and marketable securities and are classified as Level 2 within the
valuation hierarchy. The Company values its marketable securities utilizing independent pricing services which normally derive security
prices from recently reported trades for identical or similar securities, making adjustments based on significant observable transactions.
At each balance sheet date, observable market inputs may include trade information, broker or dealer quotes, bids, offers or a
combination of these data sources.
The following table reflects the activity for the Company’s contingent consideration liabilities measured at fair value using Level 3
inputs for the year ended December 31, 2022 (in thousands):
Balance at December 31, 2021
Fair value adjustments included in operating expenses
Balance at December 31, 2022
Other Liabilities:
Contingent
Consideration
6,862
(6,862)
—
$
$
The valuation technique used to measure fair value of the Company’s Level 3 liabilities, which consist of contingent consideration
related to the acquisition of Kolltan in 2016 (Note 17), was primarily an income approach. The significant unobservable inputs used in
the fair value measurement of the contingent consideration are estimates, including probability of success, discount rates and amount of
time until the conditions of the milestone payments are met.
During the year ended December 31, 2022, the Company recorded a $6.9 million gain on fair value remeasurement of contingent
consideration primarily due to the Company’s decision to deprioritize the CDX-1140 program. The assumptions related to determining
the value of contingent consideration include a significant amount of judgment, and any changes in the underlying estimates could have a
material impact on the amount of contingent consideration adjustment recorded in any given period.
The Company did not have any transfers of assets or liabilities between the fair value measurement classifications during the years
ended December 31, 2022 and 2021.
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(5) Marketable Securities
The following is a summary of marketable debt securities, classified as available-for-sale:
December 31, 2022
Marketable securities
U.S. government and municipal obligations
Maturing in one year or less
Maturing after one year through three years
Total U.S. government and municipal obligations
Corporate debt securities
Maturing in one year or less
Maturing after one year through three years
Total corporate debt securities
Total marketable securities
December 31, 2021
Marketable securities
U.S. government and municipal obligations
Maturing in one year or less
Maturing after one year through three years
Total U.S. government and municipal obligations
Corporate debt securities
Maturing in one year or less
Maturing after one year through three years
Total corporate debt securities
Total marketable securities
Amortized
Cost
Gross
Unrealized
Gains
Gross
Unrealized
Losses
(In thousands)
Fair
Value
$
$
97,246
—
97,246
$ 179,613
—
$ 179,613
$ 276,859
$
80,674
51,319
$ 131,993
$ 170,034
67,782
$ 237,816
$ 369,809
$
$
$
$
$
$
$
$
$
$
5
—
5
$
$
— $
—
— $
$
5
— $
—
— $
— $
—
— $
— $
(369) $
—
(369) $
96,882
—
96,882
—
(972) $ 178,641
—
(972) $ 178,641
(1,341) $ 275,523
80,541
(133) $
(184)
51,135
(317) $ 131,676
(28) $ 170,006
(357)
67,425
(385) $ 237,431
(702) $ 369,107
The Company holds investment grade marketable securities, and none were considered to be other-than-temporarily impaired as of
December 31, 2022. Marketable securities include $0.8 million and $1.3 million in accrued interest at December 31, 2022 and December
31, 2021, respectively.
(6) Property and Equipment, Net
Property and Equipment, net includes the following:
Laboratory equipment
Manufacturing equipment
Office furniture and equipment
Leasehold improvements
Construction in progress
Total property and equipment
Less: accumulated depreciation and amortization
Property and equipment, net
December 31, December 31,
2022
2021
(In thousands)
$
$
9,250
2,558
3,454
9,613
498
25,373
(21,626)
3,747
$
$
8,581
2,571
3,362
9,531
632
24,677
(21,126)
3,551
Depreciation and amortization expense related to property and equipment was $1.4 million, $1.6 million and $2.0 million for the
years ended December 31, 2022, 2021 and 2020, respectively.
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(7) Leases
The Company has operating leases of office, manufacturing and laboratory space, which have remaining lease terms of one to three
years and may include one or more options to renew.
During the years ended December 31, 2022, 2021, and 2020, the Company recorded right of use assets and lease liabilities of $2.5
million, $1.0 million and 1.9 million related to new leases and lease extensions, respectively.
Operating lease expense was $1.9 million, $1.9 million and $2.3 million for years ended December 31, 2022, 2021 and 2020,
respectively. Variable lease expense was $0.8 million, $0.7 million and $1.2 million for years ended December 31, 2022, 2021 and 2020,
respectively.Cash paid for amounts included in the measurement of operating lease liabilities was $1.9 million, $1.8 million and $2.4
million for the years ended December 31, 2022, 2021 and 2020, respectively. As of December 31, 2022, the weighted-average remaining
lease term was 2 years and the weighted-average discount rate was 10.0%, compared to a weighted-average remaining lease term of 2
years and weighted average discount rate of 10.0% as of December 31, 2021.
Future minimum lease payments under non-cancellable leases as of December 31, 2022 were as follows:
2023
2024
2025
Total lease payments
Less imputed interest
Present value of operating lease liabilities
(8) Intangible Assets
$
$
1,776
1,876
896
4,548
(515)
4,033
At December 31, 2022 and 2021, the carrying value of the Company’s indefinite-lived intangible assets was $27.2 million.
Indefinite-lived intangible assets consist of acquired in-process research and development (“IPR&D”) related to the development of the
anti-KIT program (including barzolvolimab). Barzolvolimab is in Phase 2 development. As of December 31, 2022, the IPR&D asset
related to the anti-KIT program had not reached technological feasibility nor did the asset have alternative future uses.
The Company performs an impairment test on IPR&D assets at least annually, or more frequently if events or changes in
circumstances indicate that IPR&D assets may be impaired. During the fourth quarter of 2020, the Company decided that although it had
developed promising data for the AxL target within the TAM program, it would focus its efforts on out-licensing opportunities for its
TAM program, a broad antibody discovery effort to generate antibodies that modulate the TAM family of RTKs, comprised of Tyro3,
AxL and MerTK. As a result, the Company evaluated the TAM program IPR&D asset for potential impairment due to the change in
projected development and regulatory timelines related to the program. The Company used a discounted cash flow fair value model and
recorded a non-cash partial impairment charge of $14.5 million for the fourth quarter of 2020. During the third quarter of 2021, the
Company evaluated its out-licensing progress since December 31, 2020 and the status and expectation for the TAM program. Despite the
Company’s efforts to out-license, there was a lack of interest in the program from third parties. Therefore, the Company evaluated the
TAM program IPR&D asset for potential impairment using a discounted cash flow fair value model and concluded that the TAM IPR&D
asset was fully impaired. A non-cash impairment charge of $3.5 million was recorded for the third quarter of 2021. The Company
evaluated the CDX-3379 IPR&D asset for potential impairment as a result of the discontinuation of the CDX-3379 program in the
second quarter of 2020. The Company concluded that the CDX-3379 IPR&D asset was fully impaired, and a non-cash impairment
charge of $3.5 million was recorded during the second quarter of 2020. The Company performed its annual impairment test of the
IPR&D asset related to the development of the anti-KIT program (including barzolvolimab) during the fourth quarter of 2022 and
concluded that the IPR&D asset was not impaired. Due to the nature of IPR&D projects, the Company may experience future delays or
failures to obtain regulatory approvals to conduct clinical trials, failures of such clinical trials or other failures to achieve a commercially
viable product, and as a result, may recognize further impairment losses in the future.
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(9) Accrued Expenses
Accrued expenses include the following:
Accrued payroll and employee benefits
Accrued research and development contract costs
Accrued professional fees
Other accrued expenses
(10) Other Long-Term Liabilities
Other long-term liabilities include the following:
Net deferred tax liabilities related to IPR&D (Note 15)
Deferred income from sale of tax benefits
Contingent milestones (Note 4)
Deferred revenue (Note 13)
Total
Less current portion
Long-term portion
December 31,
December 31,
2022
2021
(In thousands)
$
$
7,526
4,223
766
320
12,835
$
$
7,968
2,871
878
283
12,000
December 31,
December 31,
2022
2021
(In thousands)
$
$
1,613
4,650
—
60
6,323
(990)
5,333
$
$
1,613
—
6,862
433
8,908
(1,554)
7,354
In March 2022, the Company received approval from the New Jersey Economic Development Authority and agreed to sell New
Jersey tax benefits of $5.0 million to an independent third party for $4.7 million. Under the agreement, the Company must maintain a
base of operations in New Jersey for five years or the tax benefits must be paid back on a pro-rata basis based on the number of years
completed.
In November 2015, the Company received approval from the New Jersey Economic Development Authority and agreed to sell New
Jersey tax benefits of $9.8 million to an independent third party for $9.2 million. During the year ended December 31, 2020, the
Company recorded $1.8 million to other income related to the sale of these tax benefits.
(11) Stockholders’ Equity
Common Stock
In November 2020, the Company filed an automatic shelf registration statement with the SEC to register for sale any combination of
the types of securities described in the shelf registration statement.
In May 2016, the Company entered into a controlled equity offering sales agreement (the “Cantor Agreement”) with Cantor
Fitzgerald & Co. (“Cantor”) to allow the Company to issue and sell shares of its common stock from time to time through Cantor, acting
as agent. During the year ended December 31, 2020, the Company issued 7,125,004 million shares of its common stock, under the
agreement with Cantor resulting in net proceeds to the Company of $29.4 million, after deducting commission and offering expenses. At
December 31, 2022, the Company had $50 million remaining in aggregate gross offering price available under the Company’s November
2020 prospectus.
In July 2021, the Company issued 6,845,238 shares of its common stock in an underwritten public offering resulting in net proceeds
to the Company of $269.9 million, after deducting underwriting fees and offering expenses.
In June 2020, the Company issued 15,384,614 shares of its common stock in an underwritten public offering resulting in net
proceeds to the Company of $141.4 million, after deducting underwriting fees and offering expenses.
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Convertible Preferred Stock
At December 31, 2022, the Company had authorized 3,000,000 shares of preferred stock all of which have been designated Class C
Preferred Stock including 350,000 shares which have been designated Series C-1 Junior Participating Cumulative Preferred Stock (the
“Series C-1 Preferred Stock”). No shares of Series C-1 Preferred Stock were outstanding at December 31, 2022 or 2021.
(12) Stock-Based Compensation
The Company has the following stock-based compensation plans: the 2004 Employee Stock Purchase Plan (the “2004 ESPP Plan”),
the 2008 Stock Option and Incentive Plan (the “2008 Plan”) and the 2021 Omnibus Equity Incentive Plan (the “2021 Plan”). There are
no shares available for future grant under the 2008 Plan. Outstanding options under the 2008 Plan will be rolled into the 2021 Plan if
canceled.
Employee Stock Purchase Plan
At December 31, 2022, a total of 276,666 shares of common stock are reserved for issuance under the 2004 ESPP Plan. Under the
2004 ESPP Plan, each participating employee may purchase shares of common stock through payroll deductions at a purchase price
equal to 85% of the lower of the fair market value of the common stock at either the beginning of the offering period or the applicable
exercise date. During the years ended December 31, 2022, 2021 and 2020, the Company issued 12,243, 21,867 and 39,817 shares under
the 2004 ESPP Plan, respectively. At December 31, 2022, 176,232 shares were available for issuance under the 2004 ESPP Plan.
Employee Stock Option Plan
The 2021 Plan permits the granting of incentive stock options (intended to qualify as such under Section 422A of the Internal
Revenue Code of 1986, as amended), non-qualified stock options, stock appreciation rights, performance share units, restricted stock and
other awards of restricted stock in lieu of cash bonuses to employees, consultants and non-employee directors.
The 2021 Plan allows for grants of new awards until April 19, 2031. As of December 31, 2022, there were 2,227,595 shares
outstanding under the 2008 Plan that will be rolled into the 2021 Plan if canceled. The Company’s Board of Directors determines the
term of each option, option price, and number of shares for which each option is granted and the rate at which each option vests. Options
generally vest over a period not to exceed four years. The term of each option cannot exceed ten years (five years for options granted to
holders of more than 10% of the voting stock of the Company), and the exercise price of stock options cannot be less than the fair market
value of the common stock at the date of grant (110% of fair market value for incentive stock options granted to holders of more than
10% of the voting stock of the Company). Vesting of all employee and non-employee director stock option awards may accelerate upon a
change in control as defined in the 2021 Plan.
A summary of stock option activity for the year ended December 31, 2022 is as follows:
Options outstanding at December 31, 2021
Granted
Exercised
Canceled
Options outstanding at December 31, 2022
Options vested and expected to vest at December 31, 2022
Options exercisable at December 31, 2022
Shares available for grant under the 2021 Plan
Weighted
Average
Exercise
Price
Per Share
Weighted
Average
Remaining
Contractual
Term (In Years)
8.0
—
—
—
7.9
7.8
6.6
—
30.02
23.19
8.22
48.36
29.26
29.40
40.05
—
Shares
4,077,667
$
$
1,620,000
(458,254) $
(153,751) $
5,085,662
$
$
4,970,769
2,100,491
$
1,837,968
The total intrinsic value of stock options exercised during the years ended December 31, 2022, 2021 and 2020 was $12.8 million,
$9.4 million and $0.8 million, respectively. The weighted average grant-date fair value of stock options granted during the years ended
87
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December 31, 2022, 2021 and 2020 was $17.60, $22.16 and $8.08, respectively. The total fair value of stock options vested during the
years ended December 31, 2022, 2021 and 2020 was $15.6 million, $5.9 million and $2.4 million, respectively.
The aggregate intrinsic value of stock options outstanding at December 31, 2022 was $122.6 million. The aggregate intrinsic value
of stock options vested and expected to vest at December 31, 2022 was $120.1 million. The aggregate intrinsic value of stock options
exercisable at December 31, 2022 was $54.1 million. As of December 31, 2022, total compensation cost related to non-vested employee
and non-employee director stock options not yet recognized was approximately $42.9 million, net of estimated forfeitures, which is
expected to be recognized as expense over a weighted average period of 2.6 years.
Valuation and Expenses Information
Stock-based compensation expense for the years ended December 31, 2022, 2021 and 2020 was recorded as follows:
Research and development
General and administrative
Total stock-based compensation expense
2022
8,082
7,529
15,611
2021
(In thousands)
4,525
$
4,428
8,953
$
$
$
2020
1,933
1,982
3,915
$
$
The fair values of employee and director stock options granted during the years ended December 31, 2022, 2021 and 2020 were
valued using the Black-Scholes option pricing model with the following assumptions:
Expected stock price volatility
Expected option term
Risk-free interest rate
Expected dividend yield
2022
90 - 97%
6.0 Years
1.7 - 4.2%
None
2021
97 - 98%
6.0 Years
0.8 - 1.4%
None
2020
91 - 98%
6.0 Years
0.5 - 0.7%
None
The Company estimates expected term based on historical exercise patterns. The Company uses its historical stock price volatility
consistent with the expected term of grant as the basis for its expected volatility assumption. The risk-free interest rate is based upon the
yield of U.S. Treasury securities consistent with the expected term of the option. The dividend yield assumption is based on the
Company’s history of zero dividend payouts and expectation that no dividends will be paid in the foreseeable future.
(13) Revenue
Product Development and Licensing Revenue
The Company’s agreement with Rockefeller University, as amended, (the “Rockefeller Agreement”) provides for the Company to
perform manufacturing and development services for Rockefeller University for their portfolio of antibodies against HIV. This portfolio
was licensed to Gilead Sciences in January 2020 from Rockefeller University (“Rockefeller Transaction”). Pursuant to the Rockefeller
Agreement, the Company received an upfront payment of $1.8 million as a result of the Rockefeller Transaction which was recorded to
revenue during the first quarter of 2020. The Company is eligible to receive additional payments from Rockefeller University if this
portfolio progresses through clinical and commercial development.
Contract and Grants Revenue
The Company has entered into the Rockefeller Agreement and an agreement with Gilead Sciences pursuant to which the Company
performs manufacturing and research and development services on a time-and-materials basis or at a negotiated fixed price. The
Company recognized $1.8 million, $4.1 million and $4.5 million in revenue under these agreements during the years ended December
31, 2022, 2021 and 2020, respectively.
During the third quarter of 2020, the Company was awarded a Small Business Innovation Research (“SBIR”) grant from the
National Institutes of Health (NIH) to support the Company’s CDX-1140 and CDX-301 programs. The Company recognized $0.5
million, $0.4 million and $0.4 million in grant revenue under the award during the years ended December 31, 2022, 2021 and 2020,
respectively.
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Contract Assets and Liabilities
At December 31, 2022 and 2021, the Company’s right to consideration under all contracts was considered unconditional, and as
such, there were no recorded contract assets. At December 31, 2022, the Company had $0.1 million in contract liabilities recorded, which
is expected to be recognized during the next 12 months as manufacturing and research and development services are performed. At
December 31, 2021, the Company had $0.4 million in contract liabilities recorded. Revenue recognized from contract liabilities as of
December 31, 2021 during the year ended December 31, 2022 was $0.4 million.
(14) Collaboration Agreements
The Company has entered into license agreements whereby the Company has received licenses or options to license technology,
specified patents and/or patent applications. These license and collaboration agreements generally provide for royalty payments equal to
specified percentages of product sales, annual license maintenance fees, continuing patent prosecution costs and potential future
milestone payments to third parties upon the achievement of certain development, regulatory and/or commercial milestones.
Nonrefundable license fee expense of $0.1 million, $0.1 million and $0.2 million was recorded to research and development expense for
the years ended December 31, 2022, 2021 and 2020, respectively.
Yale University (Yale)
Under a license agreement with Yale, the Company may be required to make a one-time payment to Yale of $3.0 million with
respect to barzolvolimab upon achievement of a specified commercial milestone. In addition, the Company may be required to pay a low
single-digit royalty on annual worldwide net sales of barzolvolimab. Unless earlier terminated by us or Yale, the Yale license agreement
is due to expire no later than May 2038 but may expire earlier on a country-by-country basis under specified circumstances.
(15) Income Taxes
The components of income tax benefit (provision) are as follows:
2022
Year Ended December 31,
2021
(In thousands)
2020
Income tax benefit (provision):
Federal
State
Expiration of NOLs and R&D credit
Deferred tax valuation allowance
$ 17,484
9,606
(16,862)
10,228
(10,228)
$ 18,513
7,082
(14,210)
11,385
(11,158)
227
$ 16,615
5,802
(20,294)
2,123
(956)
1,167
$
$
— $
A reconciliation between the amount of reported income tax and the amount computed using the U.S. statutory rate is as follows:
Pre-tax loss
Loss at statutory rates
Research and development credits
State taxes
Other
Change in fair value remeasurement of contingent consideration
Expiration of NOLs and R&D credit
Change in valuation allowance
Income tax (benefit) provision
89
2020
2022
2021
(In thousands)
$ (112,325) $ (70,738) $ (60,947)
(12,799)
(1,778)
(5,802)
(1,152)
(886)
20,294
956
(227) $ (1,167)
(23,588)
(3,876)
(9,606)
11,421
(1,441)
16,862
10,228
(14,855)
(2,422)
(7,082)
(941)
(295)
14,210
11,158
— $
$
Table of Contents
Deferred tax assets and liabilities are recognized based on temporary differences between the financial reporting and tax basis of
assets and liabilities using future expected enacted rates. The principal components of the deferred tax assets and liabilities at December
31, 2022 and 2021 are as follows:
Gross deferred tax assets
Net operating loss carryforwards
Tax credit carryforwards
Deferred research and development expenses
Stock-based compensation
Fixed assets
Accrued expenses and other
Gross deferred tax liabilities
IPR&D intangibles
Total deferred tax assets and liabilities
Valuation allowance
Net deferred tax liability
December 31, December 31,
2022
2021
(In thousands)
$
$
188,255
50,688
67,494
9,993
1,193
373
317,996
(6,840)
311,156
(312,769)
$
(1,613) $
183,711
47,927
59,753
14,719
1,287
370
307,767
(6,840)
300,927
(302,540)
(1,613)
The Company has evaluated the positive and negative evidence bearing upon the realizability of its net deferred tax assets and
considered its history of losses, ultimately concluding that it is “more likely than not” that the Company will not recognize the benefits of
federal, state and foreign deferred tax assets and, as such, has maintained a full valuation allowance on its deferred tax assets.
In response to COVID-19, the Coronavirus Aid, Relief, and Economic Security Act (the “CARES Act”) was enacted on March 27,
2020. Among other provisions, the CARES Act included (i) the ability to use net operating losses to offset income without the 80%
taxable income limitation enacted as part of the Tax Cuts and Jobs Act (“TCJA”) for net operating losses incurred in the 2018, 2019 or
2020 tax years; and (ii) the ability to claim a current deduction for interest expense up to 50% of adjusted taxable income for the 2019
and 2020 tax years (rather than 30% of adjusted taxable income pursuant to the TCJA). We do not expect that any of the provisions of the
CARES Act will result in a material impact to the financial statements.
The net deferred tax liability of $1.6 million at December 31, 2022 and 2021, relates to the temporary differences associated with the
IPR&D intangible assets acquired in previous business combinations and are not deductible for tax purposes. The Company recorded an
income tax benefit of $0.2 million during the year ended December 31, 2021 due to a decrease in deferred tax liabilities resulting from
the impairment of the TAM program IPR&D asset in the third quarter of 2021.
As of December 31, 2022, the Company had federal and state net operating loss carryforwards of $623.1 million and $879.9 million,
respectively, which may be available to offset certain future income tax liabilities and begin to expire in 2023 and 2029, respectively. Of
the federal net operating loss carryforwards of $623.1 million, approximately $374.8 million are from 2018, 2019, 2020, 2021 and 2022
and have no expiration date. As of December 31, 2022, the Company also had federal and state research and development tax credit
carryforwards of $41.4 million and $11.7 million, respectively, which may be available to offset future income tax liabilities and begin to
expire in 2023 and 2022, respectively.
Utilization of the net operating loss carryforwards and research and credit carryforwards may be subject to a substantial annual
limitation under Section 382 of the Internal Revenue Code of 1986, or Section 382, due to ownership changes that occurred previously or
that could occur in the future. These ownership changes may limit the amount of carryforwards that can be utilized annually to offset
future taxable income. In general, an ownership change, as defined by Section 382, results from transactions increasing the ownership of
certain shareholders or public groups in the stock of a corporation by more than 50% over a three-year period. The Company has
estimated the amounts of net operating loss and research and development tax credit carryforwards which will expire unutilized as a
result of its estimated annual limitations under Section 382 and has excluded those amounts from the carryforward amounts disclosed
above and in the deferred tax assets and liabilities table included in this footnote. The Company has concluded Section 382 studies
through 2015 for Celldex generated NOLs.
As of December 31, 2022 and 2021, the Company did not have any unrecognized tax benefits.
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Massachusetts, New Jersey, New York and Connecticut are the jurisdictions in which the Company primarily operates or has
operated and has income tax nexus. The Company is not currently under examination by these or any other jurisdictions for any tax year.
Generally, in U.S. federal and state taxing jurisdictions, all years which generated net operating losses and/or tax credit carryforwards
remain subject to examination to the extent those carryforwards are utilized in a subsequent period.
(16) Retirement Savings Plan
The Company maintains a 401(k) Plan which is available to substantially all employees. Under the terms of the 401(k) Plan,
participants may elect to contribute up to 60% of their compensation or the statutory prescribed limits. The Company may make 50%
matching contributions on up to 4% of a participant’s annual salary. Benefit expense for the 401(k) Plan was $0.4 million, $0.4 million
and $0.3 million for the years ended December 31, 2022, 2021 and 2020, respectively.
(17) Kolltan Acquisition
On November 29, 2016, the Company acquired all of the share and debt interests of Kolltan, a clinical-stage biopharmaceutical
company, in exchange for 1,217,200 shares of the Company’s common stock plus contingent consideration of up to $172.5 million
payable in cash, in shares of Celldex’s common stock or a combination of both, in the sole discretion of Celldex and subject to provisions
of the Agreement and Plan of Merger, dated November 1, 2016 (the “Merger Agreement”) with such contingent consideration based on
the achievement of development, regulatory approval or sales-based milestones (“Kolltan Milestones”).
In October 2019, the Company received a letter from SRS, the hired representative of the former stockholders of Kolltan, notifying
the Company that it objected to the Company’s characterization of the development, regulatory approval and sales-based Kolltan
Milestones relating to CDX-0158 as having been abandoned and contending instead that the related milestone payments are due from
Celldex to the Kolltan stockholders.
On August 18, 2020, Celldex filed a Verified Complaint in the Court of Chancery of the State of Delaware against SRS (acting in its
capacity as the representative of the former stockholders of Kolltan pursuant to the Merger Agreement) seeking declaratory relief with
respect to the rights and obligations of the parties relating to certain contingent milestone payments under the Merger Agreement relating
to the discontinued CDX-0158 program (the “Litigation”).
On June 20, 2022, the Company entered into a binding settlement term sheet (the “Term Sheet”) with SRS, related to the Litigation,
which, upon execution of a definitive settlement agreement and the payment of the Initial Payment (as defined below), would result in
the joint dismissal, with prejudice, of all claims and counterclaims in the Litigation. The definitive settlement agreement between the
Company and SRS was executed on July 15, 2022 (the “Settlement Agreement”) and the Company and SRS jointly filed a Stipulation of
Dismissal with prejudice relating to the Litigation on July 19, 2022.
Pursuant to the terms of the Term Sheet and the Settlement Agreement, all milestone payments provided for by the Merger
Agreement are replaced in their entirety with the following payments, each of which is payable only once:
(i) The Company paid $15.0 million upon execution of the Settlement Agreement (the “Initial Payment”).
(ii) The Company shall pay $15.0 million upon the Successful Completion (as defined in the Term Sheet) of a Phase 2 Clinical
Trial (as defined in the Merger Agreement) of barzolvolimab, subject to the $2.5 million contractual credit as set forth in the
Merger Agreement.
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(iii) The Company shall pay $52.5 million upon the first United States Food and Drug Administration or European Medicines
Agency, or, in each case, any successor organization, regulatory approval of a Surviving Company Product (as defined the Term
Sheet).
The above payment obligations replace, in their entirety, the contingent consideration in the form of development, regulatory
approval and sales-based milestones of up to $172.5 million contained in the Merger Agreement.
Under the Settlement Agreement, each of the Company and SRS provided broad mutual releases of all claims relating to or arising
out of the Merger Agreement, including without limitation, all claims brought in the Litigation or that could have been brought in the
Litigation.
The Company paid the Initial Payment in cash in July 2022. Any future milestone payments related to the barzolvolimab program,
which was subject to the Litigation, will be recorded when and if payment becomes probable and reasonably estimable in accordance
with the loss contingency model under ASC 450. Milestones related to the remaining Surviving Company Products are measured at fair
value in accordance with the contingent consideration model (refer to Note 4). When and if any of the remaining payments described
above become due, they shall be payable, at the Company’s sole election, in either cash or stock (as set forth in the Merger Agreement)
or a combination thereof.
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Table of Contents
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
As of December 31, 2022, our management evaluated, with the participation of our Chief Executive Officer and Chief Financial
Officer, the effectiveness of our disclosure controls and procedures (as defined in Rules 13a- 15(e) and 15d-15(e) under the Securities
Exchange Act of 1934, as amended (the “Exchange Act”)). Based on that evaluation, our Chief Executive Officer and Chief Financial
Officer concluded that our disclosure controls and procedures were effective at the reasonable assurance level as of December 31, 2022.
Our disclosure controls and procedures are designed to provide reasonable assurance that information required to be disclosed in the
reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within time periods specified by
the SEC’s rules and forms, and that such information is accumulated and communicated to our management, including our Chief
Executive Officer and Chief Financial Officer, as appropriate to allow timely decisions regarding required disclosure.
Management’s Annual Report on Internal Control Over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over our financial reporting. Internal
control over financial reporting is defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act as a process designed by, or under
the supervision of, our Chief Executive Officer and Chief Financial Officer, and effected by our Board of Directors, management and
other personnel, to provide reasonable assurance regarding the reliability of our financial reporting and the preparation of our financial
statements for external purposes in accordance with generally accepted accounting principles, and includes those policies and procedures
that:
● pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of
assets;
● provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in
accordance with generally accepted accounting principles, and that receipts and expenditures are being made only in
accordance with the authorizations of management and directors; and
● provide reasonable assurance regarding the prevention or timely detection of unauthorized acquisition, use or disposition of
assets that could have a material effect on our financial statements.
Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,
projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate because of
changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.
Under the supervision and with the participation of our management, including our Chief Executive Officer and Chief Financial
Officer, we conducted an evaluation of the effectiveness of our internal control over financial reporting based on the framework provided
in Internal Control — Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway
Commission. Based on this evaluation, our management concluded that our internal control over financial reporting was effective as of
December 31, 2022.
The effectiveness of the Company’s internal control over financial reporting as of December 31, 2022, has been audited by
PricewaterhouseCoopers LLP, an independent registered public accounting firm, as stated in their report which appears in Item 8 above.
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Changes in Internal Control Over Financial Reporting
There were no changes in our internal control over financial reporting during the three months ended December 31, 2022 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.
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Item 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE
PART III
The information required by this Item 10 will be included in the definitive Proxy Statement for our 2023 Annual Meeting of
Stockholders, or the 2023 Proxy Statement, under “Information Regarding Our Current Directors and Executive Officers,” “Delinquent
Section 16(a) Reports,” “Code of Business Conduct and Ethics” and “The Board of Directors and Its Committees” and is incorporated
herein by reference. If the 2023 Proxy Statement is not filed with the SEC within 120 days after the end of our most recent fiscal year, we
will provide such information by means of an amendment to this Annual Report on Form 10-K.
Item 11. EXECUTIVE COMPENSATION
The information required by this Item 11 will be included in the 2023 Proxy Statement under “Executive Compensation,” and
“Compensation Committee Interlocks and Insider Participation,” and is incorporated herein by reference. If the 2023 Proxy Statement is
not filed with the SEC within 120 days after the end of our most recent fiscal year, we will provide such information by means of an
amendment to this Annual Report on Form 10-K.
Item 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED
STOCKHOLDER MATTERS
The information required by this Item 12 will be included in the 2023 Proxy Statement under “Security Ownership of Certain
Beneficial Owners and Management” and “Equity Compensation Plan Information” and is incorporated herein by reference. If the 2023
Proxy Statement is not filed with the SEC within 120 days after the end of our most recent fiscal year, we will provide such information
by means of an amendment to this Annual Report on Form 10-K.
Item 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE
The information required by this Item 13 will be included in the 2023 Proxy Statement under “Election of Directors” and “Approval
of Related Person Transactions and Transactions with Related Persons” and is incorporated herein by reference. If the 2023 Proxy
Statement is not filed with the SEC within 120 days after the end of our most recent fiscal year, we will provide such information by
means of an amendment to this Annual Report on Form 10-K.
Item 14. PRINCIPAL ACCOUNTING FEES AND SERVICES
The information required by this Item 14 will be included in the 2023 Proxy Statement under “Independent Registered Public
Accounting Firm” and is incorporated herein by reference. If the 2023 Proxy Statement is not filed with the SEC within 120 days after
the end of our most recent fiscal year, we will provide such information by means of an amendment to this Annual Report on Form 10-K.
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PART IV
Item 15. EXHIBITS, FINANCIAL STATEMENT SCHEDULES
(A)
The following documents are filed as part of this Form 10-K:
(1) Financial Statements:
The Financial Statements and Supplementary Data are included in Part II Item 8 of this report.
(2) Financial Statement Schedules:
Schedules are omitted since the required information is not applicable or is not present in amounts sufficient to require
submission of the schedule, or because the information required is included in the Financial Statements or Notes thereto.
(3) Exhibits:
No.
Description
Plan of Acquisition, Reorganization, Arrangement, Liquidation or Succession
Incorporated by Reference to
Form and
SEC File No.
Exhibit
No.
SEC
Filing Date
2.1
2.2
2.3
Agreement and Plan of Merger, dated as of
November 1, 2016, by and among Kolltan
Pharmaceuticals, Inc., Celldex Therapeutics, Inc.,
Connemara Merger Sub 1 Inc. and Connemara
Merger Sub 2 LLC.
Binding Settlement Term Sheet, dated June 20,
2022, by and between Shareholder Representatives
Services LLC, solely in its capacity as Stockholders
Representative, and Celldex Therapeutics, Inc.
Confidential Settlement Agreement and Mutual
Release, dated July 15, 2022, by and between
Shareholder Representatives Services LLC, solely
in its capacity as Stockholders Representative, and
Celldex Therapeutics, Inc.
Articles of Incorporation and By-Laws
3.1
3.2
3.3
3.4
3.5
3.6
3.7
Third Restated Certificate of Incorporation
Certificate of Amendment of Third Restated
Certificate of Incorporation
Second Certificate of Amendment of Third
Restated Certificate of Incorporation
Third Certificate of Amendment of Third Restated
Certificate of Incorporation
Fourth Certificate of Amendment of Third Restated
Certificate of Incorporation
Fifth Certificate of Amendment of Third Restated
Certificate of Incorporation
Sixth Certificate of Amendment of Third Restated
Certificate of Incorporation
96
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
S-4
(333-59215)
S-4
(333-59215)
S-4
(333-59215)
10-Q
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
10-Q
(000-15006)
2.1
11/1/16
10.1
6/23/22
10.1
7/18/22
3.1
3.1
3.2
3.1
3.1
3.2
3.7
7/16/98
7/16/98
7/16/98
5/10/02
3/11/08
3/11/08
11/10/08
Table of Contents
3.8
3.9
Seventh Certificate of Amendment of Third
Restated Certificate of Incorporation
Second Amended and Restated By-Laws of Celldex
Therapeutics, Inc., dated November 3, 2022
Instruments Defining the Rights of Security Holders
4.1
4.2
4.3
Specimen of Common Stock Certificate
Certificate of Designations, Preferences and Rights
of a Series of Preferred Stock classifying and
designating the Series C-1 Junior Participating
Cumulative Preferred Stock
Description of Securities
Material Contracts-Leases
10.1
10.2
10.3
10.4
*10.5
10.6
10.7
10.8
10.9
10.10
10.11
10.12
Commercial Lease Agreement of May 1, 1996
between the Company and Fourth Avenue Ventures
Limited Partnership
Extension of Lease Agreement of May 1, 1997
between the Company and DIV Needham 53 LLC
(successor in interest to Fourth Avenue Ventures
Limited Partnership) dated as of August 23, 2001
First Amendment to Lease by and between the
Company and DIV Needham 115 LLC (successor in
interest to Fourth Avenue Ventures Limited
Partnership) dated November 29, 2005
Second Amendment to Lease by and between the
Company and DIV Needham 115 LLC dated as of
August 1, 2015
Lease Agreement, by and between the Company and
the Massachusetts Development Finance Agency,
dated as of December 22, 2003
First Amendment to Lease between Massachusetts
Development Finance Agency and the Company
dated March 17, 2005
Second Amendment to Lease by and between the
Company and the Massachusetts Development
Finance Agency dated as of November 4, 2005
Third Amendment to Lease between Massachusetts
Development Finance Agency and the Company
dated December 20, 2006
Fifth Amendment to Lease between Massachusetts
Development Finance Agency and the Company
dated October 3, 2008
Sixth Amendment to Lease between Massachusetts
Development Finance Agency and the Company
dated August 20, 2009
Seventh Amendment to Lease by and between the
Company and the Massachusetts Development
Finance Agency dated as of June 22, 2010
Eighth Amendment to Lease by and between the
Company and University of Massachusetts
Dartmouth dated as of November 1, 2015
97
8-K
(000-15006)
10-Q
(000-15006)
8-K
(000-15006)
8-A
(000-15006)
Filed herewith
10-Q/A
(000-15006)
10-K
(000-15006)
10-K
(000-15006)
10-K/A
(000-15006)
10-Q
(000-15006)
10-K/A
(000-15006)
10-K
(000-15006)
10-K/A
(000-15006)
10-K/A
(000-15006)
10-K/A
(000-15006)
10-Q
(000-15006)
10-K/A
(000-15006)
3.1
3.1
4.1
3.1
2/8/19
11/9/22
2/8/19
11/8/04
10.11
8/23/96
10.9
3/27/02
10.40
3/16/06
10.4
10.1
10.6
2/25/16
4/30/04
12/23/10
10.41
3/16/06
10.7
10.8
10.9
10.1
12/23/10
12/23/10
12/23/10
8/5/10
10.12
2/25/16
Table of Contents
10.13 Ninth Amendment to Lease by and between the
Company and University of Massachusetts Dartmouth
dated as of October 1, 2019
10.14 Tenth Amendment to Lease by and between the
Company and University of Massachusetts Dartmouth
dated as of August 1, 2022
10.15 Lease Agreement dated as of May 1, 2013 by and
between Crown Perryville, LLC and the Company.
10.16 First Amendment to Lease between Company and
Crown Perryville, LLC dated as of June 17, 2015
10.17 Second Amendment to Lease Agreement between the
Company and Crown Perryville, LLC dated as of
March 8, 2019
10.18 Third Amendment to Lease Agreement between the
Company and Perryville SPE LLC (successor-in-
interest) to Crown Perryville, LLC dated as of May 23,
2022
10.19 Extension of Lease Agreement between the Company
and University of Massachusetts Dartmouth dated as of
July 1, 2020
10-K
(000-15006)
10-Q
(000-15006)
10-Q
(000-15006)
10-Q
(000-15006)
10-Q
(000-15006)
10-Q
(000-15006)
10-Q
(000-15006)
Material Contracts-License, Collaboration, Supply and Distribution Agreements
*10.20 Amended and Restated License Agreement by and
between the Company and Yale University dated as of
July 26, 2022
Material Contracts-Stock Purchase, Financing and Credit Agreements
10.21 Sales Agreement, dated May 19, 2016, by and between
Celldex Therapeutics, Inc. and Cantor Fitzgerald & Co.
Material Contracts-Management Contracts and Compensatory Plans
†10.22 Celldex Therapeutics, Inc. 2021 Omnibus Equity
Incentive Plan
†10.23 Celldex Therapeutics, Inc. Amended and Restated
2008 Stock Option and Incentive Plan (as amended,
effective June 18, 2020).
†10.24 Celldex Therapeutics, Inc. Amended and Restated
2004 Employee Stock Purchase Plan (effective as of
June 19, 2019)
†10.25 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Anthony S. Marucci
†10.26 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Sam Martin
†10.27 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Tibor Keler, Ph.D.
†10.28 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Ronald Pepin, Ph.D.
†10.29 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Sarah Cavanaugh
98
10-Q
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
10.13
3/26/20
10.2
10.1
10.2
10.1
10.3
11/9/22
5/03/13
8/10/15
5/7/19
8/8/22
10.1
8/6/20
10.1
11/9/22
1.1
10.1
10.1
10.2
10.1
10.2
10.3
10.4
10.5
5/19/16
6/17/21
6/18/20
6/19/19
7/1/21
7/1/21
7/1/21
7/1/21
7/1/21
10.6
10.7
10.8
10.9
7/1/21
7/1/21
7/1/21
7/1/21
10.10
7/1/21
10.2
10.3
10.4
10.5
10.1
10.42
6/17/21
6/17/21
6/17/21
6/17/21
8/08/18
3/12/10
Table of Contents
†10.30 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Margo Heath-Chiozzi, M.D.
†10.31 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Elizabeth Crowley
†10.32 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Richard Wright, Ph.D.
†10.33 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Diane Young, M.D.
†10.34 Amended and Restated Employment Agreement, dated
as of July 1, 2021, by and between Celldex
Therapeutics, Inc. and Freddy Jimenez
†10.35 Celldex Therapeutics, Inc. 2021 Plan Form of
Restricted Stock Award Agreement
†10.36 Celldex Therapeutics, Inc. 2021 Plan Form of
Incentive Stock Option Grant Agreement
†10.37 Celldex Therapeutics, Inc. 2021 Plan Form of
Nonqualified Stock Option Grant Agreement
†10.38 Celldex Therapeutics, Inc. 2021 Plan Form of
Restricted Stock Unit Award Agreement
†10.39 2008 Plan Form of Stock Option Agreement
†10.40 2008 Plan Form of Restricted Stock Award
21.1 Subsidiaries of Celldex Therapeutics, Inc.
23.1 Consent of PricewaterhouseCoopers LLP, an
Independent Registered Public Accounting Firm
31.1 Certification of President and Chief Executive Officer
31.2 Certification of Senior Vice President and Chief
Financial Officer
32 Section 1350 Certifications
101.INS 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
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
8-K
(000-15006)
10-Q
(000-15006)
10-K
(000-15006)
Filed herewith
Filed herewith
Filed herewith
Filed herewith
Furnished herewith
Filed herewith
101.SCH Inline XBRL Taxonomy Extension Schema Document
101.CAL Inline XBRL Taxonomy Extension Calculation
Filed herewith
Filed herewith
Linkbase Document
101.DEF Inline XBRL Taxonomy Extension Definition Linkbase
Filed herewith
Document
101.LAB Inline XBRL Taxonomy Extension Label Linkbase
Filed herewith
Document
101.PRE Inline XBRL Taxonomy Extension Presentation
Filed herewith
Linkbase Document
104 Cover Page Interactive Data File (formatted as Inline
XBRL and contained in Exhibit 101)
* Certain confidential portions of this exhibit were redacted. Celldex Therapeutics, Inc. agrees to furnish supplementally to the U.S.
Securities and Exchange Commission a copy of any omitted schedule and/or exhibit upon request. The confidential portions of this
exhibit were omitted by means of marking such portions with asterisks because the identified confidential portions (i) are not
99
Table of Contents
material, (ii) would be competitively harmful if publicly disclosed and (iii) contain information that Celldex Therapeutics, Inc,
customarily and actually treats as private or confidential.
†
Indicates a management contract or compensation plan, contract or arrangement.
Item 16. FORM 10-K SUMMARY
None.
100
Table of Contents
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly caused this report
to be signed on its behalf by the undersigned, thereunto duly authorized.
SIGNATURES
Date
February 28, 2023
CELLDEX THERAPEUTICS, INC.
By:
/s/ ANTHONY S. MARUCCI
Anthony S. Marucci
President and Chief Executive Officer
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed by the following persons on behalf
of the registrant and in the capacities and on the dates indicated.
Signature
Title
/s/ ANTHONY S. MARUCCI
Anthony S. Marucci
President, Chief Executive Officer, and Director
(Principal Executive Officer)
Senior Vice President,
Chief Financial Officer and Treasurer
(Principal Financial and Accounting Officer)
Date
February 28, 2023
February 28, 2023
/s/ SAM MARTIN
Sam Martin
/s/ KAREN L. SHOOS
Karen L. Shoos
/s/ KEITH L. BROWNLIE
Keith L. Brownlie
/s/ CHERYL L. COHEN
Cheryl L. Cohen
/s/ HERBERT J. CONRAD
Herbert J. Conrad
/s/ RITA I. JAIN, M.D,
Rita I. Jain, M.D.
/s/ JAMES J. MARINO
James J. Marino
/s/ GARRY A. NEIL, M.D.
Garry A. Neil, M.D.
/s/ HARRY H. PENNER, JR.
Harry H. Penner, Jr.
Director, Chair of the Board of Directors
February 28, 2023
February 28, 2023
February 28, 2023
February 28, 2023
February 28, 2023
February 28, 2023
February 28, 2023
February 28, 2023
Director
Director
Director
Director
Director
Director
Director
101
Exhibit 4.3
DESCRIPTION OF THE REGISTRANT’S SECURITIES REGISTERED PURSUANT TO SECTION 12 OF THE
SECURITIES EXCHANGE ACT OF 1934
The following description of our common stock summarizes the material terms and provisions of our common stock. The
following description of our capital stock does not purport to be complete and is subject to, and qualified in its entirety by,
our Third Restated Certificate of Incorporation, as amended, (the “Certificate of Incorporation”) and our Amended
and Restated By-Laws (the “Bylaws”) which are exhibits to the Annual Report on Form 10-K filed with the Securities and
Exchange Commission, of which this Exhibit 4.3 forms a part. The terms of our common stock may also be affected by
Delaware law.
General
We are authorized to issue up to 297,000,000 shares of common stock, $0.001 par value per share. We are also authorized to
issue up to 3,000,000 shares of preferred stock, all of which have been designated as Class C Preferred Stock, including
350,000 shares which have been designated as Series C-1 Junior Participating Cumulative Preferred Stock, the terms of
which are to be determined by our Board of Directors.
Our common stock is listed on the Nasdaq Capital Market under the symbol “CLDX”.
Description of Common Stock
Dividends
The Board of Directors may, out of funds legally available, at any regular or special meeting, declare dividends to the
holders of shares of our common stock as and when they deem expedient, subject to the rights of holders of the preferred
stock, if any.
Voting
Each share of common stock entitles the holders to one vote per share on all matters requiring a vote of the stockholders,
including the election of directors. No holders of shares of common stock shall have the right to vote such shares
cumulatively in any election for the Board of Directors.
Rights Upon Liquidation
In the event of our voluntary or involuntary liquidation, dissolution, or winding up, the holders of our common stock will be
entitled to share equally in our assets available for distribution after payment in full of all debts and after the holders of
preferred stock, if any, have received their liquidation preferences in full.
Miscellaneous
No holders of shares of our common stock shall have any preemptive rights to subscribe for, purchase or receive any shares
of any class, whether now or hereafter authorized, or any options or warrants to purchase any such shares, or any securities
convertible into or exchanged for any such shares, which may at any time be issued, sold or offered for sale by Celldex.
Anti-Takeover Provisions
Certain provisions in our third restated certificate of incorporation, as amended, our second amended and restated by-laws
(the “by-laws”) and applicable Delaware corporate law, may have the effect of discouraging a change of control of Celldex,
even if such a transaction is favored by some of our stockholders and could result in stockholders receiving a substantial
premium over the current market price of our shares. The primary purpose of these provisions, which are summarized below
is to encourage negotiations with our management by persons interested in acquiring control of our corporation.
·
·
Special Meetings. Our by-laws provide that, except as otherwise required by law, special meetings of our
stockholders can only be called by the chair of the board, our president, secretary or our board of directors.
Advance Notice Requirements for Stockholder Proposals. Our by-laws establish an advance notice procedure for
stockholder proposals to be brought before an annual meeting of stockholders, including proposed nominations of
persons for election to our board of directors. Stockholders at an annual meeting are only able to consider proposals
or nominations specified in the notice of meeting or brought before the meeting by or at the direction of our board of
directors or by a stockholder of record on the record date for the meeting who is entitled to vote at the meeting and
who has delivered timely written notice in proper form to our secretary of the stockholder’s intention to bring such
business before the meeting. These provisions could have the effect of delaying until the next stockholder meeting
stockholder actions that are favored by the holders of a majority of our outstanding voting securities.
· Delaware Business Combination Statute. We are subject to Section 203 of the General Corporation Law of the
State of Delaware. Subject to certain exceptions, Section 203 prevents a publicly held Delaware corporation from
engaging in a “business combination” with any “interested stockholder” for three years following the date that the
person became an interested stockholder, unless the interested stockholder attained such status with the approval of
our board of directors or unless the business combination is approved in a prescribed manner. A “business
combination” includes, among other things, a merger or consolidation involving us and the “interested stockholder”
and the sale of more than 10% of our assets. In general, an “interested stockholder” is any entity or person
beneficially owning 15% or more of our outstanding voting stock and any entity or person affiliated with or
controlling or controlled by such entity or person.
·
Exclusive Forum Selection. Our by-laws provide that, unless we consent in writing to the selection of an
alternative forum, the Court of Chancery of the State of Delaware (or, if the Court of Chancery does not have, or
declines to accept, jurisdiction, another state court or a federal court located within the State of Delaware) will be the
sole and exclusive forum for any complaint asserting any internal corporate claims. Such claims include claims in
the right of the Company that are based upon a violation of a duty by a current or former director, officer, employee
or stockholder in such capacity, or as to which the Delaware General Corporation Law (the “DGCL”) confers
jurisdiction upon the Court of Chancery. Our by-laws also provide that unless otherwise selected or consented to by
the Company, the federal district courts of the United States of America will be the sole and exclusive forum for any
complaint asserting a cause of action arising under the Securities Act of 1933, as amended.
Computershare Trust Company, N.A. is presently the transfer agent and registrar for our common stock.
SUBSIDIARIES OF CELLDEX THERAPEUTICS, INC.
Name
Celldex Therapeutics Switzerland GmbH
Exhibit 21.1
Jurisdiction of
Organization
Switzerland
Ownership
Percentage
100%
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We hereby consent to the incorporation by reference in the Registration Statements on Form S-8 (Nos. 333-257137, 333-239463,
333-232253, 333-232255, 333-219867, 333-219869, 333-205694, 333-189336, 333-182142, 333-151728 and 333-117602) and on Form
S-3 (Nos. 333-249917, 333-239199, 333-235399 and 333-215747) of Celldex Therapeutics, Inc. of our report dated February 28, 2023
relating to the financial statements and the effectiveness of internal control over financial reporting, which appears in this Form 10-K.
Exhibit 23.1
/s/ PricewaterhouseCoopers LLP
Boston, Massachusetts
February 28, 2023
Exhibit 31.1
I, Anthony S. Marucci, certify that:
1.
I have reviewed this annual report on Form 10-K of Celldex Therapeutics, Inc.;
CERTIFICATION
2. 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;
3. 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;
4. The registrant’s other certifying officer 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 the Exchange Act
Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
(a)
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;
(b)
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;
(c)
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
(d)
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 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)
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
(b)
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: February 28, 2023
By /s/ ANTHONY S. MARUCCI
Name: Anthony S. Marucci
Title: President and Chief Executive Officer
Exhibit 31.2
I, Sam Martin, certify that:
1.
I have reviewed this annual report on Form 10-K of Celldex Therapeutics, Inc.;
CERTIFICATION
2. 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;
3. 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;
4. The registrant’s other certifying officer 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 the Exchange Act
Rules 13a-15(f) and 15d-15(f)) for the registrant and have:
(a)
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;
(b)
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;
(c)
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
(d)
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 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)
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
(b)
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: February 28, 2023
By /s/ SAM MARTIN
Name: Sam Martin
Title: Senior Vice President and Chief Financial Officer
CERTIFICATION OF CHIEF EXECUTIVE OFFICER
AND CHIEF FINANCIAL OFFICER PURSUANT TO
18 U.S.C. SECTION 1350, AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
Exhibit 32
Each of the undersigned hereby certifies, pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-
Oxley Act of 2002, in his capacity as an officer of Celldex Therapeutics, Inc. (the “Company”), that, to his knowledge, the Annual
Report of the Company on Form 10-K for the period ended December 31, 2022 (the “Form 10-K”), fully complies with the requirements
of Section 13(a) or 15(d) of the Securities Exchange Act of 1934 (15 U.S.C. §78m or 78o(d)) and that the information contained in such
report fairly presents, in all material respects, the financial condition and results of operations of the Company. This written statement is
being furnished to the Securities and Exchange Commission as an exhibit to the Form 10-K. A signed original of this statement has been
provided to the Company and will be retained by the Company and furnished to the Securities and Exchange Commission or its staff
upon request.
Date: February 28, 2023
Date: February 28, 2023
By: /s/ ANTHONY S. MARUCCI
Name: Anthony S. Marucci
Title: President and Chief Executive Officer
By: /s/ SAM MARTIN
Name: Sam Martin
Title: Senior Vice President and Chief Financial Officer
This certification shall not be deemed “filed” for any purpose, nor shall it be deemed to be incorporated by reference into any filing
under the Securities Act of 1933 or the Exchange Act.