UNITED STATES
SECURITIES AND
EXCHANGE COMMISSION
Washington, D.C.
20549
FORM 10-K
(Mark One)
For the fiscal year ended December 31,
2024
OR
For the transition period from
to
Commission file number 001-38914
Celularity Inc.
(Exact name of registrant as specified in its
charter)
(Address of principal executive offices) (Zip Code)
Registrant’s telephone number,
including area code: (908)768-2170
Securities registered pursuant to Section 12(b) of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
Securities registered pursuant to Section 12(g) of the Act: None
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 15(d) of the Act. Yes ☐No☒
Indicate by check mark whether the registrant: (1) has filed
all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for
such shorter period that the Registrant was required to file such reports), and (2) has been subject to such filing requirements for the
past 90 days. Yes☒ No ☐
Indicate by check mark whether the registrant
has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405
of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes☒ No ☐
Indicate by check mark whether the registrant
is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company.
See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,”
and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ 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 Exchange Act). Yes ☐
No ☒
The aggregate market value of the voting
and non-voting common equity held by non-affiliates of the registrant, based on the closing price of the shares of Class A common stock
on the Nasdaq Stock Market on June 30, 2024, was $38.5 million.
The number of shares of the registrant’s
Class A common stock outstanding as of May 6, 2025 was 23,949,229.
DOCUMENTS INCORPORATED BY REFERENCE
None
Table of Contents
Page
PART I
Item 1. Business 1
Item 1A. Risk Factors 31
Item 1B. Unresolved Staff Comments 68
Item 1C. Cybersecurity 68
Item 2. Properties 69
Item 3. Legal Proceedings 69
Item 4. Mine Safety Disclosures 69
PART II
Item 6. [Reserved] 70
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 82
Item 8. Financial Statements and Supplementary Data 82
Item 9A. Controls and Procedures 140
Item 9B. Other Information 141
Item 9C. Disclosure Regarding Foreign Jurisdiction that Prevents Inspections 141
PART III
Item 10. Directors, Executive Officers and Corporate Governance 142
Item 11. Executive Compensation 142
Item 14. Principal Accounting Fees and Services 142
PART IV
Item 15. Exhibits, Financial Statement Schedules 142
Unless the context indicates
otherwise, references in this annual report on Form 10-K to the “Company,” “Celularity,” “we,” “us,”
“our” and similar terms refer to Celularity Inc. (f/k/a GX Acquisition Corp.) and its consolidated subsidiaries (including
Celularity LLC, or Legacy Celularity).
The Celularity logo,
Celularity IMPACT, Biovance, Biovance 3L, Rebound, Interfyl, Lifebank, CentaFlex and other trademarks or service marks of Celularity Inc.
appearing in this annual report on Form 10-K are the property of Celularity Inc. This annual report on Form 10-K also contains registered
marks, trademarks and trade names of other companies. All other trademarks, registered marks and trade names appearing herein are the
property of their respective holders. Solely for convenience, trademarks and trade names referred to, including logos, artwork and other visual displays, may appear without
the ® or TM symbols, but such references are not intended to indicate, in any way, that their respective owners will not assert,
to the fullest extent under applicable law, their rights thereto.
On February 28, 2024, we
effected a 1-for-10 reverse stock split of our outstanding shares of Class A common stock. Unless specifically provided otherwise herein,
all share and per share information in this annual report on Form 10-K has been adjusted to reflect the reverse stock split.
i
SUMMARY RISK FACTORS
Our business involves significant
risks. Below is a summary of the material risks that our business faces, which makes an investment in our securities speculative and risky.
This summary does not address all these risks. These risks are more fully described below under the heading “Risk Factors”
in Part I, Item 1A of this annual report on Form 10-K. Before making investment decisions regarding our securities, you should carefully
consider these risks. The occurrence of any of the events or developments described below could have a material adverse effect on our
business, results of operations, financial condition, prospects and stock price. In such event, the market price of our securities could
decline, and you could lose all or part of your investment. In addition, there are also additional risks not described below that are
either not presently known to us or that we currently deem immaterial, and these additional risks could also materially impair our business,
operations or market price of our Class A common stock.
ii
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
Some of the statements
contained in this annual report on form 10-K constitute forward-looking statements within the meaning of Section 27A of the Securities
Act of 1933, as amended, or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, or the Exchange Act. Forward-looking
statements relate to expectations, beliefs, projections, future plans and strategies, anticipated events or trends and similar expressions
concerning matters that are not historical facts. These statements relate to our future events, including our anticipated operations,
research, development and commercialization activities, clinical trials, operating results and financial condition. These forward-looking
statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements
to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements.
Forward-looking statements may include, but are not limited to, statements about:
● our ability to regain compliance with Nasdaq’s continued listing standards;
●
● our use of cash and other resources; and
In some cases, you can
identify these forward-looking statements by the use of terminology such as “anticipate,” “believe,” “can,”
“contemplate,” “continue,” “could,” “estimate,” “expect,” “forecast,”
“intends,” “may,” “might,” “outlook,” “plan,” “possible,” “potential,”
“predict,” “project,” “seek,” “should,” “strive,” “target,” “will,”
“would” and the negative version of these words or other comparable words or phrases, but the absence of these words does
not mean that a statement is not forward-looking. These statements reflect our current views with respect to future events, are based
on assumptions and are subject to risks and uncertainties. Given these risks and uncertainties, you should not place undue reliance on
these forward-looking statements. We discuss many of these risks in greater detail under the headings “Risk Factors” and “Management’s
Discussion and Analysis of Financial Condition and Results of Operations” in this annual report on Form 10-K. Because forward-looking
statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond
our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected
in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the
forward-looking statements.
iii
Moreover, we operate in a
very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict
all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may
cause actual results to differ materially from those contained in any forward-looking statements we may make. In light of these risks,
uncertainties and assumptions, the forward-looking events and circumstances discussed in this annual report may not occur and actual results
could differ materially and adversely from those anticipated or implied in the forward-looking statements.
You should not rely upon forward-looking
statements as predictions of future events. Although we believe that the expectations reflected in the forward-looking statements are
reasonable, we cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the
forward-looking statements will be achieved or occur. Moreover, except as required by law, neither we nor any other person assumes responsibility
for the accuracy and completeness of the forward-looking statements. We undertake no obligation to update publicly any forward-looking
statements for any reason after the date of this annual report on Form 10-K to conform these statements to actual results or to changes
in our expectations.
You should read this annual
report on Form 10-K and the documents that we reference in this annual report on Form 10-K completely and with the understanding that
our actual future results may be materially different from what we expect. We qualify all of our forward-looking statements by these cautionary
statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained
herein, whether as a result of any new information, future events, changed circumstances, or otherwise. Readers are cautioned not to place
undue reliance on the forward-looking statements, which speak only as of the date of this annual report on Form 10-K.
iv
PART I
Item 1. Business.
Overview
We are a regenerative and
cellular medicines company focused on addressing aging-related and degenerative diseases. We believe that by harnessing the placenta’s
unique biology and ready availability, we will be able to develop therapeutic solutions that address a significant unmet global need for
effective, accessible and affordable therapeutics. Our advanced biomaterials business today is comprised primarily of the sale of Biovance
3L and Rebound product lines, both directly and through our distribution network. Biovance 3L is a tri-layer decellularized, dehydrated
human amniotic membrane derived from the placenta of a healthy, full-term pregnancy. It is an intact, natural extracellular matrix that
provides a foundation for the wound regeneration process and acts as a scaffold for restoration of functional tissue. Rebound is a full
thickness extracellular matrix that contains amnion and chorion. We are developing new placental biomaterial products to deepen the biomaterials
commercial pipeline. We also develop off-the-shelf placental-derived allogeneic cell therapy product candidates including mesenchymal-like
adherent stromal cells, or MLASCs, for which we have clinical datasets from Phase I and Phase II clinical studies and are prioritizing
advanced stage programs in diabetic foot ulcer, or DFU, and Crohn’s Disease, or CD. It also includes natural killer, or NK cells,
product candidates for which we have clinical datasets from Phase I and Phase II clinical studies and are currently investigating in preclinical
studies as senoablatant candidates. We also are leveraging our core expertise in cellular therapeutic development and manufacturing to
generate revenues by providing contract manufacturing and development services to third parties. The initial focus of this new service
offering is to assist development stage cell therapy companies and others with the development and manufacture of their therapeutic candidates
for clinical trials.
We are working toward a set
of milestones with respect to off-the-shelf placental-derived allogeneic biomaterial product candidates and cell therapy product candidates,
respectively. With respect to our biomaterial product candidate pipeline, we expect to submit a 510(k) application for our Celularity
Tendon Wrap, or CTW, in the second half of 2025. We expect to advance the development of our FUSE Bone Void Filler, or FUSE, with the
objective of a 510(k) filing in the second half of 2026, and to advance the development of our Celularity Placental Matrix, or CPM, with
the objective of a 510(k) filing in the second half of 2027. With respect to our MLASCs cell therapy product candidate for DFU (PDA 002),
we expect in the first half of 2025 to request an end of Phase 2, or EOP2, meeting with the FDA as part of which we intend to discuss
with the FDA our Phase 3 plan and protocols. In addition, with respect to our MLASCs cell therapy product candidate (PDA 001), we expect
to complete, in the first half of 2025, our safety and efficacy assessment of previously generated data that is one factor in determining
whether to progress our MLASCs cell therapy product candidate in CD to a Phase 3 clinical trial.
Our Celularity IMPACT manufacturing
platform is a seamless, fully integrated process designed to optimize speed and scalability from the sourcing of placentas from full-term
healthy informed consent donors through the use of proprietary processing methods, cell selection, product-specific chemistry, manufacturing
and controls, or CMC, advanced cell manufacturing and cryopreservation. The result is a suite of allogeneic inventory-ready, on demand
placental-derived cell therapy products. We also operate and manage a commercial biobanking business that includes the collection, processing
and cryogenic storage of certain birth byproducts for third-parties. A biobank is an organized collection of biological human material,
and its associated information stored for future retrieval and use in research, regenerative medicine, and innovation. We provide a fee-based
biobanking service to expectant parents who contract with us to collect, process, cryogenically preserve and store certain biomaterial,
including umbilical cord blood and placenta derived cells and tissue. We receive a one-time fee for the collection, processing, and cryogenic
preservation of the biomaterials, and a storage fee to maintain the biomaterials in our biobank payable annually generally over a period
of 18 to 25 years. We intend to explore opportunities to diversify our biobanking business, including adult cell banking.
Our current science is the
product of the cumulative background and effort over two decades of our seasoned and experienced management team. We have our roots in
Anthrogenesis Corporation, or Anthrogenesis, a company founded under the name Lifebank in 1998 by Robert J. Hariri, M.D., Ph.D., our founder
and Chief Executive Officer, and acquired in 2002 by Celgene Corporation, or Celgene. The team continued to hone their expertise in the
field of placental-derived technology at Celgene through August 2017, when we acquired Anthrogenesis. We have a robust global intellectual
property portfolio comprised of over 290 patents and patent applications protecting our Celularity IMPACT platform, our processes, technologies
and cell therapy programs that we are actively developing on our own or seeking to out-license or to find a collaboration partner to develop.
We believe this know-how, expertise and intellectual property will drive the rapid development and, if approved, the commercialization
of these potentially lifesaving therapies for patients with unmet medical needs.
Our Advanced Biomaterial Products
We develop and market off-the-shelf
placental-derived allogeneic advanced biomaterial products including allografts and connective tissue matrices for soft tissue repair
and reconstructive procedures in the treatment of degenerative disorders and diseases including those associated with aging. Our advanced
biomaterial products include:
We also are developing new
placental-derived advanced biomaterial products to deepen our commercial pipeline. We plan to explore opportunities to generate revenue
and leverage our core expertise in advanced biomaterial product manufacturing by providing contract manufacturing services under which
we manufacture one or more of our advanced biomaterial products for a distributor to sell under its own brand name(s). We also pursue
opportunities to generate revenues that leverage our core expertise in cellular therapeutic development and manufacturing by providing
contract manufacturing and development services to third parties. Contract manufacturing and development optimization services can help
accelerate translational and clinical discoveries and mitigate the complexity and risk associated with introducing new cell therapeutics,
including process variability, vulnerable supply chains, and manufacturing capacity constraints on scalability. Likewise, our biomaterial
contract manufacturing and development services support scale-up for small and large commercial volumes, including tissue procurement,
prototyping, private branding, and product distribution. Leveraging over three decades of experience in human tissue procurement and biobanking,
we maintain a supply of cryopreserved placental tissue procured from informed consent donors so it is available on demand to be converted
rapidly to finished biomaterial products, thereby addressing the structural vulnerabilities and inefficiencies inherent to most tissue
supply chains.
Addressable Markets
According to Global Market
Insights, the global tendon repair market was valued at approximately $2.2 billion with a 10-year compounded annual growth rate of
7.8% and the global bone graft substitute market was valued at approximately $3.4 billion with a 10-year compounded annual growth
rate of 6.8%. Furthermore, according to Nova 1 Advisors, the U.S. wound care market was valued at approximately $14.6 billion
with a 10 year compounded annual growth rate of 5.1% and, according to Allied Market Research, the global dermal filler market is
estimated to be approximately $5.1 billion with a 10 year compounded annual growth rate of 10.8%.
Our Strategy
Our goal is to lead the next
evolution in regenerative and cellular medicine by delivering off-the-shelf allogeneic cellular therapies, at greater scale and quality
with attractive economics. We believe achieving this goal will result in placental-derived allogeneic cellular therapies becoming a standard
of care in various indications across aging-related and degenerative diseases, and enable us to make potentially lifesaving therapies
more readily accessible to more patients throughout the world. We plan to achieve this mission by:
Our Pipeline
Leveraging our Celularity
IMPACT platform, we can derive four allogeneic cell types from a single source material, the postpartum human placenta: T cells, or pT
cells; unmodified NK cells, or pNK cells, or CYNK-001; MLASCs, or PDA-001 and PDA-002; and HPDSCs, or PSC-100. In 2022, we had active
and approved clinical trials under development utilizing CYNK-001, a placental derived unmodified NK cell, for the treatment of AML, a
blood cancer, and for glioblastoma multiforme, or GBM, a solid tumor cancer. We also had an active clinical trial utilizing CYNK-101,
a genetically modified NK cell, for the treatment of HER2+ gastric cancer. Due to a need to prioritize corporate resources, in January
2023 we announced our intention to cease recruitment in the GBM and the HER2+ gastric trials. In addition, in April 2023, we announced
based on the preliminary results of the Phase 1 trial data of CYNK-001, the AML trial would be closed to further enrollment and completed
follow up. We are not actively investigating CYNK-001 for any indication although we are evaluating it in senolytic/senoablation for age-related
conditions while we seek a collaboration partner. During the second quarter of 2023, we fully impaired the in-process research and development,
or IPR&D, assets associated with CYNK-001. In the first quarter of 2022, we submitted an IND to investigate CYCART-19, a placental-derived
CAR-T cell therapy targeting the cluster of differentiation 19, for the treatment of B-cell malignancies. In late May 2022, we received
formal written communication from FDA requesting additional information before we could proceed with the Phase 1/2 clinical trial. After
assessing the status of the IND to determine an optimal path forward for the CYCART-19 program, we elected to terminate development of
CYCART-19 for B-cell malignancies during the third quarter of 2023 and have discontinued our internal CYCART development efforts. We may
continue pre-clinical development of other T-cell candidates. MLASC is in development for the treatment of Crohn’s disease, and
other degenerative diseases. Due to an internal alignment of corporate resources, we paused development in exosomes to focus on other
priorities.
In addition, we can derive
genetically modified versions of three of these cell types: a pT cell that is genetically modified with a CAR, or CYCART; a pNK cell that
is genetically modified with a CAR, or CYNK; and a MLASC that is genetically modified via CRISPR-mediated tissue factor gene knockout,
or APPL. We also are researching a placenta-derived adherent cell exosome, or pEXO, and an exosome derived from a placental-derived immune
cell such as a pT cell or a pNK cell.
In the fourth quarter 2023
following a strategic review, we refocused our cellular therapeutics pipeline. We plan to continue to develop T cell and NK cell products
at the IND-enabling study stage to target aging-related and degenerative disease indications. These programs have built on the learnings
from our previous clinical programs to help us ensure we have product candidates that are optimized for efficacy, safety, and persistence
to offer first-in-class or best-in-class potential. We have developed a novel approach to addressing age-related conditions by using our
healthy young NK cell to attack and destroy senescent cells using the mechanism of attacking stress-ligand expressing cells, a process
we have termed “senoablation”. Data on our preclinical NK cell senoablation study has also been submitted for presentation
at the American Society of Gene and Cell Therapy. We continue to assess opportunities to advance our preclinical autoimmune candidates,
modified NK cells and T cells, in SLE, scleroderma and multiple sclerosis. We are evaluating CYNK-001 and seeking collaboration partners
in senolytic/senoablation for aging-related conditions. We also plan to continue to explore the opportunity to investigate PDA-001 and
PDA-002 to build on our existing data for our MLASC in Crohn’s disease, an autoimmune disease that leads to chronic inflammation
of the gastrointestinal tract; Facioscapulohumeral muscular dystrophy, or FSHD, a rare progressive genetic muscle disease; and Sarcopenia,
or age-related muscle loss.
Also following a strategic
review in fourth quarter 2023, we reconfirmed our advanced biomaterial product pipeline’s focus on three developmental-stage medical
devices intended to treat aging-associated and other degenerative diseases and disorders characterized by the progressive loss of function
and/or structure of the affected tissues. The three medical devices are Celularity Tendon Wrap, or CTW, Celularity Bone Void Filler, or
CBVF, and Celularity Placental Matrix, or CPM. We are developing our CTW medical devices for the treatment and management of tendon injuries
in which there has been no substantial loss of tendon tissue as a structural barrier for injured tendon tissue and does not depend on
chemical action (pharmacological activity) to mediate this effect. We are developing our CBVF medical device for use as a passive osteoconductive
bone filler in the pelvis, extremities, and posterior-lateral spinal fusion settings as well as other skeletal defects that are not dependent
on chemical action to mediate an effect. We are developing our CPM medical device for use as a passive temporary wound covering which
is not meant to achieve its primary intended purpose through chemical action (pharmacological activity) and is not dependent on being
metabolized for the achievement of its intended purpose. CPM is a fully resorbable device composed of extracellular matrix, or ECM derived
from decellularized human placental tissue and intended to treat partial and full-thickness wounds, pressure ulcers, venous ulcers, diabetic
ulcers, chronic vascular ulcers, tunneled/undermined wounds, surgical wounds, trauma wounds, and draining wounds. We intend to seek premarket
review and clearance by the FDA for CTW, CBVF and CPM through the 510(k) premarket notification procedure. With respect to our biomaterial
product candidate pipeline, we expect to:
● Submit a 510(k) application for CTW in the second half of 2025.
TCR KO = T-cell receptor knock out, TF
KO = tissue factor knock out, MCL = mantle cell lymphoma
Regulatory Pathway denotes FDA submissions.
We also intend to develop
and commercialize cellular medicine therapeutic product candidates, advance our preclinical pipeline, and utilize our technical operations
infrastructure and expertise in multiple clinical areas, subject to the availability of research funding and the prioritization described
above regarding our three developmental-stage medical devices.
Mesenchymal-like Adherent Stromal Cells (MLASCs)/Placenta-Derived
Adherent Cells (PDA)
PDA cells are a mesenchymal-like
cell population derived from normal, full-term human placental tissue. PDA-001 for intravenous administration and PDA-002 for intramuscular
administration.
PDA-001: Five indications
were studied with PDA-001 product among 88 patients. CD was the first indication where in one Phase 1, one Phase 2a, and one Phase 1b
studies were completed among 53 patients. The first Phase I clinical study involved investigating two dose levels of PDA-001 (150 million
and 600 million cells) among six patients each. On both day 365 and day 730, a clinical response of 83% and a clinical remission of 50%
were observed among the 150 million PDA-001 cell group after only two doses of treatment. During the second Phase 2a study, the primary
efficacy endpoint of clinical response at both weeks four and six was achieved in 33.3% of patients who received 150 million PDA-001 cells
in comparison to 0% response within the placebo group. The secondary endpoint of clinical remission was noted to be 13.3% in patients
who received 150 million PDA-001 cells versus 0% in the placebo group. In the third Phase 1b study, a lower dose of 37 million PDA-001
cells was investigated with only seven patients treated among the PDA-001 group versus five patients within the placebo group. The PDA-001
cell group demonstrated a 42% clinical response and 28% clinical remission versus 0% placebo patients that were assessed on the day 365
follow-up visit. The overall safety among all three studies was concluded to be favorable with Grade 1 and Grade 2 local thrombophlebitis
being the most common adverse event.
The second indication with
PDA-001 included a Phase 2a Multiple Sclerosis study where six patients in each of the two dose levels of PDA-001 (150 million and 600
million cells) were compared to four patients within the placebo group. The study met the primary endpoint of Cutter’s rule ( ≥
five new lesions present on two consecutive monthly scans), warranting a proof-of-concept study. The remaining three indications for PDA-001
cells included Rheumatoid arthritis (17 patients), stroke (two patients), and Sarcoidosis (four patients) which were closed.
PDA-002: Two indications
were studied with PDA-002. DFU with or without Peripheral Artery Disease was the first indication wherein one Phase I and one Phase II
studies were completed. The Phase II study was a randomized, placebo-controlled, double-blind study that investigated two doses of PDA-002
intramuscularly at three dose levels (3 x 106, 10 x 106, 30 x 106 cells) versus placebo. Safety was well-tolerated with injection-site
reactions being the most comment adverse event among the 145 patients. The primary efficacy endpoint was the rate of response, defined
as complete wound closure within three months after dosing and retention of wound closure for the subsequent four weeks. The highest response
rate, observed in the 3 x 106 PDA-002 cells group was 38.5% compared to the 22.6% response rate within the placebo group. The response
rates were 29.6% in the 10 x 106 PDA-002 cells group and 35.7% in the 30 x 106 PDA-002 cells group. A sub-group analysis was conducted
to compare the ulcer closure at 12-week and 20-week timepoints with the currently approved FDA products which demonstrated equivalent
closure rate of 42.8% and 53.8% with 3 x 106 PDA-002 dose level.
Diabetic Peripheral Neuropathy
was the second indication that involved a Phase 2a study wherein 16 patients were treated with PDA-002 cells versus nine patients with
placebo. The safety was well-tolerated. An increase in nerve fiber density was observed, warranting a proof-of-concept study.
CYNK-001 [discontinued internal
development in oncology]: CYNK-001 is an allogeneic off-the-shelf cell therapy enriched for CD56+/CD3- NK cells expanded from human placental
CD34+ cells. We conducted four clinical trials of CYNK-001 among four indications: the CYNK-001-AML-001 is a Phase 1, open-label dose-escalation
study in adults with either Minimum Residue Disease, or MRD, or Relapsed/Refractory, or R/R, AML patients. In December 2023, the results
of this study were presented at the American Society of Hematology. A total of eight patients (17 with R/R AML and 11 with MRD positive
AML) were enrolled during dose escalation, and 27 received at least one dose of CYNK-001. In R/R AML patients treated, three of the six
patients achieved an objective response of Morphologic Leukemia-Free State on day 28. One of the three patients with MRD positive patients
achieved MRD negativity until day 120.
The remaining three clinical
studies were completed in Multiple Myeloma (CYNK-001-MM-002), Glioblastoma (CYNK-001-GBM-001), and COVID-19 (CYNK-001-COVID-19) wherein
a total of nine, three, and seven subjects were treated respectively. The safety was well-tolerated among all 46 patients with Grade 1
and 2 Cytokine Release Syndrome being the most common adverse event. There were no events of GvHD associated with the CYNK-001 treatment.
We are evaluating CYNK-001
and seeking collaboration partners in senolytic/senablation for age-related conditions.
CYNK-101 [discontinued internal
development]: CYNK-101 is a human placental hematopoietic stem/progenitor cell derived NK cell product, that is genetically modified to
express a variant of CD16, Fc gamma receptor III (FcγRIII), via lentiviral vector transduction. We initiated a Phase 1 open-label
study of CYNK-101 in combination with Trastuzumab and Pembrolizumab in newly diagnosed patients with Locally Advanced Unresectable or
Metastatic HER2-Positive Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma. One patient was treated with five doses of CYNK-101
with no reported safety concerns.
Celularity IMPACT Platform
Placental-derived cellular
therapies offer potentially lifesaving therapies for patients with unmet medical needs. We have developed and acquired proprietary technology
for collecting, processing, and storing placental stem cells with potentially broad therapeutic applications in the treatment of aging-associated
and other degenerative disorders and diseases. These span various therapeutic areas for which aging is known to be a major risk factor,
including cancer, regenerative medicine, and immune disorders.
Common to all degenerative
disorders and diseases is the progressive loss of function or structure (or both) of affected tissues and organs based on a continuous
process of degenerative cell changes. We use our proprietary Celularity IMPACT platform for the development of allogeneic cellular therapies
that we believe exert immunomodulatory and regenerative effects. Immunomodulation is the regulation and modulation of immunity achieved
by reducing or enhancing the immune response, for example, promoting immune tolerance to cellular therapies. We believe that by harnessing
the placenta’s unique biology and ready availability, we will be able to develop therapeutic solutions that address a significant
unmet global need for effective, accessible, and affordable therapeutics.
Our Celularity IMPACT manufacturing
process is a seamless, fully integrated process that is built to optimize speed and scale, from the sourcing of human full term healthy
postpartum placentas from informed consent donors through proprietary processing methods, cell selection, product-specific CMC, advanced
cell manufacturing, and cryopreservation resulting in allogeneic inventory-ready and on-demand cellular therapy products. The fully integrated
process is housed in our purpose-built manufacturing, translational research, and biobanking facility located in Florham Park, NJ.
Our Celularity IMPACT platform
capitalizes on our integrated processes and the unique biologic characteristics of placental-derived allogeneic cells to target degenerative
disorders and diseases including those associated with aging that span various therapeutic areas including cancer, regenerative medicine,
and immune disorders, and infectious diseases. The platform is designed to accelerate the speed at which therapies can be provided to
patients while ensuring manufacturing excellence of high quality and pure placental-derived cellular therapy products at a lower cost.
We believe our IMPACT platform enables cellular therapy inventory to be available to physicians on demand to treat patients in need and
to enable repeat dosing regimens that other cellular therapy platforms will not be able to support.
Allogeneic Placental-Derived Cells
Biomaterials Collection
The initial source material
for our four allogeneic cell types is the postpartum human placenta. We source human placental birth material used for the manufacture
of our products from accredited hospitals and birth centers, with collections performed by licensed health care professionals. Eligibility
for donation is determined by a donor screening process that includes education about the donor program, obtaining informed consent from
the donor, and completion of a detailed maternal health questionnaire and family health history. These forms are completed by the donor,
with assistance from trained collection technicians as needed. Donors providing birth materials do not encounter any fees and are not
renumerated.
Licensed health care professionals
collect donor material utilizing our proprietary collection kits, which include barcode labels for biomaterials (cord blood, placenta,
and maternal blood samples) along with appropriate chain of custody documentation. Once collected, the donated material and a maternal
blood sample are shipped in an insulated container via courier to our Florham Park, New Jersey laboratory and manufacturing facility.
Upon arrival at our facility,
the donated material is reviewed for labeling completeness and accuracy of the barcoded kit and is electronically coded into a validated
software database. If all quality criteria are met, the donated material is then individually evaluated and forwarded to the appropriate
production suite for processing and manufacturing. We believe that our sourcing is rapidly scalable due to numerous established procurement
relationships that provide a constant renewable supply to meet current and future manufacturing needs.
Unique Biology of Placenta-Derived Cells
Placental-derived cells
have unique biology related to immunological naïveté, stemness, persistence and proliferation that makes them a biologically
preferred starting material with the potential for less toxicity and superior biological activity relative to adult bone marrow or peripheral
blood-derived cells.
Research has shown that
the human placenta is a novel and valuable source of multi potential stem/progenitor cells of mesenchymal and hematopoietic origin, which
have multiple therapeutic applications. Our characterization data show that approximately one to five percent of placental-derived cells
are CD34+ hematopoietic stem cells, or HSCs, among which expression of certain markers suggests that such HSCs have more self-renewal
capacity and the potential to facilitate the early engraftment of the placental-derived cells. In addition, further characterization has
shown low T-cell content and immature T subpopulations. This demonstrated immunological naïveté further suggests the potential
for low or no GvHD in transplant. Furthermore, mesenchymal-like cells have been shown to possess other characteristics, capabilities,
and effects (e.g., osteogenic, chondrogenic, adipogenic differentiation capabilities and immunomodulatory effects). The high quantity
of mesenchymal-like cells and Treg cells indicate that placental-derived cells can potentially contribute to prevention of GvHD and host
microenvironment modulation. In summary, we believe the stemness, potential capacity of proliferation and persistence of placental-derived
cells support multiple potential therapeutic applications, including those in development by us.
We are also researching placental-derived
exosomes for potential therapeutic applications. Exosomes are a kind of extracellular vesicle that act as communication channels between
cells and cause functional changes in recipient cells. Exosomes enable intercellular communication by transferring specific cargo contents
to a recipient cell and can confer epigenetic changes in the recipient cells by delivering microRNAs, or miRNAs. Exosomes have been identified
as the primary factors responsible for paracrine effects detected in all types of stem cells and for the transfer of genetic material
from stem cells to the tissue-specific cell that needs regeneration. Exosomes have been shown to possess powerful regenerative potential,
including immune-modulatory properties and anti-inflammatory properties. We discovered a type of exosome that we call a placenta-derived
adherent cell exosome, or pEXO. Rich in growth factors, deoxyribonucleic acid, or DNA, fragments, miRNAs, and messenger RNAs, pEXO exhibit
particular markers that distinguish them from other exosomes that are not derived from placenta-derived adherent cells. We are investigating
purified pEXO formulated into pharmaceutical compositions for human administration to promote angiogenesis and/or vascularization, to
modulate immune activity, and to repair tissue damage.
Overview of CAR-T Cells
White blood cells are a component
of the immune system and responsible for defending the body against infectious pathogens and other foreign material. T cells are a type
of white blood cell and are involved in both sensing and killing infected or abnormal cells, including cancer cells, as well as coordinating
the activation of other cells in an immune response.
Unlike adult peripheral
blood mononuclear cell, or PBMC, derived T cells, placental-derived T cells are mostly naïve and can be readily expanded while maintaining
an earlier differentiation phenotype, such as greater expression of naïve/memory markers and lower expression of effector/exhaustion
markers. These characteristics allow for greater proliferative potential of these cells ex vivo. Placental-derived T cells are
also known to have greater immune tolerance and display impaired allogeneic activation, contributing to lower incidences of severe GvHD,
which makes them an attractive cell population for use as an allogeneic, adoptive cellular therapy. We have developed a robust process
for the isolation, transduction, and expansion of placental-derived T cells to generate “off-the-shelf” allogeneic CAR-T cells.
Allogeneic human placental
T cells are derived from healthy donor placentas. We separate out mononuclear cells using a mononuclear cell separation method to isolate
placental T cells prior to cryopreservation. Our allogeneic CAR-T cell product begins with the thawing and activation of the isolated
placental T cells, followed by viral transduction of the cancer-targeting CAR construct and an additional genetic modification step to
minimize any risk of GvHD. Once transduced and transfected, the CAR-T cells are expanded to yield large quantities of these cells prior
to harvest, final formulation, and cryopreservation of the cellular therapeutic.
Overview of NK cells — Unmodified
and Genetically Modified
NK cells are potent effector
cells of the innate immune system responsible for identifying and eliminating abnormal and stressed host cells. They are equipped with
NK cell-specific activating receptors that recognize conserved antigens induced by cellular stress while being simultaneously tuned with
inhibitory receptors to avoid mistakenly targeting healthy cells. NK cells are particularly relevant in combating viral infections and
mediating anti-tumor immunity in which normal cellular processes are stressed for the purposes of perpetuating viral infection and cancer
cell proliferation.
Commercializing NK cellular
therapies has been limited by the difficulty and cost to scale the production of mature NK cells for clinical dosing. Utilizing our Celularity
IMPACT platform, our proprietary process has mitigated these limitations by expanding and differentiating placental-derived stem cells
into NK cells over a period of 35 days. We derive the HSCs from healthy donor placentas, then propagate and differentiate these cells
into NK cells. This process can produce hundreds of doses per donor placenta. We also developed technologies that can achieve high genetic
modification efficiency by transducing placenta HSCs and producing downstream stable gene modified CYNK cells with enhanced cancer killing
activities. These cells are then cryopreserved and available to be shipped upon request.
For our genetically modified
NK cells, our allogeneic modified NK cell product begins with the thawing and activation of the isolated placental NK cells. We then use
a lentiviral vector transduction to augment the effector functions of the NK cells and to sustain their tumor-killing properties. We believe
that our genetically modified NK cells can be used in combination with therapeutic mAbs to boost antibody-dependent cellular cytotoxicity,
or ADCC, potential.
Overview of MLASCs
Placental-derived MLASCs
are a novel, culture-expanded mesenchymal-like cell population derived from placental tissue. In vivo, we demonstrated that MLASCs’
immune-modulatory properties alleviate autoimmunity and possess anti-inflammatory activity. Both intravenous and intramuscular administration
formulations of the first generation of MLASCs have been developed and investigated in clinical studies in Crohn’s Disease, multiple
sclerosis, rheumatoid arthritis, stroke, diabetic foot ulcers and diabetic peripheral neuropathy. We are developing next generation genetically
modified MLASCs for the treatment of degenerative diseases.
Allogeneic human placental
MLASCs are derived from healthy donor placentas. Our allogeneic MLASC product begins with the thawing and activation of the isolated placental-derived
MLASCs, followed by genetic modification of tissue factor to reduce potential toxicities and lower risk of adverse effects. Once modified,
we expand the MLASCs to large quantities prior to harvest, final formulation, and cryopreservation of the cellular therapeutic.
Overview of Exosomes
Exosomes are acellular, nano-size
lipid bilayer membrane particles released by cells into extracellular space and play important roles in cell to cell, tissue to tissue
and organ to organ communications. Also referred to as intraluminal vesicles, or ILVs, exosomes are a subtype of extracellular vesicles,
or EVs, along with microvesicles, or MVs, and apoptotic bodies from which exosomes are differentiated based upon their biogenesis, release
pathways, size, content, and function. Exosomes are generated from late endosomes with 30-200 nanometers in diameter. When fused with
the targeted cells, the molecular cargos (e.g., proteins, lipids, DNAs, mRNAs, and microRNAs) carried by exosomes are inserted into the
cells to exert the functions.
Recently, exosomes are being
recognized as promising candidates in the treatment of degenerative diseases. Evidence has suggested that part of the observed cell therapeutic
effects is mediated by exosomes and that mesenchymal stem cell exosomes can act as a therapeutic entity to help reduce tissue injury or
when it occurs, to contribute to injury recovery. Other evidence suggests exosome-based therapy may be superior in anti-senescence and
anti-inflammatory effects to stem cell–based therapy. Exosome therapy has certain advantages over cellular therapy such as: low/non-immunogenicity,
easy storage, and administration. In addition, due to their nano-size, exosomes can cross the brain-blood barrier and be delivered to
broader target tissues and organs than cell-based therapeutics.
pExo-001 is a human postpartum
placenta derived exosome product which consists of cytokines, chemokines, and growth factors that have been reported to have regenerative
and immuno-regulatory activities.
Allogeneic Cellular therapies — an
“Off-the-Shelf” Approach
There are two primary approaches
to engineered cellular therapies: autologous and allogeneic. Autologous therapies use engineered cells derived from the individual patient,
while allogeneic therapies use cells derived from an unrelated third-party healthy donor. We believe our human placental-derived allogeneic
platform is leading the next evolution of cellular medicine because we aim to deliver off-the-shelf allogeneic cellular therapies, at
greater scale and quality with attractive economics, potentially making lifesaving therapies more readily accessible to more patients
throughout the world.
Our human placental-derived
allogeneic cryopreserved, off-the-shelf platform currently includes placental CAR-T cells, or CYCART, NK cells MLASCs, or APPL-001, and
exosomes, or pEXO-001.
CYCART
Currently, autologous CAR-T
products are manufactured by isolating T cells from the patient’s blood through a process known as leukapheresis. The cancer-targeting
construct expressing specific CAR proteins is virally transduced into the T cells and the engineered T cells are then propagated until
a sufficient number are available for infusion. The engineered T cells are then shipped back to the clinical center for administration
to the patient. The process from leukapheresis to delivery to the clinical center takes approximately four weeks. While the autologous
approach has been revolutionary, with other companies’ previously approved products demonstrating compelling efficacy in many patients,
it can be burdened by lengthy vein-to-vein time, high production cost, variable potency, and/or manufacturing failures.
Conversely, our allogeneic
placental-derived T cells are derived from healthy donors that have undergone rigorous donor screening and selection. Manufactured drug
product can be deployed from inventory to patients immediately in sufficient quantities because administration is not limited by patient
cell sourcing and individual drug product expansion. As an “off-the-shelf” treatment, CYCART cells also offer the potential
to re-dose patients, if necessary. Healthy births are in hundreds of millions worldwide, and the placenta provides an abundant, renewable
source of healthy, ready to use lymphocytes. In addition, placental-derived T cells contain an abundance of stem cell memory T cells,
which confer high proliferation and durability. Placental T cells are known to be immune-privileged and have low donor to host toxicity,
or GvHD. We are therefore potentially a generally safer cell population. Furthermore, allogeneic placental T cells can be genetically
engineered to minimize the risk of GvHD and avoid being destroyed by the patient’s immune system. Therefore, CYCART cells may possess
an advantageous safety profile while delivering effective tumor eradication activity and durable persistence in patients. Our CYCART development
efforts were previously under IND for cancer and has been discontinued internally. We will seek to out-license the technology or find
a collaboration partner to further develop.
CYNK
Similarly, autologous NK
cells and genetically modified autologous NK cells have been used in the setting of immuno-oncology. NK cells can directly kill cancer
cells by recognizing signals of cellular stress and carry no risk of GvHD. However, autologous peripheral blood derived NK cells have
limited proliferation capacity and usually require leukemia cell line-based technology to assist production. In addition, autologous CAR-NK
was shown to encounter technical challenges due to low transduction efficiency of CAR vectors in the peripheral NK cells. Our NK platform
propagates human placenta derived HSCs and differentiates these cells into unmodified NK cells (CYNK-001). This process can produce hundreds
of doses per placenta donor. We have also developed technologies that can achieve high genetic modification efficiency by transducing
placenta HSCs and produce downstream stable gene modified CYNK cells with enhanced and selective cytotoxic and senolytic activity for
potential use in age-related diseases, including cancer, and autoimmune diseases. These cells are cryopreserved and can be shipped to
clinical administration immediately upon request. Our CYNK-001 development efforts were previously under IND for cancer and has been discontinued
internally. We are evaluating CYNK-001 as a senolytic/senablatant for age-related conditions and will seek to out-license the technology
or find a development partner.
MLASCs
Both autologous and allogeneic
bone marrow or adipose tissue derived MLASCs have been used in human clinical trials. Autologous MLASC therapies have advantages including
the absence of donor cell related adverse events and fewer regulatory hurdles since cell products are derived from a donor’s own
cells. However, autologous MLASC products carry the inherited or aging-related biological defects of the donor, which may impair therapeutic
value. Furthermore, in most cases, autologous cells still require cultivation before patient administration and there is a risk of manufacturing
failure.
Conversely, allogeneic MLASCs
can provide an off-the-shelf product with high quality and flexibility of dosing. MLASCs are regarded as immune-privileged due to their
relative low-level major histocompatibility complex class I and II protein expression. Our placenta tissue derived MLASCs are potentially
more immune privileged due to their fetal origin. In addition, because MLASCs have higher proliferative capability, they are expected
to be more suitable for genetic manipulations to engineer the cells to have specific features to enhance their functions or to mitigate
risk factors.
pEXOs
Exosomes derived from certain
cell or tissue types including mesenchymal stem cells, or MSCs, affect angiogenesis, inflammation, and bone remodeling. Recent studies
have demonstrated that MSC-derived exosomes, or MSC-EXOs, alleviate inflammation and restore matrix homeostasis in knee osteoarthritis,
or KOA, a leading degenerative joint disease in the aging population.
Therapeutic Candidate Pipeline and Development
Strategy
We are researching and developing
multiple placental-derived allogeneic cellular therapeutic candidates for the treatment of indications across aging-related and degenerative
diseases. From a single source material, the placenta, we focus on four allogeneic cell types: CAR-T cells, unmodified NK cells, genetically
modified NK cells, and MLASCs. We are also researching pEXO. Our product pipeline is presented above.
Future Pipeline Opportunities
We plan to utilize our Celularity
IMPACT platform to pursue additional targets of interest. These may include the additional indications for the four allogeneic cell types
currently in the pipeline as well as other targets that might be validated in the future. Our placental-derived T cell platform has potential
to target other receptors.
In addition, we regularly
survey the scientific and industry landscape for opportunities to license, partner or acquire technologies that may help us advance current
or new cellular therapies for the benefit of patients.
Our ability to prosecute
future opportunities including those with scientific and potential commercial merit may be influenced by our ability to raise sufficient
capital to pursue those opportunities or to find commercial partners that are willing and able to fund portions of their development.
Co-developed or partnered programs may have longer term economics that are less favorable than internally funded programs, but those programs
also may have higher odds of success with a well-capitalized development partner with specific expertise in the disease state under investigation.
Commercial Businesses
We are continuing to invest
in new biomaterials programs to expand our pipeline of placenta-derived advanced biomaterial products. We are currently developing a tendon
wrap indicated for the management and protection of tendon injuries in which there has been no substantial loss of tendon tissue; a bone
void filler product for use in orthopedic surgical markets; and a placenta-derived extracellular matrix, or PECM, for use as a passive
temporary wound covering. We have preliminary data from a knee osteoarthritis animal model that our PECM may decrease joint pain and promote
chondrogenesis in damaged cartilage. Our product pipeline is presented above.
Advanced Biomaterial Products for Degenerative
Diseases
We report sales of advanced
biomaterial products within the Degenerative Disease operating segment, which includes products for use in wound care and the treatment
of degenerative disease. The National Cancer Institute defines “degenerative disease” as a disease in which the function or
structure of the affected tissues or organs changes for the worse over time. Our advanced biomaterials business today is comprised primarily
of the sale of our Biovance 3L and Rebound products, directly or through our distribution network. Biovance 3L is a tri-layer decellularized,
dehydrated human amniotic membrane derived from the placenta of a healthy, full-term pregnancy. It is an intact, natural extracellular
matrix that provides a foundation for the wound regeneration process and acts as a scaffold for restoration of functional tissue. Rebound
is a full thickness extracellular matrix that contains amnion and chorion. We are developing new placental biomaterial products to deepen
the biomaterials commercial pipeline. We also market our Biovance and Interfyl products, directly or through our distribution network.
Biovance is decellularized, dehydrated human amniotic membrane derived from the placenta of a healthy, full-term pregnancy. It is an intact,
natural extracellular matrix that provides a foundation for the wound regeneration process and acts as a scaffold for restoration of functional
tissue. Interfyl is human connective tissue matrix derived from the placenta of a healthy, full-term pregnancy. It is used by a variety
of medical specialists to fill soft tissue deficits resulting from wounds, trauma, or surgery.
We have focused our marketing
and sales strategy within the Advanced Biomaterial Products segment on developing strong distribution partners for our products rather
than building out our own direct sales force. On May 7, 2021, we entered into a six-year supply and distribution agreement with Arthrex,
Inc., that includes: (i) an exclusive Biovance, Interfyl, and Centaflex license for distribution and commercialization within the United
States in the field of orthopedic surgery; and (ii) an exclusive license to commercialize and distribute Interfyl and Centaflex within