UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
10-K
(Mark
One)
☒ ANNUAL REPORT UNDER SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
FOR
THE FISCAL YEAR ENDED DECEMBER 31, 2025
FOR
THE TRANSITION PERIOD FROM__________ TO__________
Commission
File Number 001-37603
BIORESTORATIVE
THERAPIES, INC.
(Exact
name of registrant as specified in its charter)
40 Marcus Drive, Suite 1, Melville, New York 11747
(Address of principal executive offices) (Zip Code)
(631)760-8100
(Registrant’s
telephone number, including area code)
Securities
registered pursuant to Section 12(b) of the Act:
Title of each class Trading Symbol(s) Name of each exchange on which registered
Common Stock $0.0001 par value BRTX Nasdaq Capital Market
Securities
registered pursuant to Section 12(g) of the Act:
None
(Title
of Class)
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 Exchange 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 during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).
Yes ☒ No ☐
Indicate
by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting
company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,”
“smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.
Large accelerated filer ☐ 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 ☒
State
the aggregate market value of the voting and non-voting common equity held by non-affiliates computed by reference to the price at which
the common equity was last sold, or the average bid and asked price of such common equity, as of the last business day of the registrant’s
most recently completed second fiscal quarter.
As
of June 30, 2025, the aggregate market value of the registrant’s common stock held by non-affiliates of the registrant was $11,199,773
based on the closing sale price as reported on the Nasdaq Capital Market.
APPLICABLE
ONLY TO REGISTRANTS INVOLVED IN BANKRUPTCY
PROCEEDINGS
DURING THE PRECEDING FIVE YEARS:
Indicate
by check mark whether the registrant has filed all documents and reports required to be filed by Section 12, 13 or 15(d) of the Securities
Exchange Act of 1934 subsequent to the distribution of securities under a plan confirmed by a court. Yes ☒ No ☐
As
of March 23, 2026, there were 25,478,170 shares of common stock outstanding.
DOCUMENTS
INCORPORATED BY REFERENCE
None
INDEX
Page No.
Forward-Looking Statements 3
PART I 3
Item 1. Business. 3
Item 1A. Risk Factors. 36
Item 1B. Unresolved Staff Comments. 70
Item 1C. Cybersecurity. 70
Item 2. Properties. 71
Item 3. Legal Proceedings. 71
Item 4. Mine Safety Disclosures. 71
Item 6. [Reserved]. 72
Item 7A. Quantitative and Qualitative Disclosures About Market Risk. 80
Item 8. Financial Statements and Supplementary Data. 80
Item 9A. Controls and Procedures. 81
Item 9B. Other Information. 83
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections. 83
PART III 84
Item 10. Directors, Executive Officers and Corporate Governance. 84
Item 11. Executive Compensation. 88
Item 14. Principal Accountant Fees and Services. 95
Item 15. Exhibits and Financial Statement Schedules. 96
PART
I
Forward-Looking
Statements
This
Annual Report contains forward-looking statements as that term is defined in the federal securities laws. The events described in forward-looking
statements contained in this Annual Report may not occur. Generally, these statements relate to business plans or strategies, projected
or anticipated benefits or other consequences of our plans or strategies, projected or anticipated benefits from acquisitions to be made
by us, or projections involving anticipated revenues, earnings or other aspects of our operating results. The words “may,”
“will,” “expect,” “believe,” “anticipate,” “project,” “plan,”
“intend,” “estimate,” and “continue,” and their opposites and similar expressions are intended to
identify forward-looking statements. We caution you that these statements are not guarantees of future performance or events and are
subject to a number of uncertainties, risks and other influences, many of which are beyond our control, that may influence the accuracy
of the statements and the projections upon which the statements are based. Factors which may affect our results include, but are not
limited to, the risks and uncertainties discussed in Item 1A of this Annual Report (“Risk Factors”).
Any
one or more of these uncertainties, risks and other influences could materially affect our results of operations and whether forward-looking
statements made by us ultimately prove to be accurate. Our actual results, performance and achievements could differ materially from
those expressed or implied in these forward-looking statements. We undertake no obligation to publicly update or revise any forward-looking
statements, whether from new information, future events or otherwise.
Intellectual
Property
This
Annual Report includes references to our federally registered trademarks, BioRestorative Therapies and Dragonfly design,
BRTX-100, ThermoStem and BRTX. The Dragonfly logo is also registered with the U.S. Copyright Office. This
Annual Report also includes references to trademarks, trade names and service marks that are the property of other organizations. Solely
for convenience, trademarks and trade names referred to in this Annual Report appear without the ®, SM or TM symbols,
and copyrighted content appears without the use of the symbol ©, but the absence of use of these symbols does not reflect upon the
validity or enforceability of the intellectual property owned by us or third parties.
ITEM 1. BUSINESS.
(a)
Business Development
As
used in this Annual Report on Form 10-K, or the Annual Report, references to the “Company”, “we”, “us”,
or “our” refer to BioRestorative Therapies, Inc.
We
were incorporated in Nevada on June 13, 1997. On August 15, 2011, we changed our name from “Stem Cell Assurance, Inc.” to
“BioRestorative Therapies, Inc.” Effective January 1, 2015, we reincorporated in Delaware. Effective December 31, 2022, we
reincorporated in Nevada.
We
develop therapeutic products using cell and tissue protocols, primarily involving adult stem cells.
We
are currently pursuing our Disc/Spine Program with our initial investigational therapeutic product being called BRTX-100.
In March 2022, a United States patent issued in our Disc/Spine Program. We are conducting a Phase 2 clinical trial investigating
the use of BRTX-100 in the treatment of chronic lower back pain arising from degenerative disc disease. We have also obtained
U.S. Food and Drug Administration, or the FDA, Investigational New Drug, or IND, clearance to evaluate BRTX-100 in the treatment
of chronic cervical discogenic pain.
We
have obtained an exclusive license to use technology for investigational adult stem cell treatment of disc and spine conditions, including
protruding and bulging lumbar discs. The technology is an advanced stem cell injection procedure that may offer relief from lower back
pain, buttock and leg pain, and numbness and tingling in the leg and foot.
We
are also developing our ThermoStem Program. This pre-clinical program involves the use of brown adipose (fat) in connection with
the cell-based treatment of type 2 diabetes and obesity as well as hypertension, other metabolic disorders and cardiac deficiencies.
Patents related to the ThermoStem Program have been issued in the United States and other jurisdictions.
Further,
we operate a commercial biocosmeceuticals business. Our current commercial product, formulated and manufactured using our cGMP ISO-7
certified clean room, is a cell-based secretome containing exosomes, proteins and growth factors. This proprietary biologic serum has
been specifically engineered by us to reduce the appearance of fine lines and wrinkles and bring forth other areas of cosmetic effectiveness.
We also intend to explore the potential of expanding our commercial offering to include a broader family of cell-based biologic aesthetic
products and therapeutics via IND-enabling studies.
2025
Events
In
February 2025, we announced that the FDA granted Fast Track designation to the BRTX-100 program for the treatment of chronic lumbar
disc disease, or cLDD.
In
February 2025, we announced new preliminary 26- and 52- week blinded data from the first 15 patients with cLDD enrolled in our ongoing
Phase 2 clinical trial of BRTX-100. No serious adverse events were reported in any of the 15 subjects. In addition, there was
no dose limiting toxicity at 26-52 weeks. Further, we announced certain positive preliminary data analyses.
In
February 2025, we announced that the FDA cleared our IND application for BRTX-100 for the treatment of chronic cervical discogenic
pain.
In
March 2025, a European patent related to our ThermoStem Program was issued.
In
March 2025, an Israeli patent related to our ThermoStem Program was issued.
In
May 2025, we announced that preliminary 26-, 52- and 104- week blinded data from the first 15 patients with cLDD enrolled in our ongoing
Phase 2 clinical trial of BRTX-100 was presented by our Vice President of Research and Development at the International Society
for Cell and Gene Therapy 2025 Annual meeting. No serious adverse events were reported and there was no dose limiting toxicity at 26-104
weeks.
In
June 2025, we announced the hiring of Sandy Lipkins whose responsibilities focus on technology commercialization and business development.
In
June 2025, we announced that new preliminary blinded clinical data from 36 patients enrolled in our ongoing Phase 2 trial of BRTX-100
for the treatment of cLDD was presented by our Vice President of Research and Development at the International Society for Stem Cell
Research 2025 Annual Meeting. Over 74% of the subjects showed greater than 50% improvement in function by 52 weeks and over 72% of the
subjects reported greater than 50% in reduction in pain by 52 weeks. No serious adverse events or dose limiting toxicities were reported
between 26 and 104 weeks at the target dose.
In
June 2025, we announced that our Board of Directors authorized a stock repurchase program under which we may repurchase up to $2 million
of our outstanding common stock over a one year period. To date, no shares have been repurchased.
In
September 2025, a Japanese patent related to our ThermoStem Program was issued.
In October 2025, we issued 678,125 shares of our common stock in a registered
direct public offering to several accredited and/or institutional investors. We received gross proceeds of $1,085,000 from the offering.
Concurrently, pursuant to a private placement offering, we issued to the investors warrants to purchase up to 508,592 shares of our common
stock. In connection with the offering, we issued placement agent warrants to purchase 35,062 shares of our common stock. The warrants
and placement agent warrants have an exercise price of $2.75 per share and are exercisable commencing six months from the date of issuance
until the five year anniversary of the date of issuance.
In
October 2025, we announced that we hired Crystal Romano as our Head of Global Commercial Operations.
In
November 2025, we announced that we were granted a Type B meeting with the FDA to discuss a potential accelerated biologics license application,
or BLA, approval pathway for the Fast-Track-Designated BRTX-100 program for the treatment of cLDD. The meeting took place in December
2025. Based upon the positive official summary of the meeting, we have initiated Phase 3 enabling activities with the goal of submitting
a Phase 3 IND during 2026.
In
November 2025, a notice of allowance was issued for an Australian patent application related to our ThermoStem Program. This application
is expected to issue as an Australian patent in the near future.
2026
Events
In
February 2026, pursuant to a public offering, we issued 12,560,715 shares of our common stock, pre-funded warrants to purchase up to
1,725,000 shares of our common stock and warrants to purchase up to 14,285,715 shares of our common stock. We received gross
proceeds of $5,000,000 from the offering. The pre-funded warrants had an exercise price of $0.0001 per share, were immediately
exercisable and were exercisable until exercised in full. In February and March 2026, the 1,725,000 pre-funded warrants were
exercised. The warrants have an exercise price of $0.35 per share, are immediately exercisable and expire five years after the date
of issuance. In connection with the offering, we issued placement agent warrants to purchase 1,000,000 shares of our common stock.
Such warrants have an exercise price of $0.4375 per share, are exercisable immediately and expire five years from the date of
issuance.
In
February 2026, we announced that we had completed the enrollment of 99 patients in our Phase 2 clinical trial of BRTX-100.
(b)
Business
General
We
develop therapeutic products, using cell and tissue protocols, primarily involving adult stem cells. As described below, our two core
programs relate to the treatment of disc/spine disease and metabolic disorders. We also operate a commercial biocosmeceutical platform:
We
have also licensed an investigational curved needle device designed to deliver cells and/or other therapeutic products or material to
the spine and discs (and other parts of the body). We anticipate that FDA approval or clearance will be necessary for this device prior
to commercialization. We do not intend to utilize this device in connection with our Phase 2 clinical trial with regard to BRTX-100.
See “Curved Needle Device” below.
The
patents and patent applications for the Disc/Spine Program, the ThermoStem Program and the curved needle device are described
below under “Technology; Research and Development.”
Overview
Every
human being has stem cells in his or her body. These cells exist from the early stages of human development until the end of a person’s
life. Throughout our lives, our body continues to produce stem cells that regenerate to produce differentiated cells that make up various
aspects of the body such as skin, blood, muscle and nerves. These are generally referred to as adult (non-embryonic) stem cells. These
cells are important for the purpose of medical therapies aiming to replace lost or damaged cells or tissues or to otherwise treat disorders.
Regenerative
cell therapy relies on replacing diseased, damaged or dysfunctional cells with healthy, functioning ones or repairing damaged or diseased
tissue. A great range of cells can serve in cell therapy, including cells found in peripheral and umbilical cord blood, bone marrow and
adipose (fat) tissue. Physicians have been using adult stem cells from bone marrow to treat various blood cancers for 70 years (the first
successful bone marrow transplant was performed in 1956). Recently, physicians have begun to use stem cells to treat various other diseases.
We intend to develop cell and tissue products and regenerative therapy protocols, primarily involving adult stem cells, to allow patients
to undergo cellular-based treatments.
We
are concentrating initially on therapeutic areas in which risk to the patient is low, recovery is relatively easy, results can be demonstrated
through sufficient clinical data, and patients and physicians will be comfortable with the procedure. We believe that there will be readily
identifiable groups of patients who will benefit from these procedures. We also believe that these procedures will be significantly less
expensive than the most common surgical procedure alternatives and will compare favorably, over the long-term, to conservative treatment
costs which may persist for years.
Accordingly,
we have focused our initial developmental efforts on cellular-based therapeutic products and clinical development programs in selective
areas of medicine for which the treatment protocol is minimally invasive. Such areas include the treatment of the disc and spine and
metabolic-related disorders. Upon regulatory approval, we will seek to obtain third party reimbursement for our products and procedures;
however; if we are not successful, patients may be required to pay for our products and procedures out of pocket in full and without
the ability to be reimbursed by any governmental and other third party payers, which would adversely impact our prospects.
We
have undertaken research and development efforts in connection with the development of investigational therapeutic products and medical
therapies using cell and tissue protocols, primarily involving adult stem cells. See “Disc/Spine Program,” “Metabolic
Brown Adipose (Fat) Program” and “Curved Needle Device” below. As a result of these programs, we have seven United
States patents, 18 foreign patents and one United States patent application related to research regarding our ThermoStem Program.
We have also obtained licenses for two United States patent applications related to our Disc/Spine Program, one United States
patent related to our Disc/Spine Program, and a license for one United States patent related to a curved needle device.
We
have established a research laboratory facility with current Good Manufacturing Practice, or cGMP, capabilities to produce clinical grade
products and we will seek to further develop cellular-based treatments, products and protocols, stem cell-related intellectual property,
or IP, and translational research applications. See “Laboratory” below.
We have not generated any significant revenues to date. In February 2024,
we received approximately $8,100,000 in gross proceeds pursuant to the exercise of warrants. During 2025, we received approximately $2,000,000
of gross proceeds pursuant to what is commonly is referred to as an “at-the-market” program with Rodman & Renshaw, LLC,
or the 2024 ATM. We currently do not have the ability to raise any additional amounts under the 2024 ATM. In October 2025, we received
approximately $1,100,000 in gross proceeds pursuant to a registered direct public offering of our common stock. In February 2026, we received
$5,000,000 in gross proceeds pursuant to a public offering of our common stock and warrants.
Our
BRTX-100 program has been granted a fast track designation by the FDA which may result in a reduction in the length of time required
to complete our Phase 2 clinical trial and consequently a reduction in the costs involved. However, notwithstanding the above, we believe
that our current funds may not be sufficient for us to complete our Phase 2 clinical trial investigating the use of BRTX-100
in the treatment of chronic lower back pain arising from degenerative disc disease, as further described in this section, continue our
pre-clinical research and development efforts with respect to our ThermoStem Program and satisfy our current working capital needs
through the end of the 12 month period following the date of the financial statements included in this Annual Report. In addition, the
implementation of our business plan, as discussed below, will require the receipt of significant additional financing to fund our research
and development efforts, including our contemplated Phase 3 clinical trial with regard to BRTX-100 and our contemplated clinical
trials relating to our ThermoStem Program, and otherwise fund our operations. We intend to seek to raise capital through our 2024
ATM and warrant exercises as well as through investment bankers and from biotech funds, strategic partners and other financial institutions.
No assurance can be given that the amount of funding that we anticipate may be required for the above purposes is correct or that we
will be able to accomplish our goals within the timeframes projected. In addition, no assurance can be given that we will be able to
obtain any required financing on commercially reasonable terms or otherwise. If we are unable to obtain adequate funding, we may be required
to significantly curtail or discontinue our proposed operations.
Disc/Spine
Program
General
Among
the initiatives that we are currently pursuing is our Disc/Spine Program, with our initial product candidate being called BRTX-100.
We have obtained an exclusive license (see “Exclusive License” below) that permits us to use technology for adult
stem cell treatment of disc and spine conditions. The technology is an advanced stem cell culture and injection procedure into the intervertebral
disc, or IVD, that may offer relief from lower back pain, buttock and leg pain, and numbness and tingling in the leg and foot.
Lower
back pain is the most common, most disabling, and most costly musculoskeletal ailment faced worldwide. According to a 2016 market report
from Trinity Partners, a global life sciences consulting firm, of the 250 million American adults, nearly 25 million have chronic lower
back pain of which approximately 12 million have been diagnosed with and treated for disc degeneration and approximately 5.6 million
have pain caused by a protruding or injured disc. We believe that between 500,000 and one million invasive surgical procedures are performed
each year to try to alleviate the pain associated with these lower back conditions and that such procedures cost approximately $40 billion.
Clinical studies have documented that the source of the pain is most frequently damage to the IVD. This can occur when forces, whether
a single load or repetitive microtrauma, exceed the IVD’s inherent capacity to resist those loads. Aging, obesity, smoking, lifestyle,
and certain genetic factors may predispose one to an IVD injury. Current surgical approaches to back pain are extremely invasive (often
altering the spine’s biomechanics unfavorably and predisposing it to further disc degeneration) and are associated with unacceptably
low success rates (with a second operation occurring 10% to 20% of the time). In addition, current surgical approaches are costly with
spinal fusion surgery costing approximately $110,000, discectomy costing approximately $20,000 to $50,000 and disc replacement surgery
costing approximately $80,000 to $150,000. Even conservative treatments can be costly, with oral medications costing between $1,000 and
$2,000 per year, injection treatments costing approximately $8,000 per year and physical therapy costing approximately $20,000 annually.
We anticipate that the cost of a single treatment using BRTX-100 will compare favorably to conservative treatments which may continue
for years and will be less expensive than the most common surgical procedures.
While
once thought to be benign, the natural history of lower back pain is often one of chronic recurrent episodes of pain leading to progressive
disability. This is believed to be a direct result of the IVD’s poor healing capacity after injury. The IVD is the largest avascular
(having few or no blood vessels) structure in the body and is low in cellularity. Therefore, its inherent capacity to heal after injury
is poor. The clinical rationale of BRTX-100 is to deliver a high concentration of the patient’s own cultured MSCs into the
site of pathology to promote healing and relieve pain.
We
have developed a mesenchymal stem cell product candidate, BRTX-100, derived from autologous (or a person’s own) human bone
marrow, cultured and formulated, in a proprietary method, specifically for introduction into a painful lumbar disc. The product candidate
was developed utilizing in part the exclusive license described below under “Exclusive License.” As described below
under “BRTX-100” and “Production and Delivery,” BRTX-100 is a hypoxic (low oxygen) stem
cell product developed through a culturing process. In order to enhance the survivability of our bone marrow-derived MSCs in the avascular
environment of the damaged disc, BRTX-100 is designed to expand under hypoxic conditions. This process is intended to result in
a large cell count population with enhanced viability and therapeutic potential following injection into the injured disc.
In
February 2017, pursuant to an IND application, we received authorization from the FDA to commence a Phase 2 clinical trial investigating
the use of BRTX-100, our lead cell therapy candidate, in the treatment of chronic lower back pain arising from degenerative disc
disease. We are conducting our Phase 2 clinical trial as described below under “Clinical Trial.” We believe that,
based upon our periodic reports to the FDA as to our clinical trial, the existing IND remains effective.
In
addition to developing BRTX-100, we may also seek to sublicense the technology to a strategic third party, who may assist in gaining
FDA approval for a lumbar disc indication, or third parties for use in connection with cellular-based developmental programs with regard
to disc and spine related conditions.
We
have established a laboratory, which includes a clean room facility, to perform the production of cell products (including BRTX-100)
for use in our clinical trials, for third party cell products or for general research purposes. We may also use this laboratory to develop
our pipeline of future products and expand our stem cell-related IP. See “Laboratory” and “Technology; Research and
Development” below.
In
March 2022, a United States patent related to BRTX-100 was issued. We have been granted exclusive license rights with respect
to the patent. See “Exclusive License” below.
BRTX-100
Our
lead product candidate, BRTX-100, is an autologous hypoxic (low oxygen) cultured mesenchymal stem cell product derived from a
patient’s own bone marrow and formulated with a proprietary biomaterial carrier (platelet lysate) to increase potency, viability
and survivability. We have designed the cryopreserved sterile cellular product candidate to be provided in vials for injection into painful
lumbar discs. We anticipate the product candidate will be delivered using a standard 20 gauge 3.5 inch introducer needle and a 25 gauge
6 inch needle that will extend into the disc center upon delivery. Upon regulatory approval, we plan to provide training to medical practitioners
with regard to the approved injection procedure. It is anticipated that the delivery of the product candidate will be a 30 minute procedure.
Mesenchymal
stem cells used in BRTX-100 are similar to other MSCs under development by others; however, in order to enhance the survivability
of our bone marrow-derived MSCs in the avascular environment of the damaged disc, BRTX-100 is designed to expand under hypoxic
conditions for a period of approximately three weeks. This process is intended to result in an approximate 40 million cell count population
with enhanced viability and therapeutic potential following injection locally into injured spinal discs. Publications and scientific
literature have indicated that MSCs preconditioned in a hypoxic environment show enhanced skeletal muscle regeneration properties and
improved impacts upon circulation and vascular formation compared to MSCs cultured under normoxic (normal oxygen) conditions.
In
August 2018, the Journal of Translational Medicine published the results of our study evaluating the benefits of long-term hypoxic
culturing of human bone marrow-derived MSCs.
In
September 2021, we were awarded a National Institutes of Health Small Business Technology Transfer (STTR) Phase 1 grant for $256,000
to evaluate the therapeutic effects on our hypoxic cultured bone marrow derived mesenchymal stem cells (BRTX-100) after encapsulation
with a PEG-peptide hydrogel. The work was done in collaboration with Washington University of St. Louis.
Since
June 2022, we have entered into clinical trial agreements with 16 sites to conduct our Phase 2 clinical trial targeting chronic lumbar
disc disease. See “Clinical Trial” below.
Production
and Delivery
The
production of our product candidate, BRTX-100, begins with the physician collecting bone marrow from the patient under local anesthesia.
Peripheral blood is also collected from the patient. The physician will then send the patient’s bone marrow and blood samples to
our laboratory (or a contract laboratory) for culturing and formulation. The hypoxic culturing process is intended to result in the selection
of a cell population that is suitable for an improved possibility of survival in the internal disc environment. We anticipate that the
cell culturing process and product formulation will take approximately three weeks, with an additional two weeks required for quality
control testing required to meet product release criteria. We will then send the therapeutic cryopreserved stem cells (BRTX-100)
in a sterile vial back to the physician’s offices where it will undergo a controlled thaw prior to the procedure. The price structure
for the procedure and our services has not been determined and no assurances can be given as to the effect that such price structure
will have on the marketability of such procedure and services. The following illustrates the process:
Exclusive
License
Pursuant
to our license agreement with Regenerative Sciences, LLC, or Regenerative, that became effective in April 2012, or the Regenerative License
Agreement, we have obtained, among other things, a worldwide (excluding Asia and Argentina), exclusive, royalty-bearing license from
Regenerative to utilize or sublicense a certain method for culturing cells for use in our developmental program involving disc and spine
conditions, including protruding or painful discs and the treatment of avascular zones. The investigational technology that has been
licensed is an advanced stem cell culture and injection procedure that may offer relief from lower back pain, buttock and leg pain, and
numbness and tingling in the leg and foot. Pursuant to the Regenerative License Agreement, we have also obtained a worldwide, exclusive,
royalty-bearing license from Regenerative to utilize or sublicense a certain investigational curved needle device for the administration
of specific cells and/or cell products to the disc and/or spine (and other parts of the body). It will be necessary to advance the design
of this investigational device to facilitate the delivery of substances, including living cells, to specific locations within the body
and minimize the potential for damage to nearby structures.
The
patents that are the subject of the Regenerative License Agreement have been assigned to Regenexx, LLC which we have been advised by
Regenerative is an affiliate of Regenerative.
Animal
Study
The
efficacy and safety of our product candidate, BRTX-100, has been tested in a degenerative intervertebral rabbit disc model. In
this study, 80 rabbits underwent surgery to create a puncture in the discs. Four weeks post-surgery, each rabbit had either contrast,
a biomaterial carrier or BRTX-100 injected into the discs. In order to study the biodistribution and efficacy of BRTX-100,
the rabbits were evaluated at day 56 and day 120.
The
key safety findings of the animal study are as follows:
The
key efficacy findings of the animal study are as follows:
Clinical
Trial
Pursuant
to an IND application we submitted to the FDA, we have obtained authorization to conduct a Phase 2 clinical trial investigating the use
of BRTX-100, our lead cell therapy candidate, in the treatment of chronic lower back pain arising from degenerative disc disease.
We are conducting our Phase 2 clinical trial as discussed below.
The
following describes the Phase 2 clinical trial authorized by the FDA:
A
Phase 2 Prospective, Double-Blinded, Placebo Controlled, Randomized Study
● General
● 99 patients; randomized 2:1, BRTX-100 to control, 40 million cells/dose
● Primary efficacy endpoint at 12 months
● Patient safety and efficacy follow up at 24 months
● Included subjects must have only one symptomatic diseased disc
● Primary Efficacy Endpoint
● Additional or Secondary Endpoints
● Clinical response at 12 months
In
December 2021, we entered into a Master Service Agreement with Professional Research Consulting Inc. d/b/a PRC Clinical, a contract research
organization, or CRO, specializing in clinical trial management, to conduct our Phase 2 clinical trial.
In
April 2023, we announced that we had completed enrollment for the safety run-in component of our Phase 2 clinical study of BRTX-100.
In
May 2023, we announced that we had signed a clinical trial agreement with Northwell Health, New York State’s largest health care
provider and private employer, pursuant to which Northwell Health is participating in our Phase 2 clinical study of BRTX-100.
In
June 2023, we announced that the final subject in our BRTX-100 Phase 2 clinical trial safety cohort had been dosed.
In
June 2023, we announced that the independent Data Safety Monitoring Board, which is overseeing our Phase 2 clinical trial, unanimously
recommended the continuation of our study in accordance with the version of the protocol with no changes.
In
April 2024, we announced that the FDA cleared an important amendment to the protocol of our ongoing Phase 2 study investigating the use
of BRTX-100. The protocol amendment removed saline injection in the control arm of the study and replaced it with a sham injection.
In
November 2024, we announced new preliminary 26–52 week blinded data from the first 10 patients with cLDD enrolled in our ongoing
Phase 2 clinical trial of BRTX-100. No serious adverse events were reported in any of the 10 safety run-in subjects. In addition,
there was no dose limiting toxicity at 26-52 weeks.
In
February 2025, we announced new preliminary 26–52 week blinded data from the first 15 patients with cLDD enrolled in our ongoing
Phase 2 clinical trial of BRTX-100. No serious adverse events were reported in any of the 15 subjects. In addition, there was
no dose limiting toxicity at 26-52 weeks. Further, we announced certain positive preliminary data analyses.
In
May 2025, we announced that preliminary 26-, 52- and 104- week blinded data from the first 15 patients with cLDD enrolled in our ongoing
Phase 2 clinical trial of BRTX-100 was presented by our Vice President of Research and Development at the International Society
for Cell and Gene Therapy 2025 Annual meeting. No serious adverse events were reported and there was no dose limiting toxicity at 26-104
weeks.
In
June 2025, we announced that new preliminary blinded clinical data from 36 patients enrolled in our ongoing Phase 2 trial of BRTX-100
for the treatment of cLDD was presented by our Vice President of Research and Development at the International Society for Stem Cell
Research 2025 Annual Meeting. Over 74% of the subjects showed greater than 50% improvement in function by 52 weeks and over 72% of the
subjects reported greater than 50% in reduction in pain by 52 weeks. No serious adverse events or dose limiting toxicities were reported
between 26 and 104 weeks at the target dose.
In
November 2025, we announced that we were granted a Type B meeting with the FDA to discuss a potential accelerated biologics license application,
or BLA, approval pathway for the Fast-Track-Designated BRTX-100 program for the treatment of cLDD. The meeting took place in December
2025. Based upon the positive official summary of the meeting, we have initiated Phase 3 enabling activities with the goal of submitting
a Phase 3 IND during 2026.
In
February 2026, we announced that we had completed the enrollment of 99 patients in our Phase 2 clinical trial of BRTX-100.
The
FDA approval process can be lengthy, expensive and uncertain and there is no guarantee that the clinical trial(s) will be completed or
that the product will ultimately receive approval or clearance.
As
an alternative to undertaking any necessary clinical trials ourselves, we may explore the licensing of our rights with respect to our
product candidate, BRTX-100, to a strategic partner. Such an arrangement could possibly eliminate or significantly reduce the
need to raise the substantial capital needed to commence and complete the clinical trials and undertake the commercialization of BRTX-100
and would provide licensing-related revenue to us in lieu of product sales revenue. No assurance can be given that any licensing
agreement will be entered into, whether upon commercially reasonable terms or otherwise.
Similar
Therapies
Human
data from studies of therapies comparative to BRTX-100 have shown reduced pain, increased function, and an absence of significant
safety issues with a durable response, as shown below:
Impact
on Public Health
The
United States is the world’s leading consumer of hydrocodone (99%) and oxycodone (83%) and leads the world in per capital consumption
of such drugs (twice as much as second ranked Canada). In 2020, 91,000 persons in the United States died from overdoses.
Total
annual healthcare and lost productivity costs in the United States related to pain, including headache, back pain and neck pain, are
estimated to be $600 billion, which is twice the annual costs related to heart disease and greater than the combined annual costs related
to cancer and diabetes.
Metabolic
Brown Adipose (Fat) Program
Since
June 2011, we have been engaging in pre-clinical research efforts with respect to an investigational platform technology utilizing brown
adipose (fat) derived stem cells, or BADSCs, for therapeutic purposes. We have labeled this initiative our ThermoStem Program.
Brown
fat is a specialized adipose (fat) tissue found in the human body that plays a key role in the evolutionarily conserved mechanisms underlying
thermogenesis (generation of non-shivering body heat) and energy homeostasis in mammals - long known to be present at high levels in
hibernating mammals and human newborns. Recent studies have demonstrated that brown fat is present in the adult human body and may be
correlated with the maintenance and regulation of healthy metabolism, thus potentially being involved in caloric regulation. The pre-clinical
ThermoStem Program involves the use of a cell-based (brown adipose tissue construct) treatment for metabolic disease, such as
type 2 diabetes, obesity, hypertension and other metabolic disorders, as well as cardiac deficiencies. The diseases, disorders and syndromes
that may be targeted by our ThermoStem Program are as follows:
We
have had initial success in transplanting the brown adipose tissue construct in animals, and we are currently exploring ways to deliver
into humans. Even though present, BAT mass is very low in healthy adults and even lower in obese populations. Therefore, it may not be
sufficient to either naturally impact whole body metabolism, or to be targeted by drugs intended to increase its activity in the majority
of the population. Increasing BAT mass is crucial in order to benefit from its metabolic activity and this is what our ThermoStem
Program seeks to accomplish. We may also identify other naturally occurring biologics and chemically engineered molecules that may
enhance brown adipose tissue performance and activity.
Obesity,
the abnormal accumulation of white fat tissue, leads to a number of metabolic disorders and is the driving force behind the rise of type
2 diabetes and cardiovascular diseases worldwide. Pharmacological efforts to alter metabolic homeostasis through modulating central control
of appetite and satiety have had limited market penetration due to significant psychological and physiological safety concerns directly
attributed to modulating these brain centers. Adipose tissue is one of the largest organs in the human body and plays a key role in central
energy balance and lipid homeostasis. White and brown adipose tissues are found in mammals. White adipose tissue’s function is
to store energy, whereas BAT specializes in energy expenditure. As discussed in a 2020 article published in the International Journal
of Molecular Sciences, recent advancements in unraveling the mechanisms that control the induction, differentiation, proliferation,
and thermogenic activity of BAT, along with the application of imaging technologies for human BAT visualization, have generated optimism
that these advances may provide novel strategies for targeting BAT activation/thermogenesis, leading to efficacious and safe obesity
targeted therapies.
We
are developing cell-based product candidates to target obesity and metabolic disorders using BADSCs. Our goal is to develop a bioengineered
implantable brown adipose tissue construct intended to mimic ones naturally occurring in the human body. We have isolated and characterized
a human multipotent stem cell population that resides within BAT depots. We have expanded these stem cells to clinically relevant numbers
and successfully differentiated them into functional brown adipocytes. We intend to use adult stem cells that may be differentiated into
progenitor or fully differentiated brown adipocytes, or a related cell type, which can be used therapeutically in patients. We are focusing
on the development of treatment protocols that utilize allogeneic cells (i.e., stem cells from a genetically similar but not identical
donor).
In
order to deliver these differentiated cells into target locations in vivo, we seeded BADSCs onto 3-dimensional biological scaffolds.
Pre-clinical animal models of diet-induced obesity, that were transplanted with differentiated BADSCs supported by a biological scaffold,
presented significant reductions in weight and blood glucose levels compared to scaffold only controls. We are identifying technology
for in vivo delivery in small animal models. Having completed our proof of concept using our BAT in small animals, we are currently
developing our next generation BAT. It is anticipated that this next version will contain a higher purity of BADSC and a greater percent
of functional brown adipocytes, which is expected to increase the therapeutic effect compared to our first-generation product. In addition,
we are exploring the delivery of the therapeutic using encapsulation technology, which will only allow for reciprocal exchange of small
molecules between the host circulation and the BAT implant. We expect that encapsulation may present several advantages over our current
biological scaffolds, including prevention of any immune response or implant rejection that might occur in an immunocompetent host and
an increase in safety by preventing the implanted cells from invading the host tissues. We have developed promising data on the loading
of human stem cell-derived tissue engineered brown fat into an encapsulation device to be used as a cell delivery system for our metabolic
platform program for the treatment of type 2 diabetes, obesity, hyperlipidemia and hypertension. This advancement may lead to successful
transplantation of brown fat in humans. We are evaluating the next generation of BAT constructs that will first be tested in small animal
models. No assurance can be given that this delivery system will be effective in vivo in animals or humans. Our allogeneic brown
adipose derived stem cell platform potentially provides a therapeutic and commercial model for the cell-based treatment of obesity and
related metabolic disorders.
In
July 2024, a Japanese patent related to our ThermoStem program was issued to us.
In
March 2025, a European patent related to our ThermoStem Program was issued to us. This European patent was validated in
France, Germany, Italy, Spain and the United Kingdom.
In
March 2025, an Israeli patent related to our ThermoStem Program was issued to us.
In
September 2025, a Japanese patent related to our ThermoStem Program was issued to us.
In
November 2025, a notice of allowance was issued for an Australian patent application related to our ThermoStem Program. This application
is expected to issue as an Australian patent in the near future.
See
“Technology; Research and Development” below for a summary of our patents and patent applications with regard to our ThermoStem
Program.
We
have completed proof of concept preclinical animal studies using our first generation brown adipose derived stem cells. We intend to
undertake additional preclinical animal studies in order to optimize delivery and explore the feasibility of targeting additional indications.
We
anticipate that much of our development work in this area will take place at our laboratory facility, outside core facilities at academic,
research or medical institutions, or contractors. See “Laboratory” below.
BioCosmeceuticals
We
operate a commercial biocosmeceutical platform. Our current commercial product, formulated and manufactured using our cGMP ISO-7 certified
clean room, is a cell-based secretome containing exosomes, proteins and growth factors. This proprietary biologic serum has been specifically
engineered by us to reduce the appearance of fine lines and wrinkles and bring forth other areas of cosmetic effectiveness. Moving forward,
we also intend to explore the potential of expanding our commercial offering to include a broader family of cell-based biologic aesthetic
products and therapeutics via IND-enabling studies, with the aim of pioneering FDA approvals in the emerging biocosmeceuticals space.
We
market our biocosmeceutical products to distributors, medical spas and direct to consumers.
In
June 2025, we announced the hiring of Sandy Lipkins whose responsibilities focus on technology commercialization and business development.
In
October 2025, we announced that we hired Crystal Romano as our Head of Global Commercial Operations.