UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
10-K
☒ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For
the fiscal year ended December 31, 2024
☐TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For
the transition period from ________ to _________
Commission
file number 001-41159
IMMIX
BIOPHARMA, INC.
(Exact
name of registrant as specified in charter)
(Address of principal executive offices) (Zip code)
(310)651-8041
(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 IMMX The Nasdaq Stock Market LLC
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 Section 15(d) of the Act. Yes ☐ No ☒
Indicate
by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange
Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)
has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐
Indicate
by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule
405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant
was required to submit such files).Yes ☒ No ☐
Indicate
by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting
company, or an emerging growth company. See definition 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 by 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 as of the last business day
of the registrant’s most recently completed second fiscal quarter ended June 30, 2024 was $32,432,613 based upon the closing price
of the registrant’s common stock of $1.98 on The Nasdaq Capital Market as of that date. Further information concerning shareholdings
of our officers, directors and principal stockholders is included or incorporated by reference in Part III, Item 12 of this Annual Report
on Form 10-K.
Number
of common shares outstanding as of March 11, 2025 was 27,722,108 shares.
Documents
Incorporated by Reference: Portions of the registrant’s definitive proxy statement (the “2025 Proxy Statement”) relating
to its 2025 annual meeting of stockholders (the “2025 Annual Meeting of Stockholders”) are incorporated by reference into
Part III of this Annual Report on Form 10-K where indicated. The 2025 Proxy Statement will be filed with the U.S. Securities and Exchange
Commission within 120 days after the end of the fiscal year to which this report relates.
Table
of Contents
Page
ITEM 1. BUSINESS 7
ITEM 1A. RISK FACTORS. 35
ITEM 1B. UNRESOLVED STAFF COMMENTS 65
ITEM 1C. CYBERSECURITY 65
ITEM 2. PROPERTIES 65
ITEM 3. LEGAL PROCEEDINGS 66
ITEM 4. MINE SAFETY DISCLOSURES 66
ITEM 6. [RESERVED] 66
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 74
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA F-1
ITEM 9A. CONTROLS AND PROCEDURES 75
ITEM 9B. OTHER INFORMATION 76
PART III 77
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 77
ITEM 11. EXECUTIVE COMPENSATION 77
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 77
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 78
SIGNATURES 81
POWER OF ATTORNEY 81
CAUTIONARY
NOTE ON FORWARD-LOOKING STATEMENTS
This
Annual Report on Form 10-K contains forward-looking statements which are made pursuant to the safe harbor provisions of Section 27A of
the Securities Act of 1933, as amended (the “Securities Act”), and Section 21E of the Securities Exchange Act of 1934, as
amended (the “Exchange Act”). These statements may be identified by such forward-looking terminology as “may,”
“should,” “expects,” “intends,” “plans,” “anticipates,” “believes,”
“estimates,” “predicts,” “potential,” “continue” or the negative of these terms or other
comparable terminology. Our forward-looking statements are based on a series of expectations, assumptions, estimates and projections
about our company, are not guarantees of future results or performance and involve substantial risks and uncertainty. We may not actually
achieve the plans, intentions or expectations disclosed in these forward-looking statements. Actual results or events could differ materially
from the plans, intentions and expectations disclosed in these forward-looking statements. Our business and our forward-looking statements
involve substantial known and unknown risks and uncertainties, including the risks and uncertainties inherent in our statements regarding:
● our projected financial position and estimated cash burn rate;
● our estimates regarding expenses, future revenues and capital requirements;
● our ability to continue as a going concern;
● the success, cost and timing of our clinical trials;
● our dependence on third parties in the conduct of our clinical trials;
● the results of market research conducted by us or others;
● our reliance on third-party suppliers and manufacturers;
● the success of competing therapies and products that are or become available;
All
of our forward-looking statements are as of the date of this Annual Report on Form 10-K only. In each case, actual results may differ
materially from such forward-looking information. We can give no assurance that such expectations or forward-looking statements will
prove to be correct. An occurrence of, or any material adverse change in, one or more of the risk factors or risks and uncertainties
referred to in this Annual Report on Form 10-K or included in our other public disclosures or our other periodic reports or other documents
or filings filed with or furnished to the U.S. Securities and Exchange Commission (the “SEC”) could materially and adversely
affect our business, prospects, financial condition and results of operations. Except as required by law, we do not undertake or plan
to update or revise any such forward-looking statements to reflect actual results, changes in plans, assumptions, estimates or projections
or other circumstances affecting such forward-looking statements occurring after the date of this Annual Report on Form 10-K, even if
such results, changes or circumstances make it clear that any forward-looking information will not be realized. Any public statements
or disclosures by us following this Annual Report on Form 10-K that modify or impact any of the forward-looking statements contained
in this Annual Report on Form 10-K will be deemed to modify or supersede such statements in this Annual Report on Form 10-K.
This
Annual Report on Form 10-K may include market data and certain industry data and forecasts, which we may obtain from internal company
surveys, market research, consultant surveys, publicly available information, reports of governmental agencies and industry publications,
articles and surveys. Industry surveys, publications, consultant surveys and forecasts generally state that the information contained
therein has been obtained from sources believed to be reliable, but the accuracy and completeness of such information is not guaranteed.
While we believe that such studies and publications are reliable, we have not independently verified market and industry data from third-party
sources.
RISK
FACTOR SUMMARY
Our
business is subject to significant risks and uncertainties that make an investment in us speculative and risky. Below we summarize what
we believe are the principal risk factors but these risks are not the only ones we face, and you should carefully review and consider
the full discussion of our risk factors in the section titled “Risk Factors,” together with the other information in this
Annual Report on Form 10-K. If any of the following risks actually occurs (or if any of those listed elsewhere in this Annual Report
on Form 10-K occur), our business, reputation, financial condition, results of operations, revenue, and future prospects could be seriously
harmed. Additional risks and uncertainties that we are unaware of, or that we currently believe are not material, may also become important
factors that adversely affect our business.
Risks
Relating to Our Financial Position and Capital Needs
Risks
Relating to the Development and Regulatory Approval of Our Product Candidates
Risks
Relating to our Business and Operations
Risks
Relating to our Intellectual Property
Risks
Related to Owning our Common Stock
trademarks
and service marks
This
Annual Report on Form 10-K contains our logo and references to some of our trademarks and service marks and to those belonging to other
entities. Solely for convenience, trademarks, tradenames and service marks referred to in this Report may appear without the ®, TM
and SM symbols. References to our trademarks, tradenames and service marks are not intended to indicate in any way that we will not assert
to the fullest extent under applicable law our rights or the rights of the applicable licensors if any, nor that respective owners to
other intellectual property rights will not assert, to the fullest extent under applicable law, their rights thereto. We do not intend
the use or display of other companies’ trademarks and trade names to imply a relationship with, or endorsement or sponsorship of
us by, any other companies.
Market,
Industry and other data
Unless
otherwise indicated, information contained in this Annual Report on Form 10-K concerning our industry and the markets in which we operate,
including our general expectations about our product candidates, market position, market opportunity, market size, competitive position
and the incidence of certain medical conditions, is based on or derived from publicly available information released by industry analysts
and third-party sources, independent market research, industry and general publications and surveys, governmental agencies, our internal
research and our industry experience. Our estimates of the potential market opportunities for our product candidates include a number
of key assumptions based on our industry knowledge and industry publications, the latter of which may be based on small sample sizes
and fail to accurately reflect such information, and you are cautioned not to give undue weight to such estimates. While we believe that
our internal assumptions are reasonable, no independent source has verified such assumptions. Industry publications and third-party research
often indicate that their information has been obtained from sources believed to be reliable, although they do not guarantee the accuracy
or completeness of such information and such information is inherently imprecise. In some cases, we do not expressly refer to the sources
from which this data is derived. In that regard, when we refer to one or more sources of this type of data in any paragraph, you should
assume that other data of this type appearing in the same paragraph is derived from the same sources, unless otherwise expressly stated
or the context otherwise requires. In addition, projections, assumptions and estimates of our future performance and the future performance
of the industry in which we operate is necessarily subject to a high degree of uncertainty and risk due to a variety of factors, including
those described in Part I, Item 1A of this Annual Report on Form 10-K titled “Risk Factors” and elsewhere in this Annual
Report on Form 10-K. These and other factors could cause results to differ materially from those expressed in the estimates made by independent
third parties and by us.
PART
I
Throughout
this Annual Report on Form 10-K, references to (i);”we,” “our,” “us,” the “Company,”
“Immix,” or “Immix Biopharma” refer to Immix Biopharma, Inc., individually, or as the context requires, collectively
with its subsidiaries; (ii) “Securities Act” refers to the Securities Act of 1933,
as amended; (iii) “Exchange Act” refers to the Securities Exchange Act of 1934, as amended; and (iv) “SEC” or
“Commission” refers to the U.S. Securities and Exchange Commission.
ITEM
1. BUSINESS
Overview
Immix
Biopharma, Inc. is a clinical-stage biopharmaceutical company focused on the application of chimeric antigen receptor cell therapy (“CAR-T”)
in light chain (AL) Amyloidosis and select immune-mediated diseases. Our lead cell therapy candidate is FDA investigational new drug
(“IND”) cleared CAR-T NXC-201 (“NXC-201”), currently being evaluated in our ongoing United States Phase 1b/2
NEXICART-2 (NCT06097832) clinical trial and our ex-U.S. phase 1b/2a NEXICART-1 (NCT04720313) clinical trial.
NXC-201
has been awarded Orphan Drug Designation (“ODD”) by both the FDA and European Commission (“EMA”) in AL Amyloidosis.
Our
mission is to harness the immune system through innovative cell therapies and other modalities to deliver widely accessible cures in
select immune-mediated diseases and other indications, as we believe patients are waiting.
Our
strategy is to:
Our
N-GENIUS platform (discussed below) has produced our clinical-stage lead candidate NXC-201, a next-generation CAR-T for AL Amyloidosis
and select immune-mediated diseases.
Figure
1: ImmixBio Pipeline
NXC-201
is in clinical trials to treat relapsed/refractory AL Amyloidosis.
AL
amyloidosis is a life-threatening immunological disorder in which an abnormal protein called amyloid builds up in tissues and organs.
This abnormal protein is produced by long-lived plasma cells (“LLPCs”), a type of immune B-cell. The signs and symptoms of
AL amyloidosis vary among patients because build-up may occur in the heart (most frequent cause of mortality), liver, kidneys, intestines,
muscles, joints, nerves, or spleen, according to the National Institutes of Health (“NIH”). Diagnosis is frequently delayed,
due to varied and non-specific symptoms including: fatigue, weight loss, shortness of breath, dizziness, and numbness in hands and feet.
Upon diagnosis, many patients already have late-stage disease, and are not aware of available treatment options and clinical trials.
As
of March 11, 2025, there are no FDA approved drugs for relapsed/refractory AL Amyloidosis.
The
U.S. observed prevalence of relapsed/refractory AL Amyloidosis is growing 12% per year according to Staron, et al Blood Cancer Journal
2021, estimated to reach 37,270 patients in 2025. Untreated patients with AL amyloidosis and cardiac involvement have a median survival
of less than 1 year, according to Quock, et al. Journal of Comparative Effective Research, 2023. The current market size for amyloidosis
therapies is estimated at $3.6 billion, expected to reach $6 billion in 2027, according to Grand View Research.
As
of March 11, 2025, we have disclosed treatment of 6 relapsed/refractory AL Amyloidosis patients in the United States in our ongoing Phase
1b/2 multi-site NEXICART-2 (NCT06097832) U.S. clinical trial. Memorial Sloan Kettering Cancer Center is the lead NEXICART-2 clinical
site.
As
of March 11, 2025, we have disclosed treatment of 16 relapsed/refractory AL Amyloidosis patients in our ongoing Phase 1b/2a NEXICART-1
(NCT04720313) ex-U.S. clinical trial.
In
September 2023, the FDA granted ODD to NXC-201 for the treatment of AL Amyloidosis. If a product that has ODD subsequently receives the
first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusive approval (or exclusivity),
which means that the FDA may not approve any other applications to market the same drug for the same indication for 7 years (except in
limited circumstances, such as a showing of clinical superiority to the product with orphan drug exclusivity).
In
November 2023, the FDA cleared an IND application for NXC-201 to enroll U.S. patients into NXC-201 clinical trials.
In
December 2023, NXC-201 clinical data in relapsed/refractory AL Amyloidosis was presented in an oral presentation at the 65th
annual American Society of Hematology (“ASH”) meeting, covering 10 relapsed/refractory AL Amyloidosis patients treated with
NXC-201, indicating an overall response rate of 100% (10/10) and a complete response rate of 70% (7/10).
In
February 2024, the European Commission (“EC”) granted orphan drug designation to NXC-201 for the treatment of AL Amyloidosis.
Benefits of European ODD include: 10 years of market exclusivity once authorized in the EU; Access to the EU centralized authorization
procedure; and reduced fees for EU protocol assistance, marketing authorization applications, inspections before authorization, applications
for changes to marketing authorizations made after approval, and reduced annual fees.
In
December 2024, NXC-201 clinical data in relapsed/refractory AL Amyloidosis was presented in an oral presentation at the 66th
annual ASH meeting, covering 16 relapsed/refractory AL Amyloidosis patients treated with NXC-201, indicating an overall response rate
of 94% (15/16) and a complete response rate of 75% (12/16).
Our
Other Programs
Our
other programs include NXC-201 for select immune-mediated diseases, a $25 billion combined annual market size according to Grand View
Research and Fortune Business Insights and other preclinical candidates.
Since
inception, we have devoted substantially all of our resources to developing product and technology rights, conducting research and development,
organizing and staffing our Company, business planning and raising capital. We operate as one business segment and have incurred recurring
losses, the majority of which are attributable to research and development activities and negative cash flows from operations. We have
funded our operations primarily through the sale of equity securities and grant proceeds. Currently, our primary use of cash is to fund
operating expenses, which consist primarily of research and development expenditures, and to a lesser extent, general and administrative
expenditures. We expect to continue to incur significant expenses and operating losses for the foreseeable future as we advance our product
candidates through all stages of development and clinical trials and, ultimately, seek regulatory approval. In addition, if we obtain
regulatory approval for any of our product candidates, we expect to incur significant commercialization expenses related to product manufacturing,
marketing, sales and distribution. Furthermore, we incur costs associated with operating as a public company, including significant legal,
accounting, investor relations and other expenses. Our net losses may fluctuate significantly from quarter-to-quarter and year-to-year,
depending on the timing of our clinical trials and our expenses on other research and development activities.
Our
Platform and Technologies
We
believe our N-GENIUS platform has broad potential utility in hematologic and select immune-mediated diseases.
Our
in-licensed N-GENIUS platform, which has produced NXC-201, consists of three key elements: (1) Purpose-Built Cell Therapy Evidence Capture
Engine + Relational Database, which relates ImmixBio internal data to external to accelerate therapy design, manufacture, and preclinical;
(2) proprietary EXPAND technology, which is applied to multiple cell therapy indications, already utilized to create NXC-201; and (3)
Atomized, Novel Binding Scaffold Generation Engine, which allows for optimal molecule binding. We believe key characteristics of NXC-201
may apply to other products candidates produced by the N-GENIUS Platform. Those 3 key characteristics are: (a) high transduction efficiency
(supporting efficient manufacturing), (b) low tonic signaling (lower off-target toxicity may lead to lower toxicity), and (c) anti-exhaustion
capability (increased persistence may lead to activity over an extended period of time).
Our
Lead Program: NXC-201 in relapsed/refractory AL Amyloidosis
Market
Opportunity
The
first indication we intend to pursue for NXC-201 is relapsed/refractory AL Amyloidosis.
AL
amyloidosis is a life-threatening immunological disorder in which an abnormal protein called amyloid builds up in tissues and organs.
This abnormal protein is produced by long-lived plasma cells (“LLPCs”), a type of immune B-cell. The signs and symptoms of
AL amyloidosis vary among patients because build-up may occur in the heart (most frequent cause of mortality), liver, kidneys, intestines,
muscles, joints, nerves, or spleen, according to the National Institutes of Health (“NIH”). Diagnosis is frequently delayed,
due to varied and non-specific symptoms including: fatigue, weight loss, shortness of breath, dizziness, and numbness in hands and feet.
Upon diagnosis, many patients already have late-stage disease, and are not aware of available treatment options and clinical trials.
The
U.S. observed prevalence of relapsed/refractory AL Amyloidosis is growing 12% per year according to Staron, et al Blood Cancer Journal,
estimated to reach 37,270 patients in 2025. AL amyloidosis has a one-year mortality rate of 47 percent, 76 percent of which is caused
by cardiac amyloidosis, according to Alexion. The current market size for amyloidosis therapies is $3.6 billion, expected to reach $6
billion in 2027, according to Grand View Research.
As
of March 11, 2025, there are no FDA approved drugs for relapsed/refractory AL Amyloidosis.
Figure
2: NXC-201 “Blue Ocean Opportunity” in AL Amyloidosis
NXC-201
Composition and Mechanism of Action
NXC-201
is a next-generation CAR-T targeting B-cell maturation antigen (“BCMA”). CAR-T cell therapy is a type of immunotherapy that
uses the patient’s own immune cells, modified with our proprietary technology, to create NXC-201, which is then introduced into
the patient’s body. Then the patient’s modified NXC-201 CAR-T cells are able to recognize and eliminate diseased cells.
Figure
3: NXC-201: What is CAR-T Cell Therapy?
Our
N-GENIUS cell engineering platform with EXPAND technology has already produced clinical-stage CAR-T NXC-201, targeting BCMA, which we
believe is the first and only autologous CAR-T being developed to treat light-chain (AL) Amyloidosis. NXC-201 is currently being evaluated
in our ongoing Phase 1b/2a NEXICART-1 (NCT04720313) clinical trial.
Figure
4: NXC-201: First CAR-T Generated by the N-GENIUS Platform
Those
3 key characteristics of NXC-201 are: (a) high transduction efficiency (supporting efficient manufacturing), (b) low tonic signaling
(lower off-target toxicity may lead to lower toxicity), and (c) anti-exhaustion capability (increased persistence may lead to activity
over an extended period of time).
Figure
5: NXC-201: Key Characteristics
NXC-201
has been designed with a proprietary, optimized C3ζγ for enhanced signal transduction, proprietary, optimized modified-stiffness
CD8 hinge, and proprietary, optimized COBRA binder for enhanced signal binding. We believe the combination of these modifications has
the potential to allow for NXC-201 to deliver “digital” intracellular signaling, potentially eliminating neurotoxicity and
reducing CRS duration to 1 day.
Figure
6: N-GENIUS Platform – EXPAND Technology + COBRA Binder
NXC-201
was designed for high activity against disease-causing AL Amyloidosis LLPCs, which are also the source of immune-mediated diseases antibodies
in a variety of immune-mediated diseases.
NXC-201
Pre-clinical Data
In
AL Amyloidosis, we believe there are two primary challenges with CAR-T patient dosing:
a)
Uneven BCMA expression across disease-causing LLPCs; and
b)
frail patient due to pre-existing organ (heart) damage.
Published
in Clinical Cancer Research in 2022, NXC-201 was tested preclinical and clinically in AL Amyloidosis.
Figure
7: In AL Amyloidosis, BCMA expression is at a low-to-medium level
Source:
Clinical Cancer Research, Kfir-Erenfeld,et al, 2022
Our
testing demonstrated low-to-medium expression of BCMA in 18 AL Amyloidosis patient samples.
Figure
8: High Activity Level of NXC-201 in AL Amyloidosis
Source:
Clinical Cancer Research, Kfir-Erenfeld,et al, 2022
NXC-201
demonstrated high activity in the presence of AL Amyloidosis diseased plasma cells.
Figure
9: NXC-201 Targets Diseased AL Amyloidosis LLPCs in Patient Bone Marrow
Source:
Clinical Cancer Research, Kfir-Erenfeld,et al, 2022
Near-complete
elimination of diseased AL Amyloidosis LLPCs was observed in relapsed/refractory AL Amyloidosis patients treated with NXC-201.
NXC-201
Clinical Data – Relapsed/refractory AL Amyloidosis
In
December 2024, NXC-201 clinical data in relapsed/refractory AL Amyloidosis was presented in an oral presentation at the 66th
annual ASH meeting, covering 16 relapsed/refractory AL Amyloidosis patients treated with NXC-201. This data represents the largest cohort
of AL patients treated with CAR T-based therapy reported in the literature thus far.
Clinical
Results
Enrolled
AL amyloidosis patients presented with organ involvement and were heavily pretreated with prior lines of therapy (median 4, range 3-10).
All patients had refractory, progressive disease. No patients received bridging therapy.
Patient
characteristics:
● 81% (13/16) had cardiac involvement;
● Relapsed/refractory to a median 4 lines of prior therapy (range: 3-10).
Clinical
data:
● Overall response rate of 94% (15/16);
● Complete response rate of 75% (12/16);
● Median CRS duration was 2 days (range: 1-5):
○ No grade 4 CRS events; and
In
Vitro Studies
NXC-201
has demonstrated efficient eradication of plasma cells from patients with AL amyloidosis (Kfir-Erenfeld et al. 2022). Co-cultures of
plasma cells from AL amyloidosis patients and NXC-201 resulted in an almost complete eradication of the plasma cells. A control of AL
amyloidosis plasma cells with non-transduced (“NT”) cells, in contrast, did not result in a similar elimination of the plasma
cells.
Figure
10. Elimination of Plasma Cells After Co-culture with NXC-201 Compared to NT Cells
Abbreviations:
AL: amyloid light chain; NT: non-transduced; HBI0101 = NXC-201. Source: (Kfir-Erenfeld et al. 2022).
This
data suggest that NXC-201 cells were able to recognize the AL amyloidosis plasma cells and exert specific BCMA-directed antitumoral effect,
as further evidenced by the fact that following co-culture with AL amyloidosis plasma cells, NXC-201 cells underwent significant activation,
demonstrated by upregulation of the 4-1BB cell marker and increased secreted levels of inflammatory cytokines (interferon gamma: IFNγ,
tumour necrosis factor alpha: TFNα), which was not seen in NT cells. Furthermore, non-tumour bone marrow derived mononuclear cells
were not affected by co-culture with NXC-201, demonstrating the targeted effect of this therapy.
NXC-201
Development Strategy
In
our lead program, NXC-201 for relapsed/refractory AL Amyloidosis, we plan to enroll 40 patients in our open label, single-arm clinical
trial, and then submit a biologics license application (“BLA”) for FDA approval.
Figure
11: NXC-201 Clinical Development Plan Through FDA BLA Submissions
The
primary objectives in relapsed/refractory AL Amyloidosis are to study the safety and efficacy of NXC-201. The efficacy endpoints are
to evaluate response rates according to consensus recommendations for AL amyloidosis treatment response criteria in AL (Palladini et
al. 2012).
The
expected primary endpoints are complete response rate and overall response rate in our NXC-201 relapsed/refractory AL Amyloidosis clinical
trial.
Our
strategy is to pursue orphan drug indications in which open-label, single-arm clinical trials may lead to possible BLA submissions, or
indications with large populations with remaining unmet medical need.
Our
Other Programs
We
are also pursuing development of NXC-201 in immune-mediated diseases, a $25 billion combined annual market size according to Grand View
Research and Fortune Business Insights.
Manufacturing
We
have a strong track record of successful manufacturing. We have already established a track record of producing NXC-201 for patient dosing
and testing in the U.S. and ex-U.S. In addition, we have already developed a scalable, reliable manufacturing process for our TSTx according
to current Good Manufacturing Practice (“cGMP”).
We
will continue to leverage our established technical, manufacturing, analytical, quality, cGMP, project management expertise and existing
relationships to contract with appropriate CMOs to manufacture our cell therapies and TSTx moving forward.
In
January 2024, the Company entered into a long-term operating lease agreement for biopharmaceutical research and development space located
in California. To date, we have obtained active pharmaceutical ingredients (“API”) and drug product for our product candidates
from several third party contract manufacturers. We are in the process of developing our supply chain for each of our product candidates
and have entered into agreements pursuant to which third-party contract manufacturers will provide us with necessary quantities of API
and drug product on a project-by-project basis based upon our needs. We rely, and expect to continue to rely for the foreseeable future,
on FDA, EMA, or other jurisdiction-registered third-party contract manufacturing organizations to produce our product candidates for
pre-clinical and clinical testing, as well as for commercial manufacture if our product candidates receive marketing approval. As part
of the manufacture and design process for our product candidates, we rely on internal, scientific and manufacturing know-how and trade
secrets and the know-how and trade secrets of third-party manufacturers. We also contract with additional third parties for the filling,
labeling, packaging, storage and distribution of investigational drug products. We believe that this strategy allows us to maintain a
more efficient infrastructure by eliminating the need for us to invest in our own manufacturing facilities, equipment and personnel while
also enabling us to focus our expertise and resources on the development of our product candidates. We maintain agreements with our manufacturers
that include confidentiality and intellectual property, and quality provisions to protect our proprietary rights related to our product
candidates and satisfy regulatory requirements.
Competition
The
biotechnology industry is extremely competitive in the race to develop new products. We currently face and will continue to face competition
for our development programs from groups that are developing therapies for oncology and inflammation. The competition is likely to come
from multiple sources, including larger pharmaceutical companies, biotechnology companies, and academic institutions.
Companies
which have publicly disclosed developing therapies for AL amyloidosis include, but are not limited to, Prothena Corp, Caelum Biosciences
(Now Alexion/AstraZeneca), and Janssen/Johnson & Johnson.
Companies
which have publicly disclosed developing or that they intend to develop cell therapies for immune-mediated disease indications include,
but are not limited to: Kyverna Therapeutics, Inc.; Cabaletta Bio, Inc.; Fate Therapeutics Inc.; and Arcellx, Inc.
Intellectual
Property
Our
success depends in part on our ability to obtain and maintain proprietary protection for our product candidates, technology and know-how,
to operate without infringing the proprietary rights of others and to prevent others from infringing our proprietary rights. Our strategy
is to seek to protect our proprietary position by, among other methods, pursuing and obtaining patent protection in the United States
and in jurisdictions outside of the United States related to our proprietary technology, inventions, improvements, and product candidates
that are important to the development and implementation of our business. We intend to build a patent portfolio to cover our product
candidates and related components, their methods of use and processes for their manufacture, our proprietary reagents and assays, and
any other inventions that are commercially important to our business. We also rely on trademarks as well as trade secret protection of
our confidential information and know-how relating to our proprietary technology platform, and product candidates. We believe that we
have substantial know-how and trade secrets relating to our technology and product candidates.
As of March 11, 2025, our patent portfolio includes 12 U.S. and foreign granted patents, 16 pending U.S. and foreign patent applications
related to our technology platform and our product candidates. Of those, 2 patents have been granted in the U.S. and 10 patents have been
granted in the following countries: France, Germany, Ireland, Switzerland, and the United Kingdom. Three non-provisional patent applications
are currently pending in the U.S. and 9 foreign patent applications are currently pending in Australia, Brazil, Canada, Europe, Hong Kong,
Japan and Mexico. Certain platform patents are expected to remain in force until 2033. Other patents directed to platform technology could
remain in force until 2042.
The
below patents and patent applications comprise our patent portfolio. All of the patents and patent applications listed below are owned
by us.
*
Any resulting patents in this family are expected to expire in 2033 (not including any patent term adjustment and patent term extension
in the United States and equivalents in foreign countries).
**
Any resulting patents in this family are expected to expire in 2042 (not including any patent term adjustment and patent term extension
in the United States and equivalents in foreign countries).
Additionally,
as of March 11, 2025, our subsidiary Nexcella, Inc. has global exclusive rights to PCT Application No. PCT/IL2023/050142 filed in 2023.
The application is directed to our N-GENIUS platform, EXPAND technology, and to our product candidates, including NXC-201. The application
relates to a chimeric antigen receptor (CAR) molecule specific for B cell maturation antigen (BCMA), compositions and methods thereof
for the treatment of immune-related disorders. The PCT application has entered the national phase in the following countries: United
States, Europe, Israel, United Arab Emirates, Australia, Brazil, Canada, China, Indonesia, Japan, Korea, Mexico, New Zealand, Philippines,
and Singapore. Any resulting patents in this family are expected to expire in 2043 (not including any patent term adjustment and patent
term extension in the United States and equivalents in foreign countries). Nexcella also has global exclusive rights to a patent family
directed to the Generation of “Naïve-like” CART cells. This patent family has one U.S. Provisional Patent Application
pending as of March 11, 2025.
We
generally pursue multilayered patent protection covering the composition of matter including the formulations of the product candidates,
and/or the functional characteristics of the product candidates. In addition to composition of matter coverage, we also generally pursue
claims directed to methods of making, and methods of use of the product candidates.
IP
License Agreement with Immix Biopharma Australia Pty Ltd.
On
January 23, 2017, we entered into an IP License Agreement (“License Agreement”) with Immix Biopharma Australia Pty Ltd.,
our wholly-owned subsidiary (“IBAPL”), pursuant to which we granted IBAPL a non-exclusive, non-transferable license to IMX-110
intellectual property that is necessary for the purpose of, among other things, conducting or facilitating the research, development
or clinical trials relating to such intellectual property in the Commonwealth of Australia. Pursuant to the terms of the License Agreement,
during the term of the License Agreement, IBAPL shall pay us a royalty equal to a mid single digit percentage of Net Sales (as defined
in the License Agreement), subject to adjustment as set forth in the License Agreement. The License Agreement may be terminated by either
party (i) upon 20 days prior written notice to the other party, (ii) if the other party breaches any provision of the License Agreement
and fails to remedy such breach within 10 business days after receiving written notice of such breach or (iii) if the other party is
the subject to an insolvency event as set forth in the License Agreement. To date, we have not received any payments pursuant to the
License Agreement.
AxioMx
Master Services Agreement
On
December 22, 2014, we entered into a Master Service Agreement (“MSA”) with AxioMx, Inc. (“AxioMx”) which is in
the business of developing and supplying custom affinity reagents. We entered into the MSA to serve as a master agreement governing multiple
sets of projects as may be agreed upon us and AxioMx from time to time. Pursuant to the MSA, we granted AxioMx a non-exclusive, royalty-free,
worldwide, non-transferable license to certain of our intellectual property to perform services pursuant to the MSA, and AxioMx granted
us an exclusive product assignment option which grants us an exclusive, royalty-bearing right, with the right to sublicense, under the
Deliverable (as defined in the MSA) to further research, develop, use, sell, offer for sale, import and export one or more assigned products
pursuant to the MSA. We exercised the option in 2017. Pursuant to the MSA, AxioMx is entitled to royalties on the sale of any Deliverable
that is used for diagnostic, prognostic or therapeutic purposes, in humans or animals, or for microbiology testing, including food safety
testing or environmental monitoring. Specifically, we shall pay AxioMx a royalty of 3.5% of Net Sales (as defined in the MSA) of assigned
products for each Deliverable used in licensed products for therapeutic purposes. In addition, we shall pay AxioMx a royalty of 1.5%
of Net Sales of assigned products for each Deliverable used in licensed products for diagnostic or prognostic purposes; provided, however,
if three Deliverables are used in an assigned product for diagnostic or prognostic purposes, the royalty shall be 4.5%. As of December
31, 2024, the MSA has expired and the Company does not intend to extend the MSA; however, the royalty obligations described therein survived
the termination of the MSA.
Absorption
of Nexcella Subsidiary
On
May 20, 2024, Nexcella, was merged (the “Merger”) with and into the Company, with the Company as the surviving corporation.
The Merger was effected pursuant to Section 253 of the Delaware General Corporation Law (“DGCL”) when the Company filed a
Certificate of Ownership and Merger (“Certificate of Merger”) with the Secretary of State of the State of Delaware. Immediately
prior to the Merger, the Company owned greater than 95% of the outstanding common stock on a fully diluted basis of Nexcella, par value
$0.0001 per share (the “Nexcella Shares”), and 100% of the outstanding shares of each other class of capital stock of Nexcella.
Under the DGCL, the only approval required was that of the Company’s Board of Directors for the Merger to become effective. As
a result of the Merger, Nexcella ceased to exist and all assets, operations and other property and rights of Nexcella have been succeeded
to by the Company. Pursuant to the terms of the Certificate of Merger, as a result of the Merger, each of the outstanding Nexcella Shares
(other than Nexcella Shares held by the Company) were converted, into common stock of the Company (“Company Merger Shares”).
In connection with the Merger, the Company issued 989,876 shares of its common stock of the Company to the former stockholders of Nexcella
(other than shares held by the Company) (including Company common stock issued to third-party cash investors in Nexcella) (the “Merger
Shares”). In addition, the Company issued to the former participants in the Nexcella 2022 Equity Incentive Plan, 275,759 restricted
stock awards to receive common stock in the Company and options to purchase up to 595,676 shares of Company common stock at an exercise
price of $2.47 per share (the closing price on May 17, 2024), under the Company’s Amended and Restated 2021 Omnibus Equity Incentive
Plan.
Research
and License Agreement with Hadasit and BIRAD
On
December 8, 2022, our subsidiary Nexcella entered into a Research and License Agreement (the “Agreement”) with Hadasit Medical
Research Services & Development, Ltd. and BIRAD – Research and Development Company Ltd. (collectively, the “Licensors”)
pursuant to which the Licensors granted to Nexcella an exclusive, worldwide, royalty-bearing license throughout the world, except Israel,
Cyprus and other countries in the Middle East (the “Territory”), to an invention entitled “Anti-BCMA CAR-T cells to
target plasma cell” to develop, manufacture, have manufactured, use, market, offer for sale, sell, have sold, export and import
the Licensed Product (as defined in the Agreement). Pursuant to the Agreement, Nexcella paid the Licensors an upfront fee of $1,500,000
in December 2022. Additional quarterly payments totaling approximately $13.0 million are due through September 2026 along with an annual
license fee of $50,000. Nexcella has agreed to pay royalties to the Licensors equal to 5% of Net Sales (as defined in the Agreement)
during the Royalty Period. “Royalty Period” means for each Licensed Product, on a country-to-country basis, the period commencing
on December 8, 2022 and ending on the later of (a) the expiration of the last to expire Valid Claim (as defined in the Agreement) under
a Licensed Patent (as defined in the Agreement), if any, in such country, (b) the date of expiration of any other Exclusivity Right (as
defined in the Agreement) or data protection period granted by a regulatory or other governmental authority with respect to a Licensed
Product or (c) 15 years from the date of First Commercial Sale (as defined in the Agreement) of a Licensed Product in such country.
In
addition, Nexcella is required to pay milestone payments of up to $20 million upon the achievement of certain Net Sales milestones as
set forth in the Agreement and Nexcella has committed to funding NXC-201 clinical trials in Israel over 4 years for an estimated total
cost of approximately $13 million, spread on a quarterly basis over that period, which Nexcella believes will generate clinical trial
data owned by Nexcella. The term of the Agreement commenced on December 8, 2022 and, unless earlier terminated pursuant to the terms
thereof, will continue in full force and effect until the later of the expiration of the last Valid Claim under a Licensed Patent or
a Joint Patent (as defined in the Agreement) or Exclusivity Right covering a Licensed Product or the expiration of a continuous period
of 15 years during which there shall not have been a First Commercial Sale of any Licensed Product in any country in the world. Licensors
may terminate the Agreement immediately if Nexcella or its affiliates or sublicensees commences an action in which it challenges the
validity, enforceability or scope of any of the Licensed Patents or Joint Patents. In addition, either party may terminate the Agreement
if the other party materially breaches the Agreement and fails to cure such breach within 30 days. Additionally, Licensors may terminate
the Agreement if Nexcella becomes insolvent or files for bankruptcy.
The
license remains with the Company after the Nexcella Absorption.
On
December 16, 2024, Nexcella entered into the First Amendment to the Research and License Agreement (the “First Amendment”)
with the Licensors. The First Amendment includes terms specific to new licensed products and requires an additional upfront license fee
of $1,500,000, payable no later than April 30, 2025, as well as development milestone payments of up to $4.5 million upon the Company’s
achievement of certain milestones.
July
2023 ATM Offering
On
July 14, 2023, we entered into an ATM Sales Agreement (the “July 2023 Sales Agreement”) with ThinkEquity LLC (the “Sales
Agent”) pursuant to which we may offer and sell, from time to time, through the Sales Agent, shares of our common stock, subject
to the terms and conditions set forth in the July 2023 Sales Agreement. Initially, we are eligible to sell up to $4,200,000 worth of
shares of our common stock as the aggregate market value of our shares of common stock eligible for sale under the July 2023 Sales Agreement
is subject to the limitations of General Instruction I.B.6 of Form S-3 until such time that our public float equals or exceeds $75.0
million. In the event the aggregate market value of our outstanding common stock held by non-affiliates equals or exceeds $75.0 million,
then the one-third limitation on sales set forth in General Instruction I.B.6 of Form S-3 will not apply to additional sales made pursuant
to the July 2023 Sales Agreement. We agreed to pay the Sales Agent a commission rate of 3.75% of the aggregate gross proceeds from the
sale of the shares of our common stock pursuant to the July 2023 Sales Agreement and paid an expense deposit of $15,000 to the Sales
Agent, which will be applied against the actual out-of-pocket accountable expenses. In addition, we have agreed to reimburse the Sales