ITEM 1A. RISK FACTORS. 32
ITEM 1B. UNRESOLVED STAFF COMMENTS 65
ITEM 1C. CYBERSECURITY 65
ITEM 2. PROPERTIES 66
ITEM 3. LEGAL PROCEEDINGS 66
ITEM 4. MINE SAFETY DISCLOSURES 66
ITEM 6. [RESERVED] 67
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 75
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA F-1
ITEM 9A. CONTROLS AND PROCEDURES 76
ITEM 9B. OTHER INFORMATION 77
ITEM 9C. Disclosure Regarding Foreign Jurisdictions that Prevent InspectionS 77
PART III 77
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 77
ITEM 11. EXECUTIVE COMPENSATION 78
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 78
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 79
SIGNATURES 82
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;
● 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 other serious diseases. Our lead cell therapy candidate is CAR-T NXC-201 (“NXC-201”),
currently being evaluated in our ongoing United States Phase 1b/2 NEXICART-2 (NCT06097832) clinical trial and an ex-U.S. phase 1b/2a
NEXICART-1 (NCT04720313) clinical trial. NEXICART-2 is expected to enroll 40 patients, with final readout and Biologics License Application
(“BLA”) submission planned thereafter.
NXC-201
has been awarded Regenerative Medicine Advanced Therapy (“RMAT”) Designation by the FDA, Orphan Drug Designation (“ODD”)
by both the FDA and European Commission (“EC”) in AL Amyloidosis and, most recently, in January 2026, Breakthrough Therapy
designation by the FDA for the treatment of relapsed/refractory AL amyloidosis.
Our
mission is to harness the immune system through innovative cell therapies and other modalities to deliver widely accessible cures in
AL Amyloidosis and other serious diseases, 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 being designed to
treat AL Amyloidosis and other serious diseases.
Figure
1: Immix Pipeline
Recent
Developments
NEXICART-2
Clinical Trial Update
In
December 2025, we announced positive interim phase 2 safety and efficacy data from our Phase1/2 NEXICART-2 clinical trial, the first
U.S. trial of CAR-T in relapsed/refractory light chain (AL) amyloidosis, evaluating NXC-201. The results were as of November 13, 2025
and were presented by Heather Landau, MD, of Memorial Sloan Kettering Cancer Center in an oral presentation at the American Society of
Hematology’s ASH 2025 Annual Meeting. Prior to NXC-201 treatment, all patients were exposed to an anti-CD38 antibody and a proteasome
inhibitor. Median prior lines of therapy were four (range: 1-10). All patients had baseline relapsed/refractory AL Amyloidosis organ
involvement.
After
NXC-201 treatment, complete responses (“CRs”) were observed in 75% (at s/u IFE(-) level) (15 out of 20) patients as determined
by an independent review committee. In four out of five pending patients, minimum residual disease (MRD) negativity in bone marrow suggests
a future complete response may be expected. Downstream clinical improvement, including organ responses, were observed in 70% of evaluable
patients (7/10). No neurotoxicity has been observed. Grade 2 cytokine release syndrome was observed in four patients, Grade 1 cytokine
release syndrome was observed in 11 patients, with a median duration of one day.
Financial
Updates
Public
Offering
On
December 7, 2025, we entered into an underwriting agreement (the “2025 Underwriting Agreement”) with Morgan Stanley &
Co. LLC (“Morgan Stanley”), as representative of the several underwriters named in Schedule 1 thereto, relating to the issuance
and sale (the “2025 Offering”) of 19,117,646 shares (the “Shares”) of our common stock, and pre-funded warrants
to purchase up to 490,196 shares of our common stock (the “Pre-Funded Warrants”). The Shares were sold at a price of $5.10
per share and the Pre-Funded Warrants were sold at a price of $5.09 per Pre-Funded Warrant, which represents the per share offering price
for the Shares minus the $0.01 per share exercise price for each Pre-Funded Warrant. We raised gross proceeds of approximately $100.0
million in this offering.
September
2025 Securities Purchase Agreements
On
September 5, 2025 and September 11, 2025, we entered into Securities Purchase Agreements (the “September 2025 Securities Purchase
Agreements”) and Registration Rights Agreements with certain accredited investors (the “Purchasers”), pursuant to which
we sold to the Purchasers in a private placement transaction (the “Private Placement”) (i) an aggregate of 3,915,604 shares
of common stock and (ii) non-transferable warrants to purchase up to an aggregate of 2,936,709 shares of common stock (the “Warrants”).
The combined purchase price per share and Warrant was $2.37. The Private Placement closed on September 5, 2025 and September 11, 2025
and aggregate gross proceeds from both closings were approximately $9.3 million, before deducting fees and expenses payable by us. The
Warrants are exercisable over a ten-year period at an exercise price of $2.00 per share, subject to proportional adjustments in the event
of stock splits or combinations or similar events. The Warrants are not transferable other than to affiliates of the Purchasers, and
are exercisable only for cash consideration. Pursuant to the terms of the Registration Rights Agreements, we filed a resale registration
statement with the SEC on October 6, 2025 providing for the resale of the shares of common stock and the shares of common stock issuable
upon exercise of the Warrants by the Purchasers, which was declared effective by the SEC on December 1, 2025. Pursuant to the terms of
the September 2025 Securities Purchase Agreements, effective September 8, 2025, our board of directors (the “Board”) appointed
Nancy Chang, Ph.D. as a member of the Board.
Market
Update
NXC-201
is in a Phase 1b/2 clinical trial to treat relapsed/refractory AL Amyloidosis. In June 2024, we began administering NXC-201 to patients
with relapsed/ refractory AL Amyloidosis in our open label, single arm, multi-site Phase 1b/2 clinical trial. NEXICART-2 is expected
to enroll 40 patients, with final readout and BLA submission planned thereafter. See “Recent Developments- Clinical
Update- NEXICART-2” above for information regarding trial results as of November 13, 2025.
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 2026, 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 one year, according to Quock, et al. Journal of Comparative Effective Research, 2023. The
global amyloidosis treatment market size was estimated at $5.80 billion in 2024 and is projected to reach $11.13 billion by 2033, growing
at a CAGR of 7.5% from 2025 to 2033, according to Grand View Research.
As
of March 2026, our ongoing Phase 1/2 multi-site NEXICART-2 (NCT06097832) U.S. clinical trial is ongoing. Memorial Sloan Kettering Cancer
Center is the lead NEXICART-2 clinical site.
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 seven 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 investigational new drug (“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 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
July 2024, we were awarded an $8 million grant from the California Institute for Regenerative Medicine (“CIRM”) to support
the clinical development of chimeric antigen receptor T-cell therapy NXC-201 for the treatment of 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, indicating an overall response rate
of 94% (15/16) and a complete response rate of 75% (12/16).
In
February 2025, the FDA granted Regenerative Medicine Advanced Therapy (“RMAT”) designation to sterically-optimized CAR-T
NXC-201 for the treatment of relapsed/refractory AL amyloidosis. RMAT designation potentially streamlines the path to FDA approval by
allowing frequent interactions with FDA and routes to FDA Accelerated Approval and Priority Review. As of June 2024 public information,
FDA approved less than half of RMAT applications submitted to the agency during the last eight years. FDA RMAT designation requires that
a drug is an advanced regenerative medicine, targets a serious condition, with the potential to treat, modify, reverse, or cure, and
preliminary clinical evidence has indicated that the drug has the potential to address these unmet medical needs.
In
June 2025, NXC-201 clinical data in relapsed/refractory AL Amyloidosis was presented in an oral presentation at the 2025 American Society
of Clinical Oncology Annual Meeting (ASCO 2025), covering 10 relapsed/refractory AL Amyloidosis patients treated with NXC-201. After
NXC-201 treatment, all patients normalized pathological disease markers As of the ASCO data cutoff, complete responses (CRs) were observed
in 70% (7 out of 10) of patients treated with NXC-201. The remaining three patients were bone marrow minimum residual disease (MRD) negative
(10-6) at D+25, predicting future CR. These patients were confirmed as CRs by Independent Review Committee following data cutoff. Downstream
clinical improvement, including cardiac and renal organ responses, were recorded. There have been no relapses recorded and no safety
signals identified as of the date of this report. Also, as of the date of this report, no neurotoxicity has been observed and only low-grade
cytokine release syndrome has been observed.
In
July 2025, we expanded the number of clinical trial sites to 18 in our relapsed/refractory AL Amyloidosis clinical trial NEXICART-2 with
a registrational design.
In
December 2025, we announced positive interim phase 2 NXC-201 results in an oral presentation at the American Society of Hematology’s
ASH 2025 Annual Meeting, presented by Heather Landau, MD, of Memorial Sloan Kettering Cancer Center. NXC-201 demonstrated a complete
response (CR) rate of 75% (at s/u IFE(-) level) (15/20) by independent review committee.
In
January 2026, the FDA granted Breakthrough Therapy designation to sterically-optimized CAR-T NXC-201 for the treatment of relapsed/refractory
AL amyloidosis. Per FDA, Breakthrough Therapy designation aims to expedite the development and review of drugs that are intended to treat
a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available
therapy on a clinically significant endpoint.
Our
Other Programs
Our
other programs include NXC-201 for treatment of select other serious diseases and other preclinical candidates.
Our
Platform and Technologies
We
believe our N-GENIUS platform has broad potential utility in hematologic, neurologic, rheumatologic, vascular and other serious 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 Immix 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 three 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 are pursuing 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 38,500 patients in 2026. AL amyloidosis has a one-year mortality rate of 47%, 76% of which is caused by cardiac amyloidosis,
according to Alexion. The global amyloidosis treatment market size was estimated at $5.80 billion in 2024 and is projected to reach $11.13
billion by 2033, growing at a CAGR of 7.5% from 2025 to 2033, according to Grand View Research.
As
of March 2026, there are no FDA approved drugs for relapsed/refractory AL Amyloidosis.
Figure
2: NXC-201 Addresses Sizable U.S. Relapsed/Refractory AL Amyloidosis Patient Population
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
three 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 CD3ζγ 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
minimizing cytokine release syndrome (“CRS”) duration.
Figure
6: N-GENIUS Platform – EXPAND Technology + COBRA Binder
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 One Patient’s Bone Marrow After 33 Days
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.
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,
tumor necrosis factor alpha: TFNα), which was not seen in NT cells. Furthermore, non-tumor 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 are treating patients with relapsed/refractory AL Amyloidosis in
the Phase 2 portion of our Phase1/2 open label, single-arm clinical trial. NEXICART-2 is expected to enroll 40 patients, and we plan
for a final data readout and, if positive, submission of a BLA for FDA approval thereafter. See “Recent Developments- Clinical
Update- NEXICART-2” above for information regarding trial results as of November 13, 2025.
The
primary objectives in relapsed/refractory AL Amyloidosis are to study the safety and efficacy of NXC-201.
The
primary endpoints in the NEXICART-2 trial 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.
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 NXC-201 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 NXC-201 moving forward.
In
January 2024, we 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 third-party
CMOs 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 will 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. Our competitors include major multi-national pharmaceutical
companies and biotechnology companies developing both generic and proprietary therapies to treat serious diseases. Many of these companies
are well-established and possess technical, human, research and development, financial, and sales and marketing resources significantly
greater than ours. In addition, many of our potential competitors have formed strategic collaborations, partnerships and other types
of joint ventures with larger, well established industry competitors that afford these companies potential research and development and
commercialization advantages in the therapeutic areas we are currently pursuing. Academic research centers, governmental agencies and
other public and private research organizations are also conducting and financing research activities which may produce products directly
competitive to those being developed by us. In addition, many of these competitors may be able to obtain patent protection, obtain FDA
and other regulatory approvals and begin commercial sales of their products before us.
We
currently face and will continue to face competition for our development programs from groups that are developing therapies for oncology
and inflammation. Companies which have publicly disclosed developing therapies for AL amyloidosis include, but are not limited to, Abbvie,
Caelum Biosciences (n/k/a Alexion/AstraZeneca), and Janssen/Johnson & Johnson.
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 2026, we have 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, Hong Kong, Indonesia, Japan, Korea, Mexico, New Zealand, Philippines, and Singapore (see
the below table). 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).
We
also have global exclusive rights to PCT Application No. PCT/IL2025/050836 filed in 2025 (see the above table). This application is directed
to the Generation of “Naïve-like” CART cells. Any resulting patents in this family are expected to expire in 2045 (not
including any patent term adjustment and patent term extension in the United States and equivalents in foreign countries).
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.
Nexcella
Subsidiary
Nexcella
Inc., our former wholly-owned subsidiary, was merged with and into the Company in May 2024. Subsequently, a wholly-owned
subsidiary Nexcella, Inc. was created and continues to be wholly-owned.
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. Upon the merger of Nexcella with and into Immix, we assumed all of Nexcella’s rights and obligations pursuant
to the Agreement.
We
are required 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, we are required to pay milestone payments of up to $20 million upon the achievement of certain Net Sales milestones as set
forth in the Agreement. Pursuant to the Agreement, Nexcella committed to funding NXC-201 clinical trials in Israel for a period of four
years for an estimated total cost of approximately $13 million, spread on a quarterly basis over that period, the payment of which has
been, and will be, paid by us since the merger in May 2024. We expect that the clinical trial data generated by the NXC-201 clinical
trials in Israel will be owned by us. 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 we or our affiliates or sublicensees commences an action in which the validity,
enforceability or scope of any of the Licensed Patents or Joint Patents is challenged. 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 we become insolvent or file for bankruptcy.
On
December 16, 2024, our wholly-owned subsidiary, Nexcella, Inc., 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 $1.5 million, which has been paid in full as of December 31, 2025, as well as development
milestone payments of up to $4.5 million upon the Company’s achievement of certain milestones.
CIRM
Grant
On
July 25, 2024, we were awarded an $8 million grant from the California Institute for Regenerative Medicine (CIRM) to support the clinical
development of chimeric antigen receptor T-cell therapy NXC-201 for the treatment of relapsed/refractory AL Amyloidosis. The award is
payable to us upon achievement of milestones that are primarily based on patient enrollment in our clinical trials. Additionally, if
CIRM determines, in its sole discretion, that we have not complied with the terms and conditions of the grant, CIRM may suspend or permanently
cease disbursements. Funds received under this grant may only be used for allowable project costs specifically identified with the CIRM-funded
project. Such costs can include, but are not limited to, salary for personnel, itemized supplies, consultants, and itemized clinical
study costs. Under the terms of the grant, both CIRM and we will co-fund the research project and the amount of our co-funding requirement
is predetermined as a part of the award. We signed the grant agreement in November 2024 and began receiving funds from the grant in November
of 2024. As of March 20, 2026, we have received $6.2 million in grant reimbursements under the grant agreement.
Government
Regulations
United
States Regulation of Drugs and Biologics
We
expect that NXC-201 will be regulated by the FDA as a biologic and plan to submit a BLA to the FDA after
the final readout from our NEXICART-2 trial. We expect to pursue United States and global regulatory designations, vouchers, conditional
approvals and accelerated approvals where appropriate.
Our
business activities are subject to various laws, rules and regulations of the United States as well as of foreign governments. In the
United States, the FDA regulates pharmaceutical and biological products under the Federal Food, Drug and Cosmetic Act, Public Health
Service Act, and implementing regulations. Products are also subject to other federal, state and local statutes and regulations. Failure
to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval,
may subject an applicant to administrative or judicial sanctions. FDA sanctions could include, among other actions, refusal to approve
pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls or withdrawals from the market, product
seizures, total or partial suspension of production or distribution injunctions, fines, refusals of government contracts, restitution,
disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us.
The
FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among
other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging,
storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting
of drug products such as those we are developing. We, along with third-party contractors, will be required to navigate the various pre-clinical,
clinical and commercial approval requirements of the governing regulatory agencies of the countries in which we wish to conduct studies
or seek approval or licensure of our product candidates.
The
process required by the FDA before drug candidates may be marketed in the United States generally involves the following:
● satisfactory completion of an FDA Advisory Committee review, if applicable;
Pre-clinical
and Clinical Development
Prior
to beginning the first clinical trial with a product candidate, we must submit an IND to the FDA. An IND is a request for authorization
from the FDA to administer an investigational new drug product to humans. The central focus of an IND submission is on the general investigational
plan and the protocol(s) for clinical trials. The IND also includes results of animal and in vitro studies assessing the toxicology,
pharmacokinetics, pharmacology and pharmacodynamic characteristics of the product; chemistry, manufacturing and controls information;
and any available human data or literature to support the use of the investigational product. An IND must become effective before human
clinical trials may begin. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day
time period, raises safety concerns or questions about the proposed clinical trial. In such a case, the IND may be placed on clinical
hold and the IND sponsor and the FDA must resolve any outstanding concerns or questions before the clinical trial can begin. Submission
of an IND therefore may or may not result in FDA authorization to begin a clinical trial.
Clinical
trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in
accordance with cGCP, which include the requirement that all research subjects provide their informed consent for their participation
in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the
parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND
must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments. Furthermore,
an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and
its informed consent form before the clinical trial begins at that site, and must monitor the study until completed. Regulatory authorities,
the IRB or the sponsor may suspend a clinical trial at any time on various grounds, including a finding that the subjects are being exposed
to an unacceptable health risk or that the trial is unlikely to meet its stated objectives. Some studies also include oversight by an
independent group of qualified experts organized by the clinical trial sponsor, known as a data safety monitoring board, which provides
authorization for whether or not a study may move forward at designated check points based on access to certain data from the study and
may halt the clinical trial if it determines that there is an unacceptable safety risk for subjects or other grounds, such as no demonstration
of efficacy. There are also requirements governing the reporting of ongoing clinical trials and clinical trial results to public registries.
For
purposes of NDA or BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap.
A
registrational trial is a clinical trial that adequately meets regulatory agency requirements for the evaluation of a drug candidate’s
efficacy and safety such that it can be used to justify the approval of the drug. Generally, registrational trials are Phase 3 trials
but may be Phase 2 trials if the trial design provides a reliable assessment of clinical benefit, particularly in situations where there
is an unmet medical need.
In
some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain
more information about the product. These so-called Phase 4 studies may be made a condition to approval of the NDA or BLA. Concurrent
with clinical trials, companies may complete additional animal studies and develop additional information about the characteristics of
the product candidate and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.
The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other things,
must develop methods for testing the final product. Additionally, appropriate packaging must be selected and tested and stability studies
must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.
NDA
or BLA Submission and Review
Assuming
successful completion of all required testing in accordance with all applicable regulatory requirements, the results of product development,
non-clinical studies and clinical trials are submitted to the FDA as part of an NDA or BLA requesting approval to market the product
for one or more indications. The NDA or BLA must include all relevant data available from pertinent pre-clinical and clinical trials,
including negative or ambiguous results as well as positive findings, together with detailed information relating to the product’s
chemistry, manufacturing, controls, and proposed labeling, among other things. A determination by the FDA within 60 days of the receipt
of an NDA or BLA to file the application for review for its completeness is initiated at the time of submission. If the FDA determines
there is significance to the missing or incomplete information in the context of the proposed drug product, the proposed indication(s)
and the amount of time needed to address any given deficiency, it can issue a refusal-to-file letter. The submission of an NDA or BLA
requires payment of a substantial application user fee to FDA, unless a waiver or exemption applies.
Once
an NDA has been submitted, the FDA’s goal is to review standard applications within ten months after it accepts the application
for filing, or, if the application qualifies for priority review, six months after the FDA accepts the application for filing. In both
standard and priority reviews, the review process is often significantly extended by FDA requests for additional information or clarification.
The FDA reviews an NDA or BLA to determine, among other things, whether a product is safe and effective. The FDA may convene an advisory
committee to provide clinical insight on application review questions. Before approving an NDA or BLA, the FDA will typically inspect
the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing
processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within
required specifications. Additionally, before approving an NDA or BLA, the FDA will typically inspect one or more clinical sites to assure
compliance with cGCP. If the FDA determines that the application, manufacturing process or manufacturing facilities are not acceptable,
it will outline the deficiencies in the submission and often will request additional testing or information. Notwithstanding the submission
of any requested additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria
for approval.
After
the FDA evaluates an NDA or BLA and conducts inspections of manufacturing facilities where the product will be produced, the FDA may
issue an approval letter or a Complete Response letter. An approval letter authorizes commercial marketing of the product with specific