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Item 1. Business

2025-03-18 compared with 2024-03-21 · 242 added, 295 removed, 947 unchanged (36% of the section changed)

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We are a biopharmaceutical company focused on

advancing innovative immune-oncology technologies addressing hard to treat cancers.

Our proprietary DNase platform is designed to improve

outcomes of existing treatments, including immunotherapies, by targeting NETs, which have been implicated in cancer progression and resistance

to cancer treatments.

The DNase platform is designed to target NETs,

advancing innovative immuno-oncology technologies addressing difficult to treat cancers.

Our proprietary DNase technology is designed to

improve outcomes of existing treatments, including immunotherapies, by targeting NETs, which are involved in cancer growth, metastasis

and progression, and contribute to immunotherapy, chemotherapy and radiotherapy resistance.

The DNase technology is designed to target NETs,

which are weblike structures composed of extracellular chromatin coated with histones and other proteins.

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cancer growth and metastasis.

We are focused on advancing the development

of our DNase platform toward a first-in-human, multicenter, dose escalation and dose-expansion study of IV rhDNase I in subjects

with locally advanced or metastatic solid tumors.

Our systemic DNase program is initially targeting multi-billion-dollar indications

including pancreatic cancer (which includes pancreatic ductal adenocarcinoma (“PDAC”)), colorectal carcinoma

(“CRC”) and other gastrointestinal cancers.

These are all cancer indications with significant unmet need, and with

opportunities for substantial improvement of the currently available therapeutic options.

PDAC has a low rate of early diagnosis, a

high mortality rate and a poor five-year survival prognosis.

Symptoms are usually non-specific and as a result, PDAC is often not

diagnosed until it reaches an advanced stage.

Once the disease has metastasized, or spread to other organs, it becomes especially

hard to treat.

Each year, about 185,000 individuals globally are diagnosed with this condition;

and in 2021, the Surveillance,

Epidemiology and End Results program, or SEER, of the National Cancer Institute estimated that in the United States there would be

approximately 60,000 individuals diagnosed with pancreatic cancer.

The overall five-year survival rate among pancreatic cancer

patients is 7-8%, which constitutes the highest mortality rate among solid tumor malignancies;

among those diagnosed with metastatic

disease, the overall five-year survival rate is only 3%.

Recent developments that have improved the survival in many cancer types

have not been effective for pancreatic cancer patients, highlighting the urgent need for the development of newer, more effective

therapeutic options.

For those few patients that present with earlier stage PDAC, surgical resection followed by chemotherapy is

possible, but for the majority of PDAC patients which present at diagnosis with advanced disease, chemotherapy is the only option,

and has only very limited benefit.

Second-line patients that were diagnosed already with metastatic disease have even fewer

therapeutic options.

The only approved regimen for second-line patients is Onivyde® in combination with 5FU and LV.

Stage IV at diagnosis patients reaching second-line therapy, median overall survival is only 4.7 months (Macarulla et al, Pancreas

We are focused on advancing the development of

our DNase technology toward a first-in-human, multicenter, dose escalation and dose-expansion study of IV rhDNase I in subjects with locally

advanced or metastatic solid tumors.

Our systemic DNase program is initially targeting multi-billion-dollar indications including pancreatic

ductal adenocarcinoma (“PDAC”), colorectal carcinoma (“CRC”) and other gastrointestinal cancers.

These are all

cancer indications with significant unmet need, and with opportunities for substantial improvement of the currently available therapeutic

PDAC has a low rate of early diagnosis, a high mortality rate and a poor five-year survival prognosis.

Symptoms are usually non-specific

and as a result, PDAC is often not diagnosed until it reaches an advanced stage.

Once the disease has metastasized, or spread to other

organs, it becomes especially difficult to treat.

There were about approximately 511,000 new cases of pancreatic cancer globally in 2022

and according to the American Cancer Society, in 2025, an estimated 67,000 people in the U.S.

will be diagnosed with pancreatic cancer,

with approximately 52,000 deaths projected from the disease;

this translates to a high mortality rate, as the five-year relative survival

rate for pancreatic cancer remains around 13%, which constitutes the highest mortality rate among solid tumor malignancies;

diagnosed with metastatic disease, the overall five-year survival rate is only 2%.

Recent developments that have improved the survival

in many cancer types have not been effective for pancreatic cancer patients, highlighting the urgent need for the development of newer,

more effective therapeutic options.

For those few patients that present with earlier stage PDAC, surgical resection followed by chemotherapy

is possible, but for the majority of PDAC patients that present at diagnosis with advanced disease, chemotherapy is the only option, and

has only very limited benefit.

Second-line patients that were diagnosed already with metastatic disease have even fewer therapeutic options.

The only approved regimen for second-line patients is Onivyde®, a liposomal irinotecan in combination with 5FU and LV.

For these Stage

IV at diagnosis patients reaching second-line therapy, median overall survival is only 4.7 months (Macarulla et al, Pancreas 2020 ).

CRC is the second most common cause of cancer

death in the United States after lung cancer.

CRC is the third most commonly diagnosed cancer in males and the second in females, globally,

according to the World Health Organization GLOBOCAN database.

In the United States, CRC is the second most common cause of cancer death

death in the U.S.

after lung cancer.

According to data from the NCI’s Surveillance, Epidemiology, and End Results (“SEER) Program, it is estimated

that in 2023 approximately 153,000 individuals in the U.S.

will be diagnosed with colon cancer, and an estimated 53,000 will die of the

CRC is in decline in older patients (>65 years) but that is offset by a steady increase in CRC diagnoses and deaths in individuals

younger than 55 years of age.

Despite continued overall declines, CRC is rapidly shifting to diagnosis at a younger age, at a more advanced

stage, and in the left colon/rectum.

CRC is the third most commonly diagnosed cancer in males and the second in females, globally, according

to the World Health Organization GLOBOCAN database.

In the U.S., CRC is the second most common cause of cancer death after lung cancer.

According to the American Cancer Society, in 2025, an estimated 154,000 people in the US will be diagnosed with colorectal cancer, with

approximately 52,900 deaths expected from the disease;

this translates to around 107,000 new colon cancer cases and 47,000 new rectal

cancer cases.

CRC is in decline in older patients (>65 years) but that is offset by a steady increase in CRC diagnoses and deaths in

individuals younger than 55 years of age.

Despite continued overall declines, CRC is rapidly shifting to diagnosis at a younger age, at

a more advanced stage, and in the left colon/rectum.

If CRC is diagnosed at a localized stage, the 5-year survival rate is 91%.

However, if the cancer

has spread to surrounding tissues or organs and/or the regional lymph nodes, the 5-year relative survival rate is 72%.

There are numerous

treatment options for earlier stage CRC patients, but as they progress to advanced and metastatic disease (“mCRC”), those

options become limited.

if the cancer has spread to surrounding tissues or organs and/or the regional lymph nodes, the 5-year relative survival rate is 72%.

are numerous treatment options for earlier stage CRC patients, but as they progress to advanced and metastatic disease (“mCRC”),

those options become limited.

Approximately 22% of CRC cases have metastasis at presentation, and 19% will develop metastasis after primary

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can impede the infiltration, activity, and survival of cytotoxic T cells in the tumor microenvironment.

Published pre-clinical models

have demonstrated the effectiveness of systemically administered DNase, alone or in combination with other agents, for the elimination

of NETs and prevention of tumor growth and metastasis.

We are currently focused on advancing our systemic DNase program into the clinic

as an adjunctive therapy for pancreatic carcinoma and locally advanced or metastatic solid tumors, including CRC.

Published preclinical models have

demonstrated the effectiveness of systemically administered DNase, alone or in combination with other agents, for the elimination of NETs

and prevention of tumor growth and metastasis.

We are currently focused on advancing our systemic DNase program into the clinic as an

adjunctive therapy for pancreatic carcinoma and locally advanced or metastatic solid tumors, including CRC.

Adoptive transfer of Chimeric Antigen Receptor

(“CAR”) T cells has emerged as one of the most promising advances in cancer immunotherapy.

To successfully treat solid tumors,

CAR T cells must be able to infiltrate, persist, and maintain anti-tumor function in a hostile tumor microenvironment that is itself adept

at immunosuppression and conducive to tumor cell survival.

Recent approaches to CAR T design include “armored” CAR-T cells,

so named because they can express additional factors to resist immunosuppression or degrade physical components of the tumor’s extracellular

matrix, including NETs.

We intend to conduct pre-clinical research with the goal of demonstrating that armoring CAR T cells to secrete

DNase can support depth and durability of response against solid tumor indications.

Engineered CAR T cells, designed to recognize cancer-associated

antigens, are capable of sustained and selective killing of tumor cells, with substantial reduction of tumor burden.

CAR T therapies have

exhibited remarkable clinical success against hematological malignancies but thus far have failed to demonstrate success in the context

of solid tumors.

CAR T cell therapy, while highly

effective against blood cancers, faces significant challenges when applied to solid tumors due to the complex tumor microenvironment which

hinders CAR T cell infiltration, persistence, and efficacy, making it difficult for them to reach and attack cancer cells within the solid

this includes barriers like dense connective tissue, abnormal blood vessels, and immunosuppressive cells that can exhaust

the CAR T cells, limiting their anti-tumor activity.

To successfully treat solid tumors, CAR T cells must be able to infiltrate, persist,

and maintain anti-tumor function in a hostile tumor microenvironment that is itself immunosuppressive and conducive to tumor cell survival

and metastasis.

Published evidence suggests that in addition to immunosuppressive factors, mechanical barriers formed by NETs can impede

T-cell penetration and occlude T-cell contact with tumor cells.

The conduct of several CAR T in vivo models has been a primary focus of

our Scripps collaboration.

Recent approaches to CAR T design include “armored” CAR-T

cells, so named because they can express additional factors to resist immunosuppression or degrade physical components of the tumor’s

extracellular matrix, including NETs.

We intend to conduct pre-clinical research with the goal of demonstrating that armoring CAR T cells

to secrete DNase can support depth and durability of response against solid tumor indications.

Engineered CAR T cells, designed to recognize

cancer-associated antigens, are capable of sustained and selective killing of tumor cells, with substantial reduction of tumor burden.

The conduct of several CAR T in vivo models has been a primary focus of our Scripps collaboration.

Our collaboration with Belgian Volition SARL Limited

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pursuant to a license of our PolyXen technology to an industry partner.

Although we hold a broad patent portfolio, the

focus of our internal efforts in 2023 was on the licensing and advancement of our DNase platform.

Although we hold a broad patent portfolio, the focus of our internal

efforts in 2024 was on the licensing and advancement of our DNase technology.

We were incorporated under the laws of the State

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PolyXen, ErepoXen and ImuXen.

Our primary focus is aimed at

advancing the systemic DNase program into the clinic as an adjunctive therapy for pancreatic cancer and other locally advanced or

metastatic solid tumors, including CRC.

Our goal is to provide solutions in the treatment of solid tumors by improving response and

overcoming resistance to checkpoint inhibitors, chemotherapy, and other standard of care treatments.

We also intend to pursue

industry collaborations and potential licenses to develop DNase for other uses and indications.

Our primary focus is aimed at advancing the systemic

DNase program into the clinic as an adjunctive therapy for pancreatic cancer and other locally advanced or metastatic solid tumors, including

Our goal is to provide solutions in the treatment of solid tumors by improving response and overcoming resistance to checkpoint inhibitors,

chemotherapy, and other standard of care treatments.

We also intend to pursue industry collaborations and potential licenses to develop

DNase for other uses and indications.

We intend to pursue orphan drug designations and

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We intend to advance development of our DNase

platform primarily through the use of contract manufacturing, contract research organizations (“CROs”) and academic institutions

technology primarily through the use of contract manufacturing, contract research organizations (“CROs”) and academic institutions

in order to efficiently manage our resources.

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Business Developments

Volition Collaboration

On August 2, 2022, we announced a research and

development collaboration with Volition to develop NETs-targeted adoptive cell therapies for the treatment of cancer.

The collaboration

is an early exploratory program to evaluate the potential combination of Volition’s Nu.Q ® technology Test and the

Company’s DNase-Armored CAR T platform to develop proprietary adoptive cell therapies potentially targeting multiple types of solid

Under the terms of the collaboration agreement, Volition will fund a research program and the two parties will share proceeds

from commercialization or licensing of any products arising from the collaboration.

On July 10, 2023, we entered into the first Collaborator

Statement of Work as part of this collaboration with Volition.

Scripps Research Institute (“Scripps

On March 17, 2023, the Company and Scripps Research,

entered into a Research Funding and Option Agreement (the “Agreement”), pursuant to which we agreed to provide Scripps Research

an aggregate of up to $938,000 to fund research relating to advancing the pre-clinical development of our DNase oncology platform technology.

The research funding is payable by us to Scripps Research on a monthly basis in accordance with a negotiated budget, which provides for

an initial payment of approximately $78,000 on the date of the Agreement and subsequent monthly payments of approximately $78,000 over

a 12-month period.

Under the Agreement, we have the option to acquire a worldwide exclusive license to Scripps Research’s rights

in the Technology or Patent Rights (as defined in the Agreement), as well as a non-exclusive, royalty-free, non-transferrable license

to make and use TSRI Technology (as defined in the Agreement) solely for our internal research purposes during the performance of the

research program contemplated by the Agreement.

Unless earlier terminated, the term of the Agreement

continues from the date of the Agreement for fifteen (15) months.

The Agreement may be terminated by us with 30 days advance written notice

to Scripps Research beginning six (6) months after the Effective Date (as defined in the Agreement) or by Scripps Research if we fail

to make timely payments due under the Agreement, subject to 30 days’ written notice to cure such nonpayment.

The Agreement may further

be terminated by either party in the event of the other party’s uncured failure to perform any obligations under the Agreement or

the bankruptcy of the other party.

University of Virginia (“UVA”)

On December 21, 2023, we entered into a Research

Funding and Material Transfer Agreement, as amended, with UVA (the “UVA Agreement”) to advance the development of our systemic

DNase program.

Under the terms of the UVA Agreement, i n

addition to advancing our existing intellectual property, we have an option to acquire an exclusive license to any new intellectual property

arising from the DNase research program.

Allan Tsung, MD, a member of the Company’s Scientific Advisory Board and Chair of

the Department of Surgery at the UVA School of Medicine, will oversee the research conducted under

the UVA Agreement.

As a surgical oncologist and scientist, Dr.

Tsung is internationally recognized for leading substantial research on

the role of NETs in tumor growth, metastasis, and resistance to existing cancer therapies.

Funding and Material Transfer Agreement with UVA (the “UVA Agreement”) to advance the development of our systemic DNase program.

Under the terms of the UVA Agreement, i n addition to

advancing our existing intellectual property, we have an option to acquire an exclusive license to any new intellectual property arising

from the DNase research program.

Allan Tsung, MD, a member of the Company’s Scientific Advisory Board and Chair of the Department

of Surgery at the UVA School of Medicine, oversees the research conducted under the UVA Agreement.

In November 2024, we entered into an amendment to extend the term of the UVA Agreement through December 2025.

UVA will build on the preclinical

and translational data produced to date and continue to investigate combinations of DNase I with immunotherapies in models of primary

and metastatic colorectal cancer.

Scripps Research Institute (“Scripps

On March 17, 2023, we entered into a Research

Funding and Option Agreement (the “Agreement”) with Scripps Research, pursuant to which we agreed to provide Scripps Research

an aggregate of up to $0.9 million to fund research relating to advancing the pre-clinical development of our DNase

Under the Agreement, we have the option to acquire a worldwide exclusive license to Scripps Research’s rights in the

Technology or Patent Rights (as defined in the Agreement), as well as a non-exclusive, royalty-free, non-transferrable license to make

and use TSRI Technology (as defined in the Agreement) solely for our internal research purposes during the performance of the research

program contemplated by the Agreement.

During the second quarter of 2024, the Company amended the Agreement to extend the term to October

31, 2024 with no additional funding required.

On November 1, 2024, we entered into a Second

Amendment to the Agreement with Scripps Research (the “Second Amendment”) extending the term of the Agreement for an additional

twelve (12) month period and to provide Scripps Research additional funding in an aggregate amount of up to approximately $400,000 to

fund continuing research.

The research funding is payable by us to Scripps Research on a monthly basis in accordance with a negotiated

budget, which provides for an initial payment of approximately $65,000 on the date of the Amendment and subsequent monthly payments of

approximately $65,000 over a 5-month period.

All other terms of the Original Agreement remain unchanged.

Our Technology and Drug Candidates

The Technologies

Potential Drug Candidates

We incorporate our patented and proprietary technologies

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to treat other conditions.

The Technologies

During the year ended December 31, 2024, the focus

of our internal development efforts was on the advancement of our DNase oncology platform.

of our internal development efforts was on the advancement of our DNase technology.

We have not been actively pursuing development

efforts for XCART or PolyXen or any of our other technologies.

The DNase platform is designed to target NETs,

The DNase technology is designed to target NETs,

which are weblike structures composed of extracellular chromatin coated with histones and other proteins.

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Exclusive license and sublicense agreements with CLS Therapeutics Ltd.

(“CLS”) to develop its interventional DNase platform, which is aimed at improving outcomes of existing treatments, including immunotherapies;

Multiple value-driving milestones expected over the next 12 -24 months;

Systemic DNase program initially targeting multi-billion-dollar indications including pancreatic carcinoma and other locally advanced or metastatic solid tumors;

(“CLS”) to develop its interventional DNase technology, which is aimed at improving outcomes of existing treatments, including immunotherapies;

Value-driving milestones expected over the next 12 -24 months;

Systemic DNase program initially targeting multi-billion-dollar indications including pancreatic carcinoma and other locally advanced or metastatic solid tumors including CRC;

Ongoing collaboration with UVA to advance the development of our systemic DNase program;

DNase-armored CAR T program in early pre-clinical development;

The Chimeric Antigen Receptor (“CAR”) T cell (“XCART”) technology platform was designed by its originators to utilize an established screening technique to identify peptide ligands that bind specifically to the unique BCR on the surface of an individual patient’s malignant tumor cells.

The peptide is then inserted into the antigen-binding domain of a CAR T cell, and a subsequent transduction/transfection process is used to engineer the patient’s T cells into a CAR T format which redirects the patient’s T cells to attack the tumor.

Essentially, the XCART screening platform is the inverse of a typical CAR T screening protocol wherein libraries of highly specific antibody domains are screened against a given target.

In the case of XCART screening, the target is itself an antibody domain, and hence highly specific by its nature.

The XCART technology creates the possibility of personalized treatment of lymphomas utilizing a CAR with an antigen-binding domain that should only recognize, and only be recognized by, the unique BCR of a particular patient’s B-cell lymphoma.

An expected result for XCART is limited off-tumor toxicities, such as B-cell aplasia.

We have suspended further development of XCART at this time, as we focus our efforts and resources on our DNase technology platform.

An enabling biological platform technology designed to extend the circulation time of drug molecules in the human body by chemically attaching PSA, to the drug molecule by a process termed polysialylation, thereby creating potentially superior next generation therapeutic candidates.

PSA, a biopolymer, comprising a chain of sialic acid molecules, is a natural constituent of the human body, although we obtain our PSA from a bacterial source.

Ongoing collaboration with Scripps Research to conduct several CAR T in vivo models and enhance the function of CAR T cells within solid tumor microenvironments.

Research, Outside Services and Collaborations

Through partner efforts, we are developing our

pipeline of next-generation bio-therapeutics and novel oncology drugs based on our DNase and PolyXen proprietary technologies.

to do this while efficiently managing our overhead, we rely on the services of contract manufacturers, CROs and our strategic collaborations.

We currently do not have in-house research facilities to pursue these initiatives.

Accordingly, continuous pipeline growth and advancement

of our technologies and drug candidates is dependent on several important collaborations and strategic arrangements, including our arrangements

pipeline of next-generation bio-therapeutics and novel oncology drugs based on our DNase proprietary technology.

In order to do this while

efficiently managing our overhead, we rely on the services of contract manufacturers, CROs and our strategic collaborations.

do not have in-house research facilities to pursue these initiatives.

Accordingly, continuous pipeline growth and advancement of our technologies

and drug candidates is dependent on several important collaborations and strategic arrangements, including our arrangements with:

Catalent Pharma Solutions LLC (“Catalent”),

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PJSC Pharmsynthez (“Pharmsynthez”), including its wholly-owned subsidiary SynBio LLC (“SynBio”), a beneficial owner of approximately 3.4% of our common stock;

Scripps Research, one of

the world’s largest, private non-profit research organizations;

Scripps Research, one of the world’s largest, private non-profit research organizations;

The University of Virginia, a non-profit, educational, research and healthcare institution.

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a Phase II(b)/III human clinical trial of ErepoXen (also known as Epolong) in Russia with patient recruitment completed in 2020.

2020, Pharmsynthez reported positive data from this clinical trial and, in February 2021, reported in a press release that it had started

the registration phase of Epolong by filing a registration dossier to obtain approval in Russia.

Pharmsynthez had reported in its press

release that it expected that the Russian stage of registration activities would be completed in 2021 and that it would be able to start

production of the product as early as the first quarter of 2022.

In the first quarter of 2023, Pharmsynthez informed us that it had received

a response letter indicating certain deficiencies in the dossier and continues to develop a gap mitigation strategy with the intent of

refiling the registration upon correction.

2020, Pharmsynthez reported positive data from this trial of Epolong, a treatment for anemia in patients with chronic kidney disease leveraging

our PolyXen technology.

Pharmsynthez filed a registration dossier to obtain approval in Russia and received a response letter indicating

certain deficiencies in the dossier.

Pharmsynthez developed a gap mitigation strategy and is currently determining next steps.

Serum Institute conducted Phase I and Phase II

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clinical trials in India of ErepoXen for in-center-dialysis patients.

Serum Institute may seek to leverage Pharmsynthez’s trial

data and potential Russian marketing authorization to request a waiver for a Phase III clinical trial in India, subject to local regulatory

authority approval.

Serum Institute is not actively pursuing this program but may seek

to leverage Pharmsynthez’ trial data and potential Russian marketing authorization to request a waiver for a Phase III clinical

trial in India, subject to local regulatory authority approval.

Pipeline Expansion Opportunities

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Significant Collaborations and Strategic Arrangements

In October 2017, we granted to Takeda the right

to grant a non-exclusive sublicense to certain patents related to our PolyXen technology that were previously exclusively licensed to

Takeda in connection with products related to the treatment of blood and bleeding disorders.

Royalty payments of approximately $2.5 million

and $1.7 million were recorded as revenue by us during the years ended December 31, 2023 and 2022, respectively, and are based on single

digit royalties on net sales of certain covered products.

On April 26, 2022, we entered into an Exclusive

Sublicense Agreement (the “Sublicense Agreement”) with CLS pursuant to which we received an exclusive license under certain

patent rights and know-how owned or controlled by CLS, to develop and commercialize certain pharmaceutical products and methods incorporating

DNase enzyme for use in the treatment of cancer (the “Sublicensed Products”).

Under the terms of the Sublicense Agreement,

we will have sole responsibility to, and shall use commercially reasonable efforts to, among other things, research, develop and obtain

marketing approval for the Sublicensed Products in the U.S.

and certain European markets, and to commercialize such Sublicensed Products

in the relevant market once marketing approval is obtained.

Concurrent with the Sublicense Agreement, we entered

into an Exclusive License Agreement (the “License Agreement”) with CLS, pursuant to which we received an exclusive license

under certain patent rights and know-how owned or controlled by CLS to develop and commercialize certain pharmaceutical products and methods

incorporating DNase in conjunction with CAR T therapies (the “Licensed Products”).

Under the terms of the License Agreement,

we will have sole responsibility to, and shall use commercially reasonable efforts to, among other things, research, develop and obtain

marketing approval for the Licensed Products in the U.S.

and certain European markets, and to commercialize such Licensed Products in

the relevant market once marketing approval is obtained.

Significant collaborations with UVA and Scripps Research are described

above under the “Business Developments” section of this Item 1 to Part I of the Form 10-K.

In October 2017, the Company granted to Takeda

the right to grant a non-exclusive sublicense to certain patents related to the Company’s PolyXen technology that were previously

exclusively licensed to Takeda in connection with products related to the treatment of blood and bleeding disorders.

Royalty payments

of approximately $2.5 million were recorded as revenue for each year by the Company during the years ended December 31, 2024 and 2023

and are based on single digit royalties on net sales of certain covered products.

Belgian Volition SARL Limited (“Volition”)

Collaboration

On August 2, 2022, we announced a research and

development collaboration with Volition to develop NETs-targeted adoptive cell therapies for the treatment of cancer and on July 10, 2023

we entered into the first Collaborator Statement of Work with Volition as part of this collaboration.

For more information regarding such

collaboration with Volition, refer to the section titled “Business Developments” above.

development collaboration with Volition to develop NETs-targeted adoptive cell therapies for the treatment of cancer.

The collaboration

is an early exploratory program to evaluate the potential combination of Volition’s Nu.Q ® Technology Test and our

DNase-Armored CAR T platform to develop proprietary adoptive cell therapies potentially targeting multiple types of solid cancers.

the terms of the collaboration agreement, Volition will fund a research program and the two parties will share proceeds from commercialization

or licensing of any products arising from the collaboration.

Catalent Pharma Solutions LLC (“Catalent”)

On June 30, 2022, we entered into a Statement

of Work (the “SOW”) with Catalent to outline the general scope of work, timeline, and pricing pursuant to which Catalent will

provide certain services to us to perform current Good Manufacturing Practices (“cGMP”) manufacturing of our recombinant protein,

Human DNase I.

The parties agreed to enter into a Master Services Agreement (“MSA”) that will contain terms and conditions

provide certain services to the Company to perform current Good Manufacturing Principles (“cGMP”) manufacturing of the Company’s

recombinant protein, Human DNase I.

The parties agreed to enter into a Master Services Agreement that will contain terms and conditions

to govern the project contemplated by the SOW and that will supersede the addendum to the SOW containing Catalent’s standard terms

and conditions.

In addition, in the event of any conflict between the project-specific terms and conditions set forth in the SOW and the

MSA, the MSA terms and conditions shall govern.

The estimated total cost of the project contemplated by the SOW is expected to be up to

approximately $5 million (exclusive of certain fees and potential alternatives) for the manufacturing services over the course of the

term of the project with each phase of the project invoiced separately in connection with the commencement of such phase.

Scripps Research

On March 17, 2023, the Company and Scripps Research

entered into the Agreement, pursuant to which we have agreed to provide Scripps Research an aggregate of up to $938,000 to fund research

relating to advancing the pre-clinical development of our DNase oncology platform technology.

For more information regarding the Agreement,

refer to the section titled “Business Developments” above.

Other Agreements

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of Pharmsynthez.

We and our collaborative partners continued to engage in research and development activities with no resultant commercial

products through December 31, 2023.

No amounts were recognized as revenue related to the Serum Institute, Pharmsynthez or SynBio agreements

during each of the years ended December 31, 2023 and 2022.

Our collaborative partners continued to engage in research and development activities with no resultant commercial products

through December 31, 2024.

No amounts were recognized as revenue related to the Serum Institute, Pharmsynthez or SynBio agreements during

each of the years ended December 31, 2024 and 2023.

Our Intellectual Property

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in certain other developed countries.

Our first issued patents began to expire in 2021 with the majority of the existing issued patents

for our PolyXen technology expiring between 2025 and 2030.

Our XCART and XDNASE patent families include patent applications that were

recently filed, with those most recently filed having an expiration date of 2042.

Our first issued patents began to expire in 2021 with the remaining PolyXen technology expiring

As these PolyXen related patents approach their expiration, we have not renewed these patents for the last years of their life.

Our XCART and XDNASE patent families include patent applications that were recently filed, with those most recently filed having an expiration

date of 2042.

Our patent strategy is to file patent applications

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As of February 28, 2025, we directly or indirectly

through a license with CLS), through our wholly-owned subsidiaries, Hesperix and Xenetic U.K., and Xenetic U.K.’s wholly-owned

subsidiaries, Lipoxen, XTI and SymbioTec, more than 170 U.S.

and international patents and pending patent applications that cover various

aspects of our technologies.

This number includes patents and patent applications that we have acquired or filed covering various aspects

of our XDNASE and XCART platform technology, including all rights throughout the world in and to patents and patent applications related

to “Articles And Methods Directed To Personalized Therapy Of Cancer,” and our PolyXen platform technology covering polysialylation

and advanced polymer conjugate technologies, respectively, as well as our other product candidates.

More specifically, our patents and

patent applications cover cancer treatments, method of use, polymer architecture, drug conjugates, formulations, methods of manufacturing

polymers and polymer conjugates along with methods of administering polymer conjugates.

We have received patent protection for certain

therapeutics that use our PolyXen technology linking the specific therapeutic to a PSA.

These include, but are not limited to, PSA-EPO,

PSA-insulin and PSA-insulin like protein, a next generation Factor VIII protein product candidate SHP656 (PSA-rFVIII), PSA-DNase I and

PSA-granulocyte colony stimulating factor (PSA-GCSF).

Further patents cover methods to prepare proteins that are linked to a PSA as well

as covering PSA linkages.

These method patents include those that link a PSA to a protein in a high pH solution as well as patents that

use a process for producing an aldehyde derivative of a sialic acid through the opening and oxidation of a sialic acid unit.

For instance,

we have patent protection for a PSA linkage that can be at the N-terminus.

We have received patent protection for the production

of PSA and the removal of endotoxin during the purification process.

The removal of endotoxin occurs through the addition of a high pH

solution to the PSA and a process to separate a polydisperse ionically charged polysaccharide, such as PSA, into fractions of different

average molecular weight.

This is accomplished through the use of a column and elution buffers with different and constant ionic strength

and pH, resulting in a fractionated polysaccharide that has a molecular weight polydispersity of 1.1 or lower.

own (e.g., through a license with CLS), through our wholly-owned subsidiaries, Hesperix and Xenetic U.K., and Xenetic U.K.’s wholly-owned

subsidiaries, Lipoxen, XTI and SymbioTec, 35 U.S.

and international patents and pending patent applications that cover various aspects

of our technologies.

This number includes patents and patent applications that we have acquired or filed covering various aspects of our

XDNASE and XCART platform technology, including all rights throughout the world in and to patents and patent applications related to “Articles

And Methods Directed To Personalized Therapy Of Cancer,” and our PolyXen platform technology covering polysialylation and advanced

polymer conjugate technologies, respectively, as well as our other product candidates.

More specifically, our patents and patent applications

cover cancer treatments, method of use, drug conjugates, formulations, along with methods of administering polymer conjugates.

We have also received patent protection for our

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present business strategy.

We currently have agreements in place with Catalent and Serum Institute whereby Catalent and Serum Institute

would produce clinical materials for use in the development of drug candidates involving our DNase and PolyXen technologies, respectively,

including candidates developed by our partners.

We do not have any agreements in place to manufacture clinical materials for use in the

development of our XCART technology and would seek a third party manufacturer for our clinical supply needs, if necessary.

We currently have the SOW in place with Catalent to produce clinical materials for use in the development of

drug candidates involving our DNase technology.

Government Regulation

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Federal Food, Drug, and Cosmetic Act (“FDCA”), and in the case of biologics, also under the Public Health Service Act (“PHSA”)

and their implementing regulations.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate federal,

state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

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.

These sanctions could include the FDA’s refusal to approve pending applications,

withdrawal of an approval, license revocation, a clinical hold, warning letters or untitled letters, product recalls, 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 process required by the FDA before a drug or biologic may be marketed

generally involves the following:

and the FDCA, and their implementing regulations.

The process of obtaining regulatory approvals and the subsequent compliance with appropriate

federal, state, local and foreign statutes and regulations require the expenditure of substantial time and financial resources.

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 actions or judicial sanctions.

These actions or sanctions could include the FDA’s refusal

to approve pending applications, withdrawal of an approval, required additional studies, license revocation, a clinical hold, warning

letters or untitled letters, product recalls, 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.

Prior to marketing a drug or biologic in the U.S.

the drug or biologic

sponsor generally must complete the following steps:

completion of preclinical laboratory tests, animal studies and formulation studies in accordance with Good Laboratory Practices (“GLP”) regulations and other applicable regulations;

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Changes in regulations, statutes or the interpretation

of existing regulations could impact our business in the future by requiring, for example:

of existing regulations, including those resulting from the new Trump Administration or the Executive Branch’s actions, could impact

our business in the future by requiring, for example:

(i) changes to our manufacturing arrangements;

(ii) additions or modifications to product labeling;

(ii) additions or modifications to

product labeling;

(iii) the recall or discontinuation of our products;

or (iv) additional record-keeping

requirements.

If any such changes were to be imposed, they could adversely affect the operation of our business.

or (iv) additional record-keeping requirements.

If any such changes

were to be imposed, they could adversely affect the operation of our business.

Reimbursement

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costs of drug products paid by consumers.

While the Biden Administration has not continued this effort, it has the authority to institute

other actions.

In December of 2020, the Trump Administration issued interim final rules focused on attempting to lower drug prices, including

permitting the importation of certain drugs from Canada, most-favored nation pricing for certain drug categories under Medicare Part B

and modifications to the Medicare Part D drug rebate program by modifying the U.S.

federal Anti-Kickback Statute.

The Part B most-favored

nation rule was blocked from taking effect on January 4, 2021, by a federal judge stating that the rule was rushed and the public was

not provided time to give comment as required by the Administrative Procedures Act.

Then, on December 29, 2021, CMS issued a final rule

that formally rescinded the most-favored nation rule.

There is also pending litigation to stay the changes to the Medicare Part D drug

rebate program and the Anti-Kickback Statute.

On January 30, 2021, the District Court for the District of Columbia granted the parties’

stipulated request to delay the effective date of the Part D rebate rule to January 1, 2023.

On August 7, 2022, Congress passed the Inflation

Reduction Act of 2022 which delayed the implementation of the changes to the Medicare Part D drug rebate program and the U.S.

Anti-Kickback Statute until January 2032.

In December of 2020, the Trump Administration issued interim final rules focused on attempting

to lower drug prices, including permitting the importation of certain drugs from Canada, most-favored nation pricing for certain drug

categories under Medicare Part B and modifications to the Medicare Part D drug rebate program by modifying the U.S.

federal Anti-Kickback

The Part B most-favored nation rule was blocked from taking effect on January 4, 2021, by a federal judge stating that the rule

was rushed and the public was not provided time to give comment as required by the Administrative Procedures Act.

Then, on December 29,

2021, CMS issued a final rule that formally rescinded the most-favored nation rule.

There is also pending litigation to stay the changes

to the Medicare Part D drug rebate program and the Anti-Kickback Statute.

On January 30, 2021, the District Court for the District of

Columbia granted the parties’ stipulated request to delay the effective date of the Part D rebate rule to January 1, 2023.

7, 2022, Congress passed the Inflation Reduction Act of 2022 which delayed the implementation of the changes to the Medicare Part D drug

rebate program and the U.S.

Federal Anti-Kickback Statute until January 2032.

As a result of the 2024 presidential election, it is unclear

whether the new Trump Administration will renew, resume, or enact any similar efforts or proposals that may impact drug pricing and/or

drug reimbursement in the U.S.

Additionally, the Inflation Reduction Act of 2022

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program rise faster than the rate of inflation.

More broadly, in 2024, the U.S.

Supreme Court

in Loper Bright Enterprises v.

Raimondo , overturned the long-standing “Chevron” doctrine, which had accorded deference

to an agency's interpretation of ambiguous laws since 1984.

Following the Loper decision, the healthcare space may face increased

judicial scrutiny of agency regulations, as courts are no longer required to defer to federal agencies' interpretations of ambiguous statutes.

Although the full impact of this reversal remains to be seen, this change could lead to significant alterations in how healthcare laws

and regulations are applied and enforced.

At the state level, legislatures have increasingly

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of the federal government to repeal or replace certain aspects of the Affordable Care Act.

For example, the former President Trump signed

Executive Orders designed to delay the implementation of certain provisions of the Affordable Care Act or otherwise circumvent some of

the requirements for health insurance mandated by the Affordable Care Act.

For example, President Trump signed Executive

Orders designed to delay the implementation of certain provisions of the Affordable Care Act or otherwise circumvent some of the requirements

for health insurance mandated by the Affordable Care Act.

In addition, the U.S.

Congress has considered legislation that

would repeal or repeal and replace all or part of the Affordable Care Act.

While Congress has not passed comprehensive repeal legislation,

it has enacted laws that modify certain provisions of the Affordable Care Act, such as removing penalties, starting January 1, 2019, for

not complying with the Affordable Care Act’s individual mandate to carry health insurance, delaying the implementation of certain

mandated fees and increasing the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part

In December 2018, a Texas U.S.

District Court Judge ruled that the Affordable Care Act is unconstitutional in its entirety because

the “individual mandate” was repealed by Congress as part of the Tax Cuts and Jobs Act of 2017, or the Tax Act.

Supreme Court ruled the plaintiffs did not have standing in June of 2021, any other executive, legislative or judicial action to “repeal

and replace” all or part of the Affordable Care Act may have the effect of limiting the amounts that government agencies will pay

for healthcare products and services, which could result in reduced demand for our products or additional pricing pressure, or may lead

to significant deregulation, which could make the introduction of competing products and technologies much easier.

Congress has considered legislation that would repeal

or repeal and replace all or part of the Affordable Care Act.

While Congress has not passed comprehensive repeal legislation, it has enacted

laws that modify certain provisions of the Affordable Care Act, such as removing penalties, starting January 1, 2019, for not complying

with the Affordable Care Act’s individual mandate to carry health insurance, delaying the implementation of certain mandated fees

and increasing the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D.

2018, a Texas U.S.

District Court Judge ruled that the Affordable Care Act is unconstitutional in its entirety because the “individual

mandate” was repealed by Congress as part of the Tax Cuts and Jobs Act of 2017, or the Tax Act.

Although the Supreme Court ruled

the plaintiffs did not have standing in June of 2021, any other executive, legislative or judicial action to “repeal and replace”

all or part of the Affordable Care Act may have the effect of limiting the amounts that government agencies will pay for healthcare products

and services, which could result in reduced demand for our products or additional pricing pressure, or may lead to significant deregulation,

which could make the introduction of competing products and technologies much easier.

Regardless of the future of the Affordable Care

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for products or how much they are reimbursed.

Moreover, whether and to what extent the new Trump Administration will take actions, whether

through new legislation, changes in regulations, or Executive Orders, that may impact pricing and/or reimbursement for pharmaceutical

products remains to be seen.

Environmental Regulation

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not carry a specific insurance policy to mitigate this risk to us or to the environment.

At December 31, 2023, we employed four full-time

At December 31, 2024, we employed two full-time

We are not a party to any collective bargaining agreement with our employees, nor are any of our employees a member of any

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from many different sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions,

and governmental agencies and public and private research institutions.

governmental agencies and public and private research institutions.

Any product candidates that we successfully develop and commercialize

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business