RNXT US Equity☆

ITEM 1A. RISK FACTORS 30

ITEM 1B. UNRESOLVED STAFF COMMENTS 72

ITEM 1C. CYBERSECURITY 72

ITEM 2. PROPERTIES 73

ITEM 3. LEGAL PROCEEDINGS 73

ITEM 4. MINE SAFETY DISCLOSURES 73

PART II

ITEM 6. [RESERVED] 74

ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 87

ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 87

ITEM 9A. CONTROLS AND PROCEDURES 87

ITEM 9B. OTHER INFORMATION 88

ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 88

PART III

ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 88

ITEM 11. EXECUTIVE COMPENSATION 89

ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 89

PART IV

ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 90

SIGNATURES 94

Solely

for convenience, trademarks and trade names referred to in this Report may appear without the ® or TM symbols.

i

CAUTIONARY

NOTE REGARDING FORWARD-LOOKING STATEMENTS

This

Annual Report on Form 10-K, or Form 10-K (this “Report”), particularly in the sections captioned “Business,”

“Risk Factors,” and “Management’s Discussion and Analysis of Financial Condition and Results of

Operations” contains forward-looking statements within the meaning 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”), that are based on our management’s beliefs and assumptions and on information currently available to our

management. Forward-looking statements are inherently subject to significant risks and uncertainties, some of which cannot be

predicted or quantified and some of which are beyond our control. All statements other than present and historical facts and

conditions contained in this Report, including statements regarding our future revenues and other results of operations and

financial position, business strategy, plans and our objectives for future operations, are forward-looking statements. In some

cases, you can identify forward-looking statements by terminology such as “anticipate,” “believe,”

“can,” “continue,” “could,” “estimate,” “expect,” “intend,”

“may,” “might,” “objective,” “ongoing,” “plan,” “potential,”

“predict,” “project,” “should,” “will,” or “would,” or the negative of

these terms or other comparable terminology. Actual events or results may differ from those expressed in these forward-looking

statements, and these differences may be significant and adverse. Forward-looking statements include, but are not limited to,

statements about:

● our financial performance;

● our anticipated use of our existing cash, cash equivalents, and investments;

● the progress and focus of our current and future clinical trials;

ii

We

have based the forward-looking statements contained in this Report primarily on our current expectations and projections about future

events and trends that we believe may affect our business, financial condition, results of operations, prospects, business strategy and

financial needs. The outcome of the events described in these forward-looking statements is subject to risks, uncertainties, assumptions

and other factors described in the section titled “Risk Factors” and elsewhere in this Report. These risks are not exhaustive.

Other sections of this Report include additional factors that could adversely affect our business and financial performance. Moreover,

we operate in a very competitive and rapidly changing environment. New risks and uncertainties emerge from time to time and it is not

possible for us to predict all risks and uncertainties that could have an impact on the forward-looking statements contained in this

Report. We cannot assure you that the results, events and circumstances reflected in the forward-looking statements will be achieved

or occur, and actual results, events or circumstances could differ materially from those described in the forward-looking statements.

In light of the significant uncertainties in these forward-looking statements, you should not regard these statements as a representation

or warranty by us or any other person that we will achieve our objectives and plans in any specified time frame or at all.

In

addition, statements that “we believe” and similar statements reflect our beliefs and opinions on the relevant subject. These

statements are based upon information available to us as of the date of this Report, and while we believe such information forms a reasonable

basis for such statements, such information may be limited or incomplete, and our statements should not be read to indicate that we have

conducted an exhaustive inquiry into, or review of, all potentially available relevant information. These statements are inherently uncertain

and investors are cautioned not to unduly rely upon these statements.

The

forward-looking statements made in this Report relate only to events as of the date on which such statements are made. We undertake no

obligation to update any forward-looking statements after the date of this Report or to conform such statements to actual results or

revised expectations, except as required by law.

This

Report contains market data and industry forecasts that were obtained from industry publications. These data and forecasts involve a

number of assumptions and limitations, and you are cautioned not to give undue weight to such information. We have not independently

verified any third-party information. While we believe the market position, market opportunity and market size information included in

this Report is generally reliable, such information is inherently imprecise.

In

this Report, unless the context otherwise indicates, the terms “RenovoRx,” the “Company,” “we,” “our,”

and “us” refer to RenovoRx, Inc., a Delaware corporation. Unless otherwise stated, references to particular years, quarters,

months or periods refer to our fiscal years ended in December and the associated quarters, months and periods of those fiscal years.

iii

PART

I

ITEM

1. BUSINESS

Overview

We

are a life sciences company offering RenovoCath®, a novel, U.S. Food and Drug Administration (“FDA”)-cleared

local drug-delivery device, targeting high unmet medical needs, with a present focus on difficult to treat cancers. Our mission is to transform the lives of cancer patients by providing innovative

solutions to enable targeted therapeutic delivery.

We

are both a clinical stage and a commercial stage enterprise. Our clinical stage lead product candidate is a novel drug-device combination

product consisting of intra-arterial delivery of the chemotherapy gemcitabine via RenovoCath -- we refer to our lead product candidate

herein as “IAG.” IAG is currently the subject of a pivotal Phase III clinical study for the treatment of locally

advanced pancreatic cancer (“LAPC”). At the same time, we are commercializing RenovoCath for standalone use by interventional

radiologists, oncologists and other medical professionals who can use RenovoCath to treat patients within its FDA-cleared fields

of use.

RenovoCath

utilizes our patented Trans-Arterial Micro-Perfusion (TAMPTM) therapy platform, which is designed to ensure precise

therapeutic delivery across the arterial wall near the target tumor site to bathe the tumor, while potentially minimizing a

therapy’s toxicities versus systemic intravenous (or IV) therapy, including traditional chemotherapy. Our novel approach to

targeted treatment offers the potential for increased safety, tolerance, and improved efficacy. RenovoCath is indicated for

temporary vessel occlusion in applications including arteriography, preoperative occlusion, and chemotherapeutic drug

infusion.

For

the past several years, we have focused our efforts on progressing IAG through clinical trials. However, based on organic demand

from doctors in the field who have become familiar with our technology, in 2024, we made the decision to launch an effort to

commercialize RenovoCath as a standalone product within its FDA cleared uses. Commenced in the field in late 2024, this commercial

effort has already begun to achieve initial traction. To accommodate increased need for RenovoCath supply, we expanded our

relationship with Medical Murray, Inc., our U.S.-based third-party RenovoCath manufacturer. In December 2024, we announced that over

ten medical institutions had initiated the process for RenovoCath purchase orders, and in February 2025, we announced additional

purchase orders received from several esteemed, high volume National Cancer Institute-designated centers and that utilization of

RenovoCath devices by our initial customers led to repeat purchase orders.

We

have begun to generate revenues, and expect to grow revenues meaningfully, from the sale of our RenovoCath devices directly to customers

(i.e., hospitals and cancer treatment centers). Importantly, we believe our current commercial strategy can be accomplished without a

material increase in our capital expenditures, regardless of whether we self-commercialize or choose to partner with a larger organization

with an existing sales force. Following our late 2024 commercial launch, we generated a small amount (approximately $43,000) of initial

revenues from RenovoCath sales in our fourth quarter ended December 31, 2024. We expect revenues to increase to the low six figure range

for the first quarter ended March 31, 2025 followed by sequential quarter-over-quarter increases in revenues during the remainder of 2025.

Our goal will be to continue revenue growth in the years to come.

We have identified our initial target market for RenovoCath

to be approximately $400 million in peak annual U.S. sales, based on our internal assumptions. Our current assumptions regarding

our initial addressable market include: (i) pressure-mediated delivery catheters on market today, which are analogous

to RenovoCath, have an average selling price of $6,500-$8,500 per unit; (ii) approximately 7,000 initial target patients at peak market

penetration; and (iii) an average of approximately 8 annual procedures per patient.

Moreover,

expansion opportunities across other clinical indications could create a several billion-dollar total addressable market potential for

RenovoCath over time. We believe that we can achieve meaningful market penetration with a small commercial team targeting the top 200

high-volume treatment centers. Furthermore, and importantly, there is a current reimbursement code with the Centers for Medicare and

Medicaid Services covering specialty pressure-mediated delivery catheters, which creates incentives for hospitals to adopt more advanced

technology, like RenovoCath.

In

parallel to our RenovoCath commercialization efforts, we are completing enrolment in our ongoing pivotal Phase III randomized

multi-center clinical trial (called TIGeR-PaC) to investigate IAG for the treatment of LAPC. This trial is being conducted under a

U.S. Investigational New Drug (“IND”) application that is regulated by the FDA’s 21 CFR 312 pathway. IAG has received Orphan Drug Designation for pancreatic cancer and bile duct

cancer, which provides 7 years of market exclusivity upon approval by the FDA. We may also evaluate RenovoCath with gemcitabine and

other agents as a potential therapy in other indications.

Intra-arterial

Infusion of Gemcitabine with RenovoCath: IAG Clinical Process to Date

The

current standard of care for pancreatic cancer treatment is primarily systemic IV gemcitabine and nab-paclitaxel

or FOLFIRINOX chemotherapy; however, systemic chemotherapy is well known to cause debilitating side effects

for patients. Unlike other tumors with extensive blood supply, pancreatic tumors have a limited vascular network so systemic chemotherapy

may not adequately reach the tumor. Thus, the standard of care may be less effective in treating this type of cancer because the blood

vessels are critical for transporting systemic administration of chemotherapy to the tumor.

We

have completed clinical studies and observational registry studies evaluating treatment with IAG, with 20 and 25 patients (including

2 patients who participated in both studies), respectively, who were diagnosed with LAPC. In the 43 unique pooled patients evaluable

in these two studies, 9 patients pretreated with radiation followed by treatment with RenovoCath with gemcitabine experienced a median

Overall Survival (“OS”) of 27.1 months. Based on previous large randomized clinical trials, the expected survival of LAPC

patients is 12.0 to 18.8 months in patients receiving only IV systemic chemotherapy or IV chemotherapy plus radiation (which are both

considered standard of care). Unlike the randomized trials that established these standard of care results, our prior clinical studies

did not prospectively control the standard of care therapy received prior to administration of RenovoCath with gemcitabine. Based on

FDA safety review of our prior clinical studies, the FDA allowed us to proceed to evaluate RenovoCath with gemcitabine within our Phase

III TIGeR-PaC clinical trial.

Our ongoing TIGeR-PaC clinical trial is studying IAG to treat LAPC following stereotactic body radiation therapy (“SBRT”).

The study compares the treatment of LAPC using intra-arterial delivery of gemcitabine with RenovoCath versus systemic, standard of care,

IV administration of gemcitabine and nab-paclitaxel. Our TIGeR-PaC protocol involves systemic chemotherapy and SBRT during the induction

phase of the study (prior to randomization). Patients receiving SBRT during the induction phase are required to complete 5 treatments,

over 5 consecutive days, and do not receive oral chemotherapy vs. previously utilized intensity-modulated radiation therapy (“IMRT”)

where patients must complete 25 radiation treatments in combination with oral chemotherapy during the induction phase of the study, which

takes between 35 and 56 days to complete. In December 2021, we amended our protocol and statistical analysis plan for TIGeR-PaC (the

“Modified SAP”) to (i) enroll and analyze only patients receiving SBRT during the induction phase, (ii) include a second

interim analysis, (iii) change the total number of patients randomized in the study to 114 with a total of 86 events (deaths) from SBRT

patients required to complete the final analysis, and (iv) repower the study from 90% to 80%. The change to the 80% power calculation

aligns with common practice for clinical trials and we believe this design will shorten the timeframe needed to complete the study, as

well as significantly decrease our costs. We have had some interactions with FDA regarding

the Modified SAP, but we cannot

provide any assurance that the FDA will agree with these modifications.

The

first interim analysis in the Phase III TIGeR-PaC study at the 26th event (death) of the specified events was completed

in March 2023, with the Data Monitoring Committee recommending a continuation of the study. The interim analysis showed a 6-month median

overall survival benefit (Figure 1) for patients (nearly a 60% improvement) versus the study control arm and current standard of care:

IV administration of gemcitabine and nab-paclitaxel (p < 0.057). Patients also had greater than 65% reduction in adverse events (Figure

2) with IAG versus the standard of care.

Figure

1: TIGeR-PaC Phase III Update (1st Interim Analysis) showing 6-month median OS benefit with TAMP utilizing intra-arterial gemcitabine

delivered via the RenovoCath vs. IV/systemic gemcitabine and nab-paclitaxel (control).

Figure

2: TIGeR-PaC Phase III Update (1st Interim Analysis) showing with TAMP utilizing IAG observes fewer AEs and SAEs vs. gemcitabine

and nab-paclitaxel (Gem + Nab-Pac).

During

the fourth quarter 2024, we added several additional renowned clinical oncology sites to participate in the TIGeR-PaC study. The initiation

of new patient enrollment at the Sarah Cannon Research Institute Oncology Partners in Nashville, TN and at the Northwell Health Cancer

Institute Clinical Site in New Hyde Park, NY are key additions to the number of clinical sites to support our path to completing patient

enrollment for the trial. We are continuing to target additional clinical oncology sites, with the expectation that the study will achieve

full enrollment during 2025.

The

current protocol and statistical analysis plan for the TIGeR-PaC trial requires 114 randomized patients, with 86 events (deaths) necessary

to complete the final analysis. As of March 31, 2025, 90 patients have been randomized with 50 events having occurred. A second interim

analysis will be triggered by the 52nd event, which we currently anticipate to occur during the second quarter of 2025.

The

timing required to analyze the data after the 52nd event is expected to take several months and includes a full review with

recommendations by the TIGeR-PaC Data Monitoring Committee. The key recommendation from the Data Monitoring Committee on whether or not

to continue the study based on the data reviewed is expected to be announced in the second half of 2025.

Our

TAMP Therapy Platform

Our

patented TAMP therapy platform is focused on optimizing drug concentration in solid tumors by delivering oncology therapies with our

RenovoCath device. TAMP is designed to enable physicians to isolate segments of the vascular anatomy closest to tumors and ensure precise

therapeutic delivery, while potentially minimizing a therapy’s toxicities versus systemic intravenous therapy. Specifically, our

patented approach enables physicians to pre-treat patients with standard-of-care radiation therapy and utilize our RenovoCath device

to use pressure to force chemotherapy across the arterial wall near the tumor site to bathe the target tumor.

Figure

3: Mechanism: Trans-Arterial Micro-Perfusion (TAMP)

We

believe there are many advantages to our TAMP therapy platform, including:

We

received our first FDA 510(k) clearance for RenovoCath in 2014, a second clearance to use RenovoCath for infusion of chemotherapy agents

in 2017, a further clearance to use RenovoCath with a power-injector in 2019, and a fourth clearance in 2021 to expand vessel diameter

range to 3-11 mm, implement certain changes in the Instructions for Use (“IFU”), change the recommended saline to contrast

solution ratio, among other changes and improvements.

We

are also routinely in discussions regarding collaborations and potential out-licenses of our lead product candidate IAG, as we prepare

for an FDA New Drug Application (“NDA”) filing in the coming years (assuming we meet our study endpoints) as well as other

collaborations with our TAMP platform.

For

further information regarding our RenovoCath Instructions for Use please see: IFU-10004-Rev.-F-Universal-IFU.pdf.

Commercialization

of RenovoCath

In

recent years, we have focused our efforts primarily on progressing IAG through our ongoing Phase III TIGeR-PaC study for LAPC. As a result

of the introduction of our RenovoCath device as part of the TIGeR-PaC study and the resulting unsolicited (and subsequently

solicited) feedback we have received from oncologists, surgeons, and interventional radiologists indicating increased demand for targeted

delivery of diagnostic and/or therapeutic agents, during the first half of 2024, we began to actively explore a new opportunity to market

and sell RenovoCath as a standalone device. We launched this effort with relatively little capital outlay, and in December 2024, we announced

our receipt of our first commercial purchase orders for RenovoCath devices with over ten medical institutions initiating the process

for RenovoCath purchase orders, and we are in discussions with more than twenty other institutions. Moreover, we believe that the twenty

cancer centers that have used RenovoCath as part of the TIGeR-PaC trial could also be potential customers for RenovoCath

after completion of TIGeR-PaC enrollment later in 2025.

During

2024, we began a process of increasing production of RenovoCath devices through our U.S.-based contract manufacturing organization

(known as a CMO), Medical Murray Inc. of North Barrington, IL (“Medical Murray”). In September 2024, we announced the signing

of a new project work order with Medical Murray for an expanded relationship to meet anticipated demand for both our clinical and commercial

efforts. To establish performance-based incentives for Medical Murray, we issued a warrant allowing them to purchase up to 709,500 shares

of our common stock. This warrant vests and becomes exercisable over time in tranches and is contingent upon the achievement of specific

manufacturing milestones over time.

Beyond

LAPC, we believe there are many clinical applications for RenovoCath to improve targeted delivery of diagnostic and therapeutic agents.

This leads us to market development opportunities that would also likely result in the launch of relatively inexpensive post-market device

“registry” clinical studies and investigator-initiated clinical studies of the RenovoCath device to gather additional data

to support both our clinical and commercial efforts. We are also in active discussions with many interested customers to purchase supplies

of RenovoCath as well as potential distribution partners.

We

believe our initial target and potentially expanded addressable markets for RenovoCath are promising based on the following

assumptions: (i) pressure-mediated delivery catheters on the market today, which are analogous to RenovoCath, have an average

selling price of $6,500-$8,500 per unit; (ii) approximately 7,000 initial target patients at peak market penetration; and (iii) an

average of approximately 8 annual procedures per patient. In addition, we believe we can achieve deep market penetration with a

small commercial team targeting the top 200 high-volume treatment centers. Based on these assumptions, we believe that our initial

target market could eventually generate approximately $400 million in peak annual U.S. sales of RenovoCath as a standalone device.

Moreover, expansion opportunities across other indications could create a several billion-dollar total addressable market potential

for RenovoCath over time.

We

plan on penetrating this market through expanding our relationships with the 200 high-volume cancer treatment centers noted above as

well as networking with surgical oncologists, medical oncologists, and interventional radiologists generally. While we are currently

engaging in this activity on our own, we are in discussions with potential medical device commercial partners to find the most cost-effective

commercial path forward for success. Importantly, there is a current Centers for Medicare and Medicaid Services reimbursement

code covering specialty pressure-mediated delivery catheters like RenovoCath, which creates incentives for hospitals to adopt more expensive

technology like RenovoCath.

Figure

4: RenovoCath device.

RenovoCath

Advantages

We

believe that RenovoCath offers particular advantages versus the standard of care of IV systemic chemotherapy and other medical device

technologies to both oncology patients and physicians which offers us competitive advantages.

RenovoCath Patient Experience Other Patient Experience

RenovoCath Physician Experience Other Physician Experience

Research

and Development Pipeline

While

the oncology field has made progress with the treatment of cancers over the past few decades, the limited effectiveness of chemotherapy

accompanied by debilitating side effects remains a barrier to the success of standard of care treatment. The common objective in chemotherapy

treatment innovation is to enhance the dosing of the drug, while minimizing systemic toxicity. The standard of care for most cancers

is systemic (intravenous) chemotherapy, which delivers chemotherapy throughout the body.

Our

proprietary TAMP therapy platform is designed to ensure precise therapeutic delivery across the arterial wall near the

tumor site to bathe the target tumor, while potentially minimizing a therapy’s toxicities versus systemic intravenous therapy.

Our novel approach to targeted treatment offers the potential for increased safety, tolerance, and improved efficacy. Our Phase III

lead clinical development stage product candidate is IAG, a novel oncology drug-device combination product. It is being

investigated under a U.S. investigational new drug application that is regulated by the FDA’s 21 CFR 312 pathway.

IAG

utilizes RenovoCath, which is indicated for temporary vessel occlusion in applications including arteriography, preoperative

occlusion, and chemotherapeutic drug infusion. IAG is currently being evaluated for the treatment of LAPC by the Center for Drug

Evaluation and Research (the drug division of FDA) (“CDER”). The TAMP therapy platform is currently being evaluated in

the Phase III TIGeR-PaC clinical trial in LAPC. Depending on our clinical progress with IAG and our RenovoCath commercial efforts,

we may look to expand our development pipeline into additional cancer tumors and explore new commercial and clinical business

development opportunities with our therapeutic technology. IAG received FDA Orphan Drug Designation for pancreatic cancer and bile

duct cancer which provides 7 years of market exclusivity upon New Drug Application approval.

Locally

Advanced Pancreatic Cancer (LAPC)

Our ongoing

Phase III TIGeR-PaC clinical trial is studying the intra-arterial administration of gemcitabine to treat LAPC following stereotactic

body radiation therapy (“SBRT”). The study compares the treatment of LAPC using intra-arterial delivery of gemcitabine with

RenovoCath versus systemic, standard of care, IV administration of gemcitabine and nab-paclitaxel. Our protocol for TIGeR-PaC involves

systemic chemotherapy and SBRT during the induction phase of the study (prior to randomization). Patients receiving SBRT during the induction

phase are required to complete 5 treatments, over 5 consecutive days, and do not receive oral chemotherapy vs. previously utilized intensity-modulated

radiation therapy (“IMRT”) where patients must complete 25 radiation treatments in combination with oral chemotherapy during

the induction phase of the study, which takes between 35 and 56 days to complete. In December 2021, we amended our protocol and statistical

analysis plan for TIGeR-PaC (the “Modified SAP”) to (i) enroll and analyze only patients receiving SBRT during the induction

phase, (ii) include a second interim analysis, (iii) change the total number of patients randomized in the study to 114 with a total

of, 86 events (deaths) from SBRT patients required to complete the final analysis, and (iv) repower the study from 90% to 80%. The change

to the 80% power calculation aligns with common practice for clinical trials and, we believe this design will shorten the timeframe needed

to complete the study, as well as significantly decrease our costs. We have not discussed the protocol amendment or the Modified SAP

with the FDA, and we cannot provide any assurance that the FDA will agree with these modifications, but these modifications have been

submitted to the FDA.

The

first interim analysis in the Phase III TIGeR-PaC study at the 26th event (death) of the specified events, was completed

in March 2023, with the Data Monitoring Committee recommending a continuation of the study. The interim analysis showed a 6-month median

overall survival benefit for patients (nearly a 60% improvement) versus the study control arm and current standard of care: IV administration

of gemcitabine and nab-paclitaxel (p < 0.057). Patients also had greater than 65% reduction in adverse events with RenovoCath with

gemcitabine vs. standard of care.

Other

Potential Clinical Indications

Beyond

LAPC, we believe there are many clinical applications (Figure 5) for RenovoCath and TAMP to improve targeted delivery of diagnostic and

therapeutic agents. This could lead to market development opportunities that would also likely result the inexpensive launch of post-market

device “registry” clinical studies and investigator-initiated clinical studies of the RenovoCath device to gather additional

data to support both our clinical and commercial efforts. We are also in active discussions with many interested customers to purchase

supplies of RenovoCath as well as potential distribution partners.

Figure

5: TAMP broad market opportunity in potential target cancer tumor including locally advanced pancreatic cancer, extra-hepatic cholangiocarcinoma

(eCCA), non-small cell lung cancer (NSCLC), glioblastoma and uterine tumors.

Current

Treatments and Limitations of Approaches

Currently,

solid tumors are typically treated using one or a combination of treatment modalities: surgery, radiation, and pharmacological therapies

(chemotherapy). For solid tumors, if the tumor is detected at an early stage and is localized to the affected organ, surgical removal

of the entire tumor may be an effective and potentially curative treatment. In most cases, surgery is undertaken and/or completed prior

to commencing additional treatment approaches. However, multiple solid tumor types, including pancreatic cancer, are diagnosed at advanced

stages, which precludes surgery as a treatment approach. In many of these circumstances, the tumor has grown into adjacent anatomical

structures making surgery difficult or impossible.

IV, also known as systemic, chemotherapy

is considered standard of care for most solid tumors, but limitations include less than acceptable efficacy, systemic toxicities, and

other side effects. Leading chemotherapy regimens include gemcitabine and nab-paclitaxel) which has a seven-week survival benefit over

IV gemcitabine alone and FOLFIRINOX.

For

the treatment of some localized solid tumors, targeted trans-arterial chemoembolization (TACE) is an established first line therapy.

Many companies have developed therapeutic products for use in this approach to treat tumors of the liver, uterus, and prostate. Many

solid tumors have a dedicated blood supply from small blood vessels, called tumor feeder blood vessels, that branch off of larger native

arteries and terminate in the tumors to provide nutrition to the tumors. A key aspect of TACE is to identify and isolate these tumor

feeder blood vessels during x-ray angiography and then deliver the desired therapy including chemotherapy and embolic agents. In patients

with LAPC, no tumor feeder blood vessels are visible during angiography due to the hypovascular (lack of visible blood vessels) nature

of these tumors. This limitation has rendered TACE ineffective in the treatment of patients with LAPC, extra-hepatic cholangiocarcinoma

(eCCA), and a subset of other solid tumors. The limitations of TACE translate to low survival rates in these tumor subtypes. The use

of TACE with or without immuno-oncology treatment approaches, which harness the body’s immune system to treat cancer, has not significantly

improved survival rates in these subtypes. For example, due to the inability of immune cells to reach and penetrate the tumor tissue,

early studies of targeted immunotherapies in pancreatic cancer have demonstrated limited success.

Our

Platform: TAMP

Hypovascular

tumors might benefit the most from TAMP

Certain

tumor types are sufficiently vascularized (i.e., tumors with dedicated blood vessels to enable use of standard of care systemic chemotherapy

and local therapy techniques. In Figure 6, below, for example, the panel on the left depicts visualization of a hepatocellular carcinoma

(“HCC”), or primary liver cancer tumor, under x-ray angiography as dye injected through the arteries reaches the tumor itself.

Further, visible tumor feeder blood vessels can be reached by simple end-hole catheters or single occlusion or balloon catheters to deliver

targeted therapy to these liver tumors. In contrast, the panel on the right illustrates the typical lack of tumor feeder blood vessels

to pancreatic and other hypovascular tumors. Given the lack of tumor feeder blood vessels, the dye does not reach the tumor, rendering

the tumor “invisible” under x-ray angiography challenging to current treatment options.

Figure

6: Showing liver tumors that are highly vascularized, and pancreatic tumors that are hypovascular.

TAMP

has been under development for over 15 years

In

2009, our founder Dr. Ramtin Agah, an experienced interventional cardiologist with a degree in biomedical engineering, developed the

concept for TAMP as a way to deliver chemotherapy locally to treat poorly vascularized tumors. He joined forces with Kamran

Najmabadi, who brought significant medical device engineering experience, to found our company in 2009. Subsequently, we engaged a

contract manufacturer to prototype and manufacture our RenovoCath delivery devices. We received our first FDA 510(k) clearance for

RenovoCath in 2014, a second clearance to use the RenovoCath for infusion of chemotherapy agents in 2017, a further clearance to use

RenovoCath with a power-injector in 2019, and a fourth clearance in 2021 to expand vessel diameter range to 3-11mm, and implement

certain changes in the Instructions for Use, among other changes and improvements. RenovoCath is intended for the isolation of blood

flow and delivery of fluids, including diagnostic and/or therapeutic agents, to selected sites in the peripheral vascular system.

RenovoCath is also indicated for temporary vessel occlusion in applications including arteriography, preoperative occlusion, and

chemotherapeutic drug infusion. RenovoCath is intended for general intravascular use in the peripheral vasculature in arteries 3 mm

and larger as well as for use in arteries from 3 mm in diameter for vessel entry and to occlude vessels ranging between 3 mm to 11

mm in diameter. We are evaluating our lead product candidate, IAG, under an IND filed in 2018, and the FDA has determined that IAG

will be regulated as, and if approved we expect will be reimbursed as, a new oncology drug product.

How

it works: we developed TAMP as an attempt to solve the problems of treating hypovascular tumors

To

overcome the limitations resulting from a lack of tumor feeder blood vessels, we explored a different approach to locally deliver anti-cancer

drugs. By isolating a section of the blood vessel and then increasing the intravascular pressure in the isolated segment, we can introduce

chemotherapy directly across the arterial wall into the surrounding tissue via pressurized diffusion, which we call Trans-Arterial Micro-Perfusion

(for the acronym TAMP). To isolate the vessel and create this pressure gradient, we developed RenovoCath, a patented adjustable double

balloon catheter to occlude the proximal and distal (upstream and downstream) part of the vessel. Using the TAMP technique in explanted

(dissected out of the animal and used separately in a saline water bath) pig aorta and iliac arteries (peripheral arteries that carry

blood to the legs, reproductive organs and pelvis), we were able to validate our hypothesis by demonstrating >99% gemcitabine pressurized

diffusion across the arterial wall in the absence of feeder vessels. This mechanism of action was further supported by exploratory acute

animal studies measuring the pressure gradient within the artery during double balloon occlusion. Figure 7 demonstrates the change in

intra-arterial pressure over time from catheter introduction to balloon inflation, start of infusion, and pressure plateau when chemotherapy

is forced across the blood vessel wall and out of the vessel. These changes in pressure are a result of pressure declining as the first

balloon blocks blood inflow and then rising as the drug is administered and fills up the space between the balloons.

Figure 7: Occluding the vessel with RenovoCath,

after adjusting the balloon-to-balloon distance to exclude all blood vessel branches, established an intravascular interstitial pressure

in the isolated blood vessel segment of approximately 20 mmHg. With subsequent infusion of fluids between the balloons at 6 mLs/minute,

the intravascular pressure increases to above 45 mmHg, trans-arterially forcing drug across the arterial wall via diffusion (this patented

process of perfusing the vessel wall is Trans-Arterial Micro-Perfusion, or TAMP).

Our

TAMP platform therapy utilizes pressure mediated delivery of gemcitabine across the arterial wall to bathe the pancreatic tumor tissue

in 120 mL of saline with 1,000 mg/m2 of drug over a 20-minute delivery period (delivering 1,500 - 2,000 mg of drug depending

upon patient body surface area. This blanketing approach of large fluid volume delivery over time may enable the drug to approach these

difficult-to-reach tumors.

Developing

a therapeutic platform using an adjustable two-balloon catheter

By

isolating the vessel adjacent to the tumor and creating a pressure gradient across the arterial wall between the isolated vessel segment

and the surrounding tissue or tumor, physicians are able to force chemotherapy across the vessel wall directly into surrounding tissue

or tumor. To accomplish this, we invented and developed a minimally invasive technique to isolate the blood vessel next to the tumor,

exclude any branches that can cause washout of chemotherapy away from the target, and then infuse the chemotherapy into the isolated

segment to achieve pressure mediated diffusion through the vessel wall and into the tumor tissue. This was accomplished with our patented

RenovoCath device. RenovoCath is a double balloon catheter designed with the capability to isolate the proximal and distal sections of

the vessel through the adjustment of the distance between the balloons, thereby excluding any branching blood vessel offshoots. Using

standard interventional techniques, an interventional radiologist inserts the RenovoCath device into the body through the femoral artery

under x-ray fluoroscopic guidance and positions it in the artery closest to the tumor. Once the balloons are inflated and the position

is confirmed, chemotherapy is delivered through the handle and exits the device between the balloons. It is forced through the vessel

wall into the tissue over a 20-minute period. The RenovoCath device is depicted below in Figure 8.

Figure

8: RenovoCath device illustrating two balloon configuration to isolate the target vessel segment and chemotherapy delivery port and

exit hole.

After

the procedure is complete, the RenovoCath is removed from the patient and discarded. Patients are generally discharged the same day.

On average, the entire procedure takes approximately 90 minutes including the 20-minute infusion. According to the ongoing Phase III

TIGeR-PaC study protocol, IA treatment is administered through RenovoCath every other week for a maximum of 8 treatments for approximately

16 weeks. Interventional radiologists using the device are typically proctored for their first 2-3 cases only and then able to do procedures

on their own without support from our company. In addition, platform training for our primary indication should transfer to other indications.

First

Product Candidate for LAPC: IAG

Disease

Overview

According

to the American Cancer Society’s Cancer Facts & Figures 2024 and PanCAN, respectively, pancreatic cancer has a 5-year all stages

combined relative survival rate of 13% (Stages I-IV) and is on track to be the second leading cause of cancer-related deaths before 2030.

LAPC is diagnosed when the disease has not spread far beyond the pancreas, however, has advanced to the point where it cannot be surgically

removed. LAPC is typically associated with patients in Stage 3 of the disease as determined by the TNM (tumor, nodes and metastasis)

grading system.

Current

Treatment Landscape and Limitations

Pancreatic

cancer has limited treatment options including one or a combination of surgery, radiation, chemotherapy, and/or some targeted therapies.

Only a small subset of pancreatic cancer patients is eligible for surgery (“Resectable” at the time of presentation (Stage

I-II: 15%); the rest are distributed between having tumors with unresectable LAPC (Stage III: 30%) and metastatic pancreatic cancer (Stage

IV: 50%).

Chemotherapy

is at the forefront of systemic therapy for cancer. It can be used in the neoadjuvant (before surgery) setting to attempt to decrease

tumor size in resectable or borderline resectable patients, in the adjuvant (after surgery) setting, or first line in the metastatic/advanced

setting. The backbone drug of our first product candidate, gemcitabine, is a nucleoside metabolic inhibitor that exhibits antitumor activity

by blocking the synthesis of new DNA, which results in cell death. Gemcitabine administered systemically as an IV infusion has an established

role in the treatment of all stages of cancer including resectable, unresectable LAPC, and metastatic pancreatic cancer. Since its introduction

in the U.S. as Gemzar® (gemcitabine for injection) in 1996 with an FDA approved indication as such, it remains in the guidelines as

standard of care. It has been demonstrated to provide clinical benefit for subjects (decreased pain and improved performance status)

as well as to improve the time to tumor progression and survival for subjects with metastatic pancreatic cancer and LAPC. However, major

improvement in the survival curve of all pancreatic cancer subjects has been a clinical challenge, with an average median survival time

for LAPC stalled at 12-18.8 months from time of diagnosis even with newer drug combinations.

A

key limitation of conventional chemotherapy in these tumors can be attributed to their hypovascular nature and desmoplasia (fibrosis

or the growth of scar tissue) that impedes drugs reaching the tumor cells. Pancreatic tumor cells have a thick and poorly perfused stroma,

or connective tissue, and high interstitial pressure. This can potentially constrict blood vessels leading to a hypovascular environment

that impedes chemotherapy from reaching tumor cells in high enough volume, rendering them relatively resistant to chemotherapy.

In

patients with metastatic disease, two chemotherapy combination regimens have shown superiority to gemcitabine, albeit with increased

toxicity. First, the combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin (FOLFIRINOX) in a relatively young cohort of

metastatic pancreatic cancer patients appears superior to gemcitabine by improving survival from 6.8 to 11.1 months. Second, in the Metastatic

Pancreatic Adenocarcinoma Clinical Trial (MPACT) trial, the combination of gemcitabine plus nab-paclitaxel (Abraxane) demonstrated an

OS benefit of 9 weeks versus gemcitabine alone at the cost of increased toxicity.

A

major focus of clinicians is determining the optimal method to treat patients with LAPC, patients with localized disease who are not

surgical candidates, roughly 30% of all pancreatic cancer patients. IV, or systemic, administration of chemotherapy has yielded unsatisfactory

results in these patients. Various localized treatments have included high dose local radiation, direct attempts at local injection of

drugs, and use of adenoviral vectors to deliver toxic agents. These treatment options have demonstrated limited success in the treatment

of LAPC. The lack of successful treatment options represents a recognized unmet medical need for this patient population.

Standard

of care chemotherapy for the treatment of pancreatic cancer has historically shifted a couple of times with the addition of erlotinib

to gemcitabine 15 years ago resulting in a 14-day survival benefit. In 2013, the addition of Abraxane (nab-paclitaxel) to gemcitabine

was approved, with immediate deep market penetration based on an 8-week survival benefit despite higher systemic drug toxicities.

Our

Solution

We believe that our lead investigational drug-device combination product

candidate, which we refer to as IAG, using the TAMP therapy platform and the RenovoCath device has the potential to address the recognized

unmet medical need. Utilizing our patented TAMP therapy platform, we believe IAG can enhance local drug concentration, thereby increasing

efficacy and decreasing systemic exposure and toxicity to improve patient outcomes. IAG is regulated by the FDA, and if approved we expect

will be reimbursed as a new oncology drug product.

Based

on primary market research and analysis of the U.S. market sponsored by us and conducted by third parties, we believe that over 5,5000

patients per year would be excellent candidates and undergo TAMP treatment once it is approved in the U.S. The

independent oncologists interviewed stated their dissatisfaction with the current standard of care and the strong desire for a therapy

like ours to extend potential survival while maintaining quality of life. Further, the analysis suggests, based on analogous oncology

drugs with only a modest efficacy benefit, a novel drug can expect 50-80%+ penetration in a first line setting. The results of

the Key Opinion Leader, or KOL interviews revealed that a majority of oncologists would refer 90%+ of their LAPC patients who are eligible

for the procedure for TAMP if the current Phase III trial demonstrates at least a 4-month survival benefit over systemic chemotherapy.

The

first interim analysis in the Phase III TIGeR-PaC study at the 26th event (death) of the specified events, was completed

in March 2023, with the Data Monitoring Committee recommending a continuation of the study. The interim analysis showed a 6-month median

overall survival benefit for patients (nearly a 60% improvement) versus the study control arm and current standard of care: IV administration

of gemcitabine and nab-paclitaxel (p < 0.057). Patients also had greater than 65% reduction in adverse events with RenovoCath with

gemcitabine vs. standard of care.

As noted above, the timing required to analyze the data after the 52nd

event is expected to take several months and includes a full review with recommendations by the TIGeR-PaC Data Monitoring Committee. We

currently anticipate the 52nd event to occur during the second quarter of 2025. The key recommendation from the Data Monitoring

Committee on whether or not to continue the study based on the data reviewed is expected to be announced in the second half of 2025.

Positive

Early-Stage Clinical Data Published in International Peer-Reviewed Journal, The Oncologist®

In

July 2024, we announced that positive early-stage clinical data relating to the TAMP therapy platform in the international peer-reviewed

journal, The Oncologist. The Oncologist is an international peer-reviewed journal for practicing oncologists and hematologists.

It is dedicated to translating the latest research developments into the best multidimensional care for cancer patients and is committed

to helping physicians excel in this ever-expanding environment through the publication of timely reviews, original studies, and commentaries

on important developments.

The

scholarly article, titled “Treatment of Locally Advanced Pancreatic Cancer (LAPC) Using Localized Trans-Arterial Micro

Perfusion (TAMP) of Gemcitabine: Combined Analysis of RR1 and RR2,” is a publication of early-stage clinical data, primarily

procedure safety, overall survival (OS), and evaluation of factors associated with OS, in LAPC patients undergoing TAMP from the

foundational studies we have previously conducted. The studies included the intra-arterial administration of

gemcitabine utilizing the TAMP read in an early Phase I/II dose escalation safety study (RR1) and acquired data from a

post-marketing post-treatment observational registry study (RR2). The lead author, Hassan Hatoum, MD, is an oncologist and

hematologist at the University of Oklahoma Health Sciences Center.

TAMP

is designed to bypass traditional systemic delivery methods to provide precise drug-delivery through the artery near the tumor site to

bathe the target tumor in chemotherapy. This approach creates the potential to minimize systemic toxicities. The RR1 and RR2 foundational

studies investigated an unmet medical need for a more effective locoregional LAPC therapy to improve survival and increase resectability

of the cancer.

For

purposes of this publication, data from RR1 and RR2 were pooled. The aims of the analysis were to assess TAMP procedure safety, OS,

and evaluate factors associated with OS. The median OS for the 35 evaluable patients with LAPC disease was 12.6 months,

TAMP-delivered chemotherapy in LAPC patients with prior radiation was associated with significantly longer OS (27.1 months) compared

to prior systemic chemotherapy (14.6 months) or no prior treatment (7.0 months). The most common side effects were

gastrointestinal-related (abdominal pain, emesis, and vomiting); the most common Grade 3 toxicity was sepsis. Study results

concluded that treatment with TAMP-mediated drug-delivery in patients with LAPC is potentially safe, feasible, and provides several

potential clinical benefits.

TIGeR-PaC

Phase III Trial (RR3)

With

inclusion of data from prior of completed clinical an registry studies within the IND submission package, FDA permitted us to proceed

with the Phase III TIGeR-PaC trial in February 2018 comparing TAMP with IA gemcitabine (IAG) to standard of care. In the

FDA pre-IND meeting, the FDA confirmed the study design and endpoints and indicated that this Phase III study should result in New Drug

Application approval if successful. In April 2018, we obtained Orphan Drug Designation for the use of our first clinical development

stage product candidate, IAG in patients with pancreatic cancer. Depending on the progress of the trial and the potential observed benefit

of our first product candidate, we will evaluate submitting a request to the FDA for Breakthrough Therapy Designation.

The

primary endpoint of the study is overall survival, from time of randomization until death. Secondary endpoints include but are not limited

to progression free survival and quality of life questionnaire results. The study is a multi-center, open-label, randomized active-controlled

study of subjects with locally advanced pancreatic adenocarcinoma which is unresectable according to NCCN guidelines. The study is currently

enrolling patients in the U.S.

The

study design is as follows: all patients receive an approximate four-month induction phase of IV chemotherapy and radiation (SBRT per

December 2021 amendment) prior to randomizing to 4 cycles (8 treatments) of TAMP or 4 cycles of continuation of IV chemotherapy., and

follow-up until death. In March of 2024 we amended the protocol to extend the duration of follow-up from 3.5 years post-randomization

to 5 years post-randomization.

A

study flowchart is shown below (see Figure 9). Subjects with stable or responding disease after induction therapy and who are not surgical

candidates will then be randomized 1:1.

Figure

9: TIGeR-PaC Study Flowchart. All subjects undergo a 4-month induction phase that includes IV gemcitabine + Abraxane (nab-paclitaxel)

and radiation therapy. If the subjects are stable with LAPC post-induction, they are randomized 1:1 into control group (IV gemcitabine

+ Abraxane) versus treatment group (IA gemcitabine via TAMP therapy). Subjects are then administered continuation therapy until disease

progression and followed through survival.

Clinical

Pharmacokinetic (PK) Data in Patients with LAPC Treated with Gemcitabine via TAMP

We

expect IA gemcitabine delivered via the TAMP technique to have a pharmacokinetic profile that is distinct from intravenous gemcitabine

dosing. Furthermore, with local delivery of gemcitabine into the tissue via TAMP and drainage into the liver prior to systemic circulation,

we anticipate lower systemic levels of gemcitabine.

A

pharmacokinetic data abstract was presented at ASCO GI 2025 in January 2025 by TIGeR-PaC Phase III clinical trial Investigator, Paula

Novelli, MD, from the University of Pittsburgh Medical Center. The sub-study of the pivotal Phase III TIGeR-PaC clinical trial offers

insight that supports the potential effectiveness of our TAMP therapy platform in locally advanced pancreatic cancer. Of

the 16 patients analyzed in this sub-study, 11 patients received intra-arterial gemcitabine via TAMP, and 5 patients received treatment

via intravenous gemcitabine. Peak plasma gemcitabine concentrations were monitored in patients. Concentrations were lower with TAMP treatment

despite a 50% higher drug concentration during infusion (1000 mg/m2 over 20 minutes vs 30 minutes for intravenous gemcitabine. Results

of the sub-study showed our intra-arterial delivery of gemcitabine via TAMP approach to drug delivery via TAMP decreased

systemic levels of gemcitabine versus standard of care. In addition to providing increased local drug potency, the intra-arterial delivery

of gemcitabine via TAMP approach may also be beneficial to decreasing gemcitabine-related systemic side effects. TAMP is designed to

ensure precise therapeutic delivery across the arterial wall near the tumor site to bathe the target tumor, while potentially minimizing

a therapy’s toxicities versus systemic intravenous therapy.

Broad

Potential Market Opportunity for TAMP in Target Cancers

Beyond

IAG, and depending our IAG progress and the progress of our RenovoCath commercial efforts, we may also evaluate RenovoCath with gemcitabine

and other agents via TAMP as potential therapies in other indications.

Figure

10: TAMP broad market opportunity in potential target cancers tumors including locally advanced pancreatic cancer, extra-hepatic cholangiocarcinoma

(eCCA), non-small cell lung cancer (NSCLC), glioblastoma and uterine tumors.

Intellectual

Property (IP)

Our

success depends in part on our ability to obtain patents and trademarks, maintain trade secret and know-how protection, enforce our proprietary

rights against infringers, and operate without infringing on the proprietary rights of third parties. Because of the length of time and

expense associated with developing new products and bringing them through the regulatory approval process, the health care industry places

considerable emphasis on obtaining patent protection and maintaining trade secret protection for new technologies, products, processes,

know-how, and methods.

Our

intellectual property protection stems from several issued device and method patents on our RenovoCath device that optimizes delivery

of the anti-cancer drug and the TAMP therapy platform. Our issued patents also provide exclusivity as it relates to utilizing RenovoCath

with anti-cancer drugs.

We

have developed and patented targeted combination therapies to improve therapeutic outcomes for cancer patients undergoing treatment.

Our proprietary TAMP therapy platform enables physicians to isolate segments of the vascular anatomy closest to tumors and force

chemotherapy across the blood vessel wall to bathe these difficult-to-reach solid tumors while minimizing the therapy’s

toxicities versus systemic, e.g., intravenous therapy. This therapy may include pre-treatment of the local blood vessels and tissue

with radiation therapy to decrease chemotherapy washout. TAMP may be performed using a dual-occlusion catheter system (e.g., the

RenovoCath device) to control the application of a therapeutic agent to vascular regions to optimize drug concentrations. We hold a

strong IP portfolio with 19 issued or allowed patents and 11 pending patents. In December 2025, we published a new international