RNXT US Equity☆

UNITED

STATES

SECURITIES

AND EXCHANGE COMMISSION

Washington,

D.C. 20549

FORM

10-K

For the fiscal year ended December 31, 2021

For the transition period from________ to________

Commission

File Number: 001-40738

RENOVORX,

INC.

(Exact

name of registrant as specified in its charter)

4546

El Camino Real, Suite B1, Los Altos, CA94022

(Address

of principal executive offices, including zip code)

(650)284-4433

(Registrant’s

telephone number, including area code)

Securities

registered pursuant to Section 12(b) of the Act:

Title of each class Trading symbol(s) Name of each exchange on which registered

Common Stock, $0.0001 par value RNXT Nasdaq Capital Market

Securities

registered pursuant to Section 12(g) of the Act: None

Indicate

by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ☒

Indicate

by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ☒

Indicate

by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange

Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2)

has been subject to such filing requirements for the past 90 days. Yes ☒ No ☐

Indicate

by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule

405 of Regulation S-T (§ 232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant

was required to submit such files). Yes ☒ No ☐

Indicate

by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting

company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,”

“smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer ☐ Accelerated filer ☐

Non-accelerated filer ☒ Smaller reporting company ☒

Emerging growth company ☒

If

an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying

with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate

by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness

of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered

public accounting firm that prepared or issued its audit report. ☐

Indicate

by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act). Yes ☐ No ☒

The

aggregate market value of the voting and non-voting common equity held by non-affiliates of the registrant, based on the closing price

of the shares of common stock on The Nasdaq Stock Market on December 31, 2021 was approximately: $37.3 million. The

registrant has elected to use December 31, 2021, which was the last business day of the registrant’s most recently completed fiscal

year, as the calculation date because on June 30, 2021 (the last business day of the registrant’s mostly recently completed second

fiscal quarter), the registrant was a privately-held company.

As

of March 25, 2022, the registrant had 9,029,305 shares of common stock, $0.0001 par value per share, outstanding.

DOCUMENTS

INCORPORATED BY REFERENCE

None.

RENOVORX,

INC. FORM 10-K

TABLE OF CONTENTS

PART I

ITEM 1. BUSINESS 3

ITEM 1A. RISK FACTORS 36

ITEM 1B. UNRESOLVED STAFF COMMENTS 63

ITEM 2. PROPERTIES 63

ITEM 3. LEGAL PROCEEDINGS 63

ITEM 4. MINE SAFETY DISCLOSURES 63

PART II

ITEM 6. [RESERVED] 66

ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK 74

ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA 74

ITEM 9A. CONTROLS AND PROCEDURES 75

ITEM 9B. OTHER INFORMATION 76

ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS 76

PART III

ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE 77

ITEM 11. EXECUTIVE COMPENSATION 79

ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES 87

PART IV

ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES 89

SIGNATURES 92

POWER OF ATTORNEY 93

Solely

for convenience, trademarks and trade names referred to in this Form 10-K may appear without the ® or TM symbols.

Table of Contents

Special

Note Regarding Forward-Looking Statements

This

Annual Report on Form 10-K, or Form 10-K, and the information incorporated herein by reference, particularly in the sections titled

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

and “Business,” contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended,

or the Securities Act, and Section 21E of the Securities Exchange Act of 1934, as amended, or 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 risks and uncertainties, some of which cannot be predicted or quantified. All statements other than present and historical

facts and conditions contained in this Form 10-K, including statements regarding our future 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 material 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 success of competing therapies that are or may become available;

We

have based the forward-looking statements contained in this Form 10-K 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 Form 10-K. These risks are

not exhaustive. Other sections of this Form 10-K 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 Form 10-K. 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 Form 10-K, 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.

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The

forward-looking statements made in this Form 10-K 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 Form 10-K or to conform such statements to actual results

or revised expectations, except as required by law. Unless the context otherwise indicates, “RenovoRx,” the “Company,”

“we,” “our,” and “us” refer to RenovoRx, Inc., a Delaware corporation. All information presented

herein is based on our fiscal calendar. Unless otherwise stated, references to particular years, quarters, months or periods refer to

the Company’s fiscal years ended in December and the associated quarters, months and periods of those fiscal years.

This

Form 10-K 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 Form 10-K is generally reliable, such information is inherently imprecise.

Risk

Factors Summary

Investing

in shares of our common stock involves a high degree of risk because our business is subject to numerous risks and uncertainties, including

those outside of our control, that could cause our actual results to be harmed. The principal factors and uncertainties that make investing

in shares of our common stock risky and impact our ability to execute on our business strategy include risks regarding the following,

among others:

In

addition, we face other risks and uncertainties that may materially affect our business prospects, financial condition, and results of

operations. You should consider the risks discussed in “Risk Factors” and in our other public filings before investing in

our securities.

Table of Contents

PART

I

ITEM

1. BUSINESS

Overview

We

are a clinical-stage biopharmaceutical company focused on developing therapies for the local treatment of solid tumors. We are currently

conducting a Phase 3 registrational trial for our lead product candidate RenovoGemTM. Our therapy platform, RenovoRx Trans-Arterial

Micro-Perfusion, or RenovoTAMPTM, utilizes approved chemotherapeutics with validated mechanisms of action and well-established safety

and side effect profiles, with the goal of increasing their efficacy, improving their safety, and widening their therapeutic window by

combining such chemotherapeutics with our proprietary drug delivery system. RenovoTAMP combines our patented US Food and Drug Administration,

or FDA cleared delivery system, RenovoCath®, with small molecule chemotherapeutic agents that can be forced across

the vessel wall using pressure, targeting these anti-cancer drugs locally to the solid tumors. While we anticipate investigating other

chemotherapeutic agents for intra-arterial delivery via RenovoTAMP, our clinical work to date has focused on gemcitabine, which is a

generic small molecule drug. Our first product candidate, RenovoGem, is a drug /device combination consisting of intra-arterial gemcitabine

and RenovoCath. FDA has determined that RenovoGem will be regulated as, and if approved we expect will be reimbursed as, a new oncology

drug product. We have secured FDA Orphan Drug Designation for RenovoGem in two rare diseases: pancreatic cancer and cholangiocarcinoma

(bile duct cancer, or CCA). We have completed our RR1 Phase 1/2 and RR2 observational registry studies, with 20 and 25 patients respectively,

in locally advanced pancreatic cancer, or LAPC. These studies demonstrated a median overall survival of 27.9 months in patients pre-treated

with radiation followed by treatment with RenovoGem. Based on previous large randomized clinical trials, the expected survival of LAPC

patients is 12 - 15 months in patients receiving only intravenous (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 RR1 and RR2

clinical trials did not prospectively control the standard of care therapy received prior to administration of RenovoGem. Based on an

FDA safety review of our Phase 1/2 study, FDA allowed us to proceed to evaluate RenovoGem within our Phase 3 registrational clinical

trial. As of March 15, 2022, our Phase 3 trial had achieved approximately 50% of the target enrollment under the current

statistical analysis plan (SAP). The SAP includes a planned interim analysis when a total of 65 deaths have occurred in the study. We

expect to conduct the interim analysis between the fourth quarter of 2022 and the first quarter of 2023; however, given that it is predicated

on the number of deaths in the study, it is difficult to predict the exact timing. We intend to evaluate RenovoGem in a second

indication in a Phase 2 trial in extrahepatic (or outside the liver) cholangiocarcinoma (or eCCA), cancer that occurs in the bile ducts

that lead out of the liver and join with the gallbladder. We have now completed our evaluation of the different approaches to treat this

patient population and are in the process of refining our clinical protocol. We plan to meet with FDA during the second or third quarter

of 2022 to discuss our trial design. If FDA does not object to our study protocol, we anticipate launching the eCCA trial in the second

half of 2022. In addition, we may evaluate RenovoGem in other indications, potentially including locally advanced lung cancer, locally

advanced uterine tumors, and glioblastoma (an aggressive type of cancer that can occur in the brain or spinal cord). To date, we are

focused on developing drug/device candidates with gemcitabine, but in the future, we may develop other product candidates with other

chemotherapeutic agents for intra-arterial delivery via our RenovoTAMP therapy platform.

Our

RenovoTAMP therapy platform is focused on optimizing drug concentration in solid tumors using approved small molecule chemotherapeutics.

Our 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 tumors in chemotherapy. Specifically, our patented approach allows physicians to combine,

on the one hand, pre-treatment of the local blood vessels and tissue with standard-of-care radiation therapy to decrease chemotherapy

washout and, on the other hand, local delivery via our patented RenovoCath delivery system which utilizes pressure to force small molecule

chemotherapy into the tumor tissue. We believe there are many advantages to our RenovoTAMP therapy platform:

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Research

and Development Pipeline

Our

portfolio of cancer therapies is based on our RenovoTAMP therapy platform. Our current pipeline is summarized below:

RenovoGem

Product Pipeline Addresses Multiple Indications

Figure

1 RenovoGem Clinical Pipeline detailing our potential portfolio of cancer therapies based on our RenovoTAMP therapy platform.

Our

lead product candidate, RenovoGem, consists of gemcitabine administered through our patented delivery system, RenovoCath, and is regulated

by the FDA as a new oncology drug product. Gemcitabine has been considered standard of care for several solid tumors, and the

drug’s anti-cancer tumor effects are well profiled. Our RenovoTAMP 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 the drug over a 20-minute

delivery period (delivering 1,500-2,000 mg of drug depending upon patient body surface area). RenovoCath is a double balloon catheter

designed with the capability to isolate sections of the blood vessel through the adjustment of the distance between the balloons, thereby

excluding any branching blood vessel offshoots in order to create the pressure head needed to push drug across the blood vessel wall.

We

intend to explore applications of our RenovoTAMP platform in additional indications, including locally advanced lung cancer, locally

advanced uterine cancer, and glioblastoma. We have completed and presented data on a lung cancer application in preclinical studies,

and additional preclinical experiments in lung cancer may be conducted.

We

are using gemcitabine in our initial anti-cancer product candidate, RenovoGem. However, multiple small molecule therapeutics are compatible

with our RenovoTAMP platform. We intend to opportunistically develop additional anti-cancer product candidates using small molecule therapeutics

in combination with our therapy platform.

While

the field of oncology has seen progress in treating a handful of deadly cancers over the last few decades, there is a common objective

in chemotherapy: enhanced dosing of the drug to impact the tumor while minimizing systemic toxicity. The characteristics of the blood

vessels, within and surrounding the tumor, can limit or thwart the achievement of this goal. For example, LAPC and eCCA are more difficult

to treat due to the lack of blood vessels that feed these tumors, making it difficult to expose tumors to chemotherapy, which is typically

delivered intravenously. Trans-arterial chemoembolization (TACE) is an established first line therapy for solid tumors. A key component

of this approach is to identify and isolate vessels feeding the tumor, known as tumor feeder blood vessels. However, in patients with

pancreatic cancer, no tumor feeder blood vessels are visible despite attempts to image them using a variety of modalities. In the absence

of visible tumor feeder blood vessels, our therapy platform has the potential to introduce drugs directly across the arterial wall into

the surrounding tissue via pressurized diffusion.

RenovoGem

in Locally Advanced Pancreatic Cancer (LAPC)

We

are currently evaluating RenovoGem in patients with LAPC in our TIGeR-PaC Phase 3 trial in the United States. In December 2021, we elected

to close our sites in Belgium, because these sites were not meeting enrollment milestones as a result of, among other factors, COVID-related

recruiting challenges and differences in systemic chemotherapy standard of care compared to the US which impacted patient eligibility.

We recently amended our protocol to only allow for Stereotactic Body Radiation Therapy (SBRT) radiation during the induction phase of

the study, removing intensity-modulated radiation therapy (IMRT) from our study going forward. Patients receiving IMRT were required

to complete 25 treatments prior to being randomized into our study. In comparison, patients receiving SBRT are only required to complete

5 treatments. IMRT is generally less tolerable than SBRT, and we had observed a higher drop out for patients on IMRT. As of March 15,

2022, our Phase 3 trial had achieved approximately 50% of the target enrollment under the current SAP. The SAP includes

a planned interim analysis when a total of 65 deaths have occurred in the study. We expect to conduct the interim analysis between the

fourth quarter of 2022 and the first quarter of 2023; however, given that it is predicated on the number of deaths in the study,

it is difficult to predict the exact timing. We have secured Orphan Drug Designation for the treatment of pancreatic cancer, which would

provide us with seven years of orphan exclusivity to market RenovoGem for our LAPC indication upon NDA approval, provided that we are

the first sponsor to obtain FDA approval for intra-arterial gemcitabine for the LAPC indication.

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For

our initial indication, LAPC, we have completed two studies. We launched RR1, our first-in-human, dose escalation, Phase 1/2 safety study,

in May 2015 to evaluate our RenovoTAMP platform by delivering intra-arterial gemcitabine via our patented RenovoCath delivery system.

In this safety study, 20 patients with a diagnosis of Stage 3 pancreatic cancer were enrolled. After completion of enrollment and demonstration

of an early survival efficacy signal in this study, we launched our RR2 observational registry study in June 2016 to examine the tolerability

and initial efficacy of the RenovoTAMP procedure. A combination analysis of these two studies demonstrated that survival in “all

comers” (n = 31) receiving at least one cycle (two treatments over one month) was 29% at two years. In the prior-radiation therapy

subset (n = 10), 24-month survival was 60% with a median overall survival (mOS) of 27.9 months. This compares favorably to IV chemotherapy,

with 12% at two years, and to chemotherapy + radiation with survival of 5% at two years, and mOS of 12 - 15 months as demonstrated in

historical studies.

RenovoGem

in Extrahepatic Cholangiocarcinoma (eCCA)

We

intend to evaluate RenovoGem in a second indication in a Phase 2 trial in eCCA, cancer that occurs in the bile ducts that lead out

of the liver and join with the gallbladder. We have now completed our evaluation of the different approaches to treat this patient

population and are in the process of refining our clinical protocol. We plan to meet with FDA during the second or third quarter of

2022 to discuss our trial design. If FDA does not object to our study protocol, we anticipate launching the eCCA trial in the second

half of 2022. We have also secured FDA Orphan Drug Designation for RenovoGem for the treatment of cholangiocarcinoma, which would

provide us with seven years of orphan exclusivity to market RenovoGem for our eCCA indication upon NDA approval, provided that we

are the first sponsor to obtain FDA approval for intra-arterial gemcitabine for the eCCA indication.

Our

Team

Our

management team, Board of Directors, and Scientific Advisors provide us with expertise across multiple sectors to drive success through

clinical development and subsequent commercialization of our novel therapy platform. Our Chief Executive Officer, Shaun Bagai, gained

extensive experience running clinical trials and launching, creating, and developing new markets for novel therapies at TransVascular,

Medtronic, Ardian, and HeartFlow. Dr. Ramtin Agah, our Co-Founder and Chief Medical Officer, is a practicing cardiovascular specialist

who has 20 years of research experience in vascular biology and disease in both academia and industry. Our Board of Directors includes

a wide range of public and private company management, board and life sciences experience, including drug/device combination

and oncology experience. Clinical advisors include experts across many specialties who treat solid tumors. Dr. Daniel Von Hoff, a medical

oncologist, was instrumental as the Principal Investigator who brought to market standard of care therapies for pancreatic cancer. Dr.

Michael Pishvaian, also a medical oncologist, has extensive experience running oncology studies and is an Associate Professor, and Director of the Gastrointestinal, Developmental Therapeutics, and Clinical Research Programs at

the NCR Kimmel Cancer Center at Sibley Memorial Hospital Johns Hopkins University School of Medicine. Dr. Pishvaian is the Principal

Investigator / Global Study Chair of our TIGeR-PaC Phase 3 study. Dr. Karyn Goodman serves as the Radiation Monitor for our TIGeR-PaC

Phase 3 study and Professor and Vice Chair of Clinical Research, Department of Radiation Oncology at the Icahn School of Medicine at

Mount Sinai, and Associate Director of Clinical Research at the Tisch Cancer Institute at Mount Sinai.

Strategy

RenovoGem

is a combination of intra-arterial gemcitabine and our patented delivery system, RenovoCath, and is regulated by the FDA as a new

oncology drug product. Our near-term goal is to develop RenovoGem to address the unmet medical needs of LAPC and eCCA patients. We

intend to broaden application of our RenovoTAMP therapy platform by exploring additional cancer indications, including locally

advanced lung cancer, locally advanced uterine cancer, and glioblastoma. Our long-term goal is to expand applications of our RenovoTAMP

platform beyond RenovoGem by acquiring or licensing other small molecule therapies to continue to address unmet medical needs of cancer

patients. To achieve our near-term and long-term goals, we intend to pursue the following strategies:

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Our

Strengths

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, when possible, surgical resection of the tumor is the most frequently employed treatment approach.

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 LAPC and eCCA 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.

Intravenous

(IV), or systemic chemotherapy, is considered standard

of care for most solid tumors, but limitations include less than acceptable efficacy, systemic toxicities, and other side effects.

For

the treatment of some localized solid tumors, 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: 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 avascular (lack of blood vessels) nature of these tumors. This limitation has rendered TACE ineffective in the

treatment of patients with LAPC, 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

penetrate the tumor tissue, early studies of targeted immunotherapies in pancreatic cancer have demonstrated limited success.

Our

Platform: RenovoTAMP

RenovoTAMP

may work best with avascular tumors

Certain

tumor types are sufficiently vascularized to enable use of systemic chemotherapy and standard of care local therapy techniques. In Figure

2 below, for example, the panel on the left depicts visualization of an actual tumor, hepatocellular carcinoma (HCC), or primary liver

cancer, 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 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 a pancreatic tumor. Given the lack of tumor feeder blood vessels, the dye does not

reach the tumor, rendering the tumor “invisible” under x-ray angiography.

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Tumors

in Liver are Different from Hypovascular Tumors in the Pancreas

Figure

2 Showing liver tumors that are highly vascularized, and pancreatic tumors that are avascular.

RenovoTAMP

has been under development for over 12 years

In

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

concept for RenovoTAMP 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 RenovoRx 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, implement certain changes in the

Instructions for Use, change the recommended saline to contrast solution ratio, 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 RenovoGem under an IND filed in 2018. FDA has determined

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

How

it works: we developed RenovoTAMP as an attempt to solve the problems of treating avascular 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, or Trans-Arterial

Micro-Perfusion (RenovoTAMP). To isolate the vessel and create this pressure gradient, we developed RenovoCath, a patented adjustable

double balloon catheter to occlude the proximal and distal part of the vessel. Using the RenovoTAMP technique in explanted (dissected

out of the animal and used separately in a saline water bath) pig aorta and iliac arteries, 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 3 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 out of 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.

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In

procedures developed for the RenovoTAMP platform, interventional radiologists utilize RenovoCath to pressurize an isolated vessel segment

Figure

3 Occluding the vessel with RenovoCath, while 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 the small molecule drug across the arterial wall via diffusion (this patented process of perfusing the vessel wall is Trans

Arterial Micro Perfusion, or RenovoTAMP).

Our

RenovoTAMP 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.

Some advantages of RenovoTAMP include:

● High local concentration of drug into the tumor tissue

Developing

a therapeutic platform using an adjustable two-balloon catheter and intra-arterial gemcitabine

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, we are able to force the small molecule chemotherapy across the vessel directly into surrounding

tissue or tumor. To accomplish this, we needed 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. We accomplished this with our patented RenovoCath

delivery system. 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 delivery system into the body through the femoral

artery 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, exiting the device between the balloons. It is forced through the vessel wall into the tissue over a

20-minute period. The RenovoCath delivery system is depicted below in Figure 4.

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RenovoCath

Delivers Chemotherapeutic Agent Between Two Balloons

Figure

4 RenovoCath delivery system illustrating two balloon configuration to isolate the target vessel segment, and chemotherapy delivery port

and exit hole.

After

the procedure is complete, RenovoCath is discarded, and the patient is generally discharged the same day. On average, the entire procedure

takes approximately 90 minutes. According to the TIGeR-PaC study protocol, intra-arterial 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. In addition, platform training for our primary indication should transfer to other indications.

RenovoGem

for LAPC

Disease

Overview

Pancreatic

cancer is one of the deadliest cancers in the US with very poor outcomes. In 2022, an estimated 62,210 new cases of pancreatic cancer

will be diagnosed in the US and 49,830 people will die from the disease. For all stages combined, the 5-year relative survival rate is

11%. Pancreatic cancer is the 3rd leading cause of cancer death in the USA and is projected to become the 2nd leading

cause by 2030. 54,000 new cases per year are diagnosed in the USA; worldwide, more than 300,000 new cases of pancreatic cancer are diagnosed

each year.

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 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 as an intravenous (IV) infusion has an established

role in the treatment of both unresectable LAPC and metastatic pancreatic cancer. Since its introduction in the US 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 12-15 months from

time of diagnosis.

A

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

the growth of scar tissue) that impedes drug delivery. 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 an avascular or 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.

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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 demonstrated limited success in the treatment of

LAPC. The lack of successful treatment options represents a recognized unmet medical need for these patients.

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 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 product candidate, RenovoGem, has the potential to address the recognized unmet medical need. Utilizing our patented

RenovoTAMP therapy platform, we believe RenovoGem can enhance local drug concentration, thereby increasing efficacy and decreasing systemic

exposure and toxicity to improve patient outcomes. RenovoGem is a drug/device combination product candidate consisting of intra-arterial

gemcitabine and our proprietary RenovoCath delivery system which forces the anti-cancer drug into the tumor. RenovoGem is regulated by

the FDA as a new oncology drug product. We do not intend to sell RenovoCath alone. Instead, we intend to sell RenovoCath only

in combination with intra-arterial gemcitabine (as RenovoGem) or potentially with other therapeutic agents.

Based

on primary market research and analysis of the US market sponsored by RenovoRx and conducted by third parties, we believe that over 5,000

patients per year would be excellent candidates and undergo RenovoGem treatment once it is approved in the US. The independent oncologists

interviewed stated their dissatisfaction with 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 RenovoTAMP

if the current Phase 3 trial demonstrates at least a 4-month survival benefit over systemic chemotherapy.

RenovoTAMP

Therapy Platform and First Product Candidate, RenovoGem

Figure

5 We invented a new therapy platform, RenovoTAMP, that uses pressure to force small molecule chemotherapeutics across the vessel wall

into the surrounding tissue using our patented RenovoCath delivery system. Our first product candidate, RenovoGem, is a drug/device combination

of intra-arterial gemcitabine and the RenovoCath delivery system, and is under development for LAPC and eCCA. We have secured Orphan

Drug Designations for RenovoGem for the treatment of both pancreatic cancer and cholangiocarcinoma.

Clinical

Development of RenovoGem in LAPC

Preclinical

Studies and Data

Once

RenovoCath is introduced via standard interventional technique to the arterial vessel segment next to the targeted tissue, both balloons

are inflated, and the vessel segment is isolated from the rest of the circulatory system. With inflation of balloons, the pressure is

observed to drop within the vessel. However, with infusion of fluids between the balloons, the intravascular pressure increases beyond

45 mmHg until plateauing, generating a gradient and trans-arterially forcing the infusate across the arterial wall via diffusion or Trans-Arterial

Micro-Perfusion (TAMP). A key aspect of this approach is to adjust the distance between the balloons to exclude any side blood vessel

branches in the isolated segment to allow the increase in pressure gradient, rather than drug washout via the side branches. Figure

6 shows a comparison, in an animal study, between proper balloon positioning with no side branches, allowing maximum drug to cross the

arterial wall, versus improper balloon positioning to include side branches, resulting in drug washing out via the side branches.

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Infusion

Pressure Achieved When Side Blood Vessel Branches Are Excluded

Figure

6 Top panel demonstrates proper balloon positioning with no side branch. Pressure increases with infusion and reaches plateau of approximately

75 mmHg higher than initial pressure. Bottom panel demonstrates improper balloon positioning with side branch between the balloons. Pressure

increases with infusion and reaches plateau of approximately only 15mmHg higher than initial pressure.

With

diffusion of fluids across the arterial wall in RenovoTAMP, we expected to be able to deliver small molecules into the surrounding tissue.

We performed the following studies to validate this hypothesis:

In

explanted (dissected out of the animal and used separately in a saline water bath) pig iliac and aortic artery, with the introduction

of RenovoCath and infusion of gemcitabine in the isolated vessel segment, we were able to measure (in a time dependent fashion) the amount

of gemcitabine crossing the arterial wall into the surrounding fluid. We isolated the arterial vessel segment using RenovoCath and then

delivered 60 mg/minute of gemcitabine into the isolated area over 20 minutes. By the end of the infusion, we measured 1,188 mg of gemcitabine

in the surrounding fluid around the vessel and 9 mg in the analyzed tissue of the vessel. This demonstrated that 99% of the drug crosses

the arterial wall and only 0.75% is retained in the arterial tissue (Figure 7).

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In

a Preclinical Study - 99% of Chemotherapy

Crosses Arterial Wall with RenovoTAMP Delivery

Figure

7 RenovoTAMP: delivery of chemotherapy through the RenovoCath and into the tissue to bathe the tumor in chemotherapy. In a preclinical

study using gemcitabine, 99% of the drug crosses the arterial wall and less than 0.75% is retained in the vessel wall tissue.

Six

pigs were treated with gemcitabine via RenovoTAMP (6 mL/min for 20 minutes). Target vessels included selection of the superficial femoral

artery (SFA) and splenic arteries from each animal (either test or saline control). A total of 6 vessels (3 SFA and 3 splenic arteries)

were treated with an equal number of control vessels. All animals survived the 7-day in-life period although two of the animals with

gemcitabine treatment in the splenic artery experienced atypical pain during the post-operative phase and required additional pain management

with eventual complete recovery.

Analysis

of the vessels demonstrated preserved vessel shape with intact endothelial cells (cells on the inside of the vessels). Minimal to no

inflammation was observed. The only vessel toxicity observed was a reduction of smooth muscles cells in the vessel wall, primarily close

to the inside of the vessel.

I. Targeted small molecule delivery (dye) into pancreatic tissue

We

further validated our approach for tissue drug delivery using acute animal experiments. Using both dye and gemcitabine infusion via the

RenovoTAMP therapy, we were able to demonstrate that fully isolating a segment of a vessel (by blocking inflow and outflow in the target

vessel as well as side branches with the RenovoCath double balloons) can lead to dye penetration greater than 4.0 cm from the vessel

wall and drug tissue concentration (gemcitabine) up to 100-fold greater than systemic administration.

In

an acute pig experiment, RenovoCath was introduced into the gastro-duodenal artery (GDA), a side branch was excluded (using small implants

that block the artery, coils), and then dye was introduced at 6mls/minute over 2 minutes. Analysis demonstrated that the blue dye diffused

covered approximately 10.56 cm2 (2.2 cm x 4.8 cm) of the pancreas.

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Dye

Demonstrates RenovoTAMP Delivery of Agent into Pancreatic Tissue

Figure

8 RenovoCath was introduced into the GDA and a side branch was excluded by coiling. This test was conducted in an acute porcine model

and demonstrated a dye coverage area of approximately 10.56 cm2 for a 2-minute dye infusion. All dimensions in above figure

are in cm.

The

study was repeated in 6 other vessel targets to validate the impact of vessel isolation on dye penetration into the surrounding tissue

with similar results.

II. Small molecule delivery (dye and gemcitabine) locally into lung tissue

In

another set of acute animal experiments, the pulmonary artery was isolated via access through the internal jugular vein. Six ml of methylene

blue dye was injected over 1 min and gemcitabine was subsequently delivered locally at rate of 6 mls/minute for 20 minutes to the lung

tissue using the RenovoTAMP procedure.

Dense

dye staining localized to the area of the isolated vessel segment was observed. Again, analysis established penetration into surrounding

tissue (4 cm). Furthermore, RenovoTAMP achieved greater than 100-fold tissue concentration of gemcitabine versus the tissue level achieved

by IV (systemic) delivery of gemcitabine at the same infusion rate.

Dye

Staining Demonstrates RenovoTAMP Delivery of Agent to Lung Tissue

Figure

9 Dense dye staining localized to the area of the isolated pulmonary artery segment and penetrating 4 cm into surrounding tissue following

1 minute dye infusion. In addition, gemcitabine was delivered via RenovoTAMP for 20 minutes demonstrating 100-fold increase in tissue

concentration of gemcitabine compared to IV delivery of gemcitabine at the same infusion rate.

We

concluded that RenovoTAMP can achieve drug penetration into the surrounding tissue and can achieve high dose concentrations in local

tissue. The tissue concentration with intravenous infusion and/or distant from RenovoTAMP site (likely after recirculation through systemic

system) were two orders of magnitude lower than tissue levels achieved with RenovoTAMP (p<0.02).

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RenovoTAMP

Increases Local Tissue Concentration of Gemcitabine Compared to IV Infusion

Figure

10 Local tissue concentration of gemcitabine.

control (Blue): Intravenous infusion versus RenovoTAMP (Orange): RenovoTAMP: intra-arterial infusion. The tissue concentration

with intravenous infusion and/or distant from RenovoTAMP site (likely after recirculation through systemic system) are 100-fold lower

than tissue levels achieved with RenovoTAMP.

This

animal lung study successfully validated the ability of RenovoCath to deliver small molecules locally and effectively to lung tissue.

In

relevant mouse models of pancreatic tumors, it has been demonstrated that targeted intra-arterial (IA) infusion of gemcitabine into the

pancreas after surgical isolation of arterial blood flow has a superior therapeutic effect with greater reduction in tumor volume compared

to the same concentration administered by conventional systemic (intravenous) injection. To achieve a comparable reduction in

tumor growth as seen with IA treatment, gemcitabine had to be given intravenously at over 300 times the dose which was associated

with increased toxicity.

RenovoTAMP

and Radiation

Traditionally

the goal of radiation includes debulking the tumor and/or acting as a chemo-sensitizer. In our RR1 dose escalation safety study and RR2

observational registry study, the benefit of RenovoTAMP appeared to be enhanced in patients with prior radiation. As we were observing

this effect months after radiation and although several randomized studies have not demonstrated a benefit of chemotherapy + radiation

versus chemotherapy alone, we hypothesized that a direct effect of radiation on the vasculature may be enhancing the effect of RenovoTAMP.

One of the side effects of radiation is a decrease in the micro-vasculature in the irradiated tissue including the small blood vessels

that exist in the vessel walls themselves. Therefore, we postulated that by eliminating microvasculature in and around the vessel wall,

radiation may enhance drug penetration into the tissue via RenovoTAMP (Figure 11). As such, a possible enhancing effect of radiation

on RenovoTAMP may involve decreasing washout of the drug as it crosses the arterial wall by preventing draining into the surrounding

microvasculature.