RenovoRx, Inc.

Overview

We are a life sciences company offeringRenovoCath®, 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 patentedTrans-Arterial Micro-Perfusion (TAMP™) 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 havehad 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 26 th 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 52 nd event, which we currently anticipate to occur during the second quarter of 2025.

The timing required to analyze the data after the 52 nd 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.

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 26 th 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/m 2 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 26 th 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 52 nd 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 52 nd 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 patent application for its TAMP therapy platform to expand our patent portfolio. We already holds strong IP including coverage of our proprietary TAMP therapy platform and RenovoCath device, with 9 issued or allowed and 5 pending U.S. patents, and 10 issued and 6 pending patents outside of the U.S., including our international application published in 2024. We continue to explore additional opportunities to further bolster our intellectual property position, and if granted, our current applications would provide patent protection through 2043. The table below describes our issued patents, all of which have been assigned to us.

• Predicted earliest expiration date. The actual expiration date will depend on factors related to patent prosecution and issuance.

******Estimated expiration dates assume all maintenance fees are paid.

Orphan drug designation provides seven years post-approval market exclusivity protection. Gemcitabine is generic; however, we have exclusivity for the IA route of administration. IAG is regulated by the FDA as a new oncology drug product. We intend to make IA gemcitabine and RenovoCath available as a combined product and not to make either component available separately. Once approved, we will have exclusivity over the use of IA gemcitabine as it will be approved by the FDA in combination with RenovoCath.

When appropriate, we actively pursue protection of our proprietary products, technologies, processes, and methods by filing United States and international patent and trademark applications. We seek to pursue additional patent protection for technology invented through research and development, manufacturing, and clinical use of our technology that will enable us to expand our patent portfolio around advances to our current systems, technology, and methods for our current applications as well as others.

There can be no assurance that the pending patent applications will result in the issuance of patents, that patents issued to or licensed by us will not be challenged or circumvented by competitors, or that these patents will be found to be valid or sufficiently broad to protect our technology or provide us with a competitive advantage.

To maintain our proprietary position, we also rely on trade secrets and proprietary technological experience to protect proprietary manufacturing processes, technology, and know-how relating to our business. We rely, in part, on confidentiality agreements with our marketing partners, employees, advisors, vendors and consultants to protect our trade secrets and proprietary technological expertise. In addition, we also seek to maintain our trade secrets through maintenance of the physical security of the premises where our trade secrets are located. There can be no assurance that these agreements will not be breached, that we will have adequate remedies for any breach, that others will not independently develop equivalent proprietary information or that third parties will not otherwise gain access to our trade secrets and proprietary knowledge.

In certain circumstances, United States patent law allows for the extension of a patent’s duration for a period of up to five years after FDA approval. We intend to seek extension for one of our patents after FDA approval if it has not expired prior to the date of approval. In addition to our proprietary protections, the FDA has granted us two orphan drug designations that provide us a seven-year period of exclusive marketing beginning on the date that our NDA is approved by the FDA for the designated orphan drug. While exclusivity only applies to the indication for which the drug has been approved, we believe that this exclusivity will provide us with added protection once commercialization of an orphan drug designated product begins.

There has been and continues to be substantial litigation regarding patent and other intellectual property rights in the pharmaceutical and medical device areas. If a third party asserts a claim against us, we may be forced to expend significant time and money defending such actions and an adverse determination in any patent litigation could subject us to significant liabilities to third parties, require us to redesign our product, require us to seek licenses from third parties, and, if licenses are not available, prevent us from manufacturing, selling or using our system. Additionally, we plan to enforce our intellectual property rights vigorously and may find it necessary to initiate litigation to enforce our patent rights or to protect our trade secrets or know-how. Patent litigation can be costly and time consuming and there can be no assurance that the outcome will be favorable to us.

Manufacturing and Supply

For the catheter component of IAG, as well as for standalone RenovoCath supply for our commercial efforts, we currently rely on a single-source contract manufacturer, Medical Murray, North Barrington, IL. However, we engaged with an additional manufacturer as a backup supplier. We are subject to regulatory requirements of the FDA’s Quality System Regulation (QSR), for medical devices sold in the United States We have an agreement in place with Medical Murray to produce the RenovoCath through October 2024 with automatic annual renewal until termination by either party with 12 months’ notice. While we believe Medical Murray has the capabilities to scale RenovoCath production to peak forecasted commercial volumes, manufacturing can be transferred to additional vendors if needed.

The FDA monitors compliance with QSR through periodic inspections of both our facility and the facility of our contact manufacturer.

Our failure or the failure of our contract manufacturer to maintain acceptable quality requirements could result in the shutdown of our manufacturing operations or the recall of products which could be detrimental to our company. If our contract manufacturer fails to maintain acceptable quality requirements, we may have to qualify a new contract manufacturer and could experience a material adverse effect to manufacturing and manufacturing delays as a result.

We do not own or operate and do not intend to establish our own gemcitabine manufacturing facilities.

Within our TIGeR-PaC Phase III trial, hospitals are sourcing generic gemcitabine labeled for IV use from their respective pharmacies to use in conjunction with the RenovoCath for the TAMP procedures. In the commercial setting, we expect to rely on contract manufacturing organizations for gemcitabine production, relabeling and co-packaging with the RenovoCath. The formulation of gemcitabine used in the TIGeR-PaC Phase III trial and in the commercial setting will be identical, however, the commercial labeling of gemcitabine will be IA gemcitabine post-approval to be used exclusively in conjunction with RenovoCath.

Government Regulation

Our products are subject to extensive and rigorous government regulation by foreign regulatory agencies and the FDA. Foreign regulatory agencies, the FDA and regulatory agencies in state and local jurisdictions impose extensive requirements upon the clinical development, pre-market clearance and approval, manufacturing, labeling, marketing, advertising and promotion, pricing, storage and distribution of pharmaceutical and medical device products. Failure to comply with applicable foreign regulatory agency or FDA requirements may result in warning letters, fines, civil or criminal penalties, suspension or delays in clinical development, recall or seizure of products, partial or total suspension of production or withdrawal of a product from the market.

United States Regulatory Environment

In the U.S., the FDA regulates drug and device products, including combination, under the Federal Food, Drug, and Cosmetic Act (“FDCA”), and its implementing regulations. IAG is subject to FDA regulation in 21 CFR 3.2(e) as a combination product, which means it is composed of both a drug component and device component. Each component of a combination product is subject to the requirements established by FDA for that type of component and if marketed individually, each component would be subject to different regulatory pathways and reviewed by different centers within the FDA. In addition to our RenovoCath device, we are also evaluating our novel Phase III drug-device combination product candidate. It is being investigated under a U.S. investigational new drug application that is regulated by the FDA’s 21 CFR 312 pathway. The intra-arterial infusion of chemotherapy, gemcitabine, utilizing the RenovoCath device is currently being evaluated for the treatment of locally advanced pancreatic cancer (LAPC) by CDER.

Our combination product candidate, IAG, which is enabled the RenovoCath device, is currently under investigation and has not been approved for commercial sale. RenovoCath with gemcitabine received Orphan Drug Designation for pancreatic cancer and bile duct cancer, which provides 7 years of market exclusivity upon NDA approval by the FDA.

In the case of IAG, the primary mode of action is attributable to the drug component of the product, which means that CDER, has primary jurisdiction over its pre-market development and review. The underlying RenovoCath drug delivery device used in our clinical development stage product candidate has been separately cleared by CDRH as a standalone Class II medical device and not in combination of a specific drug product or part of a prepackaged combination product 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. The RenovoCath is intended for general intravascular use in the peripheral vasculature in arteries 3mm and larger. The RenovoCath is intended for use in arteries from 3mm in diameter for vessel entry and to occlude vessels ranging between 3mm to 11mm in diameter.

The process required by the FDA before drug product candidates, including drug-led combination products, may be marketed in the United States generally involves the following:

The development and approval process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for our product will be granted on a timely basis, if at all.

Clinical Trials

For purposes of NDA submission and approval, clinical trials are typically conducted in the following sequential phases, which may overlap:

New Drug Applications (NDAs)

The results of drug development, preclinical studies and clinical trials are submitted to the FDA as part of an NDA. NDAs also must contain extensive chemistry, manufacturing and control information. An NDA must be accompanied by a significant user fee, which may be waived in certain circumstances. Once the submission has been accepted for filing, the FDA’s goal is to review applications within ten months of submission or, if the application relates to an unmet medical need in a serious or life-threatening indication, six months from submission. The review process is often significantly extended by FDA requests for additional information or clarification. The FDA may refer the application to an advisory committee for review, evaluation and recommendation as to whether the application should be approved. For new oncology products, the FDA will often solicit an opinion from an Oncologic Drugs Advisory Committee, or ODAC, a panel of expert authorities knowledgeable in the fields of general oncology, pediatric oncology, hematologic oncology, immunologic oncology, biostatistics, and other related professions. The ODAC panel reviews and evaluates data concerning the safety and effectiveness of marketed and investigational human drug products for use in the treatment of cancer and makes appropriate recommendations to the Commissioner of Food and Drugs. The FDA is not bound by the recommendation of an advisory committee.

Before approving an NDA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP. Additionally, the FDA will generally inspect the facility or the facilities at which the drug is manufactured. The FDA will not approve the product unless compliance with cGMPs is satisfactory, and the NDA contains data that provide substantial evidence that the drug is safe and effective in the indication studied. After the FDA evaluates the NDA and the manufacturing facilities, it issues either an approval letter or a complete response letter (“CRL”). A CRL generally outlines the deficiencies in the submission and may require substantial additional testing, or information, in order for the FDA to reconsider the application. If, or when, those deficiencies have been addressed to the FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. A CRL may require additional clinical data and/or an additional pivotal Phase III clinical trial(s), and/or other significant, expensive and time-consuming requirements related to clinical trials, preclinical studies or manufacturing. Data from clinical trials are not always conclusive and the FDA may interpret data differently than we or our collaborators interpret data. Approval may be contingent on a Risk Evaluation and Mitigation Strategy (“REMS”) that limits the labeling, distribution or promotion of a drug product. Once issued, the FDA may withdraw product approval if ongoing regulatory requirements are not met or if safety problems occur after the product reaches the market. In addition, the FDA may require testing, including Phase IV clinical trials, and surveillance programs to monitor the safety effects of approved products which have been commercialized, and the FDA has the power to prevent or limit further marketing of a product based on the results of these post-marketing programs or other information.

There are three primary regulatory pathways for an NDA under Section 505 of the FDCA: Section 505 (b)(1), Section 505 (b)(2) and Section 505(j). A Section 505 (b)(1) application is used for approval of a new drug (for clinical use) whose active ingredients have not been previously approved. A Section 505 (b)(2) application is used for a new drug that relies on data not developed by the applicant. Section 505(b)(2) of the FDCA was enacted as part of the Drug Price Competition and Patent Term Restoration Act of 1984, also known as the Hatch-Waxman Act. This statutory provision permits the approval of an NDA where at least some of the information required for approval comes from studies not conducted by or for the applicant and for which the applicant has not obtained a right of reference. The Hatch-Waxman Act permits the applicant to rely in part upon the FDA’s findings of safety and effectiveness for previously approved products. Section 505(j) application, also known as an abbreviated NDA, is used for a generic version of a drug that has already been approved.

An approval letter authorizes commercial marketing of the drug product with specific prescribing information for specific indications. As a condition of NDA approval, the FDA may require a REMS to help ensure that the benefits of the drug outweigh the potential risks. REMS can include medication guides, communication plans for healthcare professionals, and elements to assure safe use. The requirement for a REMS can materially affect the potential market and profitability of the drug. Moreover, product approval may require substantial post-approval testing and surveillance to monitor the drug’s safety or efficacy. Once granted, product approvals may be withdrawn if compliance with regulatory standards is not maintained or problems are identified following initial marketing.

Changes to some of the conditions established in an approved application, including changes in indications, labeling, or manufacturing processes or facilities, require submission and FDA approval of a new NDA or NDA supplement before the change can be implemented. An NDA supplement for a new indication typically requires clinical data similar to that in the original application, and the FDA uses the same procedures and actions in reviewing NDA supplements as it does in reviewing NDAs.

The NDA review process for drug-led combination includes a review of the device constituent. In this case, the device constituent for IAG is RenovoCath, which is cleared by the FDA.

Orphan Drug Exclusivity

Some jurisdictions, including the United States, may designate drugs for relatively small patient populations as orphan drugs. Pursuant to the Orphan Drug Act, the FDA grants orphan drug designation to drugs intended to treat a rare disease or condition, which is generally a disease or condition that affects fewer than 200,000 individuals in the United States. The orphan designation is granted for a combination of a drug entity and an indication and therefore it can be granted for an existing drug with a new (orphan) indication. Applications are made to the Office of Orphan Products Development at the FDA and a decision or request for more information is rendered in 60 days. NDAs for designated orphan drugs are exempt from user fees, obtain additional clinical protocol assistance, are eligible for tax credits up to 50% of research and development costs, and are granted a seven-year period of exclusivity upon approval. The FDA cannot approve the same drug for the same condition during this period of exclusivity, except in certain circumstances where a new product demonstrates superiority to the original treatment. Exclusivity begins on the date that the marketing application is approved by the FDA for the designated orphan drug, and an orphan designation does not limit the use of that drug in other applications outside the approved designation in either a commercial or investigational setting.

We have received orphan drug designations for IAG for pancreatic cancer and cholangiocarcinoma.

The granting of orphan drug designations does not mean that the FDA has approved a new drug. Companies must still pursue the rigorous development and approval process that requires substantial time, effort and financial resources, and we cannot be certain that any approvals for our product will be granted at all, or on a timely basis.

FDA Medical Device Regulation

Unless an exemption applies, each new or significantly modified drug delivery medical device that we develop based on the current 510(k)-cleared RenovoCath and which we seek to commercially distribute in the United States will require a premarket notification to the FDA requesting permission for commercial distribution under Section 510(k) of the FDCA, also referred to as a 510(k) clearance, unless addressed as part of a new drug application for a drug/device combination product. New medical devices without an applicable predicate device as well as higher-risk medical devices are subject to premarket approval by the FDA under a PMA or a de novo classification from the FDA. The 510(k) clearance, PMA approval, and de novo classification processes can be resource intensive, expensive, and lengthy, and require payment of significant user fees, unless an exemption is available.

Under the FDCA, medical devices are classified into one of three classes – Class I, Class II or Class III – depending on the degree of risk associated with each medical device and the extent of manufacturer and regulatory control needed to ensure its safety and effectiveness. The RenovoCath catheter is classified as a Class II device.

Class II devices are those that are subject to the general controls and special controls, as deemed necessary by the FDA to ensure the safety and effectiveness of the device. These special controls can include performance standards, patient registries, FDA guidance documents, and post-market surveillance. Most Class II devices are subject to premarket review and clearance by the FDA. Premarket review and clearance by the FDA for Class II devices is accomplished through the 510(k) premarket notification process. The RenovoCath device received initial 510(k) clearance by FDA in 2014.

The 510(k) Clearance Process

Under the 510(k) process, the manufacturer must submit to the FDA a premarket notification, demonstrating that the device is “substantially equivalent,” as defined in the statute, to a legally marketed predicate device. A predicate device is a legally marketed device that is not subject to premarket approval, i.e., a device that was legally marketed prior to May 28, 1976 (pre-amendments device) and for which a PMA is not required, a device that has been reclassified from Class III to Class II or I, or a device that was previously found substantially equivalent through the 510(k) process. The FDA’s 510(k) clearance process usually takes from three to 12 months but may take longer. The FDA may require additional information, including clinical data, to make a determination regarding substantial equivalence. In addition, FDA collects user fees for certain medical device submissions and annual fees and for medical device establishments.

If the FDA agrees that the device is substantially equivalent to a predicate device currently on the market, it will grant 510(k) clearance to commercially market the device. If the FDA determines that the device is not “substantially equivalent” to a predicate device, the device is automatically classified into Class III. The device sponsor must then fulfill the much more rigorous premarketing requirements of the PMA approval process, or seek risk-based reclassification of the device through the de novo process, which is a route to market for novel medical devices that are low to moderate risk and are not substantially equivalent to a predicate device. A manufacturer can also submit a petition for direct de novo review if the manufacturer is unable to identify an appropriate predicate device and the new device or new use of the device presents a moderate or low risk.

After a device receives 510(k) clearance or de novo classification, any modification that could significantly affect its safety or effectiveness, or that would constitute a new or major change in its intended use, will require a new 510(k) clearance or, depending on the modification, could require a PMA or de novo classification. The FDA requires each manufacturer to determine whether the proposed change requires submission of a 510(k) or a PMA in the first instance, but the FDA can review any such decision and disagree with a manufacturer’s determination. Many minor modifications are accomplished by a letter-to-file in which the manufacturer documents the change in an internal letter-to-file. The letter-to-file is in lieu of submitting a new 510(k) to obtain clearance for such change. The FDA can always review these letters to file in an inspection. If the FDA disagrees with a manufacturer’s determination regarding whether a new premarket submission is required for the modification of an existing device, the FDA can require the manufacturer to cease marketing and/or recall the modified device until marketing authorization is obtained. Also, in these circumstances, the manufacturer may be subject to significant regulatory fines or penalties.

Other FDA Regulatory Requirements

Products manufactured or distributed pursuant to FDA approvals are subject to continuing regulation by the FDA, including recordkeeping, annual product quality review and reporting requirements. Adverse event experiences with the product, including both drug-related and device-related adverse events (including device malfunctions and medical device reporting), must be reported to the FDA in a timely fashion and pharmacovigilance programs to proactively look for these adverse events are mandated by the FDA. Drug and device manufacturers and their subcontractors are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with ongoing regulatory requirements, including cGMP and QSR, which impose certain procedural and documentation requirements upon us and our third-party manufacturers. Following such inspections, the FDA may issue notices on Form 483, Untitled Letters or Warning Letters that could cause us or our third-party manufacturers to modify certain activities. A Form 483 Notice, if issued at the conclusion of an FDA inspection, list conditions the FDA investigators believe may have violated cGMP, QSR or other FDA regulations or guidelines. In addition to Form 483 Notices and Untitled Letters or Warning Letters, failure to comply with the statutory and regulatory requirements can subject a manufacturer to possible legal or regulatory action, such as suspension of manufacturing, seizure of product, injunctive action or possible civil penalties. We cannot be certain that we or our present or future third-party manufacturers or suppliers will be able to comply with the cGMP regulations, QSR and other ongoing FDA regulatory requirements. If we or our present or future third-party manufacturers or suppliers are not able to comply with these requirements, the FDA may require us to recall our products from distribution or withdraw any potential approvals of an NDA for that product.

The FDA closely regulates the post-approval marketing and promotion of drugs and devices, including standards and regulations for direct-to-consumer advertising, dissemination of off-label information, industry-sponsored scientific and educational activities and promotional activities involving the Internet. Drugs and devices may be marketed only for the approved indications and in accordance with the provisions of the approved label. Further, if there are any modifications to the drug or device, including changes in indications, labeling, or manufacturing processes or facilities, we may be required to submit and obtain FDA approval of a new or supplemental NDA or clearance or approval of the modified device, respectively, which may require us to develop additional data or conduct additional preclinical studies and clinical trials. Failure to comply with these requirements can result in adverse publicity, Warning Letters, corrective advertising and potential civil and criminal penalties.

Physicians may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties, in particular in oncology. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, impose stringent restrictions on manufacturers’ communications regarding off-label use.

In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing Act (“PDMA”), which regulates the distribution of drugs and drug samples at the federal level and sets minimum standards for the registration and regulation of drug distributors by the states. Both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution.

Foreign Regulatory Environment

If we seek to market IAG in foreign jurisdictions, we could become subject to a variety of foreign regulations regarding development, approval, commercial sales, and distribution of our products in addition to regulations in the United States. Whether or not we obtain FDA approval for a product, we must obtain the necessary approvals by the regulatory authorities of foreign countries before we can commence clinical trials or marketing of the product in those countries. The approval process varies from country to country and can involve additional product testing and additional review periods. The review process may take longer or shorter than that required to obtain FDA approval. The requirements governing, among other things, the conduct of clinical trials, product licensing, pricing and reimbursement vary greatly from country to country. Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others. If we fail to comply with applicable foreign regulatory requirements, we may be subject to fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products, operating restrictions, and/or criminal prosecution.

Other United States Healthcare Laws

In addition to FDA restrictions on marketing of pharmaceutical and medical device products, including drug/device combination products, pharmaceutical companies are subject to additional healthcare regulation and enforcement by the federal government and by authorities in the states and foreign jurisdictions in which they conduct their business and may constrain the financial arrangements and relationships through which we research, as well as sell, market and distribute any products for which we obtain marketing authorization. Such laws include, without limitation, state and federal anti-kickback, fraud and abuse, false claims, data privacy and security, and transparency laws and regulations related to drug pricing and payments and other transfers of value made to physicians and other healthcare providers. If manufacturers’ operations, including activities engaged by their contractors or agents, are found to be in violation of any of such laws or any other governmental regulations that apply, they may be subject to penalties, including, without limitation, administrative, civil and criminal penalties, damages, fines, disgorgement, the curtailment or restructuring of operations, integrity oversight and reporting obligations, exclusion from participation in federal and state healthcare programs and imprisonment.

The federal Anti-Kickback Statute prohibits, among other things, knowingly and willfully offering, paying, soliciting or receiving remuneration to induce, or in return for, purchasing, leasing, ordering or arranging for the purchase, lease or order of any healthcare item or service reimbursable under Medicare, Medicaid, or other federally financed healthcare programs. The Affordable Care Act, or ACA, amended the intent element of the federal statute so that a person or entity no longer needs to have actual knowledge of the statute or specific intent to violate it in order to commit a violation. This statute has been interpreted to apply to arrangements between pharmaceutical manufacturers on the one hand and prescribers, purchasers and formulary managers, among others, on the other. Although there are a number of statutory exceptions and regulatory safe harbors protecting certain business activities from prosecution or other regulatory sanctions, the exceptions and safe harbors are drawn narrowly, and practices that involve remuneration intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor.

Federal civil and criminal false claims laws, including the federal civil False Claims Act, prohibit any person or entity from knowingly presenting, or causing to be presented, a false claim for payment to the federal government, or knowingly making, or causing to be made, a false statement to have a false claim paid. This includes claims made to programs where the federal government reimburses, such as Medicare and Medicaid, as well as programs where the federal government is a direct purchaser, such as when it purchases off the Federal Supply Schedule. Pharmaceutical and other healthcare companies have been prosecuted under these laws for, among other things, allegedly inflating drug prices they report to pricing services, which in turn were used by the government to set Medicare and Medicaid reimbursement rates, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product. In addition, certain marketing practices, including off-label promotion, may also violate false claims laws. Additionally, the ACA amended the federal Anti-Kickback Statute such that a violation of that statute can serve as a basis for liability under the federal False Claims Act. Most states also have statutes or regulations similar to the federal Anti-Kickback Statute and civil False Claims Act, which apply to items and services reimbursed under Medicaid and other state programs, or, in several states, apply regardless of the payor.

Other federal statutes pertaining to healthcare fraud and abuse include the civil monetary penalties statute, which prohibits, among other things, the offer or payment of remuneration to a Medicaid or Medicare beneficiary that the offeror or payor knows or should know is likely to influence the beneficiary to order a receive a reimbursable item or service from a particular supplier, and the additional federal criminal statutes created by the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which prohibits, among other things, knowingly and willfully executing or attempting to execute a scheme to defraud any healthcare benefit program or obtain by means of false or fraudulent pretenses, representations or promises any money or property owned by or under the control of any healthcare benefit program in connection with the delivery of or payment for healthcare benefits, items or services.

In addition, HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act (“HITECH”), and their respective implementing regulations, impose obligations on certain healthcare providers, health plans, and healthcare clearinghouses, known as covered entities, as well as their business associates that perform certain services involving the storage, use or disclosure of individually identifiable health information, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information, and require notification to affected individuals and regulatory authorities of certain breaches of security of individually identifiable health information. HITECH increased the civil and criminal penalties that may be imposed against covered entities, business associates and possibly other persons, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorney’s fees and costs associated with pursuing federal civil actions. In addition, many state laws govern the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, and often are not preempted by HIPAA.

Further, pursuant to the ACA, the Centers for Medicare and Medicaid Services (“CMS”) has issued a final rule that requires applicable manufacturers of covered products, including prescription drugs and certain medical devices, to collect and annually report information on certain payments or transfers of value made in the previous year to physicians (defined to include doctors of medicine and osteopathy, dentists, podiatrists, optometrists and licensed chiropractors), certain non-physician healthcare professionals (such as physician assistants and nurse practitioners, among others) and teaching hospitals, as well information regarding investment interests held by physicians and their immediate family members. The reported data is made available in searchable form on a public website on an annual basis. Failure to submit required information may result in civil monetary penalties. In addition, several states now require prescription drug companies to report certain expenses relating to the marketing and promotion of drug products and to report gifts and payments to individual healthcare practitioners in these states. Other states prohibit various marketing-related activities and/or require the posting of information relating to clinical studies and their outcomes. Some states require the reporting of certain pricing information, including information pertaining to and justifying price increases, or prohibit prescription drug price gouging. In addition, certain states require pharmaceutical companies to implement a healthcare compliance program or code of conduct. Certain states and local jurisdictions also require the registration of pharmaceutical sales representatives. Compliance with these federal and state laws is difficult and time consuming, and companies that do not comply with these state laws are exposed to liabilities and civil penalties.

Efforts to ensure that business arrangements with third parties comply with applicable healthcare laws and regulations involve substantial costs. If a drug company’s operations are found to be in violation of any such requirements, it may be subject to significant penalties, including civil, criminal and administrative penalties, damages, fines, disgorgement, imprisonment, the curtailment or restructuring of its operations, loss of eligibility to obtain approvals from the FDA, exclusion from participation in government contracting, healthcare reimbursement or other federal or state government healthcare programs, including Medicare and Medicaid, integrity oversight and reporting obligations, imprisonment, and reputational harm. Although effective compliance programs can mitigate the risk of investigation and prosecution for violations of these laws, these risks cannot be entirely eliminated. Any action for an alleged or suspected violation can cause a drug company to incur significant legal expenses and divert management’s attention from the operation of the business, even if such action is successfully defended.

Healthcare Reform

In March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, each as amended, collectively known as the ACA, was enacted, which substantially changed the way healthcare is financed by both governmental and private insurers, and significantly affected the pharmaceutical industry. The ACA contained a number of provisions, including those governing enrollment in federal healthcare programs, reimbursement adjustments and changes to fraud and abuse laws. Additionally, the ACA:

Since its enactment, there have been judicial, executive and Congressional challenges to certain aspects of the ACA. For example, in June 2021 the U.S. Supreme Court held that Texas and other challengers had no legal standing to challenge the ACA, dismissing the case on procedural grounds without specifically ruling on the constitutionality of the ACA. Thus, the ACA will remain in effect in its current form. It is possible that the ACA will be subject to judicial or Congressional challenges in the future. It is unclear how any such challenges and healthcare measures promulgated by the Biden administration will impact the ACA, our business, financial condition and results of operations.

Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers of 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2031, with the exception of a temporary suspension implemented under various COVID-19 relief legislation from May 1, 2020 through March 31, 2022, unless additional action is taken by Congress. Under current legislation, the actual reduction in Medicare payments can vary from 1% in 2022 to up to 4% in the final fiscal year of this sequester.

Moreover, there has recently been heightened governmental scrutiny over the manner in which manufacturers set prices for their marketed products, which has resulted in several Congressional inquiries and proposed and enacted federal and state legislation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drug products. For example, under the American Rescue Plan Act of 2021, effective January 1, 2024, the statutory cap on Medicaid Drug Rebate Program rebates that manufacturers pay to state Medicaid programs will be eliminated. Elimination of this cap may require pharmaceutical manufacturers to pay more in rebates than it receives on the sale of products, which could have a material impact on our business. In August 2022, Congress passed the Inflation Reduction Act of 2022, which includes prescription drug provisions that have significant implications for the pharmaceutical industry and Medicare beneficiaries, including allowing the federal government to negotiate a maximum fair price for certain high-priced single source Medicare drugs, imposing penalties and excise tax for manufacturers that fail to comply with the drug price negotiation requirements, requiring inflation rebates for all Medicare Part B and Part D drugs, with limited exceptions, if their drug prices increase faster than inflation, and redesigning Medicare Part D to reduce out-of-pocket prescription drug costs for beneficiaries, among other changes. On June 30, 2023, CMS issued new guidance detailing the requirements and parameters of the first round of price negotiations, to take place during 2023 and 2024, for products subject to the “maximum fair price” provision that would become effective in 2026. On August 29, 2023, the U.S. Department of Health and Human Services (“HHS”) announced the list of the first ten drugs that will be subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. CMS and HHS will continue to issue and update guidance as these programs are implemented. The impact of these regulations and any future healthcare measures and agency rules implemented by the Biden administration on us and the pharmaceutical industry as a whole is currently unknown.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. For example, a number of states are considering or have recently enacted state drug price transparency and reporting laws that could substantially increase our compliance burdens and expose us to greater liability under such state laws once we begin commercialization after obtaining regulatory approval for any of our products.

Coverage and Reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of any product or product candidate for which we are developing or commercializing. Sales in the U.S. will depend, in part, on the availability of sufficient coverage and adequate reimbursement from third-party payors, which include government health programs such as Medicare, Medicaid, TRICARE and the Veterans Administration, as well as managed care organizations and private health insurers. Prices at which we or our customers seek reimbursement for our product candidates can be subject to challenge, reduction or denial by third-party payors.

The process for determining whether a third-party payor will provide coverage for a product is typically separate from the process for setting the reimbursement rate that the payor will pay for the product. A third-party payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be available. Additionally, in the U.S. there is no uniform policy among payors for coverage or reimbursement. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own coverage and reimbursement policies, but also have their own methods and approval processes. Therefore, coverage and reimbursement for products can differ significantly from payor to payor. If coverage and adequate reimbursement are not available, or are available only at limited levels, successful commercialization of, and obtaining a satisfactory financial return on, any product we develop may not be possible.

Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. In order to obtain coverage and reimbursement for any product that might be approved for marketing, we may need to conduct expensive studies in order to demonstrate the medical necessity and cost-effectiveness of any products, which would be in addition to the costs expended to obtain regulatory approvals. Third-party payors may not consider our product candidates to be medically necessary or cost-effective compared to other available therapies, or the rebate percentages required to secure favorable coverage may not yield an adequate margin over cost or may not enable us to maintain price levels sufficient to realize an appropriate return on our investment in drug development.

We are developing a new drug product, which is IA gemcitabine delivered via the proprietary RenovoCath device (IAG). If the drug is approved, it is expected to be sold together with the catheter used to administer the drug in the National Drug Code (NDC) created when the drug receives FDA approval. The reimbursement pathway involves separate payments for the drug product and for the occlusion procedure to administer it. As to the latter, it is anticipated that the procedure is accurately described by an existing code with existing payment levels. Given the expectation that the drug will be a novel, non-generic drug, a unique code and payment based on pricing information for the product should be established.

For the reasons discussed above, we believe there is a clear path to reimbursement for IAG and its related procedure in both the hospital outpatient and physician office settings (which may include freestanding entities such as catheterization laboratories). As is typical for a product still in clinical development, it is difficult to predict whether there would be any Medicare coverage obstacles, which there usually are not for FDA approved drugs being used for on-label use. We believe the most important step we can take to enhance reimbursement for our products is the development of published peer-reviewed clinical literature supporting their clinical benefit. While we may also explore commercial opportunities to sell RenovoCath as a standalone catheter, which would require its own insurance reimbursement arrangements.

Competition

The oncology biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies and strong competition. While we believe that our knowledge, leadership, experience, scientific resources, intellectual property, regulatory barriers, and the advanced stage of our clinical development provide us with competitive advantages, we may face competition from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology companies, worldwide. Many potential competitors have substantially greater scientific, research, financial, technical, and/or human resources than we do.

Many companies are active in the oncology market both in terms of commercially marketed products and products in development that could potentially compete with our products and product candidates for the treatment of solid tumors. Any product candidates that we successfully develop and commercialize may compete directly with approved and/or new therapies that may be approved in the future. Our competitors may also obtain FDA or foreign regulatory approval for their products more rapidly than we may obtain approval for our product candidates, which could result in our competitors establishing a strong market position prior to us entering the market. Key competitive factors affecting the success of our product candidates, if approved, are likely to be their safety, efficacy, convenience, price, and the availability of reimbursement from government and other third-party payors. Many companies are developing new therapeutics, and we cannot predict what the standard of care will be as our product candidate progresses through clinical development.

Novocure’s PANOVA-3 study evaluating Tumor Treating Fields (TTFields) in unresectable, locally advanced pancreatic adenocarcinoma concomitantly with intravenous gemcitabine and nab-paclitaxel as a first-line treatment achieved its primary endpoint of overall survival with a 2.04-month median overall survival difference compared to chemotherapy alone.1 FibroGen’s locally advanced pancreatic cancer phase 3 did not reach its primary endpoint, failing to show an improvement in survival.2 We are aware of a number of companies in Phase I and Phase II clinical trials for the treatment of LAPC including one interventional company, TriSalus Life Sciences, as well as an upcoming ablative radiation study in locally advanced pancreatic cancer.

1 https://www.onclive.com/view/tumor-treating-fields-plus-chemotherapy-improves-os-in-unresectable-pancreatic-cancer

2 https://investor.fibrogen.com/news-releases/news-release-details/fibrogen-announces-topline-results-two-late-stage-pamrevlumab

Many of our competitors have substantially greater financial, technological, research and development, marketing and personnel resources. In addition, some of our competitors have considerable experience in conducting clinical trials, regulatory, manufacturing and commercialization capabilities. Our competitors may develop alternative treatment methods, or achieve earlier product development, in which case the likelihood of us achieving meaningful revenues or profitability will be substantially reduced.

Employees and Human Capital Resources

As of the date of this Report, we have ten employees. None of our employees are represented by a labor union or covered by a collective bargaining agreement. We focus on employee engagement and believe our relationship with our employees is good. We have 11 key consultants in the areas of quality, regulatory, finance, legal, clinical, and marketing.

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, and incentivizing our existing employees. The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives.

Facilities

In October 2024, we entered into a lease agreement for approximately 1,900 rentable square feet of office space as our administrative headquarters at 2570 West El Camino Real, Suite 320, Mountain View, CA 94040. The term of the lease began on December 1, 2024 and is scheduled to terminate on November 30, 2027. We believe that our facility is adequate for our current operations and purposes, and that suitable additional or alternative space will be available in the future on commercially reasonable terms, if required.

Legal Proceedings

From time to time, we are engaged in various legal actions, claims and proceedings arising in the ordinary course of business, none of which are expected to be material.