Thank you all for joining today's webinar, which will focus on the evolving pancreatic cancer landscape and the role of RenovoRx's TAMP platform. My name is Justin Walsh, and I am a covering healthcare analyst at JonesTrading. If anyone in the audience has questions that you would like addressed, feel free to send them to me via email at jwalsh@jonestrading.com. I will do my best to address them, time permitting. I am joined today by Shaun Bagai, CEO of RenovoRx, Dr. Dae Won Kim, Medical Oncologist at the Moffitt Cancer Center, and Dr. Ravi Shridhar, Radiation Oncologist at the AdventHealth Cancer Institute. I will let the KOLs expand on their backgrounds a bit further into today's event. With respect to format, we are going to start with a brief intro from RenovoRx before hearing from each KOL in turn.
We will then address audience Q&A with both KOLs together before turning back to RenovoRx for a final fireside chat. With that, I will turn it over to Shaun. You can please go ahead and introduce yourself, give us a little bit of background on RenovoRx, and provide any relevant disclosures and safe harbor statements.
Great. Thank you, Justin. I appreciate the opportunity here with JonesTrading, and thank you, Dr. Shridhar and Dr. Kim for joining today's KOL webinar. My name is Shaun Bagai, CEO of RenovoRx. I have spent my whole career in the medical technology space, with the hopes of helping create and then creating disruptive technologies that will really change the landscape of medicine. It looks like with RenovoRx, after 12 years of hard work, this is starting to finally come to fruition. As a very high level, when we think about cancer care and cancer therapy, it is about balancing what we do to the patients versus what we do to the tumor. Unfortunately, a lot of modern medicine really destroys the patient in the process of trying to kill the tumor.
We found a way to do that completely differently, where there may be an opportunity here where we can actually tackle the tumor and have the patients not have the same toxicities and side effects. With that, I will give you a small, short background and then turn it over to the physicians to really dive into details about how they see this in their practice. To start at high level, our disclaimers, disclosures, forward-looking statements are on our website. Just start at high level about what we are tackling and how that works. When we think about tumors, we often think about balls of tumor cells fed by a lot of blood vessels, and that is the case with many cancers in the body, like liver tumors, for example.
As a background, on the left panel, we see a cartoon image of a liver tumor that has a large blood vessel that feeds directly into the liver tumor. Many tumors in the body don't have a large blood supply and don't have these large tumor feeders, like pancreatic tumors, for example. In this case, the tumor cells are fed very slowly. There's not a big blood vessel that feeds the tumor itself. The tumor grows slowly. It actually gets necrotic on the inside, and there's a lot of fibrotic dead tissue. What this does is cause almost a barrier to chemotherapy success, where not a lot of chemotherapy gets into the tumor, causing results not to be fantastic. We overcome this via what we call a Trans-Arterial Micro-Perfusion that utilizes our RenovoCath device.
This is FDA-cleared for the delivery of chemotherapy and other therapeutics, and I'll talk about really quickly how that works in patients. When you think of systemic chemotherapy, again, we're giving current standard of care through the veins, and it really traverses the whole body, causing a lot of side effects, of course, and very little gets to tumors like pancreatic tumors. We do get some effects, in liver tumors, for example, where you do have that large blood feeder vessel going to the tumor, with the side effects. But unfortunately, in pancreatic tumors, glioblastoma, non-small cell lung cancers, bile duct cancers, and sarcomas, you don't get a high concentration of drug in the tumor because they don't have as large connection to the blood supply.
V ia our Trans-Arterial Micro-Perfusion system, or TAMP, a physician's able to position our RenovoCath device adjacent to the tumor using X-ray guidance. The patients are in and out of the operating room and out of the hospital usually in a day in an outpatient setting. It's just a small little incision, about 2 millimeters, to go to the patient's leg artery fed adjacent to the tumor. Then using the proprietary nature of our device, they can blow up two soft balloons and isolate blood flow adjacent to a tumor and then deliver a full dose and volume of therapy. Imagine a liter of fluid going into a small space that's about 1 to 2 milliliters in volume over 20 minutes, causing a pressure head, then forcing the agent through the blood vessel wall without causing much damage.
Then actually traversing the tissue and saturating the tumor in chemotherapy. What we end up seeing is about 100 times the dose at the tissue site than you would if you gave systemically, really causing a potential efficacy effect on the tumor and hopefully massively reducing side effects in patients. Just to touch on data we've shown in the past, we did have a phase III trial, a TIGeR-PaC study. We actually completed enrollment very recently, and we were able to share the interim results of the first interim analysis back in 2023, earlier in the trial. This was presented at ESMO GI. Two of the major findings we saw is we saw a 65% reduction in toxicities and side effects in these tumors, these patients.
What you're seeing here is almost across the board, we see a reduction in all the common side effects you see with systemic chemotherapy when delivered locally via the TAMP mechanism. This is one of the biggest drivers of interest from physicians and patients on wanting to go for this therapy is because of that reduction in toxicity. On the flip side, we did see a trend towards a survival benefit. The preliminary data actually showed a separation of curves, where in this first 30% look, we saw a six-month separation where patients were living six months longer, almost double as long as what you'd expect with just standard of care systemic chemotherapy. This is an interim look.
It didn't hit significance yet, but trending, but it gives us a glimpse of a possibility of what this technology could do as we wait for final trial data. But what's interesting is the RenovoCath being 510(k) cleared is actually being picked up commercially, and patients are being treated because of that promise that there's a chance of longer living, and more importantly, in some circumstances, that reduction of toxicity and side effects. So with that, I'll hand it back to Justin, and we can hear from the physicians on their usage and thought process around this technology.
Great. Thank you, Shaun. Dr. Kim, you can turn your camera back on, and we can start there. You can introduce yourself, provide any disclosures you have, and give us a sense of your clinical and professional background.
Thank you for having me.
There we go.
Thank you for having me here. My name is Dae Won Kim. I am a Gastrointestinal Medical Oncologist focusing on pancreatic cancer at Moffitt Cancer Center. I have seen the pancreatic cancer patient over 10 years. As a disclosure, I receive the research support from Revolution Medicines and RenovoCath.
Great. Maybe we could just start here. I wonder if you could provide an overview of the current standard of care in pancreatic cancer treatment.
Basically, the main treatment for the pancreatic cancer, depending on the resectability. If it is resectable, patient will have the surgery, but still, after surgery, patient need chemotherapy. If it is not resectable, the patient need chemotherapy, and depending on the location of the staging, if patient has a localized pancreatic cancer, then we give the chemotherapy radiation. If it is metastatic disease, patient only need chemotherapy. In the initial diagnosis, around 50%-55% patient will have metastatic pancreatic cancer, and then around 30%-35% patient will have locally advanced unresectable localized pancreatic cancer, and then only 10%-15% patient can go to the surgery.
Got it. What is the typical patient journey? I imagine that it is largely dependent on the distribution at diagnosis that you just cited.
Yeah. Depending on the staging, actually, the majority patient need a lifelong chemotherapy, unless it is unresectable. Basically, if either the locally advanced or metastatic pancreatic cancer, those patient need lifelong chemotherapy.
Got it. Where do you view the greatest unmet need?
As we discussed, if it is not resectable, since all the pancreatic cancer patient need lifelong chemotherapy, then they are suffering from a lot of side effect toxicity. Actually, even though I said lifelong chemotherapy, nobody can tolerate lifelong chemotherapy. That then means we need less toxic treatment to control the pancreatic cancer.
Got it. How has pancreatic cancer treatment changed in recent years?
Unfortunately, we haven't seen much of change because we are still using almost the same chemotherapy, which we used 30 or 40 years ago. The only thing is, we can discuss further, but recently, there's new targeted therapy targeting the KRAS mutation, daraxonrasib. We're expecting soon FDA may approve this daraxonrasib treatment.
Got it. When we're thinking about clinically meaningful improvement in the locally advanced pancreatic cancer patients, how do you weigh survival benefit, tolerability, ability to remain on therapy, quality of life from bo th your perspective as a physician and from the patients that you deal with?
Basically, main thing is locally advanced pancreatic cancer, unfortunately, we cannot offer the surgery because of this major vascular involvement. So those case, actually, treatment is similar with metastatic pancreatic cancer, but it's better, actually, the survival. But still, the patient should stay in the mainly chemotherapy. Of course, we can also offer some local therapy after chemotherapy, including radiation. But now, actually, also chemo treatment, field treatment is also approved, so we can also use it. But still, the main thing is actually quality of life is main key because patient need a lifelong systemic or local treatment. So that's why how to decrease the toxicity, I think is the most important in the locally advanced pancreatic cancer.
Got it. Now, I think jumping off that there, from your perspective as a high-volume TAMP user, where do you see TAMP fitting today in the treatment journey for patients with locally advanced pancreatic cancer, and how has your view evolved here with your increased clinical experience?
So basically, all the locally advanced pancreatic cancer patient need systemic chemotherapy, at least six months. Then we usually offer the radiation treatment. The problem is after the six months chemotherapy, the people usually have a lot of side effect toxicity, including low blood count, and also sev ere fatigue weakness. Because of this chemotherapy-related toxicity, after six months chemo and radiation, it's not easy to continue systemic treatment. As we can see this interim analysis of the phase III data, compared with the systemic chemotherapy, we do see significantly less side effect toxicity, including the low blood count, that those thing is much, much better with this TAMP treatm ent compared with systemic treatment.
That's why this TAMP treatment may be the good option for the patient who receive six months chemotherapy and the radiation, because patient still can have a good quality of life and then continue the tumor control with TAMP approach.
Got it. As you've used TAMP, has your, I guess, perception of it changed? Are you more likely to go for it? What were you thinking when you first started versus at this point?
Basically, again, actually, after six months of chemotherapy, we assuming those patient usually have the well-controlled disease, but still there's a risk of the tumor recurrence. Of course, we are giving the radiation treatment, so still they need some type of the maintenance treatment. But the problem is, when we go back to the chemotherapy, they will not have quality of life. That means actually they will have a lot of side effect toxicity. Since they already exposed to the chemotherapy previously, they cannot tolerate it. That's why I think eventually, I think we need some less toxic maintenance treatment. I think this TAMP is kind of the perfect fit in th ose situation.
That's why I think eventually, we will go to that, this TAMP or any kind of less toxic treatment will be needed for those patients who receive chemotherapy and then radiation treatment.
Got it. Well, maybe this is a good transition here, too. You'd mentioned the news around Revolution Medicines and the daraxonrasib a nd there's other emerging systemic or targeted approaches in pancreatic cancer. How do you see TAMP fitting into the treatment landscape as we start thinking that some of these other drugs could become more common?
Basically, right now, there's a daraxonrasib KRAS-targeted therapy will be used for the metastatic pancreatic cancer, but there's a possibility this daraxonrasib can be also used for the locally advanced pancreatic cancer with the combination with the chemo. However, still daraxonrasib has some limitation. That means daraxonrasib cannot cure the pancreatic cancer. Still, there's a possibility combination with the chemo and daraxonrasib can actually increase resection rate of the locally advanced pancreatic cancer. However, still several patient will have this localized unresectable pancreatic cancer, those patient still need local therapy with less toxicity. That's why even daraxonrasib will change the treatment field in the pancreatic cancer, still we need a local therapy to control the tumor with less toxicity.
The another problem with daraxonrasib is 80%-90% patient will have a s evere skin rash, and also still we do see the toxicity. Of course, compared with the chemotherapy, daraxonrasib has less toxicity, but still, I do see several patient should hold the treatment and then maybe reduce the dosage of daraxonrasib.
Got it. Conceptually, and from some of the data we've seen, I think it makes total sense that TAMP should reduce the toxicity. I'm wondering from your own clinical experience, how TAMP has affected the overall patient experience, particularly for the ones who might benefit from a break from the cumulative toxicity that we see with systemic chemo.
Yeah. So, what happened is I have several patients who had locally advanced pancreatic cancer receive TAMP treatment. The interesting is actually because all of them received six months of systemic chemotherapy, majority of them has a kind of decreased performance status. At that time, I couldn't offer the systemic treatment anymore because of, for example, low blood count, severe weakness. At that time, actually, those patients actually did very well because as we can see in the interim phase III analysis shows a significantly decreased side effect, treatment-related toxicity adverse event, including the fatigue, weakness, and low blood count. So those patients actually did well and tolerate planned eight treatment of this TAMP treatment.
Unfortunately, I think one patient, after completion of this TAMP treatment, patient had metastatic disease in the liver, but the tumor in the pancreas is controlled. That patient, with this TAMP treatment, he regained all strength. That's why he could go back to the chemotherapy, systemic treatment. That means that if patient continued the systemic chemotherapy, he could not continue chemo even when he developed metastatic disease, we could not offer. With this TAMP treatment, of course, we don't see mu ch of toxicity, and also patient could regain the strength. That's why I think this TAMP treatment, which is associated less toxicity, will have good option for those patients.
Yeah, I think it's always good to hear some of the real-world use cases here. I'm curious how you interpret the interim phase III TIGeR-PaC data, which evaluated TAMP delivery of intra-arterial gemcitabine via RenovoCath in locally advanced pancreatic cancer, particularly in the context of results from some other recent studies in the patient population.
Yeah. I think the trial enrollment is completed, so we are expecting the final result next year. Based on the initial interim analysis, this TAMP treatment actually imp roved the progression-free survival and also improved overall survival. But most important thing is, compare with the systemic treatment, this TAMP treatment actually associated much, much less side effect toxicity. So that, I think, is very important in that real-world patient treatment.
Got it. I think your answer there at least partially answers this, but we've heard some physicians suggest that even if the final TIGeR-PaC survival results are equivocal, TAMP's tolerability profile could still support its adoption, while, of course, a positive efficacy readout would further strengthen the case. How do you view this balance of the tolerability, which is what you're searching for, and potential for improved efficacy?
Yeah. Basically, the study design of the phase III trial of this TIGeR-PaC is actually to see the superiority of this TAMP treatment compared with this systemic chemotherapy. But the worst case, even that does not show this TAMP treatment, the final data does not show the improvement of the clinical outcomes, overall survival or the progression-free survival. What we see is, even with this interim analysis data, we do see the significantly decreased side effect toxicity. I think because what happened is, in the real world, after six months chemo and radiation for the locally advanced pancreatic cancer, we cannot offer the additional chemotherapy to control this localized pancreatic cancer.
We can not offer systemic chemotherapy most of the time because patient already have a lot of side effect toxicity they couldn't tolerate, because accumulating toxicity and also some patient have a really low blood count, platelet count, white blood cell count. So even though the worst case does not improve the clinical outcome of this treatment, then because of this significantly decreased toxicity, it got much better toxicity profile, then definitely in the real world, we can use this treatment for this patient who completed six months chemotherapy and radiation in the locally advanced pancreatic cancer.
Got it. That makes total sense. Thanks for these comments. If you can kind of stay in the background, and we'll bring you back for the Q&A. But for now, Dr. Kim, you can drop off camera, and Dr. Shridhar, you can come back.
Let's see.
There. Perfect. There we go. Good to finally hear from you. Maybe you can introduce yourself, provide any disclosures, and then give us a sense of your clinical and professional background.
Hi, I'm Dr. Ravi Shridhar. I'm a Radiation Oncologist. I was formerly at the Moffitt Cancer Center, and now I've been working at AdventHealth in Orlando for the last 12 years now. We're a large multi hospital-based system. I think we have 16 to 20 hospitals covering Central Florida from Daytona all the way down to Tampa. We have a very large program. We have a fully staffed cancer institute with surgical oncologi sts and surgeons in every different specialty. We do see quite a bit of pancreatic cancer. I've been specializing in treating pancreatic cancer for a while. I was involved in some of the early work with stereotactic radiation therapy for pancreas. That's pretty much my go-to regimen. I think very similar to the TIGeR-PaC trial. I've had disclosures with Boston Scientific and HistoSonics, which have now since lapsed.
Awesome. Well, maybe we can jump right in here and how has your experience been with TAMP and RenovoCath?
It's been, I think initially a little bit of a learning curve for new people starting, but as we've gotten the first two to three cases under our belt, I think our interventional radiologists have really gotten it down, and now we are kind of getting into a nice flow of getting patients through pretty quickly.
Got it. You've, as you just alluded to here, you've integrated TAMP into your practice relatively quickly. Demand has grown to the point where your center is now working to train additional interventional radiologists to support the procedure. I'm wondering if you could describe what is driving the demand, and what you think it says about the role TAMP is beginning to play in your practice.
Yeah. For locally advanced patients, I think like Dr. Dae Won Kim had eloquently stated, we give the six months of chemo, and we give the radiation, and maybe they can get maintenance chemo if they don't have a lot of side effects, and their cou nts are holding up. But even when we do radiation, our response is mostly minimal response to stable disease. It does control the tumor, it does kill it, but it's a very fibrotic tumor, like everyone said, poorly vascular, and we wish we could do more. But more chemotherapy does not seem to be the answer. It's also not if medical oncologists could hold chemo as long as they could, I think they're going to do that. One of the newest evolving oncologic endpoints, especially in pancreatic cancer, is a chemotherapy holiday.
It's like, can we bridge the patient with other treatments like either radiation or ablation or something else till we absolutely need the chemo to give them more time to recover before we have to reinitiate chemotherapy again? But this is a chemotherapy holiday without, but still giving targeted chemotherapy. Because you're not going to get all the major systemic side effects. Even our first patient that we treated with a bulky, locally advanced tumor and did well after the chemotherapy and radiation, we saw minimal response, but even after three infusions, with the TAMP, we saw already a 50% shrinkage of the tumor, even after three. To the point where after the fourth one, we said, "We don't think we're going to get much more response, and we're kind of holding."
She's also a little bit on the frailer side, but this is the thing, we can treat good-performing patients and also not so good-performing patients. When you're dealing with pancreatic cancer, it can negatively affect your performance status just but with the cancer itself. But this is a treatment where we can give aggressi ve but highly targeted chemotherapy to the tumor without having a lot of the side effects, and I think our medical oncologists are highly supportive of this because it gives them a break from a lot of the systemic effects because we're not seeing a lot of those systemic side effects. If anything, they have a little bit of abdominal discomfort and a little bit of nausea, but which is very well managed, and it's all outpatient.
Got it. Would you say that the demand is coming from the medical oncologists who want another option, or the interventional radiologists who are working with it and I'm just curious how this sort of plays out within the structure of the practice and who's really out there, I guess, saying like, w e need to use RenovoCath.
Yeah, so I think it's an interesting question. I think right now a lot of the biggest drivers for referral are coming from me, but also now when we're seeing some of these early results, the medical oncologists are, "Okay, give them the radiation and get them set up for TAMP, and then, we'll keep them under surveillance, and then, if they progress, then we'll reinitiate chemotherapy." I think the results are helping to drive the referrals from medical oncology. But I think coming from radiation, I can be as aggressive as I can with radiation, but there's only so much I can do and give, and it's going to only respond so much.
This is another way of getting very highly targeted therapy, and I think that's one of the bigger drivers, especially in the locally advanced setting, where this is showing that we're getting at least there's a signal now that there is a much more robust survival. When we look at early studies, we were happy with median sur vivals in the 15-18 month range, with whatever we were doing with whatever new therapy was getting. So you guys are already approaching that two-year mark, which is really kind of impressive.
Got it. So you answered this a bit here, but I'm curious which aspects of RenovoCath do you find most compelling and clinically useful at this point?
I think the nature of the treatment itself, it's once the interventional radiologist gets good, which takes about three to five cases, the procedure time is about an hour and a half at the most. So the patients come in, they get their treatment, they go home that day. And we're not seeing a lot of the blood count issues. We're not seeing a lot of these long-term side effect issues with the chemotherapy, and they seem to be tolerating it very well. So this is an aggressive approach, a good way. It's a very aggressive form of maintenance therapy after we do our initial treatments. And I think it's starting to yield benefit, not only in terms of response, but I think, patients are tolerating it well, and we're starting to see a signal for survival.
Got it. It seems like at least part of this is clinical outcomes, but I am curious what the main driving factors that enabled the adoption of RenovoCath at your center and if you could walk us through this process, whether it was particularly challenging or not.
Yeah. Interventional oncology has become a vital component to cancer therapy. I think, you can thank the Y90 folks, whether it is from Sirtex or TheraSphere, as they got all these IRs good at doing angiography. That is the key. You need a good, robust interventional oncology group that does a number of these intravascular procedures. I think, our IRs do, since we also have a pretty busy Y90 program, they are pretty well-versed in angiography. This was a little bit nuanced. There is just different placement of the catheters and understanding the balloon, but that is just another technique that takes three to five cases to really learn. But they already had the background of intravascular therapy. Mostly for liver, but now, having this on board for pancreas, our IRs were kind of excited to take on this procedure.
Now, we started at one institution, and now, when we had to get the catheter approved, it did take a little bit of effort. Whenever you are bringing a new device into a large hospital-based system, it has got to go through a number of committees and finance, this and that to get approved. It was a little bit of a process, but we were able to navigate that with the interventional radiology team. We did get the approval for the catheter, and then almost immediately right out the door, we started treating. Now we are at the point where we have two or three IRs trained to do it at one institution, but we are kind of maxing out in terms of our scheduling at that one institution. So now we are expanding.
I think we are looking at AdventHealth Tampa is going to be our next site. But we are also looking to expand it to AdventHealth Orlando and a couple of the other sites within the central division that do see a fair amount of pancreatic cancer that also have those IRs that are skilled in angiography. I think that is the key. Being in a system that does a decent number of intravascular procedures, I think this adds basically another tool in their toolbox.
Got it. As a radiation oncologist, it would be great to hear your thoughts on how different medical specialties can actually find and refer patients for TAMP. Obviously, you alluded to all the medical oncologists, and the interventional radiologists are the ones actually doing the procedure. Good to hear that and hear about how you are involved as a radiation oncologist.
Yeah. Yeah, and I think the initial TAMP data show that the ones who truly had the strong survival benefit were the ones who received radiation therapy. I think, just based on that, if we are going to go chemo, then radiation, then TAMP, radiation oncology is probably going to be the initial main drivers. For those that have had radiation maybe several months ago and are getting chemo, and now this becomes ava ilable, and it is locally advanced disease, I think once we have this more widely available across our system, I think our medical oncologists are going to end up directly referring to interventional radiology as we expand through our system. Our surgical oncologists are also very supportive.
They know that a fair number of these patients, they will attempt to do surgery and have to abort just because they are not able to get it off the vasculature. A couple of the cases we have done were aborted attempted surgeries that they could not do, and we have now been able to salvage. In fact, we have a patient that we are actually treating, that had surgery, but had a recurrence involving vasculature. It was all surrounding the vasculature, unresectable, and so we have been able to get her through the first three infusions so far. She is getting her fourth one next week, and then we are going to re-scan her. It is interesting, we were actually able to do that in the postoperative setting.
Anything that is kind of locally advanced that is by the vasculature, this seems very feasible to do. But I think as we expand across the system, as the data matures also from TIGeR-PaC, and we get that out, I think we will get more med oncs and surgeons referring across the board.
Got it. Now, as an early adopter of TAMP, how do you see its use growing within your hospital system? I know you mentioned that you're looking to go to the Tampa location. What impact are you seeing for patients, and what factors may determine whether your experience translates more broadly across other cancer centers?
I think all of that comes down to a good working relationship, and we have a strong multidisciplinary team. I have a very good working relationship with our interventional radiology team. I screen all patients that are referred to me for the potential for TAMP. I'll get a highly specialized CT scan that I'll review with the interventional radio logist, and they'll give me the thumbs up or thumbs down saying, "Just based on this CT scan, I don't think this is going to be a good case," or, "Based on this CT scan, this will be a good case." We have that kind of collaboration and communication. I think at the other institutions, there's going to be that similar communication, especially for those medical oncologists and radiation oncologists that do refer to IR for specialized procedures.
I think this'll just be another one that will require another form of communication, additional testing. But once it's available, I think that's going to be a big driver of it.
Got it. I'm sure that your field is collaborative for any indication, but I'm curious if pancreatic cancer, in particular, given its, I guess, severity and unfortunate lack of effective therapies, if maybe there's an even higher motivation for a cancer center to make sure that everyone's talking to each other and and using the most appropriate thing.
Absolutely. I think, yeah, that's key. After induction chemotherapy, they represent cases in tumor boards. Surgeons will say either, "More chemo," or, "No way, we're never going to operate on this patient." We go down the rad iation route. We have those discussions quite frequently in our GI tumor board. We have interventional radiology there as part of that.
Got it. Last question just for you before we turn to some Q&A here. I'm wondering what lessons you learned that could be helpful for other institutions that are considering adopting TAMP, and maybe you could speak a little bit to the kind of, I guess, the pricing question that took a little bit of approval. I don't know if there were specific arguments that worked on that point, or if it's just bureaucracy takes a little bit of time and they had to dig through the details.
Yeah, I think it's that latter. Every hospital system is going to be different. They're going to have their own different reviewing committees for getting in devices. It's just having your radiologist or oncology team kind of starting that process early to get the hospital to approve bringing that into the system. Once it's FDA-approved, it's hard to say no. It wasn't that they were saying no, we're such a large conglomerate. We span nine states and in Florida. When they're making decisions now, it's just not at the Florida level, it's at the corporate level nationally. Now that it's in the system here, it'll be available in all the AdventHealth systems across the country. Hospitals are going by that kind of multi hospital-based system.
Just having to learn to navigate that bureaucracy is going to be key, and just to start the process early. Because, yeah, no one's going to say no when something's FDA-approved. It's almost malpractice to do that, especially if you want to get it into the system as a very viable form of treatment.
Quick follow-up to that. I'm curious about your thoughts about. Obviously there are impediments to initial use and adoption. But I'm wondering if spreading within that system once you're approved is a bit easier. Ob viously, you can't, if it's not approved for use, you can't use it. But if it's, like now you mentioned going to the Tampa location, I'm imagining that that's going to be an easier process adopting that since you already have the blueprint from where you are.
Correct. The big key is the proctoring, right? So we were a new site, you guys had to bring in outside proctors. Our guys went to Moffitt to see that and got their training, and then brought that here, and then first three cases, we had a proctor come in. Now our guys know how to do the case. They can do the proctoring within the system. We don't have to send the guys out. They can kind of walk them through that. So once you have it in the system, then you become your own proctor within the system, and I think that helps to expedite the process.
Got it. Well, thank you. You can stay on, and then Dr. Kim, you can come back on camera. We'll, once again, like to remind anyone in the audience that if you would like to ask a question for either one of these KOLs, you can shoot me an email at jwalsh@jonestrading.com. I do have a couple of questions for our panel here. Let's just have a conversation and see how it goes from there. Maybe the first one here, someone's curious about what key benchmark data or evidence really informs your treatment decisions in pancreatic cancer? I think here they're kind of thinking about this context of course, Revolution Medicines in the metastatic si de and the TIGeR-PaC trial in locally advanced.
Curious about that, I think of relevance here, Dr. Shridhar, radiation and chemo is, of course, mainstays in pancreatic cancer, but I don't think it's too controversial to say that they're not ubiquitously effective. But, of course, we still do that. Any context on this front would be helpful.
I think from the radiation point, we've maximized, pretty much hit the ceiling with, I think, what we can do. I think maybe we can combine it with other therapies. I think when we're looking at a therapy, there's a number of things- What is the magnitude of either survival or control of the disease? Does it afford a break from traditional therapies that have known side effects or the side effects overlapping from previous studies? We take into account a number of things. Taking all of that into account, when we apply those standards to this catheter, it seems to meet all of that. We're starting to see a survival signal. It's well-tolerated. The side effect profile is very well-tolerated. It's an outpatient treatment. I think, from that aspect, I think that's how I review new treatments.
Any thoughts, Dr. Kim? I know that we talked a little bit more directly about some of these questions. Yeah, I don't know if you feel like it's really survival is the most important thing, if you have any thoughts on benchmarks or what you need to see to inform your treatment decisions in pancreatic cancer.
The couple of things we'd like to focus in this question, because one is the curre nt phase III trial, TIGeR-PaC trial. We're looking for the overall survival benefit from this TAMP approach. Historically, expected median overall survival of this locally advanced pancreatic cancer is around 16 to 18 months. That's why with this TAMP approach, we are waiting for the final result, how this TAMP approach improved overall survival. That's one goal of this trial. The second one is the quality of life is very important for the pancreatic cancer because main symptom of the pancreatic cancer comes from the primary tumor growth. Around the pancreas, there are a lot of major blood vessel and also major nerve.
If the primary tumor growth is not controlled, patient will have no quality of life because a lot of pain, a lot of symptom. This tumor is very close to gastrointestinal organ, including stomach and also the bowel. That's why if tumors continue to grow, that will induce bowel obstruction, and also that will compress a lot of major nerve that can induce a lot of severe pain, even pain medication does not control the pain. That's why local tumor growth, primary tumor growth control is also very important to improve quality of life. That's why the phase III trial result can address the overall surv ival. Even at this time, with primary tumor growth control, I think this approach can improve quality of life with less systemic toxicity. That's why I think this one is kind of promising.
Got it. Yep. I have another good question here. Since metastatic PDAC management relies heavily on balancing systemic disease control with cumulative patient toxicity, could RenovoCath be used in a sequential fashion, for instance, using TAMP to aggressively control the primary pancreatic driver before transitioning patients to a lower dose systemic maintenance regimen? Then there's a follow-up about some trials there. Any thoughts on this sort of sequencing TAMP use within the treatment regimen?
I can quickly comment on that. Right now we do not know what the role of TAMP is in the metastatic setting. I think those investigations have to happen. We do practice in the real-world setting, and this is going to be an issue, especially if someone has had radiation and then they start to progress at the tumor a nd at metastatic sites. There is trial data that has been published out of MD Anderson, where if it is like four or five tumors, we can do SBRT to those tumors, but if the primary tumor is also progressing, TAMP would be an ideal approach to also further help that if they have already had previous radiation. That is one example where I can see that could be utilized.
I 100% agree with Dr. Shridhar. Basically what happened is there is some clinical trial targeting this solitary metastatic disease with radiation. What I see is actually every pancreatic cancer will be different. Some pancreatic cancer, they have a good response to chemotherapy. I am talking about the metas tatic pancreatic cancer, and some even with aggressive chemotherapy does not respond to that chemotherapy very well. If the metastatic pancreatic cancer patient have a good response to the systemic chemotherapy, then there is a possible, after six months of chemotherapy or several months of chemotherapy, if overall disease burden is well controlled, then we may consider additional local therapy in the metastatic location and also the pancreas area with this TAMP.
Of course, in the real world, we try to use radiation first in the metastatic site and also primary pancreas site. After that, we may use this TAMP approach in the selected case. Actually, we are actually planning some clinical trial. Those patients who has metastatic pancreatic cancer and a good response, then we will try to do some additional local therapy with a systemic chemo, with this TAMP approach. We are planning that trial.
Got it. That was actually a follow-up to this, the same questioner is asking if there are any investigator-sponsored trials exploring TAMP outside of the strictly non-metastatic, locally advanced pancreatic cancer setting. I can confirm with Shaun if, follow up to that. I do not know if you guys are aware of any other trials that are ongoing on that front. Yep, okay. So, another question I have here from the audience. They are curious about your perception of how well TAMP is known or understood in your relative fields, and what do you think it would take others to try the approach?
Excuse me?
Yeah. So, how well do doctors know about TAMP? I guess that is the o ut side of your immediate sphere, do you go to medical meetings and people have heard about it? I am not sure your kind of level of awareness on that front.
I think there is several ongoing seminar for this TAMP approach. Also, I think also the main study data will be presented, announced next year. At the time, more oncologists will be aware of this approach. But you are right, mainly, I think, still I do see several medical oncologists are not aware of this, but I think the RenovoCath team, I think, are working on it, too.
Yeah. TIGeR-PaC, I'm assuming will go a decent way in pushing it as well.
Yeah. I think I'm meeting you guys up at ASTRO this year, our national meeting. I think that's kind of the best way to get the word out is at these national meetings. So if you hit up ASTRO, ASCO, and then either SIR or some of the other, like CIO, the interventional oncology meetings, that's going to be the best way to get the word out. I think the interventional radiologists are aware of this. I've spoken to a number of my IR colleagues across the country. They're about to get their programs started. So, I think the word's out. I think just to help get the word out, you just go to the national meetings. But once the paper gets published as well.
Got it. This is somewhat related here, and the last question I currently have from the audience. So if anyone has burning remaining questions, feel free to send them to me. Someone's just curious if you've seen any pushback from using the TAMP approach, either at your own institute or from colleagues. That I imagine that at least some of that is waiting on final clinical validation and maybe you overcame initial pushback and getting it approved at your relevant institutes. But just curious if there is anything on that side of things that you've heard.
I think just from my institution, the biggest hurdle has just been scheduling and resource management, I think. I'm the kind of guy that ramps up a program pretty quickly, so maybe some of that is me. But, I think that's given the push to expand this across our system. So really that's been the biggest hurdle is just the scheduling and just getting all the IRs trained in a timely manner.
Awesome. I am not showing any further questions there, so thank you both, Dr. Shridhar and Dr. Kim for participating today. Shaun, you can come back on camera, and we can talk a little bit more about the RenovoCath and get caught up on that front.
Thanks, Dr. Shridhar.
All right. You guys can go off camera. Thank you, guys. All right. We can jump right back in here, Shaun. Obviously, you guys just had an update yesterday, so we have the most up-to-date public information out there for your company. Maybe we can start here with you providing an update on commercialization efforts for RenovoCath.
Yeah. Appreciate that, Justin. It was a good earnings call yesterday, and it is great to see the progress across several fronts, the commercial side. We have always said that a predictor of the future revenue is getting new centers activated and on board. Dr. Kim has been with us now for quite some time, and Dr. Shridhar a little bit more recently, and you are starting to see that adoption take place. Last year, without any sales infrastructure, we had four active centers, really four or five active centers and ramping that to, I think, 11 to 16 was the last readout at the earnings call mid-May. Now that is going to 21 active centers treating patients. That is really starting to pay off as we have seen the revenue start to climb as well.
With only a handful of sales reps, we are able to drive that adoption already. We have got four reps in the field and a head of sales. As I have said, it is really a very focused market, so we do not need more than four or five kind of market development managers or sales reps out there working with the hospitals, trying to help them get it through the system to be able to start purchasing, then finding patients to be treated. I think that is the big differentiator, is we are seeing that commercial traction and progress with a small sales team, and we do not need a larger headcount for this.
Got it. In that context, what do you believe is driving the current adoption trends? Related to that, how much are clinical and/or economic considerations resonating with physicians so far?
These are both tailwinds. As Dr. Kim and Dr. Shridhar mentioned, there is a huge unmet need there. Given that the toxicity of current standard of care, there is a need for another option. Going from chemotherapy to radiation, plus minus surgery, if we are lucky to catch it early enough, there is a need to try to find something that is localized, that does not have the toxicity, does not have the side effects. Having a delivery system and technology that can localize therapy that way, it looks like it is really working. So there is really a clinical drive for technologies like this. Then from an economic standpoint, having reimbursement in place, the hospital can make money off the procedures, so it is profitable. The physicians are also paid as well.
So there is not an economic barrier. It is really a drive where there is something that looks like it may be helping patients, there is a huge unmet medical need, and there is not a financial headwind for hospitals to start adopting the technology.
Got it. Maybe just if we dive a little bit more on that kind of economic question, I am just curious, as Dr. Shridhar has walked us through, the process takes a little bit to get things off the ground there. I do not know if there is any color or insight that you can provide. Obviously, I am sure you are involved in the process of trying to help these centers get on board and start making use of RenovoCath.
Yeah, it is just going through the process. It is a matter of providing paperwork to the hospitals to bring a new technology in, as Dr. Shridhar described. They usually, the finance teams will look at what the reimbursement codes are. They look at what the throughput of the labs are, the cost of the technology. A lot of times they have to go through a VAC approval or a value analysis committee approval to say, "Yes, we want to bring the technology in and start purchasing." Then once that approval goes through, they start ordering devices, and patients can start coming in. That sales cycle takes anywhere between, I have seen it happen in a week, I have seen it happen in a year and a half.
But really, the range there is four to five months on average, I would say, maybe four to six months. Having local reps in the field to help physicians through that process with providing paperwork, with following up and checking in, is starting to accelerate that. That is why as we get these new centers activated, that is when adoption really starts to happen, and we are starting to see that growth trajectory now in the first two quarters of this year.
Got it. I am sure a lot of the specifics are the same, but every hospital makes you fill out their own form.
Exactly.
So, maybe we could move on here to talk a little bit about the assumptions that give you confidence in your estimates of the peak market opportunity.
Yeah. Looking at a market like pancreatic cancer, there are about 60,000 plus patients diagnosed per year. Of them, locally advanced is really where we've seen a lot of data. It is about a third of those patients. But we are starting to see interest in usage where there is a mention of metastatic pancreatic cancer. Moffitt's actually launching an IIT in metastatic pancreatic cancer, and we have several IITs in borderline resectable. So it kind of expands to make that whole 60,000-patient market eventually kind of a target. If you haircut that down, given that each patient has between five and 10 procedures, the devices with reimbursement analogous technologies are kind of in the $6,000-$9,000 range for these types of devices.
Getting even a small percentage of that 60,000-patient market, plus other indications as we have recently announced, we have started to see usage outside of pancreatic cancer, can drive us to a peak U.S. sales of about $400 million as a standalone device.
Got it. What are your expectations here for the TIGeR-PaC trial, and how much of the market depends on that outcome? You obviously just mentioned the $400 million for the device alone.
Yeah. From an update on this trial, as we recently announced, we completed enrollment in the phase III trial, so that's a big milestone for us, of course. We also have 78 of the required 86 events for the final analysis. The events are deaths, so we expect that 86th event to estimate to come in sometime first half of next year, with top-line data the second half of 2027. That gives you the expectation on timelines. As far as results go, given the ease of understanding that localizing the therapy with a drug that we know kills pancreatic tumor cells should work, and with positive first interim results, we feel confident that it looks like this is making a survival impact and obviously a toxicity impact. We feel confident in the trial and the data.
As far as the impact on commercial RenovoCath itself, there are really three buckets. On the worst case scenario, we have an equivocal efficacy result. You mentioned that, I think, what that outcome looks like. But we are seeing a definite toxicity improvement versus standard of care. As Dr. Kim mentioned, that's one of the biggest drivers we see. That's really, I think the worst case scenario is that we're no better than systemic chemotherapy, but we give what Dr. Shridhar called a chemo holiday. Patients don't have to have the systemic toxicities, but we're still doing something. We're still treating the local tumor. So I'd say that's the downside, protection. Best case scenario, we hit a P value, go for. That tells the medical field, of course, this is significantly better even with a smaller study.
Then that we could look at drug-device combination approval from there. Delcath, for example, has drug-device combinations. The reimbursement for a drug-device combination as a drug is even much higher than the numbers I explored earlier. So that could make that $400 million market more in the low single digit billions. Then the mid case scenario or the base case scenario is that we see a numerical survival benefit. So it looks like there's clinical significance, and we know the toxicity significance, and we still are able to drive RenovoCath sales, knowing that we have some benefit for the patient. So, really all three scenarios of what we come to expect are good scenarios for the technology and for patients.
Got it. I got an impromptu question from the audience, which I think is appropriate. Don't know whether or not you can make a comment here, but, someone's asking if, "As the treatment landscape for pancreatic cancer shifts towards targeted agents like KRAS inhibitors, are you actively considering or pursuing BD collaborations to evaluate TAMP as a novel delivery vehicle for next gen targeted small molecules like pan-RAS inhibitors and/or biologics?
Absolutely. This has been on our mind for a long time. gemcitabine is a very old, boring cytotoxic drug. Yet we have made it exciting because it looks like it can be effective when delivered locally. There are a lot of options out there of what else we can put through our catheter. We are a delivery platform. Looking at KRAS, we have looked at other immunotherapeutics as well, and even antibodies and viruses, and we have done some compatibility testing. It is a matter of picking the right target next. As a small, lean, focused company, we are focusing on where the current development is. We are in constant communication with larger companies on what else can be partnered with us. I do anticipate other partnerships and combinations down the road.
Looking at outside of gemcitabine, we did receive Orphan Drug Designation, as we have for gemcitabine, also for oxaliplatin for pancreatic cancer, and that is actually part of the Moffitt study we are planning on launching with the IIT, is local oxaliplatin and systemic oral therapy for Mets. One could imagine we can give something like daraxonrasib orally at the same time. There are partnerships to be had both on concurrent treatments and on local delivery of those same therapies. Those BD conversations will continue.
I am sure that any company that gets a drug approved in pancreatic cancer in particular, but in general, has a lot of incentive to have life cycle management moves like improved delivery. Look forward to hearing about that, hopefully as we get more effective therapies out there for these patients. With that, you can maybe take your time for any final comments or clarifications on the RenovoCath story and RenovoRx story, and as well as some financial expectations going into 2027.
Yeah, thanks for the opportunity there, Justin. It is interesting. Now we are really delivering on what we promised we would deliver. I think we came out saying that our mission is really threefold, is to show incremental increase in revenue, commercial growth, and success in terms of number of centers coming on board, and expansion outside of pancreatic cancer with delivery, and we have delivered on all three in this last quarter. On a commercial side, almost more than doubling our revenue. I think our revenue the first half this year is $1.5 million, and far exceeds 2025, with this last quarter of $900,000 exceeding or almost exceeding our 2025 as a whole. We are starting to see that really drive our EPS as well, where we are actually changing.
Unlike most companies, we are starting to reduce our burn over time, even with a commercial sales force in place. We are driving towards a break-even point, which is rare for a company this small, but we are targeting a potential break-even at Q4 next year. We have got the cash in the bank to start driving towards that as well. Commercial is going up, adoption is happening, and we are activating new centers, and we have got the right capital and balance sheet to get there. It is a great time for RenovoRx.
Great. Well, looking forward to hearing how that pans out. That is all of the questions that I have for you. I would like to thank everyone for tuning in. Hopefully, this was insightful. Have a great day.
Thank you.