Delcath Systems, Inc.

Greetings, and welcome to the Delcath Systems' fourth quarter 2024 earnings conference call. At this time, all participants will be in listen-only mode. The question and answer session will follow the formal presentation. If anyone today should require operator assistance, please press star zero from your telephone keypad. As a reminder, this conference is being recorded. It is now my pleasure to introduce David Hoffman, Delcath's General Counsel. Mr. Hoffman, you may begin.

Thank you, and once again, welcome to Delcat Systems' fourth quarter and full year 2024 Earnings and Business Highlights Call. With me on the call are Gerard Michel, Chief Executive Officer, Sandra Pinnell, Chief Financial Officer, Kevin Muir, General Manager, Interventional Oncology, Oya Vukovic, Chief Medical Officer, and Martha Rook, Chief Operating Officer. I'd like to begin the call by reading the Safe Harbor Statement. This statement is made pursuant to the safe harbor for forward-looking statements described in the Private Securities Litigation Reform Act of 1995. All statements made on this call, with the exception of historical facts, may be considered forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Security Exchange Act of 1934. Although the company believes that expectations and assumptions reflected in these forward-looking statements are reasonable, it makes no assurance that such expectations will prove to have been correct. Actual results may differ in a material manner from those expressed or implied in forward-looking statements due to various risks and uncertainties. For a discussion of such risks and uncertainties, which could cause actual results to differ from those expressed or implied in the forward-looking statements, please see risk factors detailed in the company's annual report on Form 10-K. Those contained in subsequently filed quarterly reports on Form 10-Q, as well as in other reports that the company files from time to time with the Securities and Exchange Commission. Any forward-looking statements included in this call are made only as of the date of this call. we do not undertake any obligation to update or supplement any forward-looking statements to reflect subsequent knowledge, events, or circumstances. Our press release with our fourth quarter and full year 2024 results is available on our website under the investor section and includes additional details about our financial results. Our website also has our latest SEC filings, which we encourage you to review. A recording of today's call will be available on our website. Now I would like to turn the call over to Gerard Michel.

Gerard, please proceed. Thanks, David, and thank you all for joining us today. 2024 was truly a transformative year for DELCAF, given the U.S. launch of Hepsado in January of that year. We generated $32.3 million of Hepsado revenue in the U.S. for the year, including $13.7 million in the fourth quarter from 14 active U.S. treatment centers. Importantly, in 2024, we secured both a permanent J-code and a new technology add-on payment, commonly called NTAP. While incremental revenue from Europe remains modest due to pricing and reimbursement structures, European growth in 2024 over 2023 was 137%, and this growth remains an important strategic component of the business. These achievements reflect the strength of our world-class commercial team, which has successfully navigated the complexities of launching Hepsado and expanding chemosat usage. Their ability to train multidisciplinary healthcare providers, secure hospital formulary approvals, and drive procedural adoption at major academic centers has been exceptional. In the fourth quarter, our cash burn was only at $1 million, and we achieved $4.6 million in positive adjusted EBITDA, a first for the company. and ended the year with $53.2 million in cash and investments with no debt. During the year, we received over $41 million in proceeds from the exercise of warrants. This financial stability enables us to expand R&D and new initiatives to maximize the hepatic delivery system's potential to treat other liver-dominant cancers. Shifting focus to the specifics of Q4 results and 2025 plans, during the fourth quarter, we activated three new U.S. treatment centers, Duke University of Utah and Mayo Jacksonville. So far in 2025, we have activated another two centers, bringing the total to 16 with an additional center scheduled for its first treatment in March and eight more centers accepting referrals. Our goal remains 30 active centers by year end. It is important to note that the centers we have activated or are in the process of being activated are leading academic centers, such as Mayo Clinic, MGH, Cleveland Clinic, and Thomas Jefferson, all of which are active, as well as Northwestern and D. Anderson, which are not yet active but accepting referrals. In Q4, the average treatment rate per site was slightly under two per month, a rate expected to continue in 2025 as we bring on new centers, which typically start at lower utilization rates before ramping up. To support this expansion, we are increasing our commercial team and expanding from four to six regions, each structure with a liver-directed therapy manager, an oncology manager, and a clinical specialist. The liver-directed therapy manager drives the hospital approval process and ensures the Habsado kit procedure team is appropriately trained and, once the site is active, supports the site as they manage the patient flow. The oncology managers engage community-based medical oncologists outside of our treatment centers with the goal of building peer-to-peer referral networks between the community oncologists and the treating centers. The clinical specialists support the treatment teams in preparation for and during the treatment with the goal of ensuring patient safety and improving patient outcomes. Additionally, we are enhancing the field support to assist centers with administrative processes, ensure accurate coding, and efficient claim submissions, which will facilitate broader adoption. Since the field force will be expanded by mid-year, we expect more than half of the incremental centers to be added this year to come on board in the second half of the year. Chemosat volumes in Europe grew 137% in 2024, with Germany up 75%, and other markets, including the UK and Turkey, doubling year over year. There were two new centers activated and one existing center reactivated in Germany. We expect modest study growth moving forward, maintaining a break-even strategy in the region. The strategic value of our European presence lies in supporting clinical trials and generating publications. In 2024, over 10 studies from European centers were published, including research on chemo sets used in intrahepatic cholangiocarcinoma. In 2025, we plan to expand into France, Italy, and Spain, complementing our strong presence in the UK, Germany, and the Netherlands. We continue to engage oncologists in both the U.S. and Europe to integrate Hepsado into treatment algorithms. In 2024, the Scandium-3 trial in Sweden began to screen patients. This 40-patient study compares two cycles of chemosat followed by ipilimumab and nivolumab versus ipilimumab and nivolumab alone. Meanwhile, the Chopin trial in the Netherlands, which sequences two chemosat treatments after initial ipilimumab and nivolumab therapy, completed enrollment with 76 patients in the third quarter of 2024. We expect the primary employee analysis of progression-free survival at one year to be reported in the second half of the year. In 2024, expert consensus identified liver-dominant metastatic colorectal cancer and metastatic breast cancer as promising new indications for HEP-SATO. Our phase two trial in metastatic CRC received FDA clearance in December, and we'll compare HEP-SATO plus trifluridine, tipuracil, babesumab versus standard of care alone in 90 patients. Enrollment is expected to begin in the second half of 2025 across 20-plus U.S. and European sites. The primary endpoint, hepatic PFS, is expected to read out by the end of 2027, with overall survival data following in 2028. Our market research estimates a total addressable market of 6,000 to 10,000 patients annually in the third-line liver-dominant metastatic CRC. The phase two metastatic breast cancer trial in a third-line setting of liver-dominant patients is expected to begin in the fourth quarter of 2025, pending FDA IMD clearance. Additional details of the trial design will be shared upon clearance. To drive further innovation, we are expanding our internal R&D capabilities. As an example, we recently appointed Dr. Michael Bruner, a former president of the Society of Interventional Radiology, with over 25 years of experience in academia and biotech leadership, a senior vice president of interventional oncology, to advance procedural improvements and explore new indications. In summary, the first year of U.S. launch of EPSADO has been a success. In 2024, we have been able to provide a novel treatment to patients suffering from metastatic uveal melanoma. This success has brought us very close to cash flow break-even and has directly led to a stronger balance sheet. We now have over $50 million in cash and investments and no debt. We are well-positioned to continue to grow revenue while investing in high-impact R&D initiatives. The future for Delcath has never been brighter. I will now hand the call over to Sandra to share further details on our financial position.

Thank you, Gerard. Revenue from our sales of Hubsado was $13.7 million, and ChemoSat was $1.4 million for the three months ended December 31, 2024, compared to 0.5 million for Chemosat during the same period in 2023. Full year 2020-2024 revenue from our sales of Hepsado was 32.3 million and Chemosat was 4.9 million compared to just 2.1 million for Chemosat during the same period in 2023. We recognized gross margins of 86% in the fourth quarter and 83% for the full year. Research and development expenses for the quarter and year-ended December 31st, 2024 were $2.9 million and $13.9 million, respectively, compared to $4.7 and $17.5 million for the same periods the prior year. Selling, general, and administrative expenses for the quarter and year ended were $7 million and $29.6 million, respectively, compared to $7 million and $22.1 million for the same periods in the previous year. Fourth quarter and full year net loss was $3.4 million and $26.4 million, compared to net losses of $11.1 million and $47.7 million for same periods in 2023. Non-GAAP positive adjusted EBITDA for the fourth quarter was $4.6 million, and full-year adjusted EBITDA loss was $2.5 million, compared to adjusted EBITDA losses of $9.3 million and $30 million for the same periods in 2023. As Gerard mentioned, we ended the year with $53.2 million in cash and investments And cash used in operations was approximately $1 million in the fourth quarter compared to $3.6 million of operating cash burned in the previous quarter. Again, as of today, we have no outstanding debt obligations. Thank you all for participating today. Last year was truly an amazing year. That concludes our prepared remarks, and I'd ask the operator to open the phone lines for Q&A.

Thank you. We'll now be conducting a question and answer session. If you'd like to ask a question at this time, please press star 1 from your telephone keypad, and a confirmation tone will indicate your line is in the question queue. You may press star 2 to remove yourself from the queue. For participants using speaker equipment, it may be necessary to pick up the handset before pressing the star keys. One moment, please, for our first question. Thank you, and the first question today comes from the line of John Newman with Canaccord Genuity. Please proceed with your questions.

Hi there. Good morning. Thanks for taking my question, and congratulations on all the excellent execution in 2024. The question I have is, as you are bringing new sites online in the United States for Hepsado, I'm wondering if you're seeing any sort of change to the number of treatment cycles that patients are receiving, given that perhaps some of the centers have some familiarity with the product through colleagues at other centers, or if you're tending to see the initial number of treatment cycles around the same place and then sort of increase over time? Thanks.

Sure. As you know, the label allows up to six treatments. And in the FOCUS trial, in that setting, it averaged out to 4.1 treatments. It takes about a year to know whether a patient's going to go the full six. But if we look at the kind of what's called the decay curve of patients when they start, or for the patients who have gone a full year, we'll look like we're going to be at least the 4 or 4.1 that we saw in the trial. So it's premature for me to say it's going to be much over that, but I'd be very surprised if, you know, a year from now it's under the 4.1. But it's been remarkably steady, to be honest. We haven't seen, you know, much of a change. Now the... from center to center as they do more treatments. Now with that said, you wouldn't expect, it really is driven by, you know, patients either not tolerating the product or alternatively having disease progression. I think the tolerability is at least as good as we saw in the trial. And I would say the results the docs are seeing anecdotally are at least better than what's seen in the trial. So those are the reasons it would end up greater than 4.1. I'm hopeful it might, but premature to say that with any degree of certainty. Great. Thank you.

Our next questions are from the line of Marie Thibault with BTIG. Please proceed with your questions.

Good morning, Gerard and Sandra, and congrats as well on a great 2024. I wanted to ask here about the plans on the sales ad, expanding from four to six regions. Help us think through how we should be thinking about your SG&A ramp. You've certainly done a very nice job of controlling OPEX, but we want to sort of understand the cadence of that coming through this year.

Sure. Sandra, can you help with that?

Yes.

For SG&A expectations, expenses in 2024, we're probably going to see about, you know, anywhere from a 30 to 40% increase over the year of 2024 into 2025. You know, I think a lot of those expenses will come, you know, probably starting in second quarter and mid-year as we begin to expand. But I know the sales and commercial team has already started that in Q1 a bit, but fully staffed by mid-year of this year.

Okay, very good. And I guess a quick one on the pipeline. Thanks for sizing up the opportunities there and updating us on the timeline. What's left to do on the device itself on, you know, making some modifications for those possible indications? And then what's left to do on kind of preparing for the trial in terms of finding interested sites, etc.? ?

Sure. In terms of device modifications, none are necessary. We're treating the METs in the liver, so whether or not the METs are from breast cancer, colorectal, uveal, it doesn't really matter. In terms of getting up and running for the trial, I'm going to ask Boyo to add some color in terms of the basics of IMV, approval of breast, et cetera.

Thank you, Gerard. So in order to get the clinical trial started for the colorectal trial and for the breast cancer trial, our strategy is to focus on existing treatment sites and engage new sets of doctors who treat the respective diseases. We expect this strategy will facilitate the activation of new sites because we'll be going to sites that are already trained and experienced in delivering the treatment. and the engagement is primarily to generate interest and support of the breast cancer and colorectal cancer medical oncology communities.

Okay, very good. Thanks for taking the questions.

Our next questions are from the line of Suzanne Loganathan with Stevens. Please receive your questions.

Hi, Gerard and Sandra. Thank you for the update here, and congrats on the progress. My first question is... regarding R&D OpEx and your, you know, aggressiveness to be enough aggressive, you know, to have meaningful progress on that front, yet maintain kind of a potential cash flow break-even or profitability profile? You know, which goal is the most important for you in 2025, you know, to be EPA profitable or be break-even and maybe more robust on the R&D front?

You know, I... as I frequently tell investors and new investors and existing investors, don't count on us always being cash flow positive. If we have adequate R&D opportunities for this platform and the cost of capital is reasonable, and that second part is critical, we will invest. Now, I would say that the bad news in my mind is that we can't get moving fast enough for the R&D opportunities to spend all our money. So we'll be cash flow positive this year without a doubt and perhaps the following year and, you know, for a while. But I'm purposely not making any promises of maintaining positive cash flow because I think that is an unnecessary set of handcuffs to put on a business when they have, you know, quite a few, you know, high potential R&D possibilities.

Got it. And my second question is I noticed, I think, a price increase to about $187,500 in early February. I think that's about 2.74% price increase. Is that expected, that cadence going to be expected every six months now or once every year for Exato? Or just kind of curious how you're viewing that.

It depends on inflation because, you know, the legislation is that – For CMS, you can't price higher. The price increases in faster than the rate of inflation. So that's essentially, it depends on what happens with inflation. Got it. Thank you.

And once again, congrats.

Our next questions are from the line of Bill Monn with ClearStreet. Please proceed with your questions.

Hey, good morning and thank you. I just want to ask about your referral network. What have you seen so far from that network? Do you believe that most patients who should be referred are being referred, or how much growth is there from, you know, strengthening, you know, that outreach effort to more local centers?

Yeah, let me ask Kevin to answer this. Sure. Thanks, Gerard. Our referral network is working well to this point. We are getting referrals from the community into the larger academic centers. Even some of our new sites that are waiting for product approval are referring their patients to existing treating sites online. and those patients will return back to the site once it is opened. We have built each of our regions out with a structure that Gerard mentioned in the brief where we have a dedicated oncology manager that is out talking to the community, understanding their needs, and helping facilitate referrals to active treating sites.

I will add that, you know, Any good management team adapts strategy as they learn more things. If you dig through the archives and find what I said we would need in terms of centers years ago, we're definitely looking at more centers, almost twice as many as I thought we would need. I said maybe 20 max two or three years ago. We're moving to 40. And that isn't because the academic centers aren't willing to accept referrals, and it's not that we aren't getting referrals there, but it's become pretty clear that to have patients, you know, fly four hours or drive seven hours, we're going to lose patients. So we need more centers. So we're working hard on referrals, but the referrals are probably, we need more centers. That referral pipeline probably isn't going to be as big a mix of the business as I personally anticipated a couple years back. But again, nobody has a perfect crystal ball.

Okay. And on the expansion of the recommendation from just liver-confined to liver-dominant, how many patients in your target patient population are hepatic-confined versus dominant?

Almost all patients eventually get extrahepatic mets. So it really is a matter, it's a moving target. It's a matter of when they're diagnosed initially. When they're first diagnosed, under half have extrahepatic mets. Whether it's 20% or 40%, it's hard to have the exact data. Our label includes patients with extrahepatic mets. The guidelines recently changed. It was strange. When the guidelines got updated just around the time we were approved, they actually changed and said, isolated liver meds, which made no sense. We got on the phone with the KOLs around the country, talked to them. They thought it made no sense. They reached out to the guy on my committee. and it got changed pretty quickly. So there's no incremental patience in terms of our TAM, because we've always included them. But that was an unexpected potential headwind, especially for docs out in the community who don't see a lot of these. If they just refer to the guidelines, that would have been a headwind for us. So we're thankful we got that changed.

Okay, and last one. I know there's no guidance, but looking at consensus numbers for 2025, I'm seeing... 77 million as consensus. So would you at least describe that as conservative or aggressive?

I'm going to say no comment.

I figured I'd try.

Thanks, though. Yeah.

Our next questions are from the line of Yael Jin with Laidlaw. Please proceed with your questions.

Good morning, and thanks for taking the question, and congrats on all the progress. Just want to get a sense of your CRC trial to start later this year. In terms of, you know, how many cycles do you think the patient may have, or was there any adjustment in terms of a dose or duration? Anything of that compared to your approved label or approved the things on the label, or there's any other adjustments?

Sure, sure. Let me ask Valeria to take that question. Sure. Thank you for the question. After discussing with leading experts in colorectal cancer, we decided to put forward a design that we believe will facilitate the adoption of liver-directed therapy into this line of treatment of metastatic colorectal cancer patients. So we basically took as a basis the standard of care, and we added the treatments with Hepzato, at the beginning to make sure that we control the liver dominant disease. So we plan to deliver two cycles of PHP followed by standard of care. Should patients progress after initially benefiting on the treatment, we have the option to re-treat them to continue the patient benefit that was delivered by the first treatment. So the base number of treatment cycles is two with the option to be more in certain cases.

Okay, great, that's very helpful. Maybe just I want to get a little bit more deeper, the orders or sequence of treatment, why you have the subsidal first followed by standard of care versus the other way around. Was there any differences in that kind of?

Yes, absolutely. The reason why we sequence PHP first, followed by sedative care, is that the definition of the patient population are those patients where the liver metastases dominate the clinical presentation. And for that reason, the liver tumor is the real problem, and that needs to be addressed first, and then the extravatic disease can be addressed later.

Okay, great. That is very helpful. And maybe the last question here is that the I know you guys have started to expand in Europe, and in the prepared remark you mentioned some of those. What is the sort of expectation of this year, 2025, for that effort, particularly from a revenue perspective?

Thanks. Yeah. The expectation, and I may be setting the bar rather low, but the expectation is, I said, modest growth. And I don't know whether or not it's 20% or 30%. In Europe, step changes will occur when we get reimbursement. We really only have reimbursement in Germany. In the Netherlands, the hospitals that use it and they consider it standard of care are taking it out of their own budget. In the UK, it's been private pay. If we do get reimbursement in a major market, it would probably be the UK is the one that's up, maybe the Netherlands. We could see a step change in those particular markets. But because it's not, that's really the big driver of future growth. New markets, which can take a while to get started, as well as reimbursement, and they're kind of binary outcomes. I'm setting the bar a little on the low side, perhaps, and just saying modest growth for now. But again, the real value there for us is not the economic value, it's the strategic value. The more centers that do it in Europe with its device label, and it can be used to treat any cancer, I think the more we see docs trying to use it and us getting efficacy signals and publications.

Okay, great. Maybe the last sort of tag on that is that do you guys need to do some sort of a pharmacoeconomic, some sort of those studies, or whether you already have that piece for request for the reimbursement.

Yeah, we're not going to do a specific pharmacoeconomic study, but we end up having to pay consultants to do models, and the models according to the particular countries, you know, and we will do it for the... Yeah, no, I know. Every country needs its own model. So the UK, we put a model together. The Netherlands will put a model together. Eventually, we're starting out in Sweden. I suspect we'll have to put a model together for them. Italy, France, et cetera, et cetera. But they're all basically we're gathering data we already have and putting it into the country's particular model, if I'd like to say.

Okay, great. Thanks a lot, and congrats on the progress. Thank you.

Thank you. As a reminder, to ask a question, you may press star 1. The next question comes from the line of Chase Knickerbocker with Craig Hallam. Please receive your questions.

Good morning. Thanks for taking the questions. Gerard, I feel like I ask this question kind of every quarter, but I'll ask it again. Sorry. But just kind of in those eight centers, now that I guess we have 16 active and those eight centers that are in queue, you know, approaching being ready to treat patients. Do you have a sense for kind of when our expectation should be that those are online? Is that something where in the first half of the year we should have all eight of those centers at some point kind of activating and treating patients? And then, you know, basically to get to 30 at the end of the year, we kind of need six incremental from there in the back half?

Yeah, so we need 16 overall for the year. We've got two now to reach the 30, okay? I expect of the balance of them, more will come on board in the second half of the year. Because we're expanding the sales force, they'll be hit the ground running and really be active in the second half of the year. So if you assume it was, you know, if you just divide by four, we need four a quarter, I think it's going to be closer to three a quarter for the first two quarters and closer to five a quarter for the back half of the year. Now, my ability to predict this has been tremendous. really poor, so we're doing well. But if I had to put some money on it, that's the pace I would conclude.

Got it. And just if you could give us a sense for kind of what percentage of volume is being driven by kind of top three accounts. Are you starting to see some of that kind of broaden out to a lot of your other recently activated centers or just kind of an idea?

Yeah, the percentage of business coming from the top three accounts has definitely been decreasing as we add more accounts. But the Pareto rule probably still holds. I don't think it's quite 80-20. Um, but maybe it's, you know, 60, 30, um, in terms of a distribution.

Got it. And then just last for me, um, you know, there's, uh, going to be a, uh, a readout, um, that will be registrational and the HLA negative disease sounds like by the end of the year. Can you just remind us how you think about that program competitively? Um, with Hepzato and, you know, how you see Hepzato fitting into the, you know, treatment paradigm if they are successful and things change and kind of HIV-negative disease as well?

Look, oncologists like systemic therapies. Our job is to remind them, I don't want to say educate, but remind them that, hey, look, these patients die of liver failure. And if you let the liver disease get out of control, at some point, even we can't help them, even our product can't help them. We think these patients should survive long enough to get both a systemic and a liver-directed, and I think they need a systemic on top of our product. It wouldn't be appropriate just to use our product in these patients. I think the systemics will battle it out amongst themselves. We will be the only liver-directed that's appropriate for this patient population. Now, the second thing I would mention is we already face a headwind from these products even before they're approved. This is a very small patient population, and most of these patients end up getting treated at academic centers that are involved in these trials. So we're already facing, you want to call it a headwind, or understanding how to work with these treatments. in that many of our patients are already first going into the trials and getting ours, because most of these trials dictate that you have to be treatment naive. So we're already living it, and I think it's appropriate that they get systemics on top of us.

Do you ultimately think we could move to something where there's some sequencing of therapy? Is that something you're looking at?

Yeah. As a matter of fact, just yesterday I was – We had a small panel of docs we were having a conversation with and that's what they do. It takes up six to eight weeks from a patient presenting and to them being ready to treat with our product for a variety of reasons ranging from prior auth to just having to map the patient and do a variety of evaluations of the patient. And these docs put them on Tebby or Ipinivo immediately, treat them for two months or so, then take them off and start sequencing with our product. When I ask them, do you put them back on or do you do the full six? They do the full six or as far as they can go before progression or... tolerability issues arise, and then they put them back on the systemic thereafter. Now, that's one doctor's or one center's protocol, but I think that's going to become increasingly common.

Got it. And then just last for me, Gerard, any meaningful off-label use that you've seen so far in other tumor types in your experience in the U.S.?

No. As I said before, we've had centers approach us who want to get open to do off-label use, and we've said, no, we have to start with uveal melanoma. I suspect we will start seeing some centers doing cases here and there. I would not bake into your model any time in the near future, like the next year or so, any meaningful revenue from that, though.

Great. Thanks, guys.

Our next question is from the line of Swamkula Ramakant with H.G. Wainwright. Please proceed with your questions.

Thank you. Gerard, congratulations. I was looking into my email archive and just about four years ago, you and I were talking about how to get all the data from the FOCUS trial in-house and file the application. And here we are with $37 million in annual revenue after four years. So huge congratulations to you and your team. Having said that, so with 16 centers now that have incorporated Hepsado, so what do you see any of them influencing the sales cycle in terms of getting new sites on board?

All right. Do I see the changing in terms of the process to get new centers on board?

Is that or then, you know, in terms of competition, saying that, hey, the other centers in the neighborhood have it, so we need to have it so that we can draw some people.

Yeah, yeah, okay, I got it. Yeah, so definitely, you know, if we use the term fear of missing out or FOMO, there's definitely a little bit of that going on among the centers. So, you know, you have your typical early adopters who jump on board, right? And then maybe it flattens out a little bit. And then that definitely has been a bit of, I think, an uptick in interest as more, and it's not necessarily local centers, but, you know, other name brand centers. You know, oh, XYZ has it, we have to have it. So I think there's a little bit of that going on. In terms of, you know, the learnings and getting centers on board, you know, I would say each, I've said this multiple times, each center is so unique. that it's tough to have a well-honed plan. I think the reps can anticipate potential problems and try to get ahead of them, and they're trying to do that. But it's still a very, I would almost say, torturous process to get this thing up and running because it's a unique bird. It's not because it's particularly difficult to do or anything like that. It's just it doesn't fit into any particular square peg round hole when it comes to approval, but we get it done.

Fantastic. Then coming down to gross margin, you know, you exit at 2024 with an 83%. What's the push and pull on that number, you know, especially thinking about 25 and beyond, at least in the short term?

Sandra?

Yes, thank you. So R&D expenses, Q4 was a bit flat versus previous quarters, but we definitely are going to see a ramp up of R&D in 2025, anywhere from $35 to $40 million. As Boyo and his team continues to start the trial and get sites open, of course, there's some wiggle room in there and how fast. Sure, I mentioned we can spend that money, but yeah, there's definitely going to be a significant increase in R&D over 2024.

And did you ask to put some taste on gross margin as well?

Yeah, that's what I was wondering. What's the push-pull on that number?

Gross margin.

Oh, gross margin. I'm sorry. So we ended Q4 with 86% gross margin, and we do expect that to continue into 2025. And you probably... could reach 90% by the end of 2025.

Perfect. Most of the expenses are just our personnel. The bill of materials is what it is. It's fixed. But we have a fair amount of leverage still with the existing team in terms of capacity, putting more through. we have a tremendous amount of excess capacity in terms of just the physical infrastructure. So I don't see any large, you know, increases in expense, CapEx, which would get loaded on over time on cost of goods. So I think we'll see, you know, incremental improvement. But with any high, high-priced drug like this, obviously you kind of reach diminishing returns on a percentage basis, even with higher throughput. Yeah, okay.

And then on the expansion of the R&D arm, you know, so what's the mandate that this group has now? What I mean is, is it more on the device improvement or is it trying to add additional either chemotherapy or biologicals in terms of administering them either to the liver tissue itself or other tissues?

Yes. So the short-term... and the relatively low-hanging fruit, although it's not that low-hanging in anything in this industry, is to treat other liver-dominant cancers. I'd love to be able to do a basket trial and have the FDA wave that through, but that's just not likely to happen. So yeah, CRC, breast, others that might make some sense in the future. I'm not saying this will happen, but ICC, pancreatic, to pick up two others that might make sense. Thereafter, sequencing therapy with immuno-oncology agents of Chopin looks good. There are lots of other, that's one place maybe we would do a basket trial. You were doing well on an IO agent, got a liver met, started progressing. That we might do as a basket trial. In terms of other agents, other chemo agents, even biologics, yeah, we have a long list of ideas. I think we're walking now and getting ready to jock. Picking up other compounds is something we're definitely going to start looking at, but it's too premature for us to give any specifics. I think it does speak to the fact that this is a platform that can treat many different diseases in the liver. As I said earlier in my remarks, if it looks like a compelling R&D opportunity, we're going to make sure we have the right team to do it, but we're going to fund it.

Perfect. Talking about starting to jog, the ex-US growth has been pretty decent in 2025 according to you know, what you were saying to us earlier. So in terms of geographic expansion, what geographies, you know, could be low-hanging for 25? Are your scientists ensure first deeper penetration of chemostat in the current geographies and then worry about expansion to new geographies? I'm trying to figure out how you're going to do this.

So we sold about as many units in Europe this year as we did in the U.S. Last year, excuse me. That gives you a sense of the differential in pricing and the value we can get. So again, I want to manage Europe where I'm not losing millions and millions of dollars every year and expand it so that we can get the clinical data out of there. Now, are there other sites where... If we ended up getting a broad first-line colorectal indication, about half of those patients end up with liver mats, and that's not our trial. It's third-line. It's a much smaller market. But if we end up getting, for example, first-line colorectal, first-line pancreatic, which are huge numbers in terms of liver involvement, then it might make sense to really push hard in other markets where we have lower pricing because the volume would help make up for it. And we probably might have to consider lowering the price in the U.S. to get on policy and such. But right now, with the pricing structure in Europe, with this particular set of data we have, which drives usage, I think Europe is going to be modest growth, but strategically important. Might we go to Japan at some point? Perhaps. It's, again, one of the long list of things the team is considering. But for now, I think, again, for the near-term model of the company, I think we think about the U.S. If we're thinking about a terminal value in your spreadsheet, I would factor in, you know, ex-U.S. sales.

Yeah, yeah, perfect. Thank you very much, Gerard and Sandra, for taking all my questions.

Sure. Thank you. That concludes our question-and-answer session, and we'll also conclude today's teleconference. We thank you for your participation. You may now disconnect your lines at this time and have a wonderful day.