Welcome to today's presentation, where we have the pleasure to present Ascelia Pharma. Today's event, of course, covering your Q4 full year report sent out yesterday. But as the situation is with you, it's maybe not the financials that's the most interesting. We have a lot of questions, so I think we will get very well around the case. But, of course, that's the occasion why we are doing this. But, let's take a broader look also at your company. To help us through it, we're joined by CEO Magnus Corfitzen. As always, there's a box down below, ask questions during the presentation. We got a lot in advance, and we need, unfortunately, a little bit after half to break off the event.
So let's see what we can catch, but for now, I will leave the floor to you, Magnus.
Yeah. Thank you, Mikael, and welcome, everyone. It's great to be here and give you all an update on the Q4. So, I will be making forward-looking statements on my presentation here. So at Ascelia Pharma we are focused on identifying, developing, and commercializing novel drugs within the rare oncology setting. And we are a Swedish company based in Malmö, traded on Nasdaq Stockholm since 2019. We have two drugs in our pipeline, the lead program, and that's where I'm going to talk, spend most of the time today is Orviglance and first-in-class diagnostic drug. We've come very far. We are in the FDA review process, and we expect a decision made on approvability by the FDA, around the third of July this year.
The other program, also very exciting, but earlier stage Oncoral, which is a patented tablet formulation of immune checkpoint, with potential in various solid tumors, gastric cancer being the lead indication as of now. So, strong pipeline, and we'll focus on Orviglance today. And the reason we want to focus on Orviglance is that we've come very far, and it's a really exciting opportunity. And what excites us and others about it is that we address a very well-defined unmet medical need within liver imaging. That's important for cancer patients and particular patients with severe renal impairment. It's an $800 million global addressable market opportunity. We have commercial-scale manufacturing in place. We have an extensive clinical program with nine individual studies, and very good results, and particularly also in the phase III trial.
As mentioned, we have submitted the NDA. I'll come back on the timeline and the specifics later in the presentation. Our clearly stated strategy is that we will commercialize with a partner. The process to find a partner is ongoing, and we'll talk more about that as well later in the presentation and in the Q&A session. Fourth quarter was a very exciting quarter for us, with a major milestone of the FDA acceptance, and that's called, in some phrases, it's called the Day 74 letter . 74 days after submission of the file, which was in September last year.
So that means the FDA has reviewed the application and considered it to be of sufficient quality and content that it warrants sort of a full deep dive review, which is obviously a major positive. We were expecting and hoping that, of course, but it's a very important milestone. We also filed a new patent application for Orviglance relating to the manufacturing process. In part of the manufacturing development, we've made a number of insights and ways to optimize and control the manufacturing, and we think that is very important IP that could provide extended protection for Orviglance. We also announced that we would have a CFO, Hansson joined the company.
We announced that in Q4, and a few weeks ago, he had his first day in the company and very happy with having him join us and be on the journey ahead of us as we are heading into sort of a transformative 2026 with key milestones. We there was a small amount of shares issued in relation to the incentive program, long-term incentive program in November, and we also announced a nomination committee, so a committee appointed by the largest shareholders that will provide recommendation for the annual general meeting this year. So a busy quarter, and here after the quarter in January, we announced that Julie will be leaving Ascelia, our Deputy CEO, to head up the CEO position in another company.
So, Julie's been with us for, for six years, and been very active in various fields. So we are happy for her and on her new opportunities and wish her best of luck in that. And she's with the company, she will start her new position in, in early April. And she's ensuring sort of a smooth handover period. So everything is working well there. So now moving into the pipeline, we'll start with Orviglance, and many of you will be familiar with Orviglance.
But for those of you that are more new to the story, the key problem that we're solving is, you know, part of a major problem in cancer care, cancer in the liver, in particular, liver metastasis, when cancer starts in one organ and metastasizes and spreads to the liver, is a major problem. You know, the gold standard today is an MRI, and with using gadolinium, which is a heavy metal, toxic heavy metal, it's put in a chelate chemical structure to minimize the toxicity. But unfortunately, in patients with severe renal impairment, there is a risk of a potentially fatal side effect called nephrogenic systemic fibrosis, and that related to the gadolinium. And because Orviglance is based on manganese-...
This risk does not, is not, existing with Orviglance. We have orphan drug designation from the FDA, for use in liver imaging, in patients with severe impairment. So we have, you know, well-defined unmet medical need, accepted in clinical practice in, and in regulatory, settings. And, and that's why we have a very strong, unique offering to this group of patients. So, this translates into this unmet medical need translates into a $800 million global addressable market opportunity. Almost half of that is in the U.S., and we are therefore, we've been focused on the U.S. opportunity in terms of the development and commercial preparations. We've also stated, that we will commercialize through partners, both in U.S. and in other geographies.
Overall, when we think about the U.S. market, this is the patient that we are targeting is a small subset of the overall cancer population, but it's about 50,000 patients a year, with about 100,000 procedures that could potentially be addressed by Orviglance. What is also interesting is that these patients, because they're very sick, suffering both severe renal disease and cancer, very often they are at some of the major medical centers. So 400 healthcare providers have 75% of the patient population in the U.S., which gives us the opportunity or the partners opportunity to address a lot of these patients through a sort of a very focused commercial effort. We're on top of doing a lot of market research in to understand the patient volume and the patient flow, patient journey.
We've done extensive work in terms of understanding the pricing and reimbursement opportunity. Based on this work, we have identified a pricing benchmark for other innovative diagnostic products in the range of $3,000-$4,500. It clearly proves that there is a good pricing opportunity for innovative diagnostics if they provide real value to patients, which we certainly believe that Orviglance does. So we are focusing on the patients with the severe renal impairment. That's where the gadolinium agents have a black box warning. That's the indication we go for. On top of this concern and issues with gadolinium, there are concerns about the fact that every time you inject gadolinium, there is deposition of gadolinium.
Most of it is excreted from the patient, but there is deposition in bone and skin, as well as the brain and other organs. And that is something that is being evaluated to understand what are the clinical implications of this. Today, it's not fully understood. Another growing concern and where more and more data is coming out is that tons of gadolinium is being used in medical imaging. And because the gadolinium, most of it is excreted through the urine, it goes into our sewage system and drinking water. The concentration of gadolinium is low, so therefore, it's very difficult to remove the gadolinium from the drinking water, which means that it's perpetually accumulating, and the increase in drinking water is quite significant over the last few decades.
Again, that's an important concern, especially for the longer term sustainability. So the way that these dynamics play out is that obviously we are leading the pack with an FDA review of a manganese agent. GE Healthcare is developing an intravenous injectable manganese agent, not liver specific like ours. They have completed phase I, so they are clearly also in the direction of finding alternatives to gadolinium. Some of the other gadolinium manufacturers are developing lower dose gadolinium, so they still use gadolinium, but have optimized the formulation so that they're able to use roughly half dose, but having similar image quality.
So all of this plays into the same, you would say, overall trend, macro trend, that there is a recognition that alternatives to gadolinium are needed, and using less gadolinium is better than using more. So we are happy to be leading this with the NDA review process that we have now with Orviglance. So one thing is getting the approval. We're well on track there. I'll come to that in a minute. But obviously, the key thing is to help patients out there. And we will need a partner to drive the commercialization. We've stated that clearly, that that is our strategy. The process is ongoing. We have, we think, a very attractive asset, highly differentiated. There's nothing out there like Orviglance, and we have shown that we have strong clinical data.
There's a good, you could say, commercial opportunity, both in terms of patient volume and value per dose. And we see a number of relevant partners that could drive the launch and the successful commercialization of Orviglance. Could be manufacturers of gadolinium products, could be other companies in the gadolinium space. It could be specifically pharma companies with sales forces at hospitals. So we think that we have a good range of potential partners. We're also talking to multiple partners who have expressed clear interest in Orviglance, and that we think would be strong commercialization partners, and these discussions are progressing. So, very happy with that progress and the outlook for getting a deal done. Switching gears from the commercial side to the regulatory side.
As mentioned, we had initially nine clinical studies completed, so almost 300 patients and healthy volunteers tested. So we have, I think, a very solid database, both in terms of the efficacy, the visualization. We also see detection of more lesions in the liver, in particular smaller lesions. And then we have a good safety profile in these very sick patients. We see some gastrointestinal side effects, nausea, diarrhea, mostly mild, which is to be expected in this population and with such a product. So nothing serious. We think this is a really good, really good package we have.
One of the things that came out obviously was from the phase III trial, is what you see here is that to the right, you see the efficacy, the primary endpoint, and you see the improvement. So this is a score that is the over enhanced score minus the comparator, which is the unenhanced score, clearly above one, which is a sort of an important improvement and from a clinical perspective, and you see the 95% error bars very far from the zero line, which means that we have a high statistical significance.
You can see the images illustration from one of the patients in the trial and sort of anecdotally and kind of visually, it shows a very strong enhancement of the visualization, which is, you know, represented in the overall scores. As mentioned, we have submitted the new drug application on the 3rd of September last year. We got the Day 74 letter acceptance of the filing from the FDA, announced on the 15th of November. So we are in good place in the regulatory process. The way such a process works is that we make the submission and the FDA team is reviewing the application, which is a lot of information.
They will ask us a number of questions throughout the process, and they continually sort of send questions and we respond to those questions. So far, we are very happy with the interaction with the FDA and feel we are in a good place and optimistic about a positive outcome. That concludes the Orviglance story. So briefly on Oncoral. So Oncoral is a tablet formulation of irinotecan. Irinotecan is a chemotherapeutic drug, very potent, and but also a very strong safety, you would say, side effect profile like any other chemotherapeutic agent. What we can do and where we can make a difference is that instead of a dose large, very large dose, every third week, we can give daily dosing.
There's a lot of data supporting that, that can, has potential for both better efficacy and better safety, and that's what we want to demonstrate here with Oncoral. Here is some of the data from a phase I study that we did, where we show that by giving daily doses, we give a comparable amount of irinotecan over a period of time, as with the infusion product. And what we also saw in the cases is that we saw sort of a better safety profile, in particular neutropenia, depletion of white blood cells. So we think that is very encouraging. We also saw activity, patient stable disease in very sick patients and patients where they've gotten the intravenous irinotecan, and progressed on that. So I think encouraging signs, and we're excited to move on.
Initially, we look at gastric cancer, but we will, there are potential in a number of other, tumor types as well. Just to round up, and time is flying quickly. So in terms of the quarterly report, we had an operating loss of about SEK 16 million in Q4. We are on a lower run rate, now, in the last couple of quarters compared to previously, reflecting that we have completed the NDA file and submission, which is obviously a lot more work than responding to questions, even though they can be extensive as well. So, we have financing until into Q4 this year. So we have SEK 50 million at the end of last year.
Overall, in a sound financial position with an expected FDA decision in the middle of the year. We have two tracks here to drive value. One is getting the drug approved. We've submitted, we got the Day 74 letter and a PDUFA date in July. Everything is on track there. We also work on maximizing the commercial potential, working with key opinion leaders and other preparations for the launch. That is on track. And then the process for getting a partnership on board is also on track and progressing as we speak. So with that, I'd like to open up to any questions.
Perfect. Let's jump into it. There's a lot on the partnering. We will cover that by some angles, but I think there was also a very good one. You were at the JPM, the biggest conference there. Some feedback you got there from their investors, potential partners. Can you talk a little bit about the talks you had in this JPM conference, and what was the surrounding? So I know it's a little bit of a broad one, but I think it's nice to hear what you were talking about over there and what you were met with.
Yeah, no, and I'm happy to elaborate on that. And you know, let me start with a sort of a caveat. I think it's partnering is super important. We're very focused on getting a deal done, and we're making good progress. It's also, I mean, it's not only our investors who are listening to what you know to this, it's also some of the potential partners that we're talking to. So, it's very much in the interest of all shareholders to make sure that we do the negotiations in the best possible way and not give away sort of negotiation chips to potential partners, but that we keep the relevant information internal. Having said that, I'm happy to sort of elaborate on where we are.
So at J.P. Morgan and, you know, it's, it's always, always good to be there, always interesting, good dynamic, and an opportunity to meet a lot of, a lot of different companies, also very senior representatives from, from the different companies. And I think that's, really what sets J.P. Morgan week apart from, from a lot of other conferences. So, so we, definitely, were there, had meetings and, I think what we have experienced and, and also put that in the Q4 report, is that, the, the Day 74 letter, the, the filing acceptance from the FDA is a clear and important milestone. We were, we were very optimistic, in advance, but, but nice to see.
But I think on the potential partner side, they see it as a clear recognition that, you know, we're doing really good quality work. This is thorough and credible. And you know, we're a small company. We are in the order of 10 people in the company. We're obviously working with consultants, but demonstrating that we meet this milestone and that we are solid on the science is an important part of the negotiation process as well. So I think that it's fair to say that that has been kind of recognized among the potential partners that we are speaking to.
Yeah. Perfect. And then there's a little bit of a question on the timeline, approval, midsummer, launch. Is that possible when you haven't had a partner in Q1, Q3 and Q4? Are you giving something away by negotiating on the timeline, or do you still think it's possible to catch this timeline in the second half even if you haven't signed up a partner yet?
Yeah. No, no, I think absolutely. I think I'm not... I want to get the right partnership for Ascelia, somebody who can, you know, drive Orviglance's launch in the best possible way. Obviously, more time is always better than less time, but I think on the other hand, when you have less time, then you tend to be more focused and pull resources together in a different way than if you feel that you are okay on timeline. So I think there are some dynamics on the partner side that will be different depending on the timeline to approval.
The other part, I mean, and part of the reason, an important part of the reason why we are taking a partner on board, and that's our strategy, is that all the capabilities that are important for launch, they should already be in place with a partner. There may be some, obviously, some product-specific knowledge with Orviglance that they will have to learn, and we will teach them. And our external networks will support as well there. So there's a learning process, of course, on the product, but all the capabilities will be in place. So from that regard, yeah, I think we are in a really good place. I don't think that's not causing any stress. Doesn't mean that it will take forever to get a deal done. Certainly don't hope so.
But I think it's not. I mean, we're not getting nervous in terms of this jeopardizing the launch or anything like that. We think we're in good place. It's important to get the right partner and get the right structure in place, and then we're on our way to do that.
And then maybe attack it from another angle, because I know I have to protect yourself in your negotiation. I'm not going to get much more from you, but key hurdles, de-risking, potential partners, what do you see as the key hurdles, for them, or you be, coming a final agreement?
It depends on who, on which partner we are speaking to. It's like when people are looking at a house and thinking about buying a house, you know, some people like the garden, some people don't like the garden, right? Some people like the kitchen, some people don't like the kitchen. So it's similar here. I think it's a little bit also a factor of, you know, their existing product portfolio in terms of what they're thinking. You know, maybe some challenges they've had with other products that influence where they put more attention in the dialogue with us. So it's not like we have one common theme that is kind of, you know, a big issue for everybody.
It's kind of a little bit mixed, which I think is a good sign. It shows that we have a good solid package all around, but obviously there's always gonna be something... When you look at something, there's always gonna be the most challenging topic. So I think we have potential partners that we talk to that you know have absolutely no concern on one topic, where that is the biggest concern for another company. So I think that illustrates quite well that it's not-- we have a good all around package, and we'll get there. But then we'll you know it requires more work.
And then regarding the review with the FDA, have you had a five-month review? I don't fit it in the timeline, but there's a question here, and is there actually something like that on the orphan drugs status approval process?
Yeah. So there is a... So we're following. We've not applied for Fast Track, which sort of compressed the review timeline, which has some advantages. On the other hand, we think the most important thing is to get through the process and have as much time as possible to respond to the FDA questions. So I think, you know, from that perspective, the process is like any other drug. In the FDA process, they have an internal. I think that's what this question is referring to. There's the FDA has a mid-cycle review, which is five months after submission, which should have been sort of Tuesday this week. And-...
That's a meeting where the FDA review team is having a conversation about, you know, where they are and what the questions and so forth.
Yeah.
It's not, you would say, an event or a milestone as such, where we will necessarily get any information out of it. We may get some additional interaction, we may not. We may get some more questions immediately after, we may not. So it really depends. I think every review process, the mid-cycle review has a different, you would say, role. So I think it's more like an internal FDA coordination meeting.
Ah.
Um, yeah.
There's a question also. You earlier said milestones and deal being significant compared to market cap. Is this still something you still stand by? You might say the question here is, why don't the shareholders then stand by it? But I know you can't answer for them, but do you still stand by this statement?
Yeah. I... If you think about the commercial opportunity, which is $800 million globally, roughly half of that in the U.S. If we think about sort of a sort of standard split of value between, you know, a biotech company and a pharma partner, and we just get sort of a reasonable subset of the U.S. opportunity in itself, it should be quite attractive economics compared to the market value. I mean, that's, at least in when I do the math, but everybody's doing their own math. And we don't have a sort of an opinion about the share price.
But when I got that question in a previous interview, that was more kind of reflecting the magnitude of, you could say, upfront milestones and launches compared to the market value. So obviously, you need to discount, if you're an investor, you need to discount with the likelihood of this happening. And that's kind of probably what is playing out. So we are very, as I said, we're very optimistic on the regulatory approval process and on the partnering process. So it's our role to deliver on that strategically and operationally in the company. And hopefully prove to everybody that there's a good reason to be excited about Orviglance.
There's a question on price, and I'll just jump back to one of your slides. I guess, you haven't told what the price is, but you kind of indicated it. Is that correct? Around similar... Sorry, I couldn't find the slide, so I go back again.
Yeah.
But, well, you're estimating something similar products could give. So could you repeat, remind us what that was?
Yeah. So, we've done and worked with sort of expert consultancies within drug pricing area. And, when we look at the value that we believe that Orviglance brings, when we look at other innovative diagnostics, they are, many of them are in the PET imaging space. But, you know, solving other important questions in the diagnosis and makeup of patient treatments. They are priced in a range of, let's say, $3,000-$4,500 per dose in the US. And, based on the work that we have done, we see a sort of a, you know, I think it's fair to assume that there is a comparable pricing window that we'll be looking at.
So we've done a lot of work, because previously our plan was to launch Orviglance with a senior-led team in the US. That's no longer the strategy, it's to partner. So we have prepared a lot of work, done a lot of market research, that once we have signed with the partner, they will obviously have access to that and use that to drive the pricing and reimbursement process.
That, and actually, there's a question that fits good in here. You know, Redeye, it's an analyst. Some analyst has other estimates that is estimating the market smaller than you are. I don't know whether you have read it or where you are disagreeing, or you just wanna keep to that you have done extensive work because you actually wanted to launch this yourself, and this is the $800 million. And it's actually been stuck there for quite a while, so I guess you're pretty comfortable with it. Has prices gone up, down, patient groups, and so on.
A little bit, I don't know whether you want to comment compared to the Redeye, but a little bit comment on why you are comfortable with this SEK 800 million opportunity.
Yeah, you're right. I will not sort of comment on specific analyst reports. I think what I would like to comment on is that, you know, the work that we have done to get to the $800 million. So what we've done, and we've done most detailed analysis on the U.S., where our most accurate data is also available. So on the volume of patients that could potentially benefit from Orviglance, we've looked at various different sources. We've looked at claims databases, which is really sort of a database of medical procedures actually being performed and billed in the U.S. system. So something that has really taken place and down to a level where you could see who was the radiologist responsible for the imaging procedure.
And then say, you know, of all those imaging procedures, which ones would be relevant for Orviglance? Estimating the value from there, using a sort of advanced epidemiology modeling to understand what, you know, from a literature perspective, and we know how many patients, cancer patients and other and renal disease patients that there are out there. What is the volume? You know, what is the expected volume? And I think though that those two approaches get us sort of pretty close in the same range, which I think is a good sign. So in terms of the patient volume, I think we've done, we've invested a lot of money, a lot of time-...
And that's also the numbers that we are, you know, speaking to potential partners with. And the same on the payer or the pricing and reimbursement, invested a lot of money and time to understand sort of what is the pricing potential and opportunity, and what is required to achieve this price? What is it we need to document and show up with in the negotiations with the payers? So I think not gonna comment on what other people think. I think we have sort of a very reasonable estimate. We say the $800 million, that's an addressable market, which also means that, I mean, there are no drugs that will ever get 100% of all potential patients.
We've not provided any revenue estimates. But I think the work we've done is good and solid.
And then finally, there's a question here: Do we need capital before a partner, before a partner decision, before a potential approval? And if you go out and seek capital before that, should we then interpret it as this is plan B? So I know it's a little bit, first we need to assume, and then we need to assume something. I don't know, so whether you wanna answer that, but on the capital side, is there anything we should be aware of?
Yeah, I mean, we're obviously not raising money now, then we would have made an announcement. But I think it's, we got some inbound interest in last year, in September, and we raised SEK 30 million. So that was a, you could say a dilution, but I think we only had a 7% dilution in that transaction. We thought that was a good number, because that would take us with a sort of meaningful buffer beyond the expected approval date of the FDA.
Yeah.
So previously we had money into Q2, then we would not be able to fund the full review process ourselves. So I think that was like a really important financial transaction to lower the financial risk of the company.
Yeah.
And I think that's, I'm very happy that we have sort of a good buffer on the back end of, you could say the approval, expected approval date. And I think that's the most important. We expect financing from the partnership in terms of an upfront, milestones and royalties and which is different to, you could say, negotiate, because potential royalties should hopefully come. Not probably not a lot, but something in this calendar year.
Perfect. And then the final question before I will let you off the hook, Magnus. You have said at some point in time that has been read, that you said before 2025, you will have the partner. And I think people read something into it, then something must be wrong. So I think maybe it's good to get clarified what you said, at that, I think it was an event in the spring. And I know it's, that's always be said, but, but maybe we should actually clarify it, because I think people read a, a lot into it, when you said, they have heard that you said it will be before 2025. And I guess that was not what you stated on that event. Is that correct?
Yeah. No, I don't think, at least not to my recollection, I have not never said it's gonna be happen. I think it, it's always very that it would happen in 2025. It's always very difficult to predict something that is outside our control. What I have said in one interview last year, early last year, was that, you know, I was asked if, you know, it would be in, a deal could happen in 2025, and I said, "That would be nice." And, you know, I stand by that, that would have been nice. I think we're still in a very, very good place. I think the important thing for me is that we are making good progress, reducing risk in the regulatory process.
We are having a good number of conversations with strong, serious strategic partners. And you know, entertaining those dialogues, I think, I think to me that is the key. So I think the timing is a bit more, you know, uncertain because I don't control the decision process on their side.
Perfect. That was the last question. I will let you off the hook, Magnus. Can you have a good weekend, and thank you to all the listeners listening in. May they also have a good weekend.
Yeah. Great to be here again. Take care.