Hi, and welcome back to ABG Sundal Collier's Investor Days. My name is Filip Ekengren. I'm a healthcare analyst here at ABG. With me today, I have the pleasure of introducing CEO of Ascelia Pharma, Magnus Corfitzen, who will introduce the company, and then we'll have a Q&A, so the floor is yours.
Thank you. Thank you, ABG, for giving me the opportunity to present here today, and all of you for joining. I'm excited to tell you the story about Ascelia Pharma and the progress that we are making. And during the course of my presentation, I will be making a number of forward-looking statements. So in Ascelia, our focus is to develop new drugs, so identify, develop, and commercialize novel drugs that address unmet medical needs within rare cancer conditions. We're a Swedish company. We're based in Malmö, in Sweden, traded on Nasdaq Stockholm since 2019. So the drugs that we have in development right now is, you know, we have two in clinical development. One has completed clinical development, if you can say, but it's not yet approved.
It's Orviglance, which is a diagnostic drug for MRI imaging of the liver in a subset of patients that have a risk of fatal side effects if they are given the existing products on the market. We have orphan drug designation, and we have submitted an application for getting approval to the FDA. And they have, you know, so far given us a PDUFA date, which means the date when they expect to make a decision on approval, which is July 3rd. I'm coming to a lot more on the progress and Orviglance later. We also have another program that we are excited about, but less advanced, which is Oncoral, which is a tablet-based chemotherapeutic agent, very exciting, but a bit earlier in development. So right now, our focus is on maximizing the value, and Orviglance have come, you know, through the development, clinical development phase.
We are in the regulatory review process and hopefully at some very important inflection points in the very, you could say, near term. So right now, our framework here, we have two activities. One is the advancing Orviglance. We have submitted the NDA. We did that on September 3rd. So send the application, which is a lot of work. Then we got a Day 74 letter, as it is called, from the FDA in November that we announced. And then in that Day 74 letter, where the FDA says, yes, the application looks, there are no major deficiencies, we will go into sort of the deep dive of the review, which is a big positive milestone. Then, of course, they also set the PDUFA date as they're required to by law, and they set it on July 3rd.
By July 3rd, the FDA expects to have a decision on approval. That's like one value driver. The other driver is to make sure that once the product is approved, the medical community knows about this product, they've heard about it, and are interested in using it. We also need a commercialization partner. We're a small company, and we don't have the infrastructure to commercialize the product in the U.S. We are working and in dialogue with a number of potential partners. Let me go into Orviglance first. This is kind of the summary that we have of Orviglance. This is why we're really excited about it. The first element is that we're addressing an unmet medical need. There's no product out there like Orviglance and can do what Orviglance is doing, liver MRI in patients with severe renal impairment.
That translates into an $800 million global addressable opportunity. We have a manufacturing partner that does the manufacturing for us. We are manufacturing at commercial scale, and we have ample capacity to supply the market. We have studied, evaluated Orviglance in nine different clinical studies with very consistent positive outcomes and strong phase III results. As mentioned, the NDA, the application for getting the approval was submitted to the FDA, and we expect a decision early July, and our strategy is to commercialize with a partner. So first, I'll go one step deeper and talk about Orviglance and what kind of problem it solves. Cancer is a major burden on healthcare globally, and cancer in the liver is an important problem. Most times when people have cancer in the liver, it's metastasis. So it's cancer starting in one organ, could be the colon, could be breast or lung.
Then it metastasizes, it spreads to the liver, and usually the cancer spreads with the blood flow. Because the liver has, you know, metabolizes a lot of things, then that is an obvious target. Very often the liver is the first organ for metastasis. 90% of cancer in the liver in Europe and U.S. is metastasis. 10% is primary liver cancer, as it's called, when it starts in the liver. The way to deal with this, and this is very important because it's also cancer in the liver is very often also the cause of death. You need to identify cancer in the liver as early as possible to treat it as aggressively as possible. The gold standard is to do a liver MRI, a medical imaging procedure to see if there are cancer tissues in the liver.
To get the best possible image and have the most accuracy for the doctors, they inject a gadolinium-based contrast agent today. Gadolinium is a rare earth metal. It's a toxic heavy metal. It's chelated, bound in a chemical structure to reduce toxicity. In most patients, it works well. In patients with severe kidney problems, there's a risk of this potentially fatal side effect called nephrogenic systemic fibrosis. That means all products containing gadolinium have a black box warning, which says that you should be extremely careful and avoid using gadolinium if at all possible in these patients. We come with Orviglance, which is based on manganese. There is no gadolinium in our product, and therefore this risk is not present with Orviglance.
We have received orphan drug designation from the FDA supporting that this is an important and serious medical condition and that we are likely to address that. So this is, you know, so we are targeting a subpopulation within the liver imaging space that have a high level of unmet medical need. That translates into an $800 million global opportunity. Almost half of that is in the U.S., and that's why we are initially focusing on the U.S. market because that's the biggest place and that's where we start. We've also said we will commercialize with partners. I'm going to talk a little bit about the market dynamics and the size and the opportunity we're addressing because we've done a lot of market research on the U.S. market in particular.
For the patients that need a liver imaging procedure and have serious renal problems, today there's about 100,000 procedures done annually where Orviglance could be, you know, the product of choice. 100,000 procedures. What is also one of the insights that we've gotten from our extensive market research is that these patients, because they are very sick, they have cancer, they have serious kidney disease, and very often also some other diseases, they are typically sent to the large medical institutions, to the large hospitals. From a commercialization perspective, that's important because those are the hospitals that we will primarily target when the commercialization takes place. It's not out in the small community imaging clinics. It's typically in the larger hospitals, and we cover 75% of it with 400 accounts.
We've done extensive work on understanding the pricing and reimbursement and have some benchmarks here, three, you know, north of $3,000 per dose. The other thing is that I think is extremely important. I mean, there's the black box warning on the gadolinium, but the medical community are well aware that gadolinium poses risks to patients, so our market research says here that more than 90% of healthcare professionals are concerned about gadolinium safety, including NSF, so it's not like we are communicating we have a problem that they never heard of. This is something that they're facing every day in the clinic, so we are focusing on the black box warning. The patients with severe renal impairment, that's where the unmet need is the highest, and that's our focus and orphan drug designation. In recent years, there's an additional focus on regardless of kidney function.
Whenever a person is injected with gadolinium, some of that gadolinium, most of it will leave together with the urine, but some of it will be deposited in the body, mostly in bone and skin, but also in the brain. And obviously, heavy metal deposition in the brain is not a good thing. So that is being studied, whether there are any medical impacts of that. Another point that is also increasingly having attention is that because the gadolinium leaves our bodies with the urine, it goes into the sewage system, into the water. The amount of gadolinium, the concentration of gadolinium in the water is very low, but the toxic threshold is also not so high. But it means that our filtration systems that we have in place for our sewage systems don't filter out the gadolinium.
Studies that look at water quality over decades show a very significant increase in gadolinium in our drinking water, which is also going into like soft drinks and beer and all kinds of other applications of when we use water. Obviously, from a sustainability perspective, we need to change. We need to do something else than using gadolinium and putting it in our environment. This focus has surfaced in recent years. We're focusing on the highest level of unmet medical need, which is the patients with renal disease. The industry is reacting, and, you know, GE HealthCare, one of the large gadolinium manufacturers, is working on an injectable manganese agent, which would be kind of complementary to ours. They have completed phase one, so a lot early in development. Some of the other gadolinium manufacturers are developing gadolinium agents with a lower amount of gadolinium.
They reduce the dose of gadolinium, but have comparable image quality because they recognize that gadolinium has some issues, as mentioned here. Our plan, as we've said, is we want a partner to drive the commercialization. We have a product that is now in the registration phase. We've met some important milestones. We got the Day 74 letter, which is an important milestone. We have done a lot of work to understand the commercial opportunity, and I shared some of the key highlights of that with you here today. It's a focused launch, so a number of different companies could be relevant partners and could be efficient in commercializing Orviglance and bringing it to patients. We are talking to a number of companies that could be relevant.
Those dialogues are continuing, and we are, you know, happy with the process and the outlook for getting a partner in place. Part of this is also, you know, interacting with the medical community. We have a very strong network and a group of advisors, medical advisors, key opinion leaders that are excited about Orviglance. We're presenting at a number of conferences. I just returned earlier today from Chicago. There's a large medical radiology conference, and some additional data was presented for Orviglance, and there's a lot of interest in this in the medical community, so this is important in terms of preparing the market and continuing to bring out awareness of Orviglance. Switching gears a little bit from the commercial partnering side, so this is on the regulatory side. We submitted the NDA. We think when we look at the package, we are happy with how it came out.
We have an attractive benefit-risk profile. We have manufacturing in place, and we have the Orphan Drug Designation, so I think what we submitted, we're happy with, and then the FDA is reviewing. They're asking questions during the process as they should. We got the Day 74 letter to say where they granted us the PDUFA date, so we're excited to continue this process and be in dialogue with the FDA, and the key component of the application is the clinical program, the manufacturing program, and the non-clinical. You could say on the clinical side, we have nine studies that we have completed with very good results, and we think we also have a good safety profile. There are some mild, mostly mild gastrointestinal-related side effects, which is to be expected, so nothing that really impairs clinical use.
We are really happy with the application and excited and optimistic about the outcome of the process. This is for illustration. I've sort of taken an image from phase III study. This is a patient where you can see the large structure that is the liver. To the left-hand side, you see the unenhanced. This is according to our market research. This is what a lot of the patients that we target; they have an unenhanced today because of the risk of gadolinium. You can see some dark structures here, and those are metastases, and they're visible. To the right-hand side, that's the same patient after getting a dose of Orviglance. The way it works is that the manganese in Orviglance goes into all the healthy liver cells. The metastases are not healthy liver cells, so they do not take it up.
So they stay dark, but the healthy tissue is bright, and they become much more visible. It's also easier to see, you could say, the blood vessels and see the exact size and location, which is really important for surgical planning or for measuring whether the tumor is responding to cancer therapeutics. What was also visible, and this is why this is a good example, is that you see on the improved detection, you see a very well-defined metastasis there, which is very difficult, if at all possible, to see on the left-hand side. And that makes a significant difference because if you want to treat the patient, if you treat based on this information, you would only be treating two tumors, but you would need to treat three. So it's very important to have a sensitive imaging agent that can provide this, which is what we have with Orviglance.
This is the illustration. To the right-hand side, we have the primary endpoint. It's a little bit complicated, but essentially they score each of the black dots on a scale from one to four. Then we see the difference. So we take the right-hand side minus the left-hand side. If it's positive, then Orviglance is better. We see, you know, 0.6 to 1 point difference, which is a very high level of difference on a four-point scale. So very good results. Now we are progressing. We are having the timeline here. Then obviously, as a small company today, we are 10 people. Focus getting the approval in the U.S. is a major undertaking. We are well on track. But obviously, there are opportunities outside the U.S., a lot of patients elsewhere that also are in need of Orviglance.
With that, I would move to the other program we have in our pipeline, which is Oncoral. Oncoral is a therapeutic drug. What we're doing is we take IV Irinotecan, which is a very potent cancer therapeutic used today as an infusion product. A patient will go to the hospital every second, third week, have an infusion, sit in an infusion chair for one to two hours, get a large dose. What we can do, what we've done is that we have taken that molecule and put into a tablet. When you have a tablet, you can take a dose every day. That gives you a different kind of dosing schedule. We think that can improve the efficacy and the safety profile because chemotherapeutic agents have a lot of safety problems.
This is from a phase one study that we have conducted where you could see here the illustration is that the high curve here. You also see it on day 21, that is the intravenous infusion. So that's when they get a large dose all at once. The dose is very high, and the patients are experiencing very severe side effects. With daily dosing, we don't give the same amount of dose at the same time all at once. We give, you know, tablets every single day. So over the course of a period, we give a comparable amount of Irinotecan. But we don't give this very high dose, which we believe and the literature supports that the very high dose is giving additional side effects in the patients. So we can give, you know, better treatment, so potential for better efficacy and certainly for better safety.
Initially, we will be looking at gastric cancer. We would be combining Oncoral with Lonsurf, which is an approved tablet therapy for cancer. Lonsurf is approved for gastric cancer, and you can see in this animal model, the combination of Lonsurf and Irinotecan, this is an injectable form, but have a synergistic effect on treating this aggressive tumor. We have a study design that kind of would look at the same combination in humans. The idea has been approved, and we work with Taiho Oncology, who was providing some guidance and some product to support us in this study, so we've not started the study yet, but we have the plans in place. Our focus has been on Orviglance, getting that one finalized phase III and getting it approved.
You could say we have an interesting opportunity in gastric cancer, but we really have with Irinotecan, we have a lot of different cancer types that are interesting where Irinotecan in some way has been proven to have an effect. Gastric cancer is one of many indications that we can pursue with Oncoral. To summarize here before we go to the Q&A, our focus is we have two key value drivers. One is getting Orviglance approved. We have submitted the application. We got the PDUFA date and the positive Day 74 letter, which is a great start. The FDA is telling us that they expect a decision by 3rd of July.
The other part is that we continue to work with the clinical and medical community, making them aware about Orviglance and also our discussions that we have with potential commercialization partners that we can work with and who will be efficient and capable of bringing Orviglance to all the patients and generate revenue. So this is our sort of value creation roadmap that we focus on here in the near term. That ends my presentation. So happy to take any questions.
Perfect. Thank you very much, Magnus. So first, would you just care to comment on recent developments in the MRI space, which do you find particularly important?
Yeah, I think it's interesting. I mean, just coming back from Chicago, having all these meetings with industry and with doctors and listening to presentations, there is, you know, I've been with this really for 11 years.
When we started on this journey, everybody was very focused on gadolinium. It's not a big problem because we've been using it for decades. It's a very different sentiment. And, you know, every year at the RSNA conference, it's more focus, more, you know, more people are getting aware that we need to do something else than continuing the way we've been doing. And manganese is a very good way to go. And, you know, I'm super excited about that we are leading that space. We are the first towards getting the approval. And I think that kind of dynamic has changed a lot. There's a lot more awareness both in the medical and in the industry side about manganese as a way to go in the future.
Cool. You touched upon this in your presentation, but could you please share some insights into the partner discussions? What are you looking for? What are you aiming for?
Yeah. Yeah, no, it's, you know, as I said, we're happy with the process we have. We are, you know, optimistic that we will get a partner in place. We have, you know, a number of dialogues ongoing with potential partners, and each of them have their strengths and you could say weaknesses so far. So there's a different kind of profiles of companies. I think the ones we're talking to, all of them would be very good at commercializing. So our job is to obviously negotiate with them and bring them, you know, to finalize the due diligence and then obviously get the deal terms that are attractive to Ascelia. So that's an ongoing process. We don't give sort of details.
We don't want to put ourselves in a corner where they can use our external communication in the negotiations to our disadvantage. So, you know, we're very excited about where we are. We look forward to, you know, the time ahead and updating our investors.
Yeah, sounds very reasonable, of course. And then perhaps final question from my side. Could you please elaborate a bit on the FDA regulatory review process, so the steps involved from?
Yeah. Yeah, so this process is governed by law, so that's very rigorous and well-defined. And the FDA has a lot of internal processes. They form a review team, and they have all kinds of things. So initially, you know, it starts way before the submission by all the meetings we've had with the FDA.
And obviously, when we had a pre-submission meeting earlier this year where we sort of aligned on the final elements that we put into the NDA. And they're basically reviewing it, and then they have set timelines for the meetings. And the Day 74 letter is sort of an important decision point in their process. So they have a meeting at day 60 where they discuss some things. And then at day 74, we get the outcome of that meeting. So at day 60, they have a decision, and then there may be some interactions possibly. But so that's an element. There are some additional meetings, but it's really an ongoing process. So they are doing audits. They are asking us a lot of questions. We are responding, and that's how it's, you know, an ongoing process. So it's not like now we send submit.
It's not like at school when you turn in your assignment and then you just wait until you get the feedback. It's a lot of interactions with the agency. And we're happy with the interactions. We certainly believe that they understand what kind of difference this product can do, and they need to make sure that they really understand the data in the correct way. So.
Perfect. Thank you. And that's time's up. Thank you very much for coming. And thanks everyone in the room. Yeah.
Thank you.