Welcome everyone to the Ascelia Pharma Investor Update live Q&A in May 2024. Thursday last week, we announced a very strong outcome of the pivotal phase III study for Orviglance, SPARKLE, where we met the primary endpoint in a highly successful way, paving the way towards NDA, regulatory approval, and commercialization. This morning, we shared presentations on the data, on the path to approval, and also moving in the commercial plans, including partnering.
I'd hope you've had an opportunity to have a look at the videos, and if not, they will be available to look at later. I will briefly share some key takeaways from the presentations, before being joined by Julie and Andreas, to answer any questions that you may have. So the results from the phase III study were very strong and solid, with three out of three readers scoring positively on the primary endpoint, showing superiority of Orviglance. Very good news. We also announced the immediate milestones ahead of us.
So one track, important track, that Andreas presented in his video is the regulatory process, where we expect to have a full clinical study report in the beginning of Q4 this year. In Q1, we expect to have conclusion from the pre-submission meeting with the FDA. That will allow us to finalize the submission, the NDA submission, and file it in the middle of next year. Julie talked about the commercial tracks, which include launch readiness, as well as partnering with a commercial partner, and the opportunities that that entails. On top of that, we still have Oncoral in our clinical development pipeline. Very attractive opportunity that we're eager to move forward with when the timing is right.
So with that, I'd like to move; w elcome, Andreas and Julie to the stage here, and we'll be able to answer any questions that you may have. On the screen, there is a field where you can enter your questions, and I will have them here on my iPad, and then we will respond to them. So great to have you here. And then to get started, I have a couple of questions that I'd like to share, and first is on the data. Andreas, data is very good. Can you tell us some more?
Absolutely. Yeah, so we have obtained highly encouraging headline data from the SPARKLE phase III study. That clearly demonstrating strong superior enhancement of visualization of focal liver lesions with Orviglance as compared to unenhanced MRI, and that is evidenced by the P values lower than 0.001 for all three readers. And the strength of this data is underscored by the fact that all three independent readers who have evaluated the efficacy confirmed the superiority of Orviglance.
For the study to be considered successful, the criteria was that at least two out of the three readers needed to report statistically significant effect. But the unanimous reporting of a highly significant effect reinforces the superiority of Orviglance over unenhanced MRI. Importantly, in the light of the issues with intra-reader variability that we reported last year, the analysis of the data also showed that, and we had an acceptable level of intra-reader variability for all of the readers, making the analysis strong and conclusive.
Thank you. Thank you, Andreas. With this, you know, very strong and conclusive data, what comes next, right? What are the milestones for towards NDA submission next year?
Yeah, now we are ramping up for the NDA activities, and we are expecting to file the NDA in mid-2025. Important milestones on the way there are the full SPARKLE report in early Q4 this year, and the pre-NDA meeting with FDA, where we expect to have the conclusions in Q1 2025.
So, Julie, with our very positive headline data and the progression towards the NDA, we are also working now in parallel to prepare for the launch. So maybe you could talk a little bit about what the commercial opportunity looks like.
Yes. So, Orviglance represents an addressable market opportunity of $800 million annually. It's an opportunity to help some very vulnerable patients with a high unmet need. These are patients who need liver imaging and also have severely impaired kidney function. That means that they are at risk of severe side effects if they use the currently available gadolinium agents. So there's a high unmet need that translates to a very attractive commercial opportunity for us.
And we have a strategy and plan in place that is both focused and ambitious, and we are also on track with the preparations. Both the preparations when it comes to product supply and distribution and when it comes to preparing for a launch. But most importantly, right now, we have the phase III data in hand, and that is really the biggest milestone towards the launch. So a little bit from there on, we are ready to progress the launch.
Yeah, Julie, also in your video, you talked about the strategy for commercialization. Could you elaborate a bit more on the strategy, what that means? What are the objectives?
Yes. Our overall strategy is to work with commercialization partners, and that is because that gives us the right balance between creating value-retaining top line and the investment required. We also know what it takes to launch. We know, for example, in the US, that we can reach 75% of the potential patients for Orviglance with an approach where we reach around 400 hospital groups in the US. We have a strong understanding of what it takes. So, beyond working with a commercialization partner, there's an opportunity for us to build value in Ascelia by developing and keeping some roles for the launch.
You talked about a commercialization partner. So, how far are we with the partnering efforts? Can you shed any light on that?
Yeah. So, partnering is an ongoing effort, and the right timing is when we have the right agreement with the right value for us and for the partner, but also a timing that makes sure that a partner and we are ready for a successful launch. So, during these ongoing dialogues, we're progressing with the NDA, and we're also progressing with our launch preparations.
And what is really important now is that we may create value every step of the way in these preparations, whether it's for the supply chain or for some of the commercial activities towards our launch. So, we have a clear strategy, and the right partner is also the one where there's the right match to create mutual value. Yeah. So now we're here, and we have the data, we have the strategies ahead. We announced the data last Thursday, and we haven't seen the share price react a lot to this. So, Magnus, how do you explain that?
Yeah, how do I explain that? I mean, to me, first and foremost, this is amazing results.
Mm-hmm.
It's very clear data that I'm confident will be valuable in our discussions with the FDA and other regulators. We have met the primary endpoint with an agreement that we have had with the FDA on that endpoint. We also know that comparable endpoints have been used for other products that have come to the market. So I think with this data, we really create a lot of value and put a lot of, you could say, risk behind us in that sense. So I think that's that makes me really excited.
Share price, I mean, that's not really for me to comment on. I think usually, when companies have this kind of data, there's a more positive share price development. But I think we're committed to bring Orviglance forward, and I think ultimately value will come. So I think that's my perspective on that. So now we'll move into some more questions, and we'll try and answer as many as we can. Yeah. So let me just see here, find a couple. Here is one: Can you briefly summarize the expected news flow until the anticipated FDA approval next year? So I think we have-
FDA submission. NDA submission.
Yeah, FDA- NDA submission next year. So I think we; y eah. Can you comment on that, Julie?
In terms of the milestones...
Yeah.
... before? So there, we both have the milestones that lead to the NDA filing. That includes, as Andreas talked about, the full study report and also outcomes from a pre-submission meeting early next year. But of course, there are other milestones in terms of preparing for launch, and those includes making sure that the supply chain is ready and making sure we're ready from the perspective of having a network of very strong and leading experts when it comes to the scientific community, the medical community, but also payers. So those are some of the things that need to progress before launch, and of course, making sure the product can be in hands of patients and physicians when we have approval.
Yeah. Another question here is how far will the current cash in the company bring us?
So our current runway is into Q2 2025, so next year. That covers the critical activities for, for the NDA and our ongoing operations. So, of course, in due time, we will look at various funding options to grow Ascelia beyond this, but of course, also to reach the NDA filing in the middle of next year.
Yeah. And, another question here is: if we look at the journey from now until, and potential FDA approval in the coming years, what should investors see as major risks, looking both at capital and clinical perspective? So maybe, Andreas, if you will take the clinical perspective in terms of what is the risk towards the...
Yeah, I think there is one very simple answer to that, and that is we have now taken out the biggest risk. We have the data, very strong, compelling data from the Phase III study, and that is always key to being successful in the NDA process.
Yeah. On the capital, do you have a perspective on the capital risks going forward?
In terms of financing risks?
Yeah, yeah.
I think what we have seen now is some of the major milestones and value-creating, you could say inflection points for the company are sort of one is behind us, the NDA filing and approval is in front of us. And these are really typically the ones that also reduce the financing risk. But what is interesting with the phase we're in now is that we have different options, and those are the options we will be looking at, of course, in due time. Towards the launch, there are different ways. There's, of course, a partner. There are other constructions that the financing options, such as loans, which we have already entered into early this year. So in due time, as we grow, we will be looking into different options there.
Yeah. There's another question here: Congratulations on the data. What is the reason it will take more than a year until you can file the NDA to the FDA? And I think it's- I mean, I can take this one here. There are some, obviously, steps, and it always takes time to prepare the NDA and once you have the data. I think in our particular case, last year, we had reduced costs to make sure our financial runway could extend all the way through, to getting the data readout. And that also meant that some of the activities, including, having the team in place that could start on day one after the data, is not there.
So we will need to ramp up, bring in some people, and we're working with vendors to make sure we have high-level quality, so we make sure that it's a single submission and that it's a successful submission. So we don't want to overstretch ourselves and put risk into the approval likelihood. So that's why it takes a little bit longer. We're all impatient, and me included, but we want to make sure we take the time to get the right quality and get the best possible label for the product. So another question here, that's for you, Julie. What is your expected financial need to get Orviglance to market?
So with our current strategy to work with partners, of course, there's an opportunity for an upfront fee and so forth. So the financing needs really depend on the road we are taking. So, we don't have further detailed comments to the financing needs, but there are definitely some opportunities to bring in financing through partnerships, and then we can decide what selected capabilities are valuable for us to invest in.
Yeah. So another question here. You recently extended your cash runway to Q2 2025, and that probably relates to the financing we did earlier this year. Realistically, are you now in a better position to extend this further if the negotiation process requires more time? So can we extend the runway further?
I think what is solid to say is that this runway includes the critical activities to prepare the NDA, and then depending on how that evolves, the runway will depend on that. But of course, in due time, we will look at different sources to get all the way to the NDA filing. But I don't know if you have any additional comments to this one?
No, and I...
Or not?
... well, I think it's a relevant question, and I think we set an activity level that makes sure that we have sufficient financial runway. We make high-value activities that create value for Orviglance and the company, and I think that should hopefully put us in a good negotiation position...
Mm-hmm.
... in relation to partnerships.
Yeah.
We have another one here. Is it not possible to get the full report, clinical study report, sooner than Q4 and accelerate the FDA dialogue NDA submission? I think that's for you, Andreas.
Yeah, well, no, we need the time to do a proper analysis. We should remember that this is the key document, if you like, in the NDA, so it has to be high quality, as Magnus mentioned. We don't want to compromise on that. And we are working together with our vendor and statisticians to make this right. It takes time, and so this is the plan we have.
Yeah. Here's another one: Blue Earth Diagnostics was acquired in 2019 for $450 million. Are you seeing interest from larger companies in such kind of deals? Anything you can comment on in regarding to that, Julie?
I think we agree that Blue Earth Diagnostics and that case is interesting because as mentioned here, it's an attractive deal, $450 million, and it's within the field of innovative radiology. So that profile of partner is also a relevant profile of partner for us. So that would be a good day.
Yeah. Would certainly.
Yeah.
So, another one here for you, Andreas: Have you looked to see if the product can be used in other use cases as well, not just for the primary, like, visualization of focal liver lesions in patients with severe renal disease?
That's an interesting question. Now we are focusing on the primary indication here, which is visualization of focal liver lesions in this target population. What happens beyond that, we have no plans for, but agreed, there are some opportunities that we would be interested in looking closer at when we have the time and resources to do that.
Yeah. So, and then we also have, and maybe this is related to the, you know, the scope for adjacent usage in the core market?
I'm not sure I understand, yeah, what else can it be used for?
Yeah.
Yeah. I mean, it is a liver-specific product, so it can be used for liver imaging purposes, MRI. What you are looking for, maybe that could be something else than focal liver lesions. But this is also something that we, of course, continuously have a dialogue with our KOLs in the business, to learn more what the opportunities are. Sorry, opportunities are.
I think maybe to add, the SPARKLE study includes patients with severe renal impairment. B ut we also know, from speaking to experts, that there are other patients where it may be medically advisable to use gadolinium. So you could say within the scope of this initial, you can say approval...
Yeah.
... there may be opportunities, there.
That's right.
But of course, that's all based on a dialogue with the FDA.
Yeah.
And then staying a little bit in this, a question related to the competitive landscape. You know, how is it, how is it changing, and are there any emerging technologies like nanoparticles or ultrasound contrast agents, et cetera?
Yeah. Should I start?
Yeah, you can-
Yeah.
You can start.
Let's go.
Yeah. Yes, markets are changing. The key thing is that an MRI is the sort of the gold standard still, and we expect that to continue for liver imaging and other imaging procedures. So the main important thing about the market dynamics at the moment is that because of these concerns related to gadolinium, both for patients with severe renal impairment, but also because we know that gadolinium is retained in the brain and other body parts, and it contaminates our water.
T here is a scrutiny into what this means for us and any of us, and for the environment. So there's a drive towards alternatives with less gadolinium or without gadolinium. So we are excited to be first-in-class with a liver-specific non-gadolinium agent. What we see for other types of use, we also receive questions about AI and so forth. Typically, it evolves with this clinical practice. So, for example, AI would further improve Orviglance or imaging or any other MRI imaging. So oftentimes, these market dynamics sort of evolve together. So for now, I don't see anything sort of significantly impacting our market opportunity. On the contrary, there is a push towards alternatives to gadolinium.
Yeah.
And I think, co-commenting specifically on, you know, the question in relation to ultrasound contrast agents. There are ultrasound contrast agents that have been available for a long time. And when you look at the, you would say, the reported effectiveness of those procedures, according to the American College of Radiology, the liver appropriateness scoring is much higher. In fact, the contrast-enhanced MR is the highest scoring element there.
So, I think it's not-- I think there are lots of dynamics. I think there are lots of opportunities. I think for the patient that we're targeting and potentially other, as commented on the questions, I think Orviglance is a very strong fit, delivers on the unmet medical need for those patients, and that's what we're dedicated to bring Orviglance to them.
Mm-hmm.
So, another question here: Any preferred profile of a commercial launch partner? Julie, what are you thinking?
Yes. First and foremost, the right partner is the partner where there's a mutual value for the partner and to Ascelia, and where Orviglance is a meaningful contribution to their value and their strategy. And, there are different ways of creating this shared value. It means, first and foremost, there are some synergies in their strategy, in their commercial operations. So these could be synergies, for example, from already having a commercial team working with hospitals.
It could be synergies in terms of already commercializing an innovative diagnostic, or it could be synergies in other ways, working with small patient populations or a high-value product, you could say, for radiology or for oncology or nephrology. So there are many angles into how there could be synergies that could create value for a partner and for Ascelia. That's a good thing for us. The right partner is the one with a mutual value and a good match to Orviglance.
Yeah. Sort of a follow-up question, sort of, to this, so if you can expand on the dialogue with prospective partners, which may have been on hold during the past period, and how that dialogue may accelerate now with your phase III success and clearing away any of the reader variability challenges. Do you expect this dialogue to lead to partnering before a new financing round is necessary?
It is true, as we talked about, that it's an ongoing process, and the right timing is when a partner is ready, but also when there's most value for us, and also when some risk has been reduced. So there's no doubt that some of these dialogues have been sort of a little bit waiting for the headline results. So it's a good time to, you can say, continue those ongoing dialogues. And so, yes, it's a different situation now that we have the phase III data, and no doubt about that. I can't comment exactly on the when it will happen, because that would be the right timing for our value.
Yeah. That leads us into our next question for you, Andreas, in terms of how do you see the risk of getting an FDA approval?
Yeah. Well, again, repeating myself, we have actually reduced the most prominent risk here by having these very encouraging phase III data. And, again, I want to underscore that they are compelling because we have seen highly significant results for all three readers. And that is a very, very good position to start with when you go into the negotiation with the FDA. So I would say that with good data, we have the same kind of risk profile that anyone else would have with this. I would- I cannot see. There are no specific risks more than the general one.
Yeah, I think it's fair to say, I mean, we have a; It's an orphan drug. We have orphan drug...
Right.
... designation from the FDA. We completed nine different clinical studies. We have tested in patients with impaired liver function and had a good outcome of that. We have tested the food effect, and we have different dose ranging studies, and very clear and compelling efficacy data. We have manufacturing, and we have everything in place. We're very confident in terms of getting the FDA approval and excited to move forward on this one.
Yeah.
A question here; congrats to the phase III results. And this is for you, Julie, I think.
Mm-hmm.
If you sell a new pill that is supposed to be better, you get instant access to all the world through drugstores, pharmacies. Maybe there are a couple of iterations on the way, but if you sell a new med tech product, you need to win each hospital. Where in between these two does a product like Orviglance end up when it comes to commercialization? So firstly, is it more like in the med tech camp or in the drug pharmaceutical camp?
Yeah, so Orviglance is a diagnostic drug, so regulated as a drug and also treated as a drug by payers. And I think this, this is an interesting case when you think about pharmaceutical launches on the one extreme. You, you may have a product that is-- can be widely used and can be distributed through pharmacies, and then some are may and could be for a broader patient population, and then some are for a smaller, well-defined patient population.
That usually comes with also a very high unmet need, with less competition, and also a significant value for the patients and the payers because of this unmet need. So in essence, Orviglance is in the segment with a small, well-defined patient population with a high unmet need. It also means that the value per patient for Ascelia is high and is higher typically than broadly used drugs, where you're addressing a broader patient population and have the higher volume.
So there is typically a bit of a trade-off, and that being said, not that it is our focus, but broad launches through pharmacies in a competitive space are also very, very, very expensive, and it's a higher investment in the launch than typically it is for a small, focused launch to a well-defined patient population. And that is our business model and our focus and our capabilities. High value, well-defined, unmet need, and a good understanding of the stakeholders who make the decision.
Yeah. Thanks, Julie. So, what looks to be the final question here, unless somebody add more, but, are there any potential competitors developing manganese-based contrasts with a broader scope/indication? How do you plan to protect the market share for Orviglance in the future? So, maybe, Julie, you can start on that, also elaborating...
Mm-hmm.
... into how we protect the Orviglance franchise.
Yeah. So the best way to protect your franchise is always to have a product that adds value to patients and to physicians, and to do that well. That will ultimately create the, you can say, the preference for your product. But if you look at the alternatives to Orviglance, we know today that a patient who has severe renal impairment today and needs liver imaging typically receive an unenhanced MRI. So we want to be better than an unenhanced MRI, and that's what our data is showing.
We know some patients receive half a dose MRI and so forth. So the alternative in terms of supporting our patients could be the trade-off of the risk, and that is our strategy to provide a better alternative to both a gadolinium contrast agent at risk or an unenhanced MRI. Now, we know that there is, as I mentioned, a drive towards less gadolinium or gadolinium-free agents.
So there are some, a product launched, which is a half-dose gadolinium agent, but it's not, you could say, in that sense, a competitor to Orviglance because it is a full body IV contrast agent, so it is not a liver-specific contrast agent. We also know that other of the gadolinium manufacturers are active in an early-stage manganese-based contrast agent. And again, these are not, you could say, a liver-specific agent. They are not, again, an alternative in that sense to Orviglance, where we are really focusing on the liver imaging need for patients.
So the best way to build value and to keep our market share, so to say, is to do it well and to serve an unmet need. We also have a second-generation compound, Orviglance, which is a patent-protected effervescent tablet, and that is an opportunity to, you could say, expand and extend our franchise in the future. But that now we need to focus on getting Orviglance right, and in parallel, we'll also be working on what the right strategy is for our second-generation compound.
Yeah, and then just to complement what you said, we have an FDA orphan drug designation, which gives us 7 years of regulatory exclusivity in the U.S., which will give us certainly a benefit. And Orviglance has now completed phase III, and the other agents we are aware of are in the phase I stage. So way ahead of the competition and with the orphan protection, so we are in a great place here. One more question has come up; w hat is the risk that potential partners want to see sort of the full clinical study report before concluding negotiations?
You could say any negotiation is, there's always something ahead of you, so it depends on the, on the timing. There's also the FDA approval, there's the launch, and, and so forth. So you can construct a deal in a way where certain things are contingent on the next step, and it's typical to also phase a deal and, and the different milestones in the deal accordingly. So, the key thing is, as all potential partners know in the industry, is that we have positive phase III headline data, and the full study report is merely sort of the, the tables and details, supporting those headline data. So, I don't personally see a, a risk in that sense, for that part. I think it's more about the right deal with the right milestones.
Yeah. Yeah, I would agree with that. It's the clinical study report is about having the right dialogue with the FDA, and they needed to be able to make their assessment and their analysis in the pre-submission meeting. I think for a partner, they will look at, you would say, the data that is available, and now we have the primary endpoint available.
Andreas, you presented on the safety, which is consistent with what we have seen previously, which we are really happy with, and no serious adverse drug reactions and so forth. So I think we have, you know, the most important data is already there, and as we start, you would say, finalizing the study report, we will have more and more details. So, I think that's not necessarily a trigger point for an industry partnership deal.
Right.
So that was the final question. Thank you so much for all the questions and, and the interest. We've been happy to, to answer your questions, and we look forward to a continued good dialogue with our shareholder and stakeholder community. So last week we had a major, major milestone, the biggest in the life of Ascelia. Very strong phase III data. Now we're progressing towards the NDA submission next, middle of next year, and in parallel, we're working on preparing the launch readiness and making sure that the drug will get out to patients once it's approved, and, and look at the partnerships. So thank you so much for your time. Have a great day.
Thank you.