With me today, I have the Deputy CEO and COO, Julie Brogren from Ascelia Pharma. To the audience, just some practical issues. On your right side, you have the possibility to post your questions. Please do while Julie is presenting. I will pass on questions to Julie. Today's event will focus exclusively on Orviglance, late finish of the phase III study and what to come. We will deep dive more into the commercial side of Orviglance. With that said, I would like to hand over the work to Julie. Welcome, Julie. Please carry on.
Thank you.
Thank you.
Thank you, Claus. I will be talking about Ascelia Pharma and our commercial opportunity for Orviglance today. I will be making some forward-looking statements, so please pay attention to this slide. Ascelia Pharma is a biotech focused on improving the life of people living with cancer to offer them better treatment options. We are focused on rare cancer conditions. Our capabilities are in identifying, developing, and commercializing these assets. We have two products in development. One is Orviglance. It's a diagnostic drug, and we have just finished the enrollment in our phase III study. We have an Orphan Drug Designation from the FDA. The other compound is Oncoral, it's a daily tablet formulation of a chemotherapy that is well-recognized in many solid tumor types today. I'll be focusing on Orviglance today.
Ascelia Pharma, we are based in Malmö, we funded into Q4 this year, and we're listed on Nasdaq in Stockholm. Today I want to talk about Orviglance because, as I mentioned, we have just finished the enrollment in our phase III study, so it's a very exciting time for us as we ramp up both towards the NDA approval and towards commercialization. Orviglance is addressing a well-defined patient population with a need for liver imaging in cancer patients with poor kidney functions. I'll talk more about that. We're addressing a global market opportunity of $800 million annually, addressing 100,000 abdominal imaging procedures in the U.S. alone. We have an ambitious and also focused plan for the launch that is progressing as we speak.
Just a little bit about Orviglance and what it is. What is the problem we want to help patients and physicians with? We are addressing a population that has cancer in the liver. That could be primary liver cancer or liver metastases. That's a critical part of cancer care because many cancer types tend to develop metastases in the liver. For example, 70% of colorectal cancer patients develop liver metastases. It's important for physicians to detect these early, to detect where they are in the liver, and to determine the course of treatment for patients. To do that, they do an imaging procedure where the gold standard is an MRI. When you have an MRI imaging procedure, you would use a contrast agent.
A contrast agent is a diagnostic drug that improves the image, so it's easier to see these cancer lesions. Today, all contrast agents for MRI imaging are based on gadolinium. That's a toxic heavy metal. It's been around for years. What happened some years ago, about 15 years ago, is that it was discovered that gadolinium was associated with a very severe, not very common, but a very severe side effect called nephrogenic systemic fibrosis. That was in particular a risk in patients who have severely impaired kidney function, so they have bad kidneys. You could even be on dialysis, for example. These patients are quite vulnerable. What happened is the authorities, implemented these black box warnings for this particular patient population.
The clinical practice for these patients today is to have an unenhanced MRI, to have an image without a contrast agent. That doesn't give the physician the same quality of the image to determine the course of treatment and to detect these lesions. Orviglance is a contrast agent for liver imaging based on manganese, not gadolinium. Essentially, we make the healthy parts of the liver brighter, and the unhealthy parts or the cancer parts of the liver will stay darker. We are targeting specifically the patients with severe impaired kidney function, so those who fall under the black box warning. To move on to where we are, we have completed a very extensive clinical program, nine studies, almost 300 patients.
Across all studies, we have consistent data supporting the efficacy and the safety of Orviglance. Our latest study, the SPARKLE study, is our phase III study, and we have completed patient enrollment very recently. We are now waiting for the headline data, which will come out in the middle of this year. Just to show you a little bit about what is it we're looking for example, for the SPARKLE study. On the left side, you see an example of two images of the liver. One is the unenhanced, which our target patient population typically will get today.
On the right side, you have an MRI image where we, the patient has received Orviglance. As you can see in the circles, there is a lesion that you can see on the right side, but you can barely see it on the left side. The endpoint as for our phase III study, the success criteria for the phase III study is that we ask, which is common, three independent radiologists to look at all the images from all the patients, and they need to determine whether or confirm and determine that on the right side, the contrast between the background and the lesion is better than on the left side.
They also need to say that the delineation, so the border of the lesion that you can see on the right side is sharper than what you can see on the left side. Two out of these readers need to say it's better on the right side than on the left side. We have achieved our headline endpoint for the Phase III study. This is what we are waiting for. As we do that, we are preparing for the launch.
Well, sorry, Julie. Just a question here. Sorry, I interrupt you.
Yeah.
There's a question about Orviglance and Orviglance as a drug.
Yeah.
Are you going to register this as a medical device or as a drug?
Contrast agents are regulated as drugs.
Okay.
We follow the drug pathway. It's a certain department and with the authorities, but it is regulated as a drug. Yeah.
just to emphasize, you have this Orphan Drug Designation.
Yeah.
Of course, that's a major help for you. Could you just very briefly elaborate, what gain for us?
What it means to have an Orphan Drug.
Yes.
Designation? Yeah.
how that helps with the phase III.
Yeah. Yes. Several things. It means, first of all, that it's recognized that you address a significant unmet need for a small patient population. When you show that, you have some support from the regulatory authorities. One is the development program is to be leaner. They will help you address questions along that process. They understand that it's difficult to invest in the very large phase III studies for small patient population. It's faster and cheaper to develop these compounds. Another part is, from a commercial perspective, is that you have a longer called exclusivity period.
Mm.
where they will not approve another drug for this exact patient population and indication. That will give us seven years exclusivity period in the U.S., for example. There's the both advantages in the development and regulatory pathway and also when you commercialize.
In your case that's, I think, due to gadolinium being only, the only alternative and, alternative with quite severe, side effects.
Yeah.
Yeah.
Yeah. That today, these patients will typically get an unenhanced MRI, which is inferior to a contrast-enhanced image.
Yes.
Yeah.
The picture you showed before.
Yeah.
Yes. Please carry on, Julie.
Yeah. Yes. Thank you. Just a little bit more about the market background seen from sort of the commercial perspective. When we ask physicians, "What are your concerns about using contrast media with gadolinium?" They are all concerned, or 90% of them are concerned about NSF and the toxicities related to using gadolinium. Many of them have experienced this very rare but quite severe side effect. This is our target patient population, that is recognized in clinical practice as well. What has happened over the last couple of years is when we look at our community, the medical community, the scientific community, and among regulators, a couple of other key topics are coming up around gadolinium.
First is that we know that gadolinium is retained in the brain and in other body parts and tissue of the organs, but we don't know what the safety impact is. Both the regulatory authorities and the bodies making the medical guidelines, they want to find out. For example, the FDA has asked the big manufacturers to conduct a long-term study where they're following patients who receive multiple procedures with gadolinium over five years. Another area is that we know that gadolinium is excreted through the kidneys into urine and into our sewage systems. It's very difficult to clean. We can find gadolinium now in our rivers, in our water. There's more scrutiny now into what does this really mean.
The industry is reacting, and what we see among the big players in manufacturing gadolinium today is that they're looking into developing compounds with less gadolinium, so half doses. The ones that are being developed now are actually for the full body, not liver specific. Another interesting development is GE HealthCare, who have completed a phase I study also with manganese. They are not as far as we are in the development. Also this is for the full body, not specific for the liver. We are excited that we are part of a future with less or without gadolinium, and that we are far ahead and will be the first to market with a manganese-based contrast agent. Into the commercial opportunity.
The addressable market for Orviglance is $800 million in the U.S., Europe, Japan, the mature rest of world markets. U.S. almost represents half of this. We have looked into real world data, we understand the volumes, and we tested our pricing assumptions to build up our addressable market and our launch plan. Because the US is such a big opportunity, by far the largest standalone opportunity, our plan is to lead the commercialization ourselves as an emerging pharma. Actually, there are more and more emerging pharmas launching on their own. A third of the launches in the U.S. are actually done by companies who do it for the first time.
Mm-hmm.
The better practices are to determine what are the strategic capabilities that we want to build, and where do we want to use some established outsourcing partners who run certain processes for a number of these companies and do it well. In other markets, rest of world, we want to find partners that they have a local infrastructure, and we can leverage that while we use the synergies across a global launch in terms of data, strategy, and so forth.
Very briefly, Julie,
Yeah.
In relation to the market estimates. The total addressable market of $800 million, out of this, you estimate that $500 million-$600 million is related to your primary target markets. Yes, this slide.
Yeah.
These $500 million-$600 million, is that the severely patient group or is it the total group of liver patients?
That is the patient population with severely impaired kidney function, so specifically the ones that fall under the black box warning.
Okay.
The way we do the market estimate is that we have real world data, so actual claims, procedures conducted with four patients where we first find out how many patients have with cancer are referred to abdominal and abdominal imaging procedures. In the U.S., that's a million patients per year.
Mm-hmm.
We ask how many procedures do they have per year, and we can see in this data they have a little bit more than two. 2.2 million procedures, abdominal imaging in cancer patients. We find out how many of these have severely impaired kidney function, it's the measured primarily by an eGFR under 30 or an acute kidney injury. We can estimate this patient population. In the U.S. it's around 50,000 patients with 100,000 procedures.
Out of those $500 million-$600 million, is that, is it fair to say that it's a little more U.S. and a little less Japan and Europe or is that unfair?
In terms of volume?
In terms of, yeah, total.
Yeah.
total market.
Yeah. In terms of volume, U.S. and Europe are a little similar. The population in Europe is larger, but in terms of the number of imaging procedures per year, some countries in Europe have a bit less than the U.S. By far the U.S. has a different pricing structure, it's a different market, different setup in terms of payers. The U.S. is driving a lot of value per patient.
Yeah.
It's not significantly different from other drugs. It's just the structure of these markets are a bit different.
Very interesting.
Yeah.
I have two more questions about the Orviglance, but I think if you carry on...
Yeah.
we take them a little further down the road.
Good. I'm looking forward to that then. I'm gonna move on here, talk a little bit about emerging pharmas. As I mentioned, it's more and more common. One third of all launches are by first time launchers. Actually out of the estimated sort of blockbusters coming out of the FDA, the $1 billion drugs, half of them are from companies who will launch for the first time. Why is this possible and why do companies do that? It's possible because over the years the significant innovation has been into improving care for very specific smaller patient populations, where you find out which patient population will really benefit from this drug. We call it more narrow indications. It's a more focused launch.
It's not so much about volume and the how many thousands of sales reps you have. It's really about focusing on working with the key opinion leaders and the payers and into the key decision makers. That's why a lot more companies are doing this. Because it's possible to focus on strategic capabilities and use and some of the... as a good well-balanced mix with some of these outsourcing partners who are out there and who run these operations that are not effective to run and build up as a single company.
They succeed really by making sure they understand the market, making sure they're focused, having a core team with the right skills, and then time the investment so you balance when you invest and when you create value, which is exactly what we want to do as well, and we are doing as well. I mentioned the U.S. market, and I think we covered the first part. To dig into this market a little bit more, as I mentioned, 50,000 patients need liver imaging and fall under the black box warning, and they have around two procedures per year in rounded numbers. We've looked at pricing $3,000 to $4,500 per dose. We looked into diagnostic drugs that address a specific small, well, patient population, so innovative diagnostics.
We tested our product profile with experts in the U.S. payers-Access experts, and that gave us a solid foundation for preparing for launch and for preparing for access and price. In terms of the U.S., what does it then take to reach these patients? These patients are vulnerable. They both have cancer and kidney disease. What we can see in this real world data set is that we need to reach around 2,000 radiologists at 400 hospital groups to address 75% of our market potential in the U.S. To do that, we need a very focused team. This is a hospital launch, so what you would have is a focused field team with field medical, field access, account managers, and some sales, of course.
It is really sort of a cross-functional, very focused team, and you build up gradually the adoption in these hospitals. An affiliate or a team in the U.S. of around 40 FTEs will drive the initial launch. We already have our manufacturing partner in New Jersey in the U.S. and that is also on track for our preparations. Just to, the last piece, our launch plan. As I mentioned, it's quite a unique opportunity addressing a well-defined unmet need for liver imaging, both with an agent that isn't associated with the gadolinium safety risks for patients with poor kidney function, but also addressing the increasing demand for alternatives to gadolinium in the future. We have a very clear ambition that we want to be the standard of care liver imaging choice for this patient population.
To reach this ambition, we need a focused and an ambitious launch, and we work with that strategy both in terms of preparing the label and the regulatory process and product supply, but also in terms of how we prepare ourselves to launch and we start the dialogue with key decision makers. We have our roadmaps, and we have a solid foundation with our strategy. We have started working with these stakeholders. We have a very experienced team. Across the team here, we have more than 20 global launches with U.S. focus in our experience, and then we would work with selected outsourcing partners. I just wanna share at the end here, one piece from our market research.
When we ask physicians about whether they would use Orviglance at launch for our target patient population, 85% say they will definitely or are very likely to use Orviglance at launch. This is even without us having been out there with our data and promoting the product. This is very exciting, we have now, you know, completed our phase III study and we are really looking forward to ramping up this work. As we start, just from a practical or real world perspective, it is ongoing already.
A lot of the key journals or industry journals that cover radiology and imaging have written some article about us and we have a lot of support from both our SPARKLE investigators who have very positive experience with the drug and are supportive of the unmet need. We are building up our partnerships in among the relevant stakeholders. I think that led me to the last slide. An exciting year for Ascelia Pharma. We've completed the patient enrollment in our phase III study for Orviglance. We will have the headline results in the middle of the year, and our preparations for the launch, including the NDA, of course, are on track.
Thanks a lot.
That was the last one. Mm-hmm.
No. Thanks a lot. With that said, we open up for a couple questions, and we have some coming in here. In relation to these readers, the blinded readers of your phase III study, have they started already to evaluate the images or how far are you?
Yes.
Okay.
Yes. You can start reading them in batches. When you have a certain volume collected, they can start reading. That has started. We are completely on track with that. So... That's going well. There's a lot of standards you need to follow so that they don't remember one image with the unenhanced and the enhanced.
Mm-hmm.
Absolutely, yes.
Good. Then, in relation to the approval, the estimate approval. So you will give us or the investors, headline data sometimes mid-year 2023.
Yeah.
If you get Ella, when you get this positive feedback, then you apply for approval, and you do that dual, both in Europe and in U.S.?
We have not communicated yet the timelines specifically for this. In our strategy we have the U.S., Europe, and then some of the other mature markets. U.S. is by far the biggest, so, but we haven't communicated the specifics of the timelines.
due to this, Orphan Drug Designation, if everything is good, you would be able to launch your soft launch in 2024?
Yes, because as you say, the focused launch is a gradual approach. Yes, you could say pre-launch in the, in industry language. That is an ongoing process we've started. Yes, we can ramp that up, when we look into 2024 to make sure we're ready, to make sure the stakeholders are ready, so the adoption can be as quick as possible.
Yes. A question here about Orviglance compared to gadolinium?
Mm-hmm.
price-wise. Could you elaborate a little on that?
Yes.
You expect a dose price of $3,000-$4,000. I know in U.S. there's a lot about insurances, rebates, and stuff like that, but that's the headline price, as I understand you.
Yeah. you mean list price?
List price. Sorry, yeah.
Yeah.
List price.
When you ask about the price and what it compares to, the advantage of addressing having an Orphan Drug Designation, or more precisely, that we address a well-defined unmet need for small patient population. It is that the alternative for these patients is to have an unenhanced MRI. That is what we compare to. That's an advantage both in terms of course, the clinical study and the regulatory process, the label, but also in terms of pricing because the payers will not compare Orviglance to the gadolinium compound. That is a generic market. They've been around for years. The newer ones are launched at slightly higher prices, but it's really not what we are comparing to.
Mm.
When we look at innovative diagnostics, for example, for PET scans and other, what they would have is, they would have specific product pricing and access and reimbursement for the drug alone, so not as part of the bundled procedure. That, that is possible for innovative diagnostics. That's not possible for these, or it's a lot more difficult for these sort of, in many cases, generic gadolinium contrast agents. That's an advantage for us.
There's a question here about your partnering. In Europe and rest of the world, you will look into a partnership.
Yeah.
That's one half. You have U.S. where you have an affiliate and where you want to not establish, as I understood you know, with Ascelia Pharma sheet workers, but more in an arm's length cooperation. Could you elaborate a little more on the strategy in U.S.?
Yeah.
You mentioned you have some pretty strong teams working there. Do you have any name or anything, you know, just to, you know, get more insight to who you're going to work with?
Yeah. We have not communicated the names yet. I mean, that's part of the ongoing process to find out what is the right mix. Currently we are working more with the established specialists who are good at, you know, developing access strategies and involving experts in areas and pricing to help us prepare, or companies that are good at helping us have a dialogue with the key opinion leaders. That's more than that or working with patient associations. We're working with selected e-experts who help us.
In terms of the strategy for the U.S., it -- when we say it's an Ascelia-led strategic launch, we do believe that we are the right ones to drive the strategic part of the capability development and the launch, and that there are some processes where it may not make sense to build it up. We have not communicated exactly what these processes are, but you... I'm not sure it's sort of you -- arm's length in that sense, you know. If... I mean, let's just say theoretically, if you have certain processes that you've outsourced, oftentimes it would still be your business card. They would still be Ascelia 100% allocated. I'm not...
We have not communicated what kind of processes, but there's a lot of the back office, think, processes. It's data and reporting. A lot of things where typically it makes more sense to find a company that has these things up and running. It's typically some of the things where it requires a bigger investment that isn't maybe the right priority right now. We want to focus on the strategic things that really drive the launch, if that makes sense.
Yeah. That makes sense a lot because, as I hear you say, you know, you would do it in a cost-efficient way.
Yeah.
You know, there's companies over there who already have systems in place.
Yeah.
you want to do it aggressively-
Yeah.
to, of course, capture-
Yes.
These market shares.
I will steal those words for next time.
Yeah. No, it's fair.
Cost effectively and aggressively. That's it.
That's fair. As soon as we have the headline data, you probably also can know, share some more insights into, to your strategy.
Yeah, exactly.
That's a very important milestone.
Yeah.
In terms Europe, can you shed some light on that? Is it a big pharma company or is this a more specialized pharma company? Or are you going to take a little same approach as in US?
In Europe and rest of the world, we are looking towards more like a full partnership, a partner with all established, back office, infrastructure and also field team. It would be their team owning it.
Mm.
That's what we're looking at now in terms of partnering. It needs to be a mix of things that will drive the right fit. It is, of course, a pharma company that has some synergies in this. As I mentioned, it's a focused launch, so some of the key synergies are really around the ability in medical affairs, I have to say, to work with these key opinion leaders and also in market access to work with payers and access stakeholders. Of course you need a field team. There are many ways to have a synergy, I think, with a field team. I think one important thing is that this is primarily a hospital drug. I think that's one part. That's probably the most important, really.
It needs to be someone where there's a good fit to their strategy and their portfolio. It could be smaller, it could be larger, but it's someone, of course, who believes in the value of a focused, well-defined launch. For smaller patient populations, someone who believes in that and have a track record of being successful with that.
Mm-hmm. Then one more question here that's more about the capital situation. If we assume you get approval and your commercial milestones are delayed, how big is your flexibility in terms of capital? Because right now you hold a pretty strong balance sheet.
Yeah.
You also announced, you know, how far the current capital situation stretched to. Could you shed some more light on that? Are you able with the current balance sheet to start up the launch in US or what are we talking about?
Yeah. We have funding into Q4 this year. Among the priorities are these things we have on this slide. Phase III, finishing that, generating the headline results and preparing the launch, including NDA and some of the selected pre-launch activities. Some of the examples that I mentioned on the previous slide, working with key opinion leaders and so forth, we are really focused on making sure that what we do now adds value. That is covered in our current activities with focus on the things that add value now. Yes, we need more resources for a launch. That's obvious. We have not communicated exactly when, of course, or how much.
If you look at benchmarks from Nordic companies or from emerging pharmas, what does it take to break even in the U.S.? If you just follow some of the benchmarks, the first break even two-three years after launch is one benchmark that you can find. Also overall, until you have a positive return, many companies are looking at around $100 million. That's of course a gradual process.
Mm-hmm.
When you get to that point, another benchmark is that, you know, some money can be raised on the stock exchange or with investors, but there are also other sources of funding. There are, for example, the partnerships that we're looking into. You know, of course, that would be cost-effective, as you said, but potentially also have some cash impact. Then companies do other mixes of funding. Again, it's about finding the right balance at the right time.
That leads me to the final question here, because now you touched upon it. Royalty rates in a partnership model, then royalty can be a combination of upfront payments, some milestone payments, and then traditional royalty when the product is in the market. Could you shed some light on that? Have you thought about that? Of course you have, but what are you looking into with this very strong product that you are ready to launch?
Yeah. Yeah. It's... Definitely the answer, yes, we have, we have looked at that. We have not communicated what our strategy is because we also want to be in the best possible situation to negotiate it.
Okay.
you could say typically, as you move along, you want to find the right timing. the further we move along, the more value we create and the lower the risk for the partner. we also need to make sure that a partner has time to prepare the launch.
Mm-hmm.
The further you move ahead, the better the deal is for you. The more potentially of the value, theoretically is what you get more in the hand than in the future. I mean, it all depends on the right mix, the right partner, roles and responsibilities. This is more like theoretical from benchmarking than specifically for us. That is typically what happens.
Good. Thanks a lot, Julie. I don't know if the audience have more questions to Julie. If that's not the case, I think I will close the event for today. First of all, very interesting future ahead for you, Julie. We really appreciate that you could shed some light on your commercial strategy today.
Thank you.
We really look forward to host you, as soon as possible.
Yes.
With that, first of all, thanks a lot for all the great questions. Julie, thanks a lot for participating in this event. We will of course, on our HC Andersen Capital platform, post the video afterwards, so you can dive more into Julie's presentation and answers to the questions. With that said, thanks a lot and enjoy your day.
Thank you.