Good morning, everyone. Thank you for joining us this early morning, to get an update on the press release that we sent out last night. First, I'll spend about 5 minutes going through the key messages of the press release and our perspectives on this, and then we'll open up to questions. You can ask questions by writing them in the window to the right in the viewer to access this event. As usual, I'll be making a number of forward-looking statements. Before going into the content of the press release, I'll just do a quick reminder to everybody about the structure of the SPARKLE clinical study. The 85 patients who have completed SPARKLE are evaluated by three independent radiologists, Reader One, two, and three.
For the primary endpoint, they are evaluating, providing a score for the border delineation and the lesion contrast. For a reader to be successful, and reach the endpoint of the study, they need to score a statistically significant improvement on both the border delineation and the lesion contrast. For the study to be successful, two out of the three readers need to be successful. I'll come to the press release. In the press release, we communicate that a reevaluation is required to reach a conclusion. I'll talk a bit more and explain why that is. It's a well-known complication that radiologists are, like human beings, will rate an image in a somewhat different way. That is why a study design has two out of three readers to be successful, because that is understood.
The surprising issue that we have run into with SPARKLE, and that we announced yesterday, is high level of intra-reader variability. What is that? Intra-reader variability is a measure of the, the difference in evaluation of an image from the first time to the second time a reader sees this. For example, if intra-reader variability is high, the radiologist may score an image with a low score the first time. When they see it the next time, they will score the image very high or the other way around. In reality, that means that the high, a high level of inconsistency, and it's, you cannot conclude on the read and the scores from such a reader. This issue is not unique to Orviglance, unfortunately, in this study.
It's something that is well known to the FDA, and that's why the FDA has provided guidance to the industry in terms of managing this issue. We have adhered to this guidance from the FDA in our dialogue with the FDA, and therefore, in the design of SPARKLE, we took a subset, a specific number of patients from the SPARKLE study, whose images would go into the database twice. That means for these images, the radiologists would all rate these images twice. When we analyzed the data, we saw for some of the readers that the intra-reader variability was high. That means they scored low and high or high or low when they looked at these images that were in the database twice.
This is, as mentioned, this makes it impossible to make a conclusion on the efficacy, and this is very unfortunate, and it's very surprising. We will look into to understand better why that happens, so we can take every precaution possible to make sure that does not happen in the reevaluation. For us to get conclusive results from the SPARKLE study, we need to do the reevaluation. We need to do it as quickly as possible, and we will align with the FDA during the process to make sure we get their input as well. We don't know the exact timeline for when the reevaluation is completed. All our efforts and activities in Ascelia Pharma will be focused on the reevaluation. It also means that we will take cost-saving initiatives to preserve the cash, to extend our runway as much as possible.
This is completely, you could say, new situation, so we don't have any planned timeline, or know the exact restructuring, and cost-saving initiatives, so we expect to have that ready to announce mid-September. Just to finish off before going into the, to the questions, the intra-reader variability issue doesn't change our confidence in Orviglance. It doesn't change the unmet medical need. The unmet medical need Orviglance is addressing is the same today as it was yesterday and will be the same tomorrow. It doesn't change the addressable market opportunity of $800 million globally. The issue doesn't change the consistent positive results we've seen in phase I and phase II. It doesn't change the positive anecdotal feedback we got from the investigators in SPARKLE, but it does change the timeline.
As frustrating and annoying that that is, it does change the timeline, and we'll come back with an updated timeline in mid-September. What we also noted in the press release yesterday was that we saw the adverse effects that we saw in SPARKLE are in line with the previous studies that we have completed. We think that is very good news, that in this more sick patient population that we've studied previously, we see a consistent pattern. We have all the images for the reading evaluation in the database. We need to align with the FDA. We need to identify new readers and do a reading process, including training, and of the readers, and that is what we are focused on at this point. We continue to be very optimistic about Orviglance and the potential and how it can help patients.
That was a, a brief explanation and summary of our press release. I'd like to open up to questions now, and I'd also like to invite our Chief Scientific Officer, Andreas Norlin, to this webcast.
Thank you. Good morning.
Welcome, Andreas.
Yeah.
We have, the first question here. Here's a question: How could this happen? Is this a common issue with contrast agent clinical studies?
Well, the answer is, it's not unheard of, because as you explained earlier, Magnus, the images are assessed by readers, radiologists, and they are, of course, experienced, then they are trained for the task, but they are human beings, so there might be some variation, and that's quite normal. As per the guidance, we have implemented this, the test to measure this variability, and when that came out, we saw that it was larger or bigger variability than what we think is acceptable. It's not unheard of. It has happened in other studies before, and that's the reason for why this guidance exists on why doing this. It's annoying, but this is the fact. Yeah.
There is another question: How long will the re-evaluation take, and how will it impact the overall timeline? We don't know exactly how long it will be, and we also appreciate that people want to have a, you know, an understanding of what this timeline is. We will communicate a sort of detailed timeline based on our planning, detailed planning in mid-September. To give some kind of, you could say, ballpark understanding of this. We want to do it as fast as possible. Our current expectation is that it will certainly be less than a year, but probably more than 6 months. That's what we expect. We will come back with a detailed timeline in September. Here is another question. Please remind us how many readers was included in the study.
Did the smaller study size of the study contribute to the risk? Andreas, maybe you can answer that one.
Yes, for sure. Yeah, there were three readers. They were all independent to doing their own assessments of the images. No, the size of the study is not related to this issue. It's entirely related to the reader and how they perform in their job.
Yeah. Another question here: Are there any measures that can be taken in order to reduce the risk for the same thing happening again with a new group of readers?
Well, I think that there is a lot to learn from this, and we are doing that analysis, as we speak, or, or that will be very high up in our focus, when planning for the re-read. There are certainly many things we can do to, to minimize this risk. I cannot say exactly what the, the root cause was at this time.
Yeah. I think, I think it's important also to note that this is not... We, we knew this was a potential issue. We have not-
Yeah
... seen it previously, we have been diligent in selecting experienced radiologists. They have reader training. There are, you would say, training processes in place. We've been diligent in understanding and taking every step on the way, but we still see this outcome, which is what, as Andreas said, we need to look in further into this to see how we can improve it to certainly avoid this again. Another question here: Did you discuss this potential issue with the FDA ahead of the Phase III design?
That was part of the discussions because the protocol was discussed and presented to the FDA. Again, it is part of the guidance to industry from the FDA. Yes, it has been addressed in the interactions with the FDA.
Yeah. Just to put into a bit more flavor on that, the reason why this is in the guidance, why the FDA is having that conversation with drug development companies, is, of course, if you have high level of intra-reader variability, you cannot firmly make a conclusion on the efficacy, and then it would not be able to go through a regulatory process. That's why this quality check is incorporated into the study design and why we can deal with this issue now and not in a review process. Another question is: Did the small study size of the study contribute to this risk?
No, that's our, our, our firm understanding, that it, it has nothing to do with the study size.
Yeah. It's, it's an issue related to radiologists...
Yeah
... having too high level-
Yeah
... of variability, too low consistency.
Yeah.
A larger study would not have any impact.
Exactly.
There's a question here: Can you elaborate on how this does not change your confidence? The confidence that we have in Orviglance is based on the clinical studies that we have conducted to date, about the available literature showing that hepatobiliary phase imaging is very important for liver imaging, the anecdotal positive feedback that we have received from the investigators in the SPARKLE clinical study, and that does not change our, our, you would say, belief and confidence in Orviglance, that, that this will be successful. We have no reason to believe that Orviglance should not be as efficacious as we thought, before getting this kind of data readout. A question here: Will your current financing be sufficient to reach a readout from the re-evaluation? The answer is that that is our ambition, but we do not know yet.
As mentioned, we will be looking at cost-saving initiatives in the company to make sure that we have funding until we get the result from the re-evaluation. That's our ambition, and we will communicate once we have the plans in place and we understand the cost implications in mid-September.