Ladies and gentlemen, welcome to the Ascelia Pharma audiocast with teleconference Q2 2021. Today, I am pleased to present Chief Executive Officer, Magnus Corfitzen, Chief Financial Officer, Kristian Borbos, Chief Medical Officer, Carl Bjartmar, and Chief Commercial Officer, Julie Waras Brogren. For the first part of this call, all participants are in listen-only mode, and afterwards there will be a question and answer session. Speakers, please begin. Thank you. Welcome everyone to the webcast for Ascelia Pharma's Q2 report in 2021. We have the management team here with me, and we look forward to updating you on our progress. Now please turn to page number two We will be making certain forward-looking statement on this call, so please pay attention to this. Now please turn to page number three. Ascelia Pharma is focused on improving the life of people with rare oncology-related conditions by developing novel drugs to address unmet medical needs. We have two drugs in clinical development. Orviglance, formerly known as Mangoral, is in an ongoing phase III clinical trial. It will be the only product targeting an addressable market of $500 million-$600 million annually. Oncoral is being prepared for phase II in the treatment of gastric cancer, based on encouraging results in phase I. We expect to start the clinical study later this year. We have a strong and experienced team headquartered in Malmo, Sweden, with a strong track record in late-stage drug development and commercialization. We have a solid financial position to reach important milestones. Now please turn to page number four. Ascelia Pharma is in a transformative phase as we're moving from late-stage development into commercial stage. Our lead program, Orviglance, is expected to be launched in the U.S. in the second half of 2023, and the preparations are ongoing. In the same timeframe, we expect that the phase II for Oncoral will be nearing completion. As part of our strategy, we might expand our portfolio with additional drugs that fit our orphan oncology strategy, and where we can make significant benefit for patients. This is an exciting time for Ascelia Pharma, and we see tremendous value creation potential as we progress. Please turn to page number five. In Q2, we continued to make progress. In April, we held an extraordinary general assembly to approve the share issuance to raise SEK 200 million to strengthen our balance sheet. The activities in the quarter were very operational. Despite a thin flow of press releases, significant progress was made in many areas. In August, after the close of Q2, we had several news releases, which I'll go through in the next slides. Please turn to slide number six. On August 10th, we announced the conditional approval of the brand name Orviglance for our oral manganese product candidate formerly known as Mangoral. The approval is a lengthy process involving a surprising amount of documentation, including risk of interchangeability with other product names. The brand name is approved by both the Food and Drug Administration for U.S. and European Medicines Agency for Europe. We will use Orviglance going forward, which is particularly important when building the brand and awareness in the broader medical community. Now please turn to page number seven. On August 13th, we announced the acceptance of our oral paper presentation at the Radiological Society of North America 2021 in Chicago, the largest radiology conference in the world. The top-line results were presented in December 2020 and includes a head-to-head comparison between Orviglance and the liver-specific gadolinium agent, MultiHance. Top-line results already announced showed that Orviglance was as effective for visualization of focal liver lesions as MultiHance, with two out of three readers having higher scores for Orviglance. It also showed Orviglance provide improved efficacy compared to unenhanced Magnetic Resonance Imaging, using the same endpoint as is being used in SPARKLE. This demonstrate the value of Orviglance and will support our interaction and communication towards patients, healthcare professionals, regulatory authorities, and payers. Please turn to page number eight. Yesterday, we sent out a press release relating to SPARKLE completion timeline. As everyone knows, COVID-19 continues to affect societies, and in particular, healthcare systems. This applies also to most clinical trials, and also to SPARKLE. We see a clear effect on enrollment in a given country when the infection rates are high. As previously communicated, we have taken measures. We have increased the number of sites as well as operational measures, such as nurse home visits for safety follow-up. We are making good progress with the enrollment curves, but nevertheless, we continue to see an effect of COVID-19. After reviewing the enrollment curves together with the board of directors, we have decided that it is more likely that the enrollment will be completed in first half of 2022, and hence sent out the press release. We're disappointed with this change, and I can assure you that the entire team is working as hard and as creatively as we can to complete the study as fast as possible. Please turn to page number nine. We'll go into more depth on our pipeline, and I'd like to hand the word over to our Chief Medical Officer, Carl Bjartmar. Thank you, Magnus. Can you go to the next slide? Yes. Orviglance is a novel oral contrast agent for liver MRI, which addresses a very specific unmet medical need. The contrast agents available today are all based on gadolinium, a heavy metal. Gadolinium should not be given to patients with poor kidney function, since it is excreted through the kidneys and slow elimination can cause serious side effects. In the future, this unmet need can be met by Orviglance. This specific target population is approximately 4% of all patients requiring a liver MRI, which corresponds to an addressable market of $500 million-$600 million annually in the major markets. The right side of the slide shows how Orviglance works in a patient with colorectal cancer. The left picture shows an unenhanced MRI scan without the contrast agent, standard procedure today in our target population. The right scan shows the same patient after administration of Orviglance. The liver has taken up Orviglance and appears bright. There's one dark area highlighted that's only visible after Orviglance enhancement. This is a metastasis which would not have been detected without contrast agent. This illustrates the importance of a contrast agent. In this case, since detected and localized, the metastasis may be removed with significantly improved prognosis for the patient. We are making good progress despite the extended timelines caused by the COVID-19 pandemic that was mentioned earlier. We should also mention that the development is validated and aided by an orphan drug designation from the FDA. Go to the next slide, 11. Thank you. Our ongoing registration study, SPARKLE, investigates the efficacy and safety of Orviglance in the target population with focal liver lesions and poor kidney function. As shown on the left, there's a strong clinical proof of concept through six individual phase I or phase II studies with very consistent results. These data were confirmed by an independent re-analysis by a blinded reader, which shows highly significant effect on endpoints that are also used in SPARKLE. The primary endpoint is lesion visualization based on the co-primary parameters lesion delineation and lesion contrast compared to background, which were both highly significant in the phase II program. The existing data also contains a direct comparison to gadolinium-based liver contrast agent, which demonstrated a similar effect on lesion visualization. As mentioned, these results have been selected to be presented at RSNA in November. On the right side of the slide shows the phase III design. The study, which is a global study with 200 patients, has been agreed with FDA and EMA, and the strategy is to repeat and confirm the phase II results using the same endpoints. Since there is no available contrast agent for patients with impaired renal function, the comparator will be unenhanced MRI, which is currently the standard procedure in these patients. It should also be mentioned here that the follow-up for each patient is very short compared to most clinical studies, and this simplifies the operational procedures, and we will also have the final data relatively sooner than a typical phase III study. Thank you. I will now turn to my colleague, Julie Waras Brogren. Thank you, Carl. On slide 12, highlights from our commercial opportunity and preparations for launch. We estimate that the value of the addressable market for Orviglance to be between $500 million-$600 million in our key markets, that is the U.S., Europe, and Japan. This estimate is driven by solid market research into both the volume potential, i.e., patients and procedures per patient, and the pricing potential based on extensive input from market access and pricing experts. Secondly, our market research shows that decision-makers understand the unmet need for our target patient population, and they understand the value that Orviglance can provide. Our preparations for launch progress as planned, for example, with the recent conditional approval of our brand name, Orviglance, and we continue to see a strong case for building our own commercial operations in the U.S. In March this year, we opened our U.S. legal entity and office in New Jersey, which marks an important step in our launch preparations. Last year in December, a patent was granted in the U.S. for our second-generation product, which provides protection up until 2040. On slide 13. For the U.S., the attractiveness and clear path to market provides a strong case for commercializing Orviglance on our own, building U.S. commercial operations. The target patient population for Orviglance has multiple health complications, suspected liver metastases, and poor kidney function. This means that decision-makers for its use are centered around 2,000 radiologists who can be found at 400 hospitals. This means that a sales team of around 20 Full-Time Equivalent can reach priority decision-makers at launch. We now have our U.S. office established, which represents an important step to engage more closely with key partners and the clinical community on the journey to make Orviglance available to physicians and patients in the U.S. We already have strong relationships with leading radiologists among our phase III clinical study SPARKLE investigators. We also have partners with specialists and organizations in manufacturing and in radiology in the U.S. Building our own commercial team in the U.S. allows us to create an attractive top line and retain profit and value in Ascelia Pharma. For other markets, the EU and Japan represent the most attractive opportunities in size and value. In these markets, our strategy is to maximize value of Orviglance by working with partners with existing local expertise and relationships with decision-makers. With this, I'll turn it to Carl and slide 14. Thank you. Now we switch to our second asset in clinical development, which is Oncoral. Please move to the next slide, 15. The active substance of Oncoral is irinotecan, an established chemotherapy with well-documented anti-cancer effects. It is currently used in several solid cancer indications, and it is approved for colorectal cancer and pancreatic cancer. In Japan, it's also approved for gastric cancer. Today, the administration is intravenous bolus infusion, typically every third week and typically high dose. Oncoral is a novel oral formulation of irinotecan. It's a tablet for daily dosing that could offer a valuable treatment option for cancer patients in the future, tomorrow. There are several potential advantages with an oral daily dosing, most important, efficacy. It's well known that many cancer types have a suboptimal treatment outcome today, and an oral daily dosing may improve efficacy through favorable pharmacokinetic and pharmacodynamic profile based on a more constant therapeutic plasma levels of the active substance. There are both non-clinical and clinical data supporting this concept, and I come back to that. There is tolerability or safety. Intravenous dosing of chemotherapy is frequently associated with severe side effects, typically gastrointestinal and hematologic. An oral daily dosing has the potential for improved tolerability by avoiding high plasma levels and by offering dosing flexibility. In addition, there's convenience and cost. It's more convenient and cost-effective to take a tablet at home than going into the hospital and prepare for an intravenous administration. Move to slide 16, please. The concept of frequent low-dose administration is called metronomic dosing, and the figure to the left illustrates the simulation model comparing levels of the active substance, SN-38, after irinotecan IV dosing every third week, that's a gray line, and oral Oncoral dose daily, that's the orange line. Over a three-week cycle, the exposure or area under the curve is comparable, although the plasma peaks associated with toxicity are avoided by daily dosing. Approximately 1/3 of the side effects observed after intravenous dosing are reported as severe or even life-threatening, as Grade 3 or Grade 4. Metronomic dosing may not only reduce the peak-related toxicity but also bring the possibility to adjust the dosing quickly if adverse events should occur. Our own Oncoral phase I results show that Oncoral was well-tolerated overall, and importantly, the hematological toxicities were mild to moderate, Grade 1 or Grade 2. We think that's very encouraging. In addition, phase I data with Oncoral indicated activity or stable disease, even in patients that previously progressed or got worse on irinotecan given intravenously. Move to next slide 17. This is an example of improved outcome, in this case, overall survival with a more frequent dosing. These are patients with metastatic breast cancer, where overall survival was improved from 20% with a dosing every third week, high dose, to 32% with weekly dosing with a slightly lower dose. This is, if you will, a proof of principle. We can move to the next slide 18. We are now preparing the phase II. The objective of the phase II study are several. First, to establish clinical proof of concept in metastatic gastric cancer. Gastric cancer is chosen partly because of strategic reasons. There is a potential for an orphan drug designation in gastric cancer, the clinical guidelines and clinical data support efficacy of irinotecan in gastric cancer. Subsequently, there is potential for label expansion into other solid tumor indications as well. Other objectives is to generate compelling phase II data for further development, potentially with a partner. The study is randomized, controlled, multicenter, multinational study comparing Oncoral on top of standard of care with standard of care alone. The primary endpoint is typical for a phase II study in oncology, progression-free survival, then we have the usual battery of secondary endpoint, response rate, Pharmacokinetics, safety, and overall survival. This will include approximately 100 patients, and we anticipate the study to start second half of this year, 2021, and continue into 2024. Can go to the next slide? Here, I'll turn over for you. Thank you, Carl. Gastric cancer is today a SEK 3 billion market. Every year, more than 1 million people are diagnosed with gastric cancer. In the U.S. and Europe, gastric cancer is an orphan disease with around 110,000 patients diagnosed every year. Around 60,000 of these receive drug treatment and progress to advanced stage disease. Gastric cancer is more common in Asian populations, where more than 500,000 patients are diagnosed every year. We can move to slide 20. We see opportunities for expansion into other indications where a daily tablet formulation can demonstrate an attractive efficacy and safety profile. Irinotecan in an IV formulation is already approved in colorectal and pancreatic cancer. In addition, irinotecan is clinically demonstrated in many other common cancer types, and it's recognized in the National Comprehensive Cancer Network guidelines for many cancer types. We will assess these opportunities for other indications as our phase II study progresses and as part of our ongoing strategic plans for Oncoral. With this, we can move to slide 21. Thank you, Julie. Please now switch to page 22. Development in earnings for Q4 as well as for H1 compared to the corresponding periods last year is the same as we discussed on recent calls. The increased loss year-over-year is as expected and reflects the increased Research and Development activity related to the phase III clinical program Orviglance, as well as the phase II preparations for Oncoral. We now turn to page 23. The key message on the liquidity position is that we stand with a solid cash balance, which was amplified by the capital raise we did in the spring. With SEK 319 million in the bank, we have financing well into 2023. The cash position will primarily be used for Orviglance ongoing phase III study, as well as pre-commercial activities, and also for Oncoral's phase II clinical study, which is about to start. With that, I'll leave the word over to Magnus Corfitzen. Yeah. Thank you, Kristian. Please move to slide number 24. I'd like to end this quarterly update with the focus on the rest of the year. Obviously, the clinical development of Orviglance is our key priority. Despite COVID-19 impact, we have continued to make successful progress, and are working with investigators and consultants to make the study a success. We are adapting to the circumstances to ensure that patients, medical staff, employees, and everybody else is safe. We expect to complete the enrollment, as previously communicated, in first half next year. We continue on preparation for Orviglance commercialization and have many activities ongoing to enable us to detail and implement the value-maximizing strategy. Launch is now planned for the second half of 2023. Another important activity is our preparations for the Oncoral phase II program, which we expect to start later this year. This was our final slide, and we'd be happy to take any questions. Thank you. Ladies and gentlemen, Our first question comes from the line of Sten Westerberg from Analysguiden. Please go ahead. Your line is now open. Yes, hello. Good morning. Thank you for taking my question. First of all, given the situation in clinical research, are you taking any particular measures to secure the quality of the clinical data that is generated in the SPARKLE study? I also wonder, given the timeline that you now are providing us, it appears to me that it will take more than two years to recruit the 200 patients, to the SPARKLE study. Is that a good reflection of the general situation in clinical research? Are there any particular features of your study which may further complicate the recruitment to this study? Thank you. Okay. Thank you, Sten. I'll start with the second part of your question, and I think you alluded to the two-year recruitment time. I think this pandemic situation, which is very challenging, affects not only our program, but all clinical research in general for various reasons. That's easy to imagine. This is a general thing. Your question is, if there are some specific issues with our study or our population, there's one thing that we could mention here, that our patient population, which have known or suspected liver lesions, a cancer diagnosis, and in addition to that, severely reduced kidney function. They are sometimes more vulnerable than other patients in clinical research. That could make them more hesitant to come to the hospital, for clinical visits, because they are simply afraid of getting infected. We've seen examples of that. That's something that we have identified, and we've seen that. What we're doing to mitigate that particular one is, and I think it was mentioned by Magnus earlier here also, that we are implementing home care services and visits. In other words, to try to reduce the required visits at the hospital. We come to them instead of the other way around. Trying to work around these specific issues, but that's one issue that we have identified. Your first part of the question, I didn't really understand that [crosstalk] t he clinical data. Can you please just elaborate on that, so I clarify the question? Yes. I've seen some reports about the possible impact on the quality of clinical research, given the current difficulties with the COVID-19. My question specifically to you is, have you taken any specific measures to guarantee the quality of the clinical data which is generated in the SPARKLE study in light of the COVID-19 situation? Right. I think that could apply to typical clinical studies where you follow patient a long time, and they are not able to come to the regular visits. There will be sort of missing data. We don't have that problem with our study, and that's because it's an imaging study. Basically, and it's a very short follow-up as we mentioned, and as you know, the patient basically comes in, and you do the imaging procedures and they titrate contrast agents within one visit, and then we have the follow-up visits. We have very thorough quality controls and quality criteria. That part I'm not really concerned of. We do for the patients we have recruited and treated so far, we have an ongoing quality control system. We haven't identified anything on that part. Also just to add a comment here. For the primary endpoint, that is based on the images that are being taken when the patient is in hospital at the visit, right? They are sent to a central database. You could say the risk of missing follow-up visits is, to the extent it applies, then that is related to safety. Again, we don't see that as a particular concern. No. It's a fair question, though, Sten. I don't think it applies to this study. Yeah. Just to add, in terms of also the percentage up, as you all know, we started this study last year, and especially last spring was a very volatile period of time. We saw, and there the getting new sites on board and finalizing the contract with the hospitals took a lot longer, because they basically were put on the back burner. We expected that, but maybe it took a little longer for the administrative part of that process to get going than we had hoped for. Now we see things are operating better and also in terms of if you look at various new sources, unfortunately one of the other consequences of COVID is that the rates of cancer diagnosis are going down. It ought to be sort of a positive piece of news, but most likely it's related to the fact that the patients are not being diagnosed as well as they should be, and as they are during normal times. That's also a factor. Again, we see things improving quite significantly, even in areas with COVID-19, societies and healthcare systems are learning to cope with the fact that COVID-19 is here to stay problem. Okay. Thank you. I'll get back in line. Thank you. Our next question comes from the line of Johan Unnérus of Redeye. Please go ahead. Your line is now open. Thank you. Thank you for taking my question. Just some practical follow-up questions. Firstly, to just increase the level of understanding of, at least on my part, is there any particular part of the process that's more exposed during this COVID-19? Is it the general checkup and diagnostics that have made it more difficult, or is it the follow-up imaging that has made it more difficult? Or just making the patients willing to participate in a study that may be perceived as more complicating the process? Okay. I'll try to address that one. Well, as I mentioned here, this exceptional situation has affected all clinical research for the last year and a half or so. Specifically, as I mentioned here, I think we have a very vulnerable patient population, make them more hesitant to come into hospitals. There's a barrier to visits and barrier to join a clinical study. In addition to that, there are various types of restrictions at the hospital, and that could be that there's a general burden of the hospital because they're just affected by the COVID situation. It could also be restrictions implemented by the management of the hospital or at the country level, for example. They implement restrictions for clinical research or certain types of clinical research or all clinical research are put on hold, basically, because they need to focus their resources on the general healthcare. Those are the kind of issues we are dealing with. Thank you. [crosstalk] Yeah. Sorry. Continue. No, I hope that answers your question. Yeah. No, that was most helpful. There is a little bit of random involved if you have a study in different states and counties, what sort of restrictions they implement. If you're very lucky, you get less exposed, and if you're somewhat unlucky, you get more exposed. That's correct, and that's also something we've seen now that it has fluctuated globally over the last year and a half. You have one period where one area is more affected, and then you have another one. You can take the U.S. as an example, where we all thought and hoped, before the summer here, that this was going to normalize, especially since there was vaccination. I think very few could foresee the development we've seen just very recently, or this week, there are new reports on curves in the U.S. going in the wrong direction. We didn't expect this. One thing we have done to mitigate that is to open up new countries in new regions. We are in Latin America, we are in North America, we are in Europe, we are in Russia, for example. Just to sort of spread the study geographically. Thank you. That probably brings us over to my second reflection or question, that perhaps it would be good idea to have just a monthly update or send out some short update to let us know where you are without causing any increased uncertainty and overloading away information. Just a short update. Yeah. Thanks, Johan Unnérus. I think we continue with our communication strategy in terms of we do our analysis, we look at the curves, and we see the progress that is being made, and then we have the overall communication on when we expect it to be completed. I think the risk is that if we're sending out a lot of different data points, I think there's a considerable risk that we get opinions all across the board, and I think it's better to have us together with our Contract Research Organization and assess the curves and then look at the projections and use that estimate. Obviously, we're very disappointed that we had to extend the timeline of the recruitment. I think that's probably best for everybody. At least that's our policy. Yeah. No, that's appreciated. Of course, it's a difficult trade-off, but yeah. Thank you. Thanks for the question. Thank you, ladies and gents. Once again, I remind you, if you do have a question for the speakers, please press zero one on your telephone keypad now. Our next question comes from the line of Sten Westerberg of Analysguiden. Please go ahead. Oh, thank you. I go for a second shot here. First of all, is it possible for you to disclose approximately the share of U.S. patients in the finalization of the study, or how many U.S. patients will there be in the 200 cohort? Second question, since this is an open-label study, are you continuously retrieving results from the patients that have been treated so far? Thank you. Yeah. We will not share the proportion of U.S. patients, not where we are now. Of course, at the end of the study, we will disclose that, and that will be public. We don't give a guidance or prognosis for that right now. The second question, if we learned anything, well, so does that refer to the data or to the study performance in general? I'm thinking of the adjudication work done by the three radiologists that are looking at the MRIs. Since it's an open-label study, are they continuously reporting outcome from the centers, or is this being summed up in a later stage? Yeah. They are continuously reading this, and they do it in batches of X number of patients, and then they do read and so on. It's a very detailed analysis that they do and a detailed readout. We don't see that data until the end of the study. That will be disclosed to us as sponsors, the numbers and the statistics around that at the end of the study. What we have received is just anecdotal feedback from the investigators and sites, because they can see the scans and sometimes they feedback. That's all positive, what we would expect based on what we saw in phase II. For the detail, the numbers and exact readout for lesion visualization and the delineation for certain scales, that data we don't see until the end of the study. Okay. Thank you so much. You're welcome. Thank you. We currently have no further audio questions. I'll hand back to the speakers for any final remarks. Thank you, everybody, for excuse me. Thank you, everybody, for taking part in this quarterly update. We are making good progress even despite the extended recruitment timeline. I can assure you, as mentioned earlier, we're working as hard as we can to get it completed sooner rather than later, and we will continue to update you on our progress. Thank you, everyone, and have a good day.