Welcome to Ascelia Pharma's Q2 presentation for 2022. This conference call is being recorded and will be posted on Ascelia Pharma's and Financial Hearing's web pages. Participants will be on listen-only mode. There will be an opportunity to ask questions afterwards. Today, I am pleased to present CEO Magnus Corfitzen, CFO Kristian Borbos, CMO Carl Bjartmar, and CCO Julie Waras Brogren. With that, I would hand over to speakers. Go ahead. Thank you, and Welcome everyone to the webcast for Ascelia Pharma's Q2 report in 2022. Together with the rest of the management team, we are pleased and looking forward to updating you on the results and the progress of the quarter. Please turn to page two. In this presentation, we will be making certain forward-looking statements, please pay attention to this page before turning to page three. Ascelia Pharma is dedicated to improve the life of people living with cancer by offering better treatment options. In particular, we focus on rare cancer conditions. Our business model is to identify, develop, and commercialize novel drugs that address unmet medical needs within orphan oncology. We have two drugs in clinical development. Orviglance is in an ongoing phase III clinical study. Once it gets to market, it will be the only product targeting an addressable market of opportunity of $500 million-$600 million annually. Oncoral is ready to start phase II in the treatment of gastric cancer based on encouraging results in phase I. We're based in Malmö, Sweden, listed on Nasdaq Stockholm. We have strong balance sheet and are funded into the second half of next year, including completion of the ongoing phase III program. 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. We are advancing Orviglance and Oncoral, and furthermore, as part of our strategy, we expect to have expanded our portfolio over the next few years by acquiring or in-licensing additional drugs that fit our ultra oncology strategy and where we can make a significant benefit to patients. In 2025, we expect to have established Orviglance as the market leader in this market. Oncoral in phase III development and having one or two more clinical-stage assets in the pipeline through acquisition or in-license. This is an exciting time for Ascelia Pharma, and we see tremendous value and creation potential as we progress. Now please turn to page five. In the second quarter, we continued to make progress. We had a number of different news items, and the first one in May we reported results from the Food Effect Study. This is where we studied Orviglance taking both on a fasting status and after receiving food before the administration. Importantly, in this study, we demonstrated that patients have strong liver enhancement with Orviglance, both if they're fasting but also if they are at a light meal before the administration. This will make it even more attractive for patients, especially patients who may have difficulties fasting because of underlying disease. We also received a notice of allowance for second Oncoral patent in the U.S. This will further strengthen our intellectual property on this asset. At ESGAR, the major European gastrointestinal radiology conference, we presented results from the reread of our previously conducted clinical study at Karolinska Hospital in Sweden. We used three independent readers and a reading protocol similar to SPARKLE, and the results demonstrated strong data for Orviglance. In June, we announced that Déspina Georgiadou Hedin will succeed Kristian Borbos as CFO, and she will start in September. After the close of the quarter, we announced in August that the results from the Food Effect Study will be presented orally at the RSNA conference as a major U.S. radiology conference, which is taking place in late November this year. Now please turn to page number six. Now we're going into more depth on our pipeline, and I'd like to hand over to our Chief Medical Officer, Carl Bjartmar. Thank you, Magnus. We can go to slide seven. Orviglance is a novel oral contrast agent for liver MRI, which addresses a very specific unmet medical need. Liver metastases are common in oncology since many cancer types tend to develop metastases in the liver over time, and many times are the cause of mortality. 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's excreted through the kidneys and slow elimination can cause serious side effects. In the future, this unmet need can be met by Orviglance. 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 contrast agent, standard procedure today for our target population. The right scan shows the same patient after administration of Orviglance. The liver is taking 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 the 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 have made good progress. The early phase program has been completed with strong data providing clinical proof of concept, and we are currently in phase III. We should also mention that the development is validated and aided by an Orphan Drug Designation from the FDA. Please go to slide eight. As mentioned, there's strong clinical proof of concept through six individual phase I or II. Confirmed by an independent re-analysis by a blinded reader, which showed highly significant effects on the endpoints that are also used in the ongoing phase III study. The phase III primary endpoint is lesion visualization based on the co-primary parameters, lesion delineation and lesion contrast, compared to background. As seen on the slide, both these were highly significant in the phase II program. It was also noted that 33% more metastases were detected with Orviglance compared to unenhanced MRI. These results clearly justify entering phase III and also provides a valuable guidance when it comes to design of the phase III study. Please move to slide nine. Our ongoing registration study SPARKLE investigates the efficacy and safety of Orviglance in the target population with focal liver lesions and poor kidney function. The study, which is a global study with 200 patients, involves some 50 sites in the U.S., Europe, and Latin America. Since there is no available contrast agents for patients with impaired renal function, the comparator will be unenhanced MRI, which is currently the standard procedure for these patients. This study design has been agreed with FDA and EMA. The strategy is to repeat and confirm the phase II results using the same endpoints, lesion both delineation and conspicuity. It should also be mentioned that the follow-up for each patient is very short compared to most clinical studies. This simplifies the operational procedure, and will also mean that we have the final data relatively sooner than a typical phase III study. Please move to slide 10. As mentioned, Orviglance program also contains two supporting studies. The food effect study addresses the effect of food intake on absorption and signal intensity of Orviglance in healthy volunteers in a crossover study design. In May, we announced the results which show that intake of a light meal prior to Orviglance administration provides a similar MRI enhancement compared to a fasting condition. This finding could further improve the convenience and ease of Orviglance administration in clinical practice. In line with previous studies, the data also confirmed robust Orviglance liver enhancement compared to an MRI image without contrast agent unenhanced. The hepatic study evaluates how patients with different degrees of hepatic impairment tolerate Orviglance. This is of interest since Orviglance is selectively taken up and excreted by the liver. The study was performed at Texas Liver Institute in the U.S. in patients with mild, moderate, and severe hepatic impairment respectively. Each severity group had six volunteers, which was matched with a control group with normal hepatic function. Preliminary data indicate good tolerability with no reported serious adverse events. The final results in this study are expected shortly in Q3 2022. Both these studies will be included in the Orviglance submission package for marketing approval, to the health authorities, including FDA and EMA. Please, turn to slide 11, and I hand over to my colleague, Julie. Thank you, Carl. The addressable market for Orviglance represents $500 million-$600 million annually in key markets, the U.S., Europe, and Japan. This potential is based on the volume of liver MRI procedures for cancer patients with severely impaired kidney function, i.e., patients falling under the black box warning for gadolinium-based contrast agents. Our data includes real-world data on realized procedures for these patients. We have also extensive input from market access and pricing experts where we have tested different price levels and collected insights on the evidence needed to support access and reimbursement. Building our own U.S. commercial team allows us to create an attractive top line and retain profit and value in Ascelia. For other markets, starting with Europe and Japan, our strategy is to maximize the value of Orviglance working with partners. Please move to slide 12. In March this year, we announced the results of our recent market research with 270 U.S. healthcare professionals. The market research explored the current clinical practice and unmet need for the target patient population of Orviglance with answers from radiologists, nephrologists, and oncologists. The results support the unmet need for Orviglance in the target patient population and are consistent with previous market research. This slide shows one of the key findings and confirms that for patients with severely impaired kidney function or acute kidney injury, around 80% of healthcare professionals prefer today to perform an MRI without a contrast agent or sometimes with a partial dose of a gadolinium contrast agent. Please move to slide 13. At the end of the market research survey, respondents were presented with a product profile of Orviglance. As a response, 84% answers that they are likely or definitely will use Orviglance for the target patient population at launch. The results of the market research confirm the commercial potential for Orviglance and help us prepare an ambitious and focused launch. Please move to slide 14. For the U.S., the attractiveness and clear path to market provide a strong case for commercializing Orviglance on our own, i.e., building a U.S. commercial affiliate. The target patient population for Orviglance has multiple health complications. Suspected liver metastases or cancer in the liver and poor kidney function. This means that decision-makers for using Orviglance are centered around 2,000 radiologists, most of whom can be found at around 400 hospitals. Therefore, a focus team and an affiliate of around 40 FTEs can reach priority decision-makers at launch. We have our U.S. office established, Ascelia Pharma Inc., which represents an important step to engage more closely with key partners and the clinical community in the U.S. on our journey to make Orviglance available to physicians and patients in this important market. Our global manufacturing partner, Cambrex, is also in New Jersey. We are gradually building our footprint and relationships with key stakeholders in the U.S. as part of our preparations for launch. This includes a number of leading radiologists, of which some are among our phase three clinical study faculty investigators. Please move to slide 15. Okay. Thank you, Julie. I will now switch to our second asset in clinical development, Oncoral. We can move to slide 16. The active substance of Oncoral is irinotecan, an established chemotherapy with well-documented anticancer effect. It's currently used in several cancer indications, and it's 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. The tablet formulation enables more frequent daily dosing that could offer several potential advantages. Most important, efficacy. It's well known that many cancer types have suboptimal treatment outcomes today. An oral daily dosing may improve efficacy through favorable pharmacokinetic and pharmacodynamic profile based on more consistent therapeutic plasma levels of the active substance. There are both non-clinical and clinical data supporting this concept. There's tolerability or safety. Intravenous dosing of chemotherapy is frequently associated with severe side effects, typically gastrointestinal and hematological. An oral daily dosing has the potential for improved tolerability by avoiding high plasma levels and by offering dosing flexibility. In addition, there is 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 next slide, 17. The concept of frequent low-dose administration is called metronomic dosing. The figure to the left illustrates a simulation model comparing levels of the active substance SN38 after irinotecan IV dosing every third week. That's the gray line. An oral Oncoral dosed daily, 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 one-third of the side effects observed after intravenous dosing are reported as severe or even life-threatening, grade 3 or 4. Metronomic dosing may not only reduce the peak-related toxicity but also brings the possibility to adjust 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. In addition, our phase I data with Oncoral indicated activity or stable disease even in patients that previously progressed on irinotecan given intravenously. Please move to next slide 18. This is an example of improved outcome, in this case, overall survival with more frequent dosing. These are patients with metastatic breast cancer, where overall survival was improved from 20% with 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. Please move to slide 19. Now we are preparing for phase II, and the objective of the phase II study is to generate the clinical proof of efficacy in metastatic gastric cancer. The strategic reason to choose gastric cancer are several. First, the clinical guidance or guidelines and clinical data support efficacy of irinotecan in gastric cancer. Second, gastric cancer is a severe cancer form with a high unmet medical need and the potential for orphan drug designation. Subsequently, there's potential for label expansion or into other solid tumor indications. Finally, as shown in the figure, there's data from gastric cancer animal models supporting a synergistic effect of irinotecan if combined with Lonsurf. Lonsurf is another oral chemotherapy which was approved for metastatic gastric cancer in 2019. This all-oral combination could potentially provide a more potent treatment alternative for these patients. Next slide, please, 20. The study is therefore a randomized, controlled, multicenter, multinational study comparing Oncoral on top of Lonsurf with Lonsurf alone. The primary endpoint is typical for a phase two study in oncology, progression-free survival. There's a battery of secondary endpoints, response rate, pharmacokinetics, safety, and overall survival. This will include approximately 100 patients and involves a clinical collaboration with Taiho Oncology, the manufacturer of Lonsurf. We are enthusiastic to eventually start a study and the necessary regulatory approvals are obtained. However, for strategic reasons, in order to focus all our internal resources on the lead program, Orviglance, we are postponing the study start for now. As soon as internal bandwidth are secured and ensuring the effective study conduct, the study will kick off, and we look forward to that. I will now hand over to Julie again. Slide 21. Thank you, Carl. We will start Oncoral development in gastric cancer, which is today a $3 billion market. For these patients, there is a high unmet need for improving outcomes and the opportunity for an Orphan Drug Designation. We also see opportunities for developing Oncoral in other solid tumor indications, where a daily dosing tablet formulations can demonstrate an attractive efficacy and safety profile. Irinotecan as an IV formulation is already approved in colorectal cancer and pancreatic cancer. It is also clinically demonstrated and recognized in the NCCN guidelines for many other cancer types. We are assessing these opportunities as part of our ongoing strategic plans for Oncoral. With this, I will pass over to Kristian. Thank you. You can now turn to page 23 and liquidity. The key message is that we continue to stand with a solid cash balance. We have SEK 209 million in the bank, and that takes us into the second half of 2023. The cash position will primarily be used for the ongoing phase III program for Orviglance, as well as pre-commercial activities for Orviglance. You can now turn to page 24. In the second quarter, we saw a largely unchanged operating loss year-over-year, and the same pattern also goes for the first half with an operating loss at the same level as the first half last year. Roughly the same pattern as for last year. With that, I hand the word over to Magnus. Yeah. Thank you, Kristian. Please move to slide number 25. I'd like to end this quarterly update with our focus on the key milestones that we have. Clinical development of Orviglance is our key priority. We expect to complete enrollment in SPARKLE this year. We also continue our preparations for Orviglance commercialization and have many activities ongoing to prepare for successful launch of Orviglance for the benefit of patients. As mentioned earlier, Déspina Georgiadou Hedin will join as our new CFO in beginning of September. This also means that this will be Kristian Borbos last quarterly call as CFO for Ascelia Pharma, and I would like to thank him for his contributions to Ascelia Pharma over the last five years. It's been a pleasure working with him, and we wish him success in his new role. For that was the last from our side, and we'd be happy to open up for any questions. Thank you. If you'd like to ask a question, you may do so by pressing zero one on your number pad. If you wish to withdraw your question, you may do so by pressing zero two. There will now be a brief pause while questions are being registered. Thank you. Our first question comes from Sten Westerberg from Analysguiden. Go ahead. Line is now open. Yes, thank you. Good morning. A question on the hepatic study. It has been ongoing for quite a while, and I've seen it delayed at several locations. I wonder if you could point any specific difficulties in this study not being yet concluded. Since these type of patients were excluded in the SPARKLE study, I wonder, is it your expectation that Orviglance will be contraindicated in patients with hepatic impairment? That would be my first question. Also, a second question regarding your strategy for the SPARKLE study where you continue to recruit new centers. At this late stage of the study, could you go into reasons why you still are recruiting new centers? Thank you. Okay. Thank you, Sten. This is Carl. I'll start with the hepatic study. Yeah, it's been slightly delayed compared to our initial guidance on timelines there, but. Well, two main reason for that. I should also say that it is, you know, completed when it comes to recruitment and treatment and so on. What we are doing now is just, you know, analyzing the data. Basically, we have the data in-house. We're just doing the final analysis of that, and we will communicate our conclusion on the data very shortly. The study is in a sense completed. One reason was that there were three groups of hepatic impairment, mild, moderate, and severe. Severe hepatic patients, they're quite rare. These are healthy volunteers with severe hepatic impairment, so they are a bit difficult to find because they're also in, you know, very bad shape physically. Usually we see and we have certain inclusion exclusion criteria that fit in. That took some time to find those six patients. That's one reason. We are analyzing the data now, and we should have that very shortly. Then for the results, we will communicate the results. We have not done that yet, but what I can say and what we have communicated is that in mild hepatic impairment, those patients are already allowed into the SPARKLE study. That was in the protocol from the beginning. We noted that for moderate hepatic impairment, there was a good, relatively good, contrast enhancement, and it was also well-tolerated. We have, you know, adjusted the study protocol to also include in the phase III, also include moderate hepatic impairment. That's what we envision to have in the future in a commercial setting that also moderate hepatic impairment patients could, you know, receive Orviglance. We have come back to the severe, but those are quite rare anyway. You know, those. There's a few numbers that have the combination of severe hepatic impairment and renal impairment and liver lesions. I hope that answer your question on the hepatic study. Yes. Thank you. All right. Then, your question was about why we're still opening sites in the SPARKLE study. We are not identifying new sites now, but there are a few sites that are still not technically open. The reason is more administrative, and our guidance is that we should have, you know, complete the study by the end of the year. Basically five months from now. To ensure that we decided earlier, before summer, basically to open up a few more sites. That was decided even before that actually in earlier this year that we are going into LATAM, for example, those countries and open up sites there. You know, sometimes the regulatory process just takes time. Those are the last, you know, outstanding sites that we are opening as we speak now, getting the last paperwork, ethical committees, you know, regulatory authorities need to review documents and, you know, again, sometimes it takes time. This is it. It's not a decision now to open up new sites. It's sort of a previous decision and we just going through the completing the process now. Okay. Thank you very much. A follow-up question, if I may. In the report you are repeating that you are continuing to support the clinical leaders, including patients at the active sites. I wonder this type of support that you're continuously providing to the clinical leaders is that sort of indicative of a product that needs to be administered with a lot of support from your side? Is this what we should expect from you after launching the product, a period of a lot of support to clinical practitioners? Yeah, it's a good question. No, I don't expect because it's the administration and the clinical handling of Orviglance is quite straightforward. You know, it's actually easier than an IV administration. It is, you know, they're used to doing this in another fashion. There could be some support. Also the support is just to ensure that they are compliant with the study protocol. That it's quite usual to have that in clinical study because it's a new study protocol. It's usually a new compound, and you need to support them just being compliant to the study protocols, you know, procedures. You don't have any deviations there. Another thing could be that, since this is a It is after all a rare population and, you know, if they request and ask for support finding patients, database search and those kind of things, we are able to support them with those kind of things. It's more, you know, from a recruitment perspective. Those needs differ from site to site, from country to country, and we try to tailor the support as much as possible. You know, some sites do not need support, so others ask for support, and then we provide that. Okay. Thank you. That concludes my questions. Thanks. Thank you, Sten. Thank you. Our next question comes from a number ending with one two three. Please introduce yourself, your company and your question. Your line is now open. We don't hear a question. There seems to be an issue with this phone number. We will hand over for closing remarks as there are no more questions. Okay. Thank you everybody. We're pleased to, you know, announce our progress and our results for this quarter. We continue dedicated to our two key objectives, completing enrollment in SPARKLE this year and preparing for a successful Orviglance launch. Thank you, everybody, and we will continue to update you as we make progress. Have a nice day.