Hello, and welcome to the Scandion Oncology Audiocast Press Conference 2021. For the first part of this call, all participants will be in a listen-only mode, and afterwards there'll be a question and answer session. Today, I'm pleased to present CEO Bo Rode Hansen. Please begin your meeting. Thank you. Welcome to this audiocast from Scandion Oncology, a cancer drug resistance company. My name is Bo Rode Hansen, and I'm the CEO of the company, and I'm here with my colleague, Peter Michael Vestlev, who is the CMO. I must say, I've been looking forward to this day, and I'm pleased to say that we have the positive data which we released this morning. Positive data from the CORIST part 1 of our phase II trial. This is an interim result. To recap, the CORIST trial is looking at treating baseline data of baseline patients that have been treated with FOLFIRI and have progressed. These patients suffer from metastatic colorectal cancer and have been treated with our drug, SCO-101, in combination with FOLFIRI. I think this is a good day for patients, and therefore, let me just start by thanking the patients and the investigators that contributed to this trial. Next slide. Quickly, a disclaimer because we will bring forward looking statements. Next slide. Then let me tell you a bit about what we'll spend the next 15 minutes with you guys on. First of all, remind you on the objectives of the CORIST part 1 trial, and then take a deeper stab or look into the results that we have found. Here I'll be seconded by Peter Michael. We will also talk about the design and where this takes us in terms of objectives and next steps. Finally, there'll be some summary of key takeaways. Let me remind you, this is also followed by an interactive Q&A session. If there should be any questions from the audience, please go from there. Next slide. First of all, let's look at the objectives. What did we set out to do in the CORIST study? This is in the part 1 of the study, which is an overall phase II study. The primary objective was to establish the maximum tolerated dose, MTD, of SCO-101 in combination with FOLFIRI. The secondary objective of this part was to evaluate pharmacokinetics and get the PK profile of SCO-101 in combination with FOLFIRI. I'm pleased to say that we checked both those boxes and achieved those objectives. Not only did we achieve those objectives, next slide please, we also managed to gain new knowledge, which I would say is added value from this study, and which gives us the opportunity to actually put a component of precision into the ongoing studies from here. The new knowledge is that we identified a biomarker, the well-known oncogene RAS, which serves as a predictive biomarker in this study, and we will explain the details of how, but this allows us to select the patients that are likely to benefit from the treatment in the ongoing fashion. Next slide. To summarize, let me give you a strong high level here. The key results from the CORIST part 1 were we found a well-tolerated dose of SCO-101 in combination with FOLFIRI, so that is established. We also saw a notable potentiation of the biological effects of FOLFIRI in the patients. Third, we identified the predictive biomarker RAS, where patients with RAS wild-type or wild-type tumors can guide our patient selection for the optimal treatment response. This significantly de-risks part 2 of our study. It's important that we found that and then we de-risked in here. Let me just run through the preliminary effectiveness measures. Five out of eight RAS wild-type patients in the study have bounced up stable disease for more than eight weeks. Two of five patients experienced a reduction in the tumor volume. We have not yet seen the 30% or more, which is guiding the risk criteria, but it's an encouraging result. One patient has been on trial for more than 24 weeks. This is a patient group that were progressing from the third line and potentially last line treatment, heavily pretreated, is still on trial 24 weeks after coming into the trial. We are now ready to advance to the proof of concept part 2 of the CORIST. Here I would like to hand over the words to Peter Michael who will take a deeper look at the data. Next slide, please. Thank you, Bo. I'll just recapitulate that this study addresses the treatment of patients with metastatic colorectal cancer who have prior received treatment with chemotherapy, including the FOLFIRI regimen, and who have progressed on that treatment, and where the options for treatments are few or non-existent. These patients had a need for new treatment options. The CORIST study, part 1, is designed to find what is called the maximum tolerated dose for the combination of chemotherapy and SCO-101. We select the dose that is going to be used in part 2 of the trial. The chemotherapy we have used is a drug regimen called FOLFIRI, which is a standard treatment for patients with metastatic colorectal cancer. The dose finding of part 1 of the trial, as you see on the left on the slide, focused on the tolerability of the combination of FOLFIRI and SCO-101. We had planned 18 patients to enter this part of the trial. 18 patients have entered. Now the dose for part 2 of the CORIST trial is being selected. When the protocol is adjusted and amended to our new knowledge, we will continue in part 2 with a further 25 patients, as you can see to the right in the slide. Next slide. This slide shows the way that SCO-101 and FOLFIRI is administered. We start treatment with oral SCO-101 for six days. On the fifth or the sixth day, we start the FOLFIRI treatment. FOLFIRI is a three-drug combination. One of the drugs, irinotecan, is given on day five. On the same day as 46-hour treatment with the two other drugs, fluorouracil and levoleucovorin start. The treatment is supplemented with growth factor treatment after the chemotherapy has been given. Now, every 8 to 10 weeks, we perform a CT scan to monitor the cancer. The patients stay on trial as long as there are no progression of the disease. Next slide. There were two dosing questions to answer. What dose of chemotherapy should we use in part 2 of the study, and what dose of SCO-101 should we use? The first 12 patients who entered the trial were treated with varying doses of chemotherapy and a fixed dose of SCO-101. This is the cohort 1. The next six patients who entered the trial were treated with a fixed reduced dose of chemotherapy and a reduced dose of SCO-101. That is cohort 2. Next slide, please. Just in the comments, we want to make sure we are on the right slide. We've got a comment that the slides didn't shift. Just make sure when it comes to slide 10 that we will be on slide 10. We are on slide 10 now. Yes. Safety and dose finding. Operator, make sure we are on slide 10. Thank you. This is an important slide. On this slide, we can see how the patients fared on the various dose levels. Toxicity of treatment is graded in grade 1, 2, 3, and 4, as is noted on the lower left of the slide. Grade 1 and 2 side effects are expected and acceptable, and we have color-coded this with green color. Grade 3 side effects are graded as severe but may be acceptable if the side effects are treatable. This is the yellow coding. Grade 4 are unacceptable side effects. We have also divided the side effects up into the hematological side effects, mainly a reduction of white blood cells, and non-hematological side effects, which are mainly general side effects such as nausea, fatigue, or diarrhea, but also other side effects. As can be seen when we looked at the first 12 patients in the cohort 1 of the trial, we found that grade 4, that is the red hematological side effects at all dose levels, and non-hematological grade 3, that is yellow side effects, at all chemotherapy dose levels. Now, this does not mean that the patients all experienced grade 4 hematological or grade 3 non-hematological toxicity, but it shows that there was a potentiation of chemotherapy and that there is an important discriminator. Next slide. This slide is the same as the former slide, but we've added an overview of the effect of the RAS discriminator. As can be seen, all patients who are in the wild-type category of RAS tolerated non-hematological side effects. You can see that with the green color coding for all the non-hematological side effects. When it comes to the hematological side effects of the combination treatment, we can see that in the special group of patients with wild-type tumors, the patients tolerated a higher dose of SCO-101 in combination with a reduced dose of chemotherapy. You can see that with the green color code at level three in cohort 1 on this slide. The tolerability of the combination of SCO-101 and chemotherapy, FOLFIRI, depends on the status of the RAS oncogene. Now, does this show in other ways? Next slide. Let us look at the duration that the patients stay on trial. This is a so-called Kaplan-Meier plot, and the plot tells us how many percent of the patients stay on trial when we follow them over time. For the full number of patients, we can see that about half the patients have left the trial before or at the time of the first stable scan. That will be around the 50-day mark, and you can see there's a dotted line at the 50-day mark that goes up to the plot, and you go off to the left and you get the 50% mark. We can also see that five patients have endured treatment for more than two months, and one patient is still ongoing seven months after entering the trial. What happens when we distinguish between patients who have RAS wild-type tumors and patients who have RAS mutated tumors? Next slide. We can see that there's a clear separation between the curves. Patients who have RAS wild-type tumors do much better than patients who have RAS mutated tumors. It is the RAS mutated tumors on the left plot, it is the RAS wild-type tumors presented on the right plot. Next slide. It can be seen that the patients who fare well are all patients with RAS wild-type tumors, while on the other hand, patients with RAS mutated tumors do not fare well. As you can see, five of the patients with RAS wild-type tumors were still ongoing after the first stable scan. One of these patients is still ongoing after half a year on the trial. You can also see that none of the patients with RAS mutated tumors continued on trial after the first stable scan. Next slide. This leads us to an update of our study plan. The emergence of the predictive RAS wild-type biomarker has led to the change of the protocol so that the proof of concept part of the trial of Part 2 of the trial will only include patients with RAS wild-type tumors. This work of changing the protocol is ongoing right now. Next slide. The objectives of Part 2 of the trial is the same as the objectives that were laid down in the original protocol. We'll now look forward to reach the goals of Part 2 of the study as outlined in this slide. We will still be accumulating data on safety and tolerability, but now our focus will be on efficacy, which includes objective response rate, clinical benefit rate, progression-free survival, overall survival, and the duration of the responses that are obtained. At the same time, we'll continue to harvest data that may reveal other predictive biomarkers. We believe we have a unique drug and can turn the tide of drug resistance for the benefit of the many patients who have experienced that the tumor has turned resistant to the treatment. Thank you for listening and participating on this exciting voyage, and I'll now return the word to our CEO, Bo Rode Hansen. Yes. Next slide. Please don't leave the audio call, we're not finished yet. Where does this take us? What does it mean? What are the next steps to maximize the benefits for patients here, and obviously also to build value for the company and its shareholders? When we look into the future, CORIST phase II, Part 2 or the Part 2 of the study aims to evaluate the efficacy, so we understand this with some significance. We will evaluate the efficacy of what we have found here, the well-tolerated dose of SCO-101 and FOLFIRI. We have a much clearer understanding of the patient population. We will look into the RAS wild-type, first of all, and for that reason, we go back and update with an amendment. This requires a little bit of time, but it's actually to the benefit and the de-risking of the trial, and thereby the value creation. We will submit an amendment to the study protocol ASAP, and this takes a bit of process time. Overall, we expect to keep within our timelines, meaning that in one year's time, we expect a substantial readout from this effect arm of the study. I want to take the caveat because we are now also opening more sites in order to recruit patients with RAS wild-type tumors, and therefore it might extend into Q3 of next year. These additional sites will mitigate that we can retain our recruitment rates. Next slide. If you only take four things from this presentation, I will give you them here. All the objectives that we set out for Part 1 were met. This is a checkbox. We identified and established a well-tolerated dose of SCO-101 in combination with FOLFIRI, and we saw a potentiation of the biological activity of FOLFIRI at this dose. We have identified a RAS biomarker that enables de-risking of the second part of the study, CORIST. We are completely ready now to advance into the second part of the study, which will give us the ability to study proof of concept. Next slide. This is, in my view, in general, a very good day for patients with resistant tumors. Let me finish this session with a testimonial or a quote from a KOL and a well-respected pioneer in new chemotherapy applications in cancer. He's thought about this view and what he states, he's called [audio distortion]. He says, "There's a need for new ways of thinking treatment of solid cancers. With the introduction of SCO-101, there is a unique possibility to modulate the metabolism and pharmacokinetics of chemotherapy. This could be the beginning of a paradigm shift in overcoming resistance to chemotherapy, which is this major unmet need, leading to potential to the 90% of the cancer deaths that are out there in the world. This ends the presentation this morning on Scandion Oncology, the cancer drug resistance company. Now we will open for Q&A. Operator, we are ready to take the questions. Thank you. If you do wish to ask a question, please press zero one on your telephone keypad. If you wish to withdraw your question, you may do so by pressing zero two to cancel. We have a question from the line of Christian Binder from Redeye. Please go ahead. Hi. Thanks for taking my questions and congratulations. I would have two questions, if possible. The first one, you saw stable disease in five out of eight RAS wild-type patients, which is certainly positive, and even reduction in tumor volume for two. With optimized conditions for part 2, do you think achieving a partial response in some patients would be possible? Thank you, Christian, and thanks for the questions. I think just to be clear on your question, we are excited that we can now, with a more precise measure of precision, select the patients for the trial, and I think that it's within range to see a response in the second part of the trial. All right. Thank you. The second- Michael, do you want to add anything here? Yes. I just add on to that and say that the trial is designed to find partial response, but it is also designed to find other effect measurements like progression-free survival, and overall survival, and duration survival. There are more effect measures. Right. Thank you. The second question would be, given the biomarker news, are there any adjustments to PANTAX phase I, or is that going to proceed as planned? Christian, that is obviously an interesting question. However, let me remind you that the PANTAX study is set up to study patients that are resistant to a different type of chemotherapy. This is the taxanes, so nab-paclitaxel and docetaxel. For that reason, we will look into the extent of the meaning of that, but that's a completely different question. All right. Thank you very much. That was all from us. Thank you. There are no further audio questions. Okay, we will go over to some questions that we received online. We have one question. Do you see the possibility to do some trials in the first line of mCRC for this patient group? I think that's also a good question. I think that really I would pass this to our MD, to Michael. Thank you very much, Bo. This is a very interesting question because what we are doing right now is that we are finding the proof of concept part of phase II study, and the ultimate aim is, of course, to get further up in the lines into first-line treatment. If that could be an answer to your question, it will be this is the perspective, yes. I think I would like to add to that question that there are two components. One is to move up in line. The other aspect is if we establish a strong proof of concept or mechanism here, we will obviously also look at other possibilities in other cancer indications than metastatic colorectal cancer where this mechanism could come into play. Thank you. We have another question. Would you say that the results that you have commented in today's press release count as POC? I think that you have to take a step back, and what we just presented here was interim results from a phase II study. This part had the objective to establish safe and maximum tolerated dose, so safe dose, and look at signs of activity, which we just presented here. The proof of concept requires that we go through the second part of the study in order to really substantiate the extent of the proof of concept and have some significant validity on the data. This is how it's constructed. I think this is a big step forward. Thank you. Another question is, how common is the mutated version of RAS? That is obviously also another good question. I think when it comes to metastatic colorectal cancer, it's about 50% of the patients that have tumors that confer a wild type phenotype, or say this in other words, 50% of the patients have a tumor with a RAS mutated status. Thank you. Another question is, can you disclose the amount in milligrams that the reduced SCO-101 dose is? Yes. The question here is on the dose, as I understand it. Well, let me first say that this information on the specific doses is proprietary information, and that means that this is subject of an ongoing patent protection activity. As much as I would like to share it here today, we are not able to disclose this information at this point because it's part of this protection. I think this is in everybody's interest that we get the maximum value out of protecting our intellectual property here. Thank you. I think we have a similar question here, which is asking how big the decrease of FOLFIRI was. I'll just refer to the answer that I just gave to the previous question. Let me repeat, it's part of an ongoing patent protection process, and for that reason, it's proprietary information that I unfortunately can't disclose here today. Thank you. Another question is, for how long did the two patients showing reduction in tumor size do it for? Only eight weeks, 16, or even 24 weeks? Yes. I think that on that specific question, I will hand it over to Peter Michael, who has been following the patients. Thank you. As you could see on the slides that we showed before, we had five patients out of eight that were stable disease after 8-10 weeks, and then we have one patient who has been treated for more than a half a year. The exact reduction and change in the tumor size will be something that will be disclosed with the final report on the patients. Thank you. Another question is, will you keep us updated when you have made the 16-week scan, or when will you update the market again with regards to the patients on this part? In general, we'll keep the market updated on the progress as we have projected and as we have said we would. In another general term, what I can tell you is that we tend to want to come out with conclusive data in order to give the market the best ability to evaluate this and de-risk on this. For that reason, we will give the market updates when we have conclusive results to report. Thank you. We have a question about dose again. Which dose of SCO-101 will be used in the second part of the study? Not to repeat myself, and I guess what we can say here is that maybe Peter Michael wants to address this. Yes. As we explained at one of the slides, we now take all the information that we have from the part 1 of the study, and we're using that information to adjust and amend the protocol. This is an ongoing process, so this is the answer I can give you today. Thank you. We have a question. Do you see possibilities for FDA fast track approval? I think that, first of all, I want to say these results are a big step forward. It's a de-risking. It's an understanding of SCO-101 in combination with FOLFIRI. I think we will use the data to exploit and explore the maximum opportunities here, including this kind of thinking of incorporating registrational components into a randomized control study following our proof of concept. For that reason, I think that we have just released the data. We will use this information to maximize the potential of this. Thank you. We have a comment here. Great news. Do you think there is a better outcome if you give the patients SCO-101 first thing after seeing the cancer in the patient? I think that there are a couple of things to consider. Of course, resistance in tumors is a complex story. There might be an advantage of coming in early. There also might be an advantage of coming in late. I think that to that question, I'll actually hand it over to our MD and have his perspective on this. Thank you, Bo. I'll refer to the answer earlier about the possibility of having this combination in the first-line treatment, and you can, of course, also go up further up and say in adjuvant treatment for these patients who have a high rate of relapse. This is, of course, an early time to conclude what we will do, but this is definitely part of the considerations that we have. Yes. Thank you. Another question here is that does this mean that the RAS-mutated patients do not have a relevant positive effect of SCO-101, and how large part of the total group of patients is it? Yes. I think as I stated earlier, or once upon a year, but 50% approximately of this type of patients have tumor which is RAS mutated. That means that the other 50% are wild type. We have found a biomarker that can give us a precision component to include the patients for the second part of the study. Let me emphasize, or let me state here, we have not given up on the RAS mutated or the patients with the RAS mutated tumors, but we just, as Peter Michael showed very clearly here, can segment them, and there's no point in having them in the same group in the same treatment. We have not given up on them. Again, now I'm here with Peter Michael, so I don't know if you have anything to add on this. I think that it's a really good question because we have a well-known problem with treating the RAS mutated patients. What we have here is a combination of one type of chemotherapy and SCO-101. What we have to look at is what is the correct combination of SCO with chemotherapy and with what chemotherapy when we're talking about RAS-mutated tumors in patients. This will be part of our future goal. Thank you. Another question is, have you shared the new data with any big pharma companies? If so, how was the reaction? To that particular question, we have just sent out the press release this morning, and everybody following us have read it. In terms of ongoing business of that nature, that's [audio distortion], this is not something we discuss in keeping public, and I would just leave that as my answer. Thank you. We have a question. I think we might have had a similar one before, I'm taking this one also. In pancreatic cancer, a very big percentage of all patients have a mutated RAS gene. Since SCO-101 works poorly on patients with mutations in colorectal cancer, are you afraid that it will be the same case in PDAC? I will refer that question to Peter Michael. Thank you, and very good question. As Bo said, we have talked a little about it before. The treatment of pancreatic cancer in the PANTAX study relates to two other drugs. It's of course SCO-101 plus paclitaxel in the form of nab-paclitaxel and gemcitabine. This is a totally different treatment regimen. We are looking forward to harvest the results of that study. Thank you. Another question is, during BIO Digital, did you experience some new sort of interest in Scandion from other companies? Let me put it in perspective also in the light of the previous question. We are active in all aspects of the company, including business development. We have active activity in all the lines of business development, clinical development, our R&D, and so on. For that reason, we will keep active on this and that's as much as I can sort of tell on an ongoing everyday operation. Thank you. We have two questions in relation to the RAS mutation. It says, to what extent is RAS mutation an indication for tumor aggressiveness and therefore for survival outcome? The second question is, to what extent is RAS mutation status an indication of superior efficacy? Peter Michael, will you address this one? Yes. The patients with RAS mutated tumors, in those patients, the RAS status is a well-known prognostic factor. It's not in the same way a predictive factor. What is new here is that we can tell something beforehand or at the start of the treatment as to how good the patients fare when they have had RAS mutated tumors and are treated with the combination of SCO-101. Thank you. Another question. You were stating that you will try to do the part 2 in other countries outside of Denmark. Which countries are you talking about? We are looking to mitigate scenarios by widening our access to patients, by opening more sites that will be both national, so Denmark, but also international. We are well on in that process, following a clear process of what it takes to open sites and it's going well. Thank you. We have a final question here. Is the result of the trial everything you could have hoped for? Well, I think it reflects a real-world scenario. The results, I would like to say, are as good as we could have hoped for, and you can say better than we could have expected. Bear in mind, I think Peter Michael Vestlev said it several times there, this is a patient population that has been through the treatment lines and have progressed from their third line option for treatment and are left with no or very few treatment possibilities. I think that this is better than we could have expected. Do you want to say something here? I just want to say that we could in principle have ended up with nothing. I think we have ended up with a unique drug that has a unique potential. I think that will be my last words. Thank you. I think we have no more questions on topics that have not already been discussed. Okay. Well, with that, we conclude this audio hearing from Scandion Oncology. I thank you for your questions, for your interest, and your participation, and look forward to the journey ongoing with Scandion Oncology, the cancer drug development. Thank you. This concludes the conference call. Thank you all for attending. You may now disconnect your lines.