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Edited Transcript of PCIB.OL earnings conference call or presentation 8-May-19 6:30am GMT

Q1 2019 PCI Biotech Holding ASA Earnings Call

May 15, 2019 (Thomson StreetEvents) -- Edited Transcript of PCI Biotech Holding ASA earnings conference call or presentation Wednesday, May 8, 2019 at 6:30:00am GMT

TEXT version of Transcript

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Corporate Participants

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* Per Walday

PCI Biotech Holding ASA - CEO

* Ronny Skuggedal

PCI Biotech Holding ASA - CFO

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Presentation

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Per Walday, PCI Biotech Holding ASA - CEO [1]

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Good morning, everyone, and welcome to the First Quarter 2019 Presentation for PCI Biotech. My name is Per Walday, I'm the CEO of PCI Biotech, and I have with me also Ronny Skuggedal, who's the CFO. We will start by reviewing the highlights and thereafter, look deeper into the 3 different programs that we are developing. And thereafter, [present] a view on the financial figures and end with the outlook. And after that, we will open up for questions that is from the audience both here in the room and also from via the webcast.

Please also note our general disclaimer. So with that, let's go into the highlights.

To start with fimaCHEM. The first sites for the pivotal RELEASE study is now open for enrollment. This is the pivotal study with a gestation intent for bile duct cancer. We have now started this and will start it with 2 treatments -- up to 2 treatments of all the patients after we now had also the successful safety read-out in the Phase I extension confirmed by the Cohort Review Committee. The full Phase I study is with this completed, and we have formally closed the recruitment into this study. We have also presented the data from this study at different conferences, key conferences. One in the U.S., the annual CCA foundation meeting and also the third Asia Pacific Cholangiocarcinoma Conference in Taiwan.

Moving to fimaVACC. We had an important release just recently around the successful translation of the fimaVACC results from the animal results that are very promising, over to also very promising and encouraging results in man. We see that we have more, we have stronger, and we have better immune responses with fimaVACC than in the control. To that end, we have also further strengthened the Scientific Advisory Committee. We have included Professor Sjoerd van der Burg, who's a renown international expert in immune oncology as into our advisory committee. And that is to provide adequate scientific support for the fimaVACC program going forward.

So let's start to look at PCI Biotech as a company at a glance. We are a listed company, as you know, on the Oslo Stock Exchange. We are focusing on cancer. We are located here at the Oslo Cancer Cluster Innovation Park. We are developing something called Photochemical Internalization, which is PCI. This technology originates from the Oslo University Hospital, the Radium Hospital, which is the building next to our building here. We are developing this technology in 3 different areas, and you can see the pipeline on the slide. The 3 different programs that we are developing is called fimaCHEM, fimaVACC and fimaNAc. fimaCHEM is enhancement of already approved cytotoxics. And we have a program, as I mentioned, a pivotal registration intent study that is just about to start in bile duct cancer. This is done after we had some very promising results in Phase I, had the regulatory interactions and now know what we need to do to start to get this to the market.

fimaVACC, the other program, is a vaccination technology. This is specifically aimed at therapeutic cancer vaccines but can also be used for prophylactic vaccines. And this study has just recently then reported out the response, the immune response data from Phase I in healthy volunteers.

And the third program is a collaborative program, fimaNAc, which is a delivery system for nucleic acid therapeutics. Large molecules that have problems getting into cells but need to get into cells to work, and we can do this with our technology.

So we are an oncology-focused company with 3 very well differentiated assets in different areas based on the same technology platform. So what is this technology platform then? What you see here is a cell, on the left hand, and the cell has a cell membrane around it that protects the vulnerable inside from everything dangerous that is outside of the cell, and it's strictly regulated. So a number of products or medicines that needs to get into cells may have problems passing the cell membrane. It's like the skin of the cell. But the cell also eats [so --] through a specific system called endocytosis. It takes in things from outside of the cell into the cell by invaginating the cell membrane. But then it's locked in capsules, so-called endosomes inside the cell.

What we have is a photosensitizer, fimaporfin, and this photosensitizer is designed so it attach itself on the inside of endosomes, and it's quite specifically located to these areas. And when we illuminate the tissue, we activate this photosensitizer, the photosensitizer go up to higher energy state and thereafter transfers its energy to singlet -- or to oxygen that become singlet oxygen, which is very reactive and reacts with components in this endosome in the membrane, and that becomes leaky. And then whatever medicines or other products that have been taken up through this endocytosis, this eating system of cells, will leak out from the endosomes and into the cell and be therapeutically active.

As mentioned, we are developing this specific platform technology in 3 different areas, we call them fimaCHEM, fimaVACC and fimaNAc. It's all based on the same photosensitizer. The photosensitizer is called fimaporfin. For fimaCHEM, we take already approved drugs on the market, cytotoxics, and we combine them with our technology, and we see to what extent can we enhance these products. We can then enable approved drugs to fulfill unmet local treatment needs. This only happens where we illuminate because it's light that induce the reaction. So when we combine this with the cytotoxic drug, we can illuminate an area of the body, and we can enhance the effect of that cytotoxic drug. And we have tried this with a number of different cytotoxic drugs, and it turns out that approximately 20% of these we can enhance.

But it can also be used to enhance vaccination, especially cellular immune responses, which are particularly important in some prophylactic diseases but generally very important for any therapeutic effect of vaccines, like cancer vaccines where you induce an immune response to an already established disease to get your own immune system to fight that disease. And we then, by combining our fimaVACC technology with an antigen, a vaccine, can enhance the cellular immune response, which thereby can make the immune system much better at attacking the cancer in the body.

And lastly, as I mentioned, fimaNAc, NAc stands for nucleic acids -- nucleic acid therapeutics. Nucleic acid therapeutics are what you could call gene therapy. These are potentially very effective medicines, but they have one major hurdle, they are very large molecules, and they need to get into cells to work. And they can't get into cells by themselves. But we can use our technology, the PCI technology, to deliver these big drugs, these gene therapies into the cells and make them work. So here we are providing a delivery solution, intra-cellular delivery for nucleic acid therapeutics. And we are then using this as collaborative program, so we are working with companies that have gene therapies, and they can use our methodology to try to increase the delivery of their products in specific disease settings.

So that's the general overview of PCI Biotech. I will now move into the specific programs and talk a bit about each of the program and the progress in those programs. So to start with then fimaCHEM, which is our lead program in what we call pivotal development, which is clinical development then, which is the last study before a potential market authorization. As I said, we have tried to use this fimaCHEM technology with a number of different cytotoxic, and we know that there's a large number of those that we can enhance, which is illustrated here. So cytotoxics that are trapped in this endosomes, in these capsules in cells and therefore not as effective as they would be, we can enhance the effect of those by releasing them from the endosomes and illuminating the target.

We are focusing on a rare disease called bile duct cancer and then, specifically, the extrahepatic bile duct cancer. Bile ducts are from the liver -- goes from the liver into the intestine. And the epithelial cell on the inside of those bile duct, in some instances, can create malignant cells, and then you get bile duct cancer. It's an orphan indication. It's quite rare. Only 1 to 2 per 100,000 in the western world. It's a very deadly disease. The average survival of inoperable patients is approximately a year, and 80% of these patients are unfortunately at presentation, when it's diagnosed inoperable. So the current management with this is for the 20% that can be operated is surgery, and that's the only potentially curative treatment of this disease.

And then the issue that you need to sort out quickly with these patients is to make sure that the bile can flow because otherwise these patients get jaundiced, and they get liver problems. So you put in stents, use endoscopes, go through the mouth, through the stomach into the intestine and up in the bile duct and put in stents. And then what these patients are put on is chemotherapy, there's nothing approved, but the studies have shown that gemcitabine and cisplatin is somewhat effective in this patient population, that is, therefore, recommended by the guidelines. So it's a combination of gemcitabine and cisplatin.

Now this is a perfect fit for the PCI technology, for fimaCHEM. Because most of these patients actually die from the local effects of the tumor in the bile duct. And what we can do is to enhance the effect of gemcitabine exactly where it's most needed in the bile duct. So we use the endoscopic stenting to illuminate the bile duct, the endoscopic stenting that's done -- or endoscopic methods that are used anyway for stenting and radiographic procedures in biopsies. And so we use the same procedure just to put in an optic fiber, illuminate the bile duct where the tumor is and thereby, get a more effective treatment of specifically that tumor, which is the most dangerous tumor for these patients. And we know from what we've done both in vitro and in vivo preclinically in animal experiments that we can enhance the effect of gemcitabine. And gemcitabine is the cytotoxic that is recommended and in combination with cisplatin for this patient population.

So there's an unmet local need. It's actually easy to illuminate the area through standard procedures, and we can enhance what is the active ingredient, what's normally used with these patients and therefore, it's a perfect fit. So we have done a Phase I study, a dose-escalation study looking at 4 different dose levels. And the result of that we've shown you before, it looks very positive. We have a median overall survival in the highest dose cohort of approximately 22 months. That is the dose level that we're going forward with in the pivotal study. And we also have a view of the active response rate that is quite high, 3 out of 5 patients in that specific group. You can also, on the right-hand side here, see the full Phase I study with all the different doses included and see that there's a clear difference between this, and there's also what we see a tumor response, what seems to be a dose-response.

Now we have the extension study also recently reported, which is a study that we've done primarily to look whether it's safe to do actually 2 treatments of fimaCHEM, to repeat the treatment further out in the cyclic treatment of gemcitabine and cisplatin. A total of 7 patients were included in this study. 5 of these patients received 2 fimaCHEM treatments. So it's those 5 patients that we now have reported, and we needed 5 without dose-limiting toxicity to report a successful safety endpoint in this study. So the safety endpoint has been reached, and the pivotal study will be initiated with up to 2 treatments. 4 of these 7 patients had what we call radiologically measurable disease at baseline. So you can have baseline go in and measure the diameter of the tumors, it's not always possible to do in these patients, approximately 60%, 70%, 75% maybe of these patients who can do that. And in this, it was 4 of the patient that you could do it. And then you can follow these target tumors and see how they react to the treatment.

Now what we saw in this extension cohort when we looked into the data afterwards is that the average tumor burden, the overall target tumor diameter of the lesions in the extension cohort is approximately twice what we've seen at the dose escalation. Well, that is the kind of effects you sometimes get when you have very small cohorts of patients, and the heterogeneity between these patient groups is quite big. So these extension study patients were more sick than the patients in the dose escalation. And you need a larger -- that's why you need a large, of course, randomized study with a number of patients to be able to equalize those kind of effects between controlled group and the treated group.

So none of these measurable local-treated tumors showed any progression during the 6 months follow-up period, but 2 of the patients had progression due to appearance of new lesions. So 3 of these 7 patients were alive at last censoring, which was March to May, and we have censoring time points for these studies. And all of these have received 2 treatments. And the emerging median overall survival is approximately, currently, 14 months for this specific group. But it's a bit early to say what it is going to end at.

So looking into the tumor response, you can also see it here, we've added to what you've seen before in relation to the tumor response at different levels or different cohorts. The tumor response in this group was also not as good as it was in the dose escalation cohort. The extension patients, you can see, are the gray patients here. There was none of those who had detected what we call real progression of the local tumor, which is the most important tumor to treat for these patients. And one of them, of those 4, had the response, which means that it was more than 30% decrease in the tumor volume.

What you can see here is that also that the tumor response is the patients that one -- each bar here is a patient, and the bars represents the change in tumor volume from baseline of the target tumors that were identified. And as you can see, where you have the strongest, we have strong responses in a number of patients, and all of those were in the 2 highest-dose cohorts.

So with the bile duct cancer, the RELEASE study, we have now achieved the safety endpoint in the extension study that has been confirmed by former review by the Cohort Review Committee that has been appointed. We have ongoing regulatory and ethics approvals that are progressing well. We have all approvals achieved in Norway, Germany, Sweden, Denmark, France and Spain, 6 countries. Ongoing site initiations progressing well, 2 sites open currently for enrollment, and we have a number of site activations, first initiations of the sites where we train them and teach them how to use this and train them in the protocol, and then you activate them afterwards, and then they can start to screen for patients. And we have now 2 sites open, and we have a number of these in the coming month. And then as I mentioned, to get more interest and awareness in the patient community and in the doctor community, we have presented these data also at the CCA foundation meeting in the U.S. and the CCA conference in Taiwan.

So fimaporfin has an orphan designation, which means that we have a number of advantages with this product if it is approved, both in the U.S. and EU with regard to market exclusivity and so on. And we have had thorough discussions with both EMA and the FDA around this program. And the fastest way to market has been determined through these regulatory interactions with the authorities. It's a first-line treatment of patients with inoperable extrahepatic bile duct cancer, so that's different from most of what you see of new oncology drugs that come on the market. They come as second line or third line, normally, but this is actually enhancement of already established first-line treatment. So is a first-line treatment. This is the first treatment the patient gets when they are diagnosed.

We have -- we're going to include approximately 40 key hospitals in Europe and the U.S. It will take, we think, approximately 36 months to an interim read of this, and 50 months approximately for the final analysis. And the reason for this is, of course, this is a rare disease, it's an orphan disease. There's a --the study has a randomization of 1 to 1, it's a total of 186 patients, so it's 93 patients in each arm. The primary endpoint is progression-free survival and overall survival is seen as a key secondary, of course. And the interim analysis primary endpoint is also PFS and is followed by [overactive] response rate. And as mentioned before, the RELEASE trial progress reporting will be key milestones and updated in quarterly reports, as given on the slide here. So we're really looking forward now to open up a number of new sites and get the patient inclusion starting in this study. It's a very hectic but a very good period for the company.

So then we're going to switch gear and go into fimaVACC and talk a bit about that. fimaVACC is the vaccination technology. And this works the same way in that it releases things from these capsules, the endosomes inside cells, but now we're really targeting the dendritic cells or the antigen-presenting cells, immune cells that take in vaccines when you vaccinate people into these specific endosomes. And then when we illuminate the area, we just mix our fimaporfin with a vaccine injected into the skin, illuminate the area where we've done the injection, we can then move the antigens, the vaccine from these capsules that you see on the slide and out into the cytosol, and by doing that, we direct more to what is called MHC class I presentation in these cells. And what that does is it generates more disease-specific cytotoxic T-cells. And these are the cells that you're -- need to attack cancer and virus-infected cells more efficiently.

So we have some very encouraging results, a proven preclinical set of results with this technology. And our aim with this Phase I study that we have done was to translate this into man. Translating immune system effects from mouse to man, to put it that way, is a very big hurdle. What we've seen here is that the Phase I study provides successful clinical translation for fimaVACC. We have proof of concept and efficacy in terms of intradermal dosing in humans, this is intradermal dosing, both with a peptide and a protein. And we have from this study a positive overall characterization of tolerability, where we see efficacy at well-tolerated doses. Professor Sjoerd van der Burg, who has now entered into the Scientific Advisory Committee, have reviewed the results and his statement is that this really merits moving into the next phase to look whether we can translate that immune response into a clinical benefit in a relevant disease.

So a little bit about the study. The overall objective of this study was to determine safety, tolerability and immune responses of fimaVACC, and we have had more than 90 subjects. These are not patients, these are healthy volunteers, subjects enrolled. And the results we can show that compared to control using fimaVACC, we induced a substantial increase in the number of T-cell responders to HPV E7 peptides, which are the less immunogenic peptides that we've used. We also using a big protein, which is quite immunogenic in itself. But what we see, clearly, a difference in is where we lose -- use the peptides that are more difficult to induce an immune response to, and that's where the hurdle is with this vaccination technologies.

We also see not only more a responders but also clearly enhanced T-cell responses so more T-cells. We see more robust CD8 T-cells, which are the cells -- the cytotoxic T cells that we need to be able to attack cancer or other disease cells in the body. And we know that those are notoriously difficult to induce with this HPV E7. And we also see an increased functionality when we analyze this, and these are analyses that have been done at Professor van der Burg's laboratory in Leiden, an increased functionality of the induced CD8 T-cells. All of these are highly sought-after features, especially for therapeutic vaccination but also for some prophylactic vaccines.

So looking a bit more at these different points, what does it mean because I know there's a lot of questions coming, so what does it mean? It's clearly enhanced, and how much is that and so on. So we've taken some -- we going to publish all of this, so we can't give you a lot of information because otherwise, high-impact journals might actually refuse publications because it's already been published, in a way, through this. So what I'm showing you here is some bits and pieces of what the results look like.

So this is the number of HPV responders and we see at the end of the vaccination schedule. And there's a [free] vaccination with HPV. And there's a substantial increase in the percentage of subjects responding. You can see the control, on the left hand, which is with a state-of-the-art adjuvant technology that is in use today in a number of clinical studies. And here you can see with increasing fimaVACC doses, a bell-shaped dose-response curve and -- or not a bell dose-response curve, dose responders curve, you can put it -- you can say. So the higher the dose here, the optimal dose here, you see quite high number of responders. It's approximately 5x the number of responders that you see in the control. And the strength of the response in this specific cohort is about 4x the strength of responses [you see] in the control. So it's more, and it's stronger.

Then we can take the specific best dose level here and look at what does this mean for the specific CD8 T-cells that we are interested in. And these are very difficult to induce with HPV E7, so it's a very high hurdle. And this is where we've looked at how often could you, during that we take a number of samples from these healthy volunteers, and this is how often could you detect CD8 T-cells. And in the control, the CD8 T-cell responses was much less frequent, and they were generally borderline what you would define as a response. It was stronger responses, clearer responses in the fimaVACC group and as you can see, more time points where you can see CD8 responses. So it's -- this is what we mean when we see -- say that we had a more robust CD8 response. They are clearer, and you can find them more often. So for example, 3 out of 6 subjects treated with fimaVACC developed CD8 T-cell responses at 2 or more time points, while none of the control did that. So it was only single time points in all the controls, and they were really borderline levels.

And then there's another thing that we were looking at and that is what is called the functionality of the CD8 T-cells. So how effective are these T-cells? What do they express? What kind of markers are they positive for? So we have looked at 4 different markers, and then you can look at the control and see how many -- when you see expressions, how many marker do you see expressions from, and how often do you have that in relation to -- in the fimaVACC-treated group. And it's the same [than] the highest level that we showed on the first slide, that cohort we're looking at. And as you can see here, the percent of poly-functional, what is called poly-functional, that induced 3 or more markers, the T-cells were approximately 4x in the fimaVACC group than in control. This is an important feature because this is the parameters that indicate the ability of the T-cells to combat cancer cells, to be effective in the body against cancer or against the viral infection. So we're very happy with these results, and we're now going to release results in hand, look at what are our strategic options and determine the right strategy for fimaVACC going forward.

And then lastly, the program [which] we call fimaNAc, which is a collaborative program. As I mentioned, the gene therapies, the nucleic acid therapeutics, they are large molecules, large molecules that need to get into cells to work, and since they are large and charged molecules, they normally can't get into cells by themselves, but they are taken up through endocytosis, and we can release them and make these effective in that sense. And we have offered then this technology to -- or we are offering this technology to gene therapy companies, companies working with this kind of technologies. And then we have collaborative research going on with a number of different companies. And these other companies that we are currently having active collaborations with, it's a top 10 large pharma that we're working for quite a long time, and we extend the agreement at the 6-months period at the time. So they actually have -- need actively to take -- make a decision on what to do with this every half year. And we now have collaboration that is extended to the end of June 2019. And we also have then collaborations recently with Immunovaccine and Bavarian Nordic established last year that are ongoing.

As mentioned previously, this is, of course, not only our technology, [it's] their technology and our delivery system. So we are not free to report results from this, but we will, in some instances, publish these results when we agree that it's sensible to publish. But otherwise, what we report of progress in this is any new agreements and a termination of agreements or any changes in form of agreements with this collaborations.

So with that, I'll leave the stage for perhaps some final words by Ronny.

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Ronny Skuggedal, PCI Biotech Holding ASA - CFO [2]

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Thank you, Per. Hello. Yes. Some words about financing. The public grants for the year is in line with previous years, so we will end up around 12 -- sorry, NOK 10 million for the year -- for the full year. The operating results here in the quarter is minus NOK 18 million compared to around NOK 15 million last year. We expect that difference to increase during the year when the pivotal study is fully kicked off and roll out of that program. But we have a healthy cash position. So we are, as said last autumn, after the capital increase, financed well into 2022 at the current stage. I think that was it.

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Per Walday, PCI Biotech Holding ASA - CEO [3]

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Very good. So a healthy cash position. That's good. So to end this, key achievements and near-term milestones, we have now -- we are starting up the pivotal study, and we have financing for that study in place. In 2018, we also established 2 new research collaborations within the fimaNAc program. And we designed and finished the design of the fimaCHEM study in the autumn, and then we had also safety of repeated treatment, preliminary reported and then confirmed also by the Cohort Review Committee in the first quarter. We have now, in the first quarter, completion of the Phase I immune analysis, a very successful completion of that. And we are now waiting for -- to have the first patient enrolled in the pivotal bile duct cancer study. 2 sites are currently open for enrollment, and we are opening up sites in the coming weeks, further sites in the coming weeks. And then in the second half, we expect to have the first U.S. patient enrolled in the pivotal bile duct cancer study and also to publish and present the fimaVACC results that we have just recently received at key conferences.

So with that, we have finished the presentation, and we will open up for questions from the room. First, before we do that, I would just like to mention something for you and ask you kindly, our shareholders, to refrain from contacting our investigators directly and asking them about the study. We have had instances where shareholders have reached out to investigators through channels that are made for patients. And there's quite a lot of annoyance with investigators, and they can become negative to the study. So please, all questions on the study to us, and we will -- we do the best we can to answer all the questions we receive.

So with that, any questions from the room first, in there -- and thereafter, we can look at the webcast?

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Questions and Answers

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Unidentified Analyst, [1]

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First, as always, thank you for a very good and a very interesting presentation. Secondly, I would like to congratulate you with what seems to be fantastic result from the fimaVACC study. Your earlier call results in mouse was spectacular, as I mentioned, this seems fantastic. How do you describe result that you have seen so far in fimaVACC Phase I study?

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Per Walday, PCI Biotech Holding ASA - CEO [2]

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I thought I've done that now.

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Unidentified Analyst, [3]

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Can you do some -- you call it spectacular, I guess, in mouse...

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Per Walday, PCI Biotech Holding ASA - CEO [4]

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In mouse, it was almost -- or actually, over 40% of the CD8 T-cells that were antigen-specific in blood were to the vaccine. We don't see something like that here. Now we have put a very high hurdle by using the E7 peptide, which is very hard to induce CD8 responses, and that we see an increase in CD8 responses and more sort of poly-functional or better CD8 responses is very positive. I wouldn't use the word spectacular, but it's -- it is good results. It's really good results. Remember that the control in this, the control here is Hiltonol. Hiltonol is a toll-like receptor 3 adjuvant that is being used in a number of clinical development programs today to try to achieve results on CD8-positive T-cells and to get better cancer therapeutic cancer vaccines.

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Unidentified Analyst, [5]

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So you have better results than the state-of-the-art technology today, so hopefully, this could be the state-of-the-art technology in the future.

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Per Walday, PCI Biotech Holding ASA - CEO [6]

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That's our hope. Yes.

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Unidentified Analyst, [7]

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Cytokines, did you miss your annual dose in the study, and why is that important, I guess?

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Per Walday, PCI Biotech Holding ASA - CEO [8]

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So what we measure in the study are different things. You can measure cytokines to see whether you get any adverse-reaction cytokines, as in cytokine storms and things like that. We haven't seen anything like that, which is quite disturbing when you get it. So we haven't seen anything like that. And that's sometimes a problem in different adjuvant technologies. The markers that we use and are looking at, if that's -- I'm not sure what you're asking for here generally, if it's positive signs or if it's -- okay. So the markers that we're looking at is interferon gamma, interleukin 2, TNF alpha, and we also looked at CD154, which is an activation marker. That's the poly-functionality markers that we looked at, at the CD8 T-cells. I don't know if that gives you any more information, but...

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Unidentified Analyst, [9]

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[Yes, of course], but hopefully someone else, I guess, will explain on the Internet what it means there. Okay. I think your plan to present result in Boston at end of June, early July?

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Per Walday, PCI Biotech Holding ASA - CEO [10]

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We will present some results there but not the main results.

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Unidentified Analyst, [11]

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I guess the plan has been that van der Burg is going to present this either at the conference or in the paper. Can you say a little bit about where this is going to be presented?

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Per Walday, PCI Biotech Holding ASA - CEO [12]

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No. We want to go to a very good conference where we have a high impact and a large audience when we present this. But I'm not going to tell you which conference it is yet. Because...

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Unidentified Analyst, [13]

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Will that be before or after the Boston conference?

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Per Walday, PCI Biotech Holding ASA - CEO [14]

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Oh, no, it will be after the Boston conference. It will be after. I mean -- So the Boston conference is -- that's the International Photodynamic Association Conference. It's not really the conference to blast out the big results on this. So that will be done in the autumn, as I mentioned. It is on the previous slide that it is on the second half of 2019 that we are going to present this.

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Unidentified Analyst, [15]

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Have you applied for any patents lately due to result from this study?

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Per Walday, PCI Biotech Holding ASA - CEO [16]

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Yes. I think we may have done that. I'm not sure actually whether we have -- I have to think about that. That was a surprise question. Not on the basis of the results of -- that we have recently received, no, we haven't. If that's your question.

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Unidentified Analyst, [17]

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What surprised you most with these results?

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Per Walday, PCI Biotech Holding ASA - CEO [18]

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I was expecting good results, so I wasn't really surprised.

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Unidentified Analyst, [19]

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What about van der Burg, can you say -- was there anything that surprised him?

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Per Walday, PCI Biotech Holding ASA - CEO [20]

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Well, he has just got the -- I haven't spoken with him after this. We have done email correspondence, I sent him the results, and he told what he think -- thought about it in very brief terms and is generally given here that really -- this really merits a continuation and looking into whether this translates into a clinical benefit as well.

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Unidentified Analyst, [21]

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So I guess next step would be to start up using this together with immune therapies. I guess based on this, you expect that it's going to work quite well with many of these immune therapies.

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Per Walday, PCI Biotech Holding ASA - CEO [22]

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Or vaccines really. I mean we're talking about vaccines. So this is a vaccination technology. You can combine it with other immune therapies as well and get an even better effect of other immune therapies in combination. But this is really a vaccination technology to enhance the effect of vaccines.

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Unidentified Analyst, [23]

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So is van der Burg -- is he finished now with the work he's doing? Or is he going to continue, I guess, analyzing the data?

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Per Walday, PCI Biotech Holding ASA - CEO [24]

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No. He's finished with the work that he had been doing. I mean they have received samples and done the analysis, and that work is finished.

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Unidentified Analyst, [25]

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But he's still going to do some work on the data?

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Per Walday, PCI Biotech Holding ASA - CEO [26]

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That's -- I mean we -- he is in our advisory board, so he's involved in this going forward.

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Unidentified Analyst, [27]

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All right. That's a lot of interesting information. I'll just try to briefly clarify something here. If you talk about the fimaCHEM, would you please define what you mean by enrolled in the study?

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Per Walday, PCI Biotech Holding ASA - CEO [28]

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Enrolled in the study means that the patient has been identified, screened, found eligible and have given informed consent and randomized to one of the arms. Then it's either control -- this -- because this is a randomized study. When the patient come in, it's eligible, then they say that this -- we are here, we have an eligible study, and there's a lottery going on more or less when they say that and back comes the answer, this goes into the experimental arm or into the control arm. And when that happens, that is when you have enrolled a patient.

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Unidentified Analyst, [29]

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Then moving on to the fimaVACC. When you were saying increased functionality, is that directly translated into the number of markers expressed?

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Per Walday, PCI Biotech Holding ASA - CEO [30]

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Yes.

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Unidentified Analyst, [31]

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Right. Is there like -- what's the maximum limit of number of markers? Is that like...

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Per Walday, PCI Biotech Holding ASA - CEO [32]

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I don't know. I mean I'm looking at [Jonas] here, whether he can help me. But I really -- I'm not an immunologist, and I don't know. I know that poly-functionality, that is 3 or more, that's very good. But...

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Unidentified Analyst, [33]

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A number of the markers you can use...

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Per Walday, PCI Biotech Holding ASA - CEO [34]

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Yes.

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Unidentified Analyst, [35]

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[What are] the most common ones and the most reliable is those you mentioned.

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Per Walday, PCI Biotech Holding ASA - CEO [36]

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Yes. So that's why we've chosen them.

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Unidentified Analyst, [37]

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Right. Okay. You also mentioned the time points when the -- in the fimaVACC. Could you say a little bit more what you mean specifically by those time points? I mean is it that they're producing more at specific time points? Additionals? Or...

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Per Walday, PCI Biotech Holding ASA - CEO [38]

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Are you referring to a specific slide now or...

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Unidentified Analyst, [39]

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Yes, sorry. I'm on Slide #19 with the CD8 T-cell responses.

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Per Walday, PCI Biotech Holding ASA - CEO [40]

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Oh, yes. It's a bit complicated, that slide maybe. Because this is where we try to show that we have a more robust -- this is -- so to take one step back. E7 from HPV is, as I've said, very difficult to induce CD8 T-cell responses in man. And what we see here is that we are able to induce in our fimaVACC-treated patients, we're looking at blood samples that are taken before each vaccination. So you look at -- after -- before the first vaccination, before the second vaccination, before the third, and then you can see what the vaccinations have had of effect. And then you look at all of these different samples, and you see where do you have CD8 responses? And if you only have it after the third vaccination, for example, you will only have it at one time point.

If you actually see it on both the first, second and the third, then after first, second and third, you will actually have then 3 time points. So that's what we mean with this and that it's more robust because the control -- we see some CD8 responses here, but it's really borderline what you would call a response in a control group. And therefore, we wanted to sort of pick out the robustness of what we see and by talking how often you see these responses. So we see more clear responses in fimaVACC, and we see them at more time points in more samples.

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Unidentified Analyst, [41]

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Can I also ask, what do you think this will have to say for a potential patient?

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Per Walday, PCI Biotech Holding ASA - CEO [42]

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So for a potential patient, depends on what kind of patient it is and what kind of vaccination you're using. But in general, if you use a vaccine where you need a strong CD8 T-cell response and functional T-cells to combat this disease, then this is a very important thing for the patient, that you actually get these poly-functional CD8 T-cells expressed that can attack the cancer or the infected cell and kill the disease. So it's an extremely important feature.

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Unidentified Analyst, [43]

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fimaCHEM, you have for some time -- or quite a long time, actually, discussing with authorities, I guess, in Asia, the possibility for including sites in Asia. You already said that it's going to be concluded by the end of first half this year. How is the chances for including hospital in Asia for the pivotal study?

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Per Walday, PCI Biotech Holding ASA - CEO [44]

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I think -- I mean we haven't really talked to authorities. That's a misunderstanding. We have looked at different ways of doing this. We could either do it ourselves in this study, or we could do it via -- work with some kind of partner, a future commercial partner that takes part of this. And as we have said earlier, we are looking at determining how we want to do this by the end of first half. So I will come back by the end of first half and tell you about this.

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Unidentified Analyst, [45]

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So there haven't been any discussing, I guess, with authorities. We don't know if you're allowed to include hospitals.

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Per Walday, PCI Biotech Holding ASA - CEO [46]

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We will be allowed to include hospitals in this study. I mean that's -- you can do that, that's not an issue. The best way of doing it is what we're discussing.

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Unidentified Analyst, [47]

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The [team's] business development officer, I guess, was signed some time ago, when do you think he's going to be replaced? Do you have some interesting names that you are talking with?

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Per Walday, PCI Biotech Holding ASA - CEO [48]

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We have started a process on that. So sometime in the autumn, I would think. In the interim, we are taking care of this. So -- and that works fine so -- for a period of time, at least.

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Unidentified Analyst, [49]

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When the industry will be presented the very good result from the fimaVACC study, how do you think they will react when they see that this is sort of state-of-the-art? This is something that we need to try out with the oral vaccines?

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Per Walday, PCI Biotech Holding ASA - CEO [50]

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Yes, that's what we hope that they will react.

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Unidentified Analyst, [51]

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Is it likely that they will view this the same way that you are doing? Hopefully, they will?

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Per Walday, PCI Biotech Holding ASA - CEO [52]

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We never know what they have up their sleeves that we haven't seen and are working with, so it's very hard to say how other people that are looking at this from a different perspective will react. But we know that there are interest into this technology out there in the world. I mean we have presented the preliminary results, and we have discussions ongoing with different companies. So we know that there is interest in this.

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Unidentified Analyst, [53]

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How do you think the chances for signing an agreement by the end of 2019 within this area here?

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Per Walday, PCI Biotech Holding ASA - CEO [54]

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I'm not going to speculate on that. I don't want to -- that's a form of guiding on agreements, and we are not in control of agreements. I'm not going to speculate on that.

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Unidentified Analyst, [55]

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Have you applied for starting up or including the U.S. in this study here yet?

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Per Walday, PCI Biotech Holding ASA - CEO [56]

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We are -- so the reason U.S. is slightly later is because we need to have the safety from the extension study included into that application. And the application will go in any day now. I think they are still going through all the data and making sure that all the adverse events are in place in the right columns and right tables and things like that, it's quite a big application that needs to go in. But it's just about to go in, I think.

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Unidentified Analyst, [57]

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Yes. On fimaVACC, do you think -- will companies need to see the final in-depth analysis to know whether this is interesting? Furthermore, do you think the results presented now is enough for them to know whether this is something they can use?

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Per Walday, PCI Biotech Holding ASA - CEO [58]

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So this is actually the in-depth. I mean what I presented here is a snapshot of the results, but it includes the -- all the analysis that we've done. We looked at the different markers, the CD8 T-cells and so on. There are a number of other things you could look at, but are -- this is what we aim to now summarize and present to potential partners.

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Unidentified Analyst, [59]

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Yes. So you think this is enough for them to understand whether this is something for them to use?

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Per Walday, PCI Biotech Holding ASA - CEO [60]

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Yes.

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Unidentified Analyst, [61]

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You've got approval now from 6 countries to start up the pivotal study. It seems like the process from you got that approval until you involve patients taking some time. You explained a little bit in presentation why so. Could you say a little bit more about why it's taking so much time before you have got approve from authorities until you start enrollment?

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Per Walday, PCI Biotech Holding ASA - CEO [62]

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Yes. So there are different things going on in parallel. One is that you get -- you need to have the ethics and regulatory approvals. They are not linked to each other, normally. So they come at different time points. And then you have a third process going on, which is negotiation with the sites. You need to have a contract in place, which is quite a comprehensive contract around the rights and everything, regulating liability and so on. And when that is done, you need to initiate the site, and then after you've initiated the site, train the site in the protocol and so on, you can activate the site. And when you've activated the site, the site can start looking for patients.

So it's a sequential process that needs to go. And when they start then to screen, they can't look -- or they can't screen patients before they have been activated. They're not allowed to do that. And when they then start to screen a patient, the first thing they do is to ask the patient whether they're interested and normally, then they get the informed consent form, which is a large document around everything in this study, what it means to you and so on. And patients then normally want to go home and look at options, and it takes a few weeks before they maybe decide that, yes, I want to go into this study. And then when they have decided, you could start screening. And then screening is going through all of these different tests that need to be done before you can say whether the patient is eligible for the study or not and when -- and that takes a couple of weeks, normally, to go through. And when you've done that and see that the patient is eligible, then you can enroll that patient.

So there's a sequential number of steps from approval to approvals in the countries to actually getting the contracts, site and the budget and everything agreed with the sites. And then there are sites out there, hospitals that take maybe 2 months just to go through the signature process, so it's -- for contracts because they are a bit bureaucratic, some of them, to put it mildly. So there are a number of different things that makes this -- you can't have an approval there and the patient the day after. That is not practically at all possible. There are weeks between these, unfortunately, but that's the way it is.

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Unidentified Analyst, [63]

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I think it was in November, you said the cooperation with Ultimovacs was canceled. Then you stopped at that time there, but you also said that they're going to be some results from that cooperation coming out quite soon, they haven't been published yet. Is that due to that you have to wait on, I guess, this presentation here or the final, I guess, presentation of the data from van der Burg before you can publish this? So why is this not out yet?

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Per Walday, PCI Biotech Holding ASA - CEO [64]

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No. It's just a range of priorities, really. These are preclinical results that are interesting, and we have agreed that we want to publish them, but it's not an urgency around doing that. Maybe you should look at the web to see whether there are any questions coming in.

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Unidentified Company Representative, [65]

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The questions are covered.

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Per Walday, PCI Biotech Holding ASA - CEO [66]

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They are all covered. Yes. Anything else? If not, thank you so much for coming and for your interest and attention.