PCI Biotech Holding ASA

2021 for PCI Biotech. My name is Per Walde, I'm the CEO of PCI Biotech and I have with me also Ronne Skuggedal, who is the CFO of PCI Biotech. First, please pay attention to this important notice. We have in this conference now a webcast but also a phone line and you have all the information on this slide for how you can post questions through the webcast or through the phone live after the presentation i will start the presentation with going through pci biotech the company in general and the technology specifically and then review each of the three different programs a bit more in detail before we go to through the financial numbers and the outlook at the end and then we take questions i think we start with live questions and then we will go over to questions from the webcast at the end So first, PCI Biotech. PCI is an oncology-focused pipeline company. We are developing a specific technology for the chemical internalization. We have three different programs. We call them Femachem, Femavac, and Femanac. And Femachem is our lead program. A product called Amfinex is developed for bile duct cancer treatment in combination with gemcitabine. And this is currently in global pivotal development. in a study with registration intent. The second program is Fimavac. It's really utilizing the same platform to enhance immunotherapeutic effects of different kind of vaccines and other immunotherapies. That has been through a phase one and with some very good results showing good immune responses with our technology. And we are now looking at taking this to the next step. And the third program is a preclinical program. It's called FEMA NAC. NAC stands for nucleic acid. And nucleic acid therapeutics is a new class of drugs that are being developed, which this platform can help to really realize the full potential for certain applications of these so-called nucleic acid therapeutics or gene therapies, as they are called. So all of this is done through a platform called photochemical internalization. I'll talk a little bit about what PCI or photochemical internalization is before I move on to the highlights for the first half and second quarter. So all cells in the body have a cell membrane around the cell. And this cell membrane is sort of the wall that protects the inside of the cell from whatever is outside of it. And a number of compounds will have problems passing through this cell membrane, getting into the cell. And then if the therapeutic target where the medicine needs to reach to actually be active is within the cell, it actually needs to pass the cell membrane. And therefore, this limits the efficacy of a number of drugs. And some drugs are completely non-efficient without being taken up by special means into cells. There is also an eating mechanism in all cells called endocytosis. This is where they invaginate a certain part of the cell membrane and create a bubble where they take in what has been outside of the cell. And this is like a digestive system afterwards in the cell. Now, a number of drugs that can't pass through this cell membrane will be taken up through this endocytosis, but is then trapped in these small bubbles inside the cell. What we have is a technology that can open up these bubbles. We have a photosensitizer that accumulates inside these so-called endosomes, these bubbles, and when we illuminate, you can rupture the membrane destabilize the membrane of these small bubbles and whatever has been taken up can leak into the cell. And thereby the therapeutic target being in this capsule can leak out and be effective. So that's the platform technology, the basis for everything we do. As mentioned, we have three different programs. One is then FEMA Chem, where we enable already approved drugs to become more effective by enhancing the local effect of them where it's most needed. Fimavac is to enhance the immune responses that are important with vaccines, for example, for a therapeutic effect. And Fimanac is to enable big nucleic acid therapeutics. These are big molecules that can't pass into cells without some kind of help. And they need to get into cells to work. We provide a delivery solution for this. So this is in a nutshell what PCI biotech is and what we do. So let's have a look then at the highlights for the first half of 2021. So to start with, going back a bit, when COVID-19 hit us in 2020, we started immediately and we saw that this really was a problem for the capacity of hospitals. We understood that this would affect the clinical trial and we started to implement a number of different initiatives and also to expand the study at that time. And these implementations was done during the autumn last year. And we saw effect of this at the beginning of this year. We saw that the opening of Asian sites and the amended protocol increased the screening and increased the enrollment to release in quarter one. And we reported then that we were cautiously optimistic. We saw a good trend. Now, unfortunately, activity declined significantly in second quarter. We had only three patients included during that quarter. And this now, with the Delta virus really having a large effect in certain regions, we can't really keep what we've said has been the time range for this. And now the expected interim analysis for a potential accelerated approval is revised to second half 2023. We currently have a financial runway to well into the second half of 2022, but not covering this interim read then. Now on the positive side, recruitment started stronger again in Q3. We had four patients enrolled in July, which is normally a relatively difficult period. And then we have August after that, which is the most difficult month in the year. On the positive side also, we had our first US patient enrolled in the release study last year, first half, I'm sorry. And we also had orphan drug designation granted in South Korea for bile duct cancer in treatment in combination with gemcitabine. And we've had good activity in South Korea. So that's a key market for us in Asia. So it was really good to have this orphan drug designation granted. Now what we are continuing to focus on is of course enrollment of patients into the release study. We're emphasizing really regular trial management, overall performance evaluation, replacement of underperforming sites with sites we think can perform better, and also to manage and proactively manage all the risks that we see in a study like this. so that we ensure that we can recruit and complete this study successfully as quickly as possible. For FEMAVAC, we had a successful phase one vaccination proof of concept study that I mentioned, published in a high impact immunology journal early in the year, Frontiers in Immunology, where we saw that the immune responses to peptide and protein based vaccines are really enhanced by our technology in Healthy Volunteers. We also had a very important patent for Firmavac granted in the US. This is in combination with immune checkpoint inhibitors. And these are normally what you today talk about as immune therapy, very important drugs for cancer treatment. Unfortunately, a number of patients do not respond to them. And this is by means of enhancing the immune response through different technologies, you may be able to increase the rate of responses to these immune checkpoint inhibitors. And that is what we think we can do with Firmavac. And in that perspective, this US patent is very important. And then the highlights for FIMANAQ. We had encouraging data on enhanced delivery of mRNA for various medical applications presented at the conference early in the year for RNA therapeutics. This was collaborative research that we've had in our collaborations as FIMANAQ is primarily a collaborative program. We also established a new research collaboration with a South Korean company, a quite extensive collaboration with Olix Pharmaceuticals, who are a leading developer of RNA interference therapeutics. In addition to this, We are also now significantly strengthening the organization. We have employed three highly skilled individuals, one experienced operational leader for release that will drive this study taking forward, and two key employees within clinical science and business development who will be focusing more on Fimavac and Fimanac. as most of our resources have had to go into the release study and ensure that we get all these initiatives implemented and which we have seen a good effect of which but unfortunately as the pandemic has not resolved as quickly as we hoped we are still seeing fluctuating recruitment this year Those were the highlights for the first half, 2021. I will now go into a deeper dive into the three different programs and start with FEMA Chem. which is in development for first-line treatment of the orphan indication bile duct cancer. We have some very positive early clinical results from a phase one study, both with tumor response and with survival data. We have had discussions with the regulatory authorities, both in Europe and in the US, and we have a pathway to market settled by these interactions. We can do a single pivotal study with a potential accelerated approval based on an interim analysis, which is now expected to be second half 2023. So what we're doing now is what we call the release study, and the release study is a global pivotal registration intent study. Excuse me. And recruitment is ongoing at approximately 50 hospitals across the three continents. And the number of hospitals will vary a bit going forward as we replace those who are underperforming and put in place new sites which we think can perform better. So there is an excellent fit between the medical need. I'm sorry, I just need to... There is an excellent fit between the medical need and existing treatments with PCI. We really can enhance the effect of gemcitabine, which is a drug that is being used as a standard drug in cholangiocarcinoma. It's also easy to illuminate cholangocarcinoma, bile duct cancer, because you can go in with an endoscope and put a fiber into the bile duct and illuminate the tumor from the inside. And it's also a disease where you need better local treatment. Most of these patients die from the local effects, so local regional control of the tumor is very important. We did a phase one study here, as I mentioned. We saw a median overall survival of almost 23 months at the selected dose for the release study in the dose escalation part of this. And the normal overall median overall survival in the standard treatment today is little less than a year. So some very encouraging but early results. I mentioned easy to use. Also, this means that since this is the first recommended first line therapy, gemcitabine in combination with cisplatin, and we enhance the first line treatment, our treatment also is the first line, which is not very common when you come with a new technology within oncology. We have, as I mentioned, also orphan drug designation, not only in South Korea, but also in EU and the US, which offers market exclusivity. And then when you look at the competition, it's not that much in development. Most of it is precision or gene or small molecules that are mainly second line or towards mutations or targets that are present primarily in intrahepatic bile duct cancer. I think the main competitor that is targeting a broader population containing our population is Nukana. But that's really the only main competitor that we see in the development pipeline. Of course, a premium price potential is expected with an orphan disease like this. It's a rare disease. So it's a good market potential for that. As I mentioned, South Korea, in May, we had the Ministry of Food and Drug Safety in South Korea granting us orphan drug designation for Femaporphine. And this is then in combination with gemcitabine in patients with inoperable locally advanced or metastatic bile load cancer, which is our target population. and this may provide the several benefits including conditional approval extended market exclusivity and exemption from required data so we have now with this as i said orphan designation granted in three major markets across all the continents where we are doing currently the release study so what is the release study then It is a study in 186 patients with a one-to-one randomization between standard of treatment today, which is gemcitabine plus cisplatin, and experimental arm where we enhanced gemcitabine in up to two different cycles with our PCI technology, with FEMA Chem. And you can see on this slide the treatment regimen at the bottom, and our treatment part of it in the little box on the right hand corner down in the right hand corner. We have 11 European countries, two Asian countries, that is South Korea and Taiwan, and the US that are open in this study. So the status of it, 47 sites currently open. We have nine sites in Asia and we have six sites in the US and the rest of the sites are in Europe. We had the first Asian patient enrolled in October 20 and the first US patient enrolled in April 21. Our first patient in Europe was enrolled in May 19. We have, as I said at the beginning, implemented several initiatives in the autumn of 2020 with the aim to recoup what we saw as the COVID-19 cause delays. And the most important there is, of course, increased number of sites. We expanded the study and also a protocol amendment where we ran through the screening log that we had to see what were the screen failures here and how can we adjust this to expand the eligible patient population. The expansion to Asia has contributed significantly to patient recruitment, specifically South Korea is a very active country, which is a quite positive sign. And they seem to have good control of the pandemic situation there for the hospitals. So this initiative, the initiatives that we did resulted in increased screening and enrollment in the first quarter. And we were positive and thought that this would increase further as the pandemic resolved more and more. Now then the Delta variant of this virus came and a number of companies reported that both sales and clinical trial enrollment decreased in second quarter, it was a difficult quarter. It was really a difficult quarter for us as well, May and June specifically. We only had three patients included during that quarter. Now, Q3 again started stronger with four patients included in July. And as mentioned, August is always a difficult month because it's the holiday season in many of the countries. So the focus now going forward with regard to the progress of this and timelines is on regular trial management as mentioned. We look at the overall performance evaluation with replacement of underperforming sites and also proactive management of study-specific risk such as retention of randomized patients that always a risk especially in open label studies like this that we lose patients from the control arm and we need to follow that and proactively manage that. So we are looking at strategies for how to best do that. And then also adherence to study procedures and eligibility criteria, which is always important for the quality of a study. Now, as I said, the previously communicated time range for interim readout, which was a year, was from second half 22 to first half 23, had a recruitment plan that from now on required 14 to 18 patients per quarter. Our best quarter to date is 10 patients, so it's a bit above our best quarter and this is the average that is needed. This was an ambitious plan and in this we looked at what could we do with the expanded sites with the eligibility criteria that had been modified. And also, when we put this plan in place, we assumed that after the summer, the COVID-19 impact would be close to gone on the study. Now, where we are today, we consider that unlikely. So therefore, on this basis, we are revising the expected timing of the planned interim analysis to second half 2023. Having said that, we now have full focus on release. We have further strengthened the team with an experienced operational leader, and we are identifying all opportunities to optimize the overall performance of this study, from the operational part to the design part of the study. The study today looks like this. We have an interim analysis for potential accelerated approval, which looks at objective response rate and is a secondary overall survival. The final analysis is progression-free survival. And the secondary endpoint there, of course, important is overall survival. We had our first patients enrolled, as I said, in 2019, 2020 and 2021, respectively in Europe, Asia and the US. US has been underperforming and there is a difficult situation also now in the US with the Delta variant. We have done a small extension of the phase one study to look at the ability to do two treatments. The data I showed you with 22.8 months for median overall survival was based on one treatment, but there's no reason to think that we can't do two treatments of this. this of the pci treatment during the cycles and therefore we did an extension to the phase one study to look at safety in a few patients we want to extend that to have idmc our independent data monitoring committee to confirm the safety of two treatments after we've treated eight patients with two treatments and they've completed the the safety window In this study, it is either one or two treatment depending on a number of factors and decided by the patient and the investigator. But we now think with the patient populations we have, that we will have the safety review this second half of this year. And then the interim analysis, second half 2023, and we have approximately second half 2024 for the final analysis, depending a bit on what happens at the interim analysis. So that is where we are currently with the release study. We have some very strong results. We have good faith in this study. We have been struggling with recruitment during COVID-19, but we really implemented in the organization and worked hard to make sure that we have the best possible study going forward. And we have good faith in the treatment and the potential of FEMA Chem for this patient population. Then let's move over to our second program, which is FEMAVAC. FEMAVAC is then using our technology to enhance immunotherapeutics. We have some really compelling preclinical results where we see particularly strong CD8 T-cell immune responses, which are important for the therapeutic effect of vaccines. We did a phase one study in healthy volunteers with peptide and protein based vaccines, and we saw some very good results that these were published earlier this year. And this is really a versatile vaccination platform because it can potentially be used with several modalities, not just protein peptide based vaccines, but also nucleic acid based technologies. And to that end, for example, intratumoral immunotherapy with naked mRNA is an interesting area. And we have some encouraging preclinical results when it comes to the increase of expression of mRNA in cells using Fimavac in TC1 tumor cells and in MC38 tumor cells. And you can see the fold increase in this figure, which is quite high, and also comparing in one of the tumors versus LNPs, lipid nanoparticles, which is the normally used technology today to deliver mRNA. So with this, you can also get systemic therapeutic effects, and you can have mRNA that either encode antigens or other immunostimulating factors. Important thing is here also that the expression is really confined to tumor. That may be important to avoid potential side effects of some of these technologies. And the positive thing that we saw clearly better effect than LMPs with Femavac. And we also have, with this photochemical treatment, with Fimavac, a modulation or a potential inherent adjuvant effect, a modulation of the microenvironment when we go in and do something directly in the tumor. So we think this is an interesting area to look further into. We have, as I said also, these were preclinical results, the previous slide. This is clinical results in Healthy Volunteers, excuse me, where we saw successful clinical proof of concept for Firmavac in healthy volunteers with regard to both tolerability and safety and immune responses. And we saw in that study what we provided with our technology was an increased number of responders, enhanced T cell responses, and also those T cells that were enhanced had an improved T cell functionality, which is important for them to work as they should in combating a tumor. So the full phase one study were published early January 2021 in Frontiers in Immunology, which is a very good immunology journal. In June 21, we also had this new US patent that was granted, which is covering the use with checkpoint inhibitors, a very important class of immunotherapeutics. We have had during this period, as I said, had to focus during the pandemic, we've had to focus a lot of our resources into release, into the initiatives and into ensuring that we had the best possible study. And it has unfortunately reduced available resources for FIMAvac. We have strong confidence in the commercial potential of this and also of FIMA NAC, which is the next program I'll talk about. So we have strengthened the organization with two highly skilled people within clinical science and business development. And they are here to drive the preparation for a potential clinical proof of concept study for a therapeutic vaccination in a relevant cancer, not just in healthy volunteers, but actually in the disease. So I hope to be able to report more progress in this going forward from now. FIMANAC, the third program, it's a preclinical program. We have some really compelling preclinical results, strong data for nucleic acid therapeutics delivery, intracellular delivery, and it works in synergy with a number of vehicles that are being used to try to enhance the effect of nucleic acid therapeutics. It addresses really the major hurdle for this class of drugs, which is getting sufficient payload of the nucleic acid therapeutics into the cells. And we have then had this as a collaborative strategy where we work with companies with nucleic acid therapeutics in their pipeline to see whether there's a synergy between their technologies and our Femanac technology that can help them enhance the effect of what they're doing. One of these collaborations produced some very promising results that were presented at an international RNA therapeutics conference early in 2021. where we show that this is a local delivery technology where you can just mix mRNAs and femoporphine, our photosensitizer, and administer that as one injection and also illuminate in the same procedure. And we can get this nice expression and transfection of mRNA in the cells. And it's also then spatially restricted to where you illuminate. It doesn't happen outside of that area. The beauty about this being a preclinical program is that it's already in clinic as a platform technology in the two other areas, in FIMAK and FIMAK-M. So we have ample safety data in humans already with our platform. And there are a number of applications where a local effect is decided, a number of different diseases and organs. And we see in this what we've done a substantial enhancement when we do this into tumor, when we do it into muscle, and when we do it into skin. And what we're now doing is we will increase our internal research efforts and actively center those to where we think the most attractive applications are to try to develop these applications to the next step and reach out in a more targeted way to where we have the biggest benefit. We have established one collaboration in the spring with Olix Pharmaceuticals. This was done in May 2021. We entered into an extensive research collaboration with this company who is in South Korea and is a leading developer of interference products in RNA, RNAi therapeutics. And we will combine our technology and know-how and explore synergies and further partnership based on this. So we have a research collaboration and we do this collaboratively really. It's a really true collaborative approach on this. And we look for synergies in these studies. It's all in preclinical with the current agreement. And then when we have the results, we will come back to see whether there is a potential to further enhance this. And it is within areas that are really interesting because there is a need and unmet medical need for better treatments in specific local disease areas where the PCI technology fits quite well in this collaboration. So generally research collaborations, we have that within FEMA-ANAC and FEMA-VAC. We have currently five collaborations spanning across different classes of drugs and different therapeutic applications. They, as I've shown you with the previous slides with some data, provide not just the collaborative effort in itself but also a lot of scientific know-how and encouraging results and also for us intellectual property so it's important even those that may not lead to commercial agreement sometimes provide a lot of value to the company and as i said the most recently with olex we are continuing to pursue new and value-added collaborative opportunities with this technology And with that, I've finished the FEMA NAC and VAC parts as well. And the next is to go through the finances. And I have Ronny Skogedal, the CFO here, who will spend some minutes to review where we are on the finances.

Thank you, Per. And first of all, it's good to see you fit and healthy here again. So I'm not alone at these presentations. So regarding the key financial figures, as you know, parts of our cash is placed in euros, meaning that we face fluctuations in the exchange rates affecting the net financial results. And these variations you clearly see here in the figures in the net financial result. The BIA grant for FIMAVAC ended now in the second quarter of 2021 with 13.4 million accumulated funding over four years from the Norwegian Research Foundation. So a big thank you to them for this valuable support. We have a solid cash position here of 146 million at the end of the quarter, compared to 187 at the year end, meaning that we have spent around 40 million during first half 2021. Partly placed in Euros, and we expect this to give us a financial runway well into second half of 2022. And I draw your attention to the revised timelines for release. On the operational side, we have a fairly stable result, around 20 million per quarter and 40 million for the first half year. I think that was it, Per.

Okay, very good. So to close this presentation then, What we're doing is really progressing the PCI technology pipeline. We have three different assets here. The most important one for us is FEMA Chem, because that's the lead project that is currently in a global clinical pivotal study for registration intent. And there is an interim read in there for potential accelerated approval, which is important in this orphan indication. We have implemented improved trial design and we've done several initiatives to optimize the execution of this study during the pandemic as the pandemic has really affected the progress of the study. We saw recruitment increasing in 2021, especially with good contributions from Asia, but it is still fluctuating, as we saw in the decline in the second quarter. The IADMC safety review of two treatments is expected this second half, and the timelines for the expected interim read is now revised to second half 2023. For Firmavac, we have done a successful study in health volunteers with enhanced immune responses that has been published in a high impact journal earlier this year. We have also now a new patent granted in the US, which is very important for combination with immune checkpoint inhibitors, the most important immunotherapy on the market today. And this technology is today available for licensing. And we are planning also for clinical proof of concept in a disease setting with Fimavac. And we have strengthened the organization significantly to drive this forward. We are also then with the third program in the preclinical setting providing an intracellular delivery solution to nucleic acid therapeutics. We had some really encouraging mRNA results presented at the conference early in the year and we have also a new extensive research collaboration established within the interference area of RNA. And we are now actually center our internal research towards the most attractive applications for local treatment with an illuminated technology like the PCI technology. So I think that was the end of the presentation. So now we are opening up for questions to start with from callers. And then after we've had those, we'll go through the webcast and see what we have of questions from the webcast.

Ladies and gentlemen, if you wish to ask a question, please press five star on your telephone keypad. To withdraw your question, please press five star again. We'll have a brief pause while questions are being registered. As a reminder, if you wish to ask a question, please press five star on your telephone keypad. The first question comes from the line of Svein Erik Syversen. Please go ahead. Your line will now be unmuted.

Good morning. Good morning. My name is Svein Erik Syversen. First, thank you for a good and interesting presentation. I think I said several times before that ideally you would like to have a partner for the release study in Asia. We have been looking for a partner for quite some time here now. Does lack of success mean that there is no interest for a partnership in Asia?

No, and I wouldn't call it lack of success. These are processes that take time. So we are still working on seeing whether we are able to establish a partner for Asia, and we want to do that as quickly as possible.

So do you have to just mean that you have discussion with any companies currently?

We are not talking about, we're not guiding around partnerships in timing or talking about discussions around things. We are actively working on this. That's what I can tell you. so does that mean that you are optimistic with regard to getting a partner let's say by the end of this year that would sound like giving some kind of guidance and i don't want to give guidance with regard to partners because we can't really control that process you have said a couple of times that

The Pima Vax study could be, not necessarily will be, but could be finished next year. There could even be some results next year. Do you still think that's possible?

Now, I think with the focus that we've had to take to the release study, I don't know. It's getting tougher to get that done. But now we have new people in the organization who will drive this forward. So we'll see what we can do. We have strengthened the organization, really. So we'll see what we can manage to do. I haven't really guided on that either. I've just asked, someone asked hypothetically about when the results could potentially be available for this. And I said in a couple of years, I think, at that time.

Thank you. Okay. The agreement with Alex, was announced I guess early May here. Can you say a little bit about the progression of that cooperation so far?

It's progressing well. Research is being done and that's a very good interaction between the companies.

Have you started to test your technology together with Ollex OLX 104C product to grow back hair on mice. that you actually started to do that preclinical?

I am not updated on what has been done and not has been done in that research program, to be honest. So this is Anders Högseth who is managing that program. But it goes according to plan. But exactly what has been done so far, I don't know, to be honest.

Olnix have said that they would like to move on with this technology and may go to clinical next year. Do you think that's possible, that that will be together with your technology?

Well, it's possible. Whether that will happen, I don't know. But it is possible.

The CEO of Olnix have also said that they would like to extend the cooperation into cancer. and RMNR vaccines. Are you discussing this possible extension with all XT-safe?

This is something that we will announce when and if that extension is done. But there is a clear wish from Olyx to also broaden this into further areas. That is correct. And that was, I think, his quote in our joint press release that we had when we established this collaboration.

You had some very good results with AstraZeneca in the cooperation you had together with them here. For the time being, you have five other corporations. Do you have encouraging results with any of these five companies that you can say a little bit about?

I can't talk too much about the different collaborations here because it's under confidentiality, all of these research collaborations, but I can tell you that we have encouraging results in some of these collaborations, clearly.

Good, okay. You have worked with Eterna for, I think it's more than five years now. I would think if you have worked that long that you have some interesting results with them. Otherwise, I would think you have terminated that cooperation. Can you confirm that you have some encouraging results with Eterna?

I'm not going into specific results on any collaboration, but I can tell you that we've had a long collaboration with Etherna, but it's been a roller coaster thing because of management changes and things happening, strategy changes happening within Etherna during this period. Been an effective, progressed collaboration through all of those years.

You took over the rights from the corporation earlier this year. Can you say a little bit about how you are promoting this technology now?

Sorry, I missed the start of your question.

You took over the rights for the work you had together with AstraZeneca January 1st this year. Can you say a little bit about how you promote this technology towards other companies?

Yeah, this is done through the regular channels that are being used for discussions around business development and research. So it's partly sharing the research and doing it at scientific conferences as we did at the RNII conference. And it's partly at the partnering and business development conferences where we meet with companies who have these kind of nucleic acid therapeutics that might have a benefit from our technology. We are also actively looking at where we best can use our technology and trying to shape up the applications within this area to have an even better concept to sell when we go out.

The research, as we know, was very good. Tell us a little bit about the response that you have got or the interest you have got for this technology from other companies. Are there clearly an interest among other companies to cooperate with you?

Yes, there is a clear interest among companies to collaborate with us, but it needs to be an application that fits what they're doing. But when there is, clearly they see the strong results that we have. And we've had very positive effects out of the results that we had with the AstraZeneca collaboration.

A couple of bold statements that we have done in the past. I guess in the annual report from 2020, it stated that Femanox is well positioned to capture a significant part of the nucleic acid therapeutic delivery market. And you have also said a couple of times that Femanox could be the new gold standard within parts of the nucleic acid therapies. Do you still believe that this is likely to happen, that Fimanaki is going to be a significant player in the future?

In applications this is absolutely a potential because it is a very efficient way of delivering and spatially restricted delivery in certain applications. So I do absolutely think that it can play a very important role to cover some unmet medical need with regards to gene therapies or nucleic acid therapeutics in specific areas.

The stock price has been quite disappointed lately. A lot of people are quite frustrated and angry about how the stock price has developed. You have talked a lot about the technology and answered some questions so far today here. Is there anything else you would like to add to those people that are feeling a little bit on the fence, not sure about what to do based on, I guess, what you have said today and what has happened in the past?

I just would like to reiterate that I think we have some very good results for FEMA Chem, early phase results. We've been unfortunate with a pandemic that has really made an impact on the progress of our study, but we have strong faith in that these results that we saw that were quite encouraging brings the potential to the further development of FEMA Chem for bile duct cancer. There's no doubt about that in my mind. Now, it will take some time, as you know. Pivotal studies are not something you do overnight. It is a long endeavor, but we have an interim read here and we have a possibility to do it on just a single study with an interim read. So I think that's a great opportunity. In addition to that, FIMAvac, is some very strong results in in phase one as you've seen and it's been published now and we have been a bit restricted lately due to in the in the progression of that program due to the all the focus the organization needed to do on our lead program but we have now strengthened the organization and i think we can hopefully provide more more progress in that area as well And for FIMANAC, clearly, just repeating what you said, there are very strong results with our technology. And for certain applications within the delivery of nucleic acid therapeutics, it has some real advantages. And this is what we need to try to exploit.

Okay. Thank you, Per.

Thank you, Sven-Erik.

Thank you. And if there are no further questions, I will hand the word back to the speakers.

Thank you. Do we have some questions from the web that has not been covered through all the questions that Sven-Erik asked? I think we need a microphone here.

Okay. Okay. Yes. We have some questions from the web. And I will start here with the release. Can you please explain a bit around early signs suggest a somewhat lower retention in the release control arm and the company's proactively pursuing strategies to address this during second half 21?

yeah so one of the risks that we have mentioned and the reason why we went to the authorities to start with to ask to do a single arm study was that this is not a study that can be blinded it has to be an open label study open label studies means that the patient knows whether they come into the control arm or into the experimental arm excuse me And there is a risk that is in all studies, in all clinical trial studies, you need to watch your attention to see that you don't lose too many patients. Now there's a higher risk, of course, it's in an open label study when patients are randomized to control arm, they know that they are randomized to control arm, they might go on to look for other therapies. It's also sometimes that continuing in the study requires travel because they go to a central hospital and and they live maybe maybe they have to travel a couple of hours to get to that central hospital and they might have a local hospital that can provide the same treatment that they get in the control arm now specifically under a pandemic when you are under this kind of treatment you don't want to travel So it even heightens sort of the risk for the retention during a pandemic. Now we have seen a slightly higher level of discontinuation from the control arm. And this is something that it's far too early to say whether this is how big this risk is. But we want to proactively manage this risk. So we are looking at all sorts of things from doing operationally into making sure that you can be compensated for travel Are there opportunities to decentralize? Is there something with the design of the study we can do? And all of these things we are now proactively looking into to see what's the best strategy to ensure that we mitigate this retention risk as early and as good as possible.

Good, thank you. And regarding recruitment, how many must be recruited per month to reach interim read in second half 23? 12.

On average.

Per quarter you meant?

Per quarter. You asked per month.

Yeah, I didn't ask it. Oh yeah, okay.

I thought the question was per quarter. So divide by three and you get per month. Four. On average, it's a fluctuating, I mean, it's an orphan disease, so it fluctuates a bit, but on average, four per month or 12 per quarter.

Are there any plans to open sites in Thailand since Asia is clearly a positive market?

Yes, we are looking into Thailand as well. It's not that easy actually in that country. It's a slightly different kind of disease because it's highly infected areas there due to this liver fluke that can give bile duct cancer. And the etiology might be slightly different. So you have to be careful so you don't sort of... tend to study in a way that it's not valid any longer for the normal cholangic carcinoma that we have in the US and Europe. But we are looking into opportunities into Thailand as well. But it's not as exciting as it might sound when you hear the high numbers, because the high numbers there in incidence is really related to a slightly different disease.

And I received a message here that there is one more question from the call. Is it possible to hear if there are any more questions on the call?

Yes, thank you. We do have a question from the line of Adam Carlson from ABG. Please go ahead. Your line will now be unmuted.

Hi, thank you for taking my questions. I wanted to ask a bit more around the signs of poor retention and the control arm that you were just mentioning. And you obviously described what the potential cause of that could be. I was wondering if you could say anything more about the implications for the interoperability of the study and whether at the rates that you're seeing now, if there's concerns that that could... have kind of a significant impact or whether things would need to get quite a bit worse for that to be a potential issue.

So I think if the rate that we've seen during the pandemic is the rate that we will see going forward, then it is a concern and we need to proactively manage it. But there are ways of managing this, of course, and there are a number of different actions you can put in place to try to manage it. If you don't manage to increase retention, or sort of keep it down to a level where you need it to be, then the other thing you could do is increase the sample size, of course, but that's not the way we want to go, of course.

Sure. Okay. And can you say anything about whether patients are leaving the control arm in order to become eligible for for kind of just standard photodynamic therapy. Is that a potential pull factor for patients leaving the trial?

That I've heard of. Not that I've heard of. I know that there are some patients leaving the control arm, but I don't really have the reason for why they've done this. So not sure.

Okay. I don't know if the numbers are enough to break it down in any way, but if there are geographical components to the poor retention, is it being seen more in certain geographies?

I don't have the figures of that in my head, actually, so I can't answer that question. But I don't think there is... Well, let's not answer that question because I don't know. So I'll have to come back to that, Adam, if that's something you want to hear more about.

Sure, sure, that's fine. And... I wanted to ask whether you've communicated this previously, if there's a specific number of US patients that you're aiming for or that you need for regulatory reasons to recruit to the trial?

There isn't a number of patients you need to recruit from regulatory reasons. I think the more patients you have or that you have a substantial cohort within is always a positive. It's not a negative when you come to the FDA. but there's not a specific number. And there are instances, of course, when FDA has approved drugs without a single American patient in, as long as you can justify that there is no difference in ethnicity or etiology or therapeutic way of handling the disease between the regions where you've done the study and the US.

Okay, great. And I was wondering if you could give any more information on what the kind of specific activities for the FEMA VAC and FEMA NAC program that you would have hoped to pursue if resources didn't need to be focused primarily or entirely on the release study. Are there specific activities that you kind of have on the agenda as such or is it a more general sense?

No, there are of course plans here and for FIMAvac it's really to move this into a disease setting and we have internal plans for how this can be done. We have also discussions with external parties for whether we can do this in some kind of a partnership. So moving it into a proof of concept in a disease setting is a high priority for FIMAvac. and preferably, of course, in an area where we think it's really commercially interesting to move it to the next level. And then for FIMANAC, it is what I mentioned. It's really to develop the applications to our own applications for having a more ready readily sellable concept to the companies. This is the application you do for this type of organ or this type of treatment, and this is the application you do for that. It's been really, for a long period, more of an opportunistic approach, where we have this technology, we've presented it to companies, and then they, if they're interested, they can start testing it. Now we're looking at whether we can develop this a bit further ourselves internally through internal receipts and actively focus it to the where we think from the results, partly that we had with the AstraZeneca collaboration, actually, which is very interesting, where we have the most potential to bring value with our technology.

OK, great. And just a final question, maybe to understand the dynamics of the poor recruitment during the pandemic. Obviously, that's not unique to yourself, affecting most trials or many trials anyway. But given the kind of the severity of the disease and so on, patients are obviously still receiving treatment one way or another, whether that's in a trial or not. And obviously you were mentioning travel inconvenience to go to a central hospital as a potential reason why patients wouldn't want to enroll and so on. But is it your kind of assessment that a significant proportion of patients who would have enrolled but didn't because of the pandemic, are they receiving photodynamic therapy of some kind? Or is this kind of the route for them to potentially receive that? That would be interesting to understand.

I don't have, I mean it's sort of a version of the same question you had, another version of the same question you had before. It's an interesting question. I think it depends on which region you look at. If you look in certain regions where photodynamic treatments of other kinds might be used by physicians, this might be an effect in certain regions. Now generally I don't think that is the case. So I do not think that this is a big factor, that they would go to a specific other photodynamic treatment.

Okay. I'm just trying to understand if these patients would be receiving similar treatment, whether in a trial or outside of a trial, whether the pandemic is then, you know, a primary reason for them not to enroll if they're still going to go to hospital to receive photodynamic therapy then and why wouldn't they just as well do that as part of a trial notwithstanding that the traveling convenience and other things um but uh but i but i understand what you're saying in terms of that being a geographical variant yeah okay okay no great thank you very much thanks adam

I think with this we say... There is one last question.

One last question here is, are you now changing the communication policy for release?

No, we're not changing the communication policy for release. The communication policy for release is that we talk about timelines and special events and countries and sites where we enroll patients. We talk about the milestones, whether we are on plan or not to reach certain milestones. The reason that we're going out with some numbers right now is to give you an understanding of the challenges that we've had and the challenges that we see going forward. So it's to provide a more transparent scene on where we are and how the pandemic have affected us. But we will keep on the same kind of communication policy for release study that is the normal industry standard going forward. Okay, with that, many thanks to all of you listening in for your attention.