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.