PCI Biotech Holding ASA

Welcome to PCI Biotech third quarter 2021 presentation. My name is Per Walday and I'm the CEO of PCI Biotech. I have with me today three other members of the management team. Ronny Skuggedal, who is the CFO, but in addition also the CMO, Amir Snapir, and the CSO, Anders Högseth. Before we continue, please notice this important disclaimer. The presentation today will be given here for the first time in a long time with a live audience, which is very nice, but also as a webcast. And we also have a phone line for callers who want to ask questions after the presentation. So it's possible to ask questions through a call system, as you can see on the current slide. We will start by doing the presentation and then we will take questions from the audience here in the room and thereafter we will do the call questions and it's also possible to ask questions through the webcast system and we'll take them last in the presentation. We've modified the presentation slightly today since we have more members participating as well. So we are not going into detail on the technology itself. There's a lot of good information around that on the website and our homepage. But we will go through the highlights and then we will have an operational review that is divided into a clinical part done by Amir Snappi, the CMO, and a preclinical part done by the Anders Högstedt, the chief scientific officer. And then Roni Skogedal will talk about the key financials, while I will do the outlook at the end. So then, let's start with the highlights for the third quarter. The pandemic still has an effect, unfortunately. And we can see that also in the hospitals and the numbers of people with COVID-19 in the society right now. And we see this clearly also in our study. Enrollment of patients into release study is still challenging. and it is fluctuating from month to month. It has a continued negative impact on the study, and also with August, due to the holiday season being normally a low recruitment month, we didn't have more than five patients, unfortunately, in the third quarter. We have enrolled three patients into release study in October and we continue to work hard with regular site calls and a lot of different activities going on to focus on recruitment into this study. We are emphasizing now regular trial management including overall performance and site replacement and we have replaced five sites during the 2021 to replace sites who are not contributing to the study with more promising other sites. We are also pursuing strategies to address recruitment and retention. We have so far in the study recruited a total of 30 patients per end October. And the timeline that we reported in the second quarter remains. It's still second half 2023. Now, as I said, we are proactively pursuing strategies to address recruitment and retention, which we talked about before. And we are in these also having interactions with both the FDA and the EMA about an alternative study design enriching the patient population, the control arm, with external patients. That is something we are working on. And Amir will come back to that later in the presentation, what we are doing with regard to retention and recruitment. Then for Firmavac, it is progressing towards the initiation of a phase two study, a clinical proof of concept study. We have product definition now. We have a study design clarified. We had comprehensive consultation with international experts. And Amir will also talk a bit more about what this study really entails and what we're doing in that area. And for the FIMANAC, we've talked about that we are now focusing our efforts to the areas which where the sort of PCI technology is most suited. And we have on the basic of strategic research and the collaboration and the result from the collaborations now focused on specific applications that Anders will talk more about later in the presentation. And also, importantly, we have strengthened in the third quarter of the organization with three new key employees, really skilled individuals, competent individuals, who, one, is an operational leader for release, who have done pivotal studies before and have done orphan disease studies before, and two key employees also within clinical science and within business development and alliance management. which is important specifically for FIMAvac and for FIMANac. So those were the highlights. Briefly about a glance of what we are. We are located here at the Oslo Cancer Cluster, very close to the Norwegian Radiome Hospital where the PCI technology originated. We have three different programs which are based on this platform technology. We call them FIMAchem, FIMAvac and FIMANac and FIMAchem. With Amphinex as the lead product, Femaporphine is the active ingredient, is in a pivotal trial, global pivotal trial in bile duct cancer, enhancing the effect with our technology of Gemcitabine in this patient population. We are also in the clinical setting with Femavac using the same platform technology as a vaccination technology where we can enhance therapeutic cancer vaccines with the technology which has attributes which really strengthens the T-cell response and that is important, specifically important for therapeutic cancer vaccines. And then for FIMANAC, Nucleic Acid Delivery Technology, we are in a preclinical stage with several collaborations in interesting areas where we are now focusing our efforts. And PCI, it is photochemical internalization. It is an intracellular delivery platform that is used to get molecules who have difficulties getting into cells to reach the target, to get them into cells. And then we will start with the operational review in the clinical side, and I will start talking a little bit about the release study before Amir talks more in details about recruitment and retention. So what we are developing here is Amphinex. This is a formulation of the active ingredient Femaporphin and it's developed as first-line treatment for the orphan indication bile duct cancer, a rare disease with a very high unmet medical need. We have some very positive early clinical results encouraging tumor response and also encouraging survival data from the phase one study. We took these to the regulatory authorities and discussed what is needed to take this to the market and we have agreed a pathway with a single pivotal study with potential accelerated approval based on an interim analysis during the study. And that study has been initiated, so we are now running a global pivotal registration intent study with recruitment ongoing at almost 50 hospitals across three different continents. So why bilock cancer and what is the fit between our technology and the need that we see in bilock cancer? Well, first of all, we have some very positive results from the phase one with regard to both tumor response and survival, as you can see on this slide. This is an illumination technology where we illuminate tumors to enhance the effect of gemcitabine. And this is easy to use in this perspective because illumination can be done through standard endoscopic methods that are being used in these patients anyway for stenting and so on. And the gemcitabine is today the first-line treatment together with cisplatin. So we can enhance what is today recommended as a first-line treatment. And we boost effect locally. And for this specific disease, what really is harmful to the patients is the effect locally. So you need better local regional control of the tumor. And in that sense, there is no direct competition with us and our technology in relation to enhancing the effect of the standard first line locally where it's most needed. We have protection on this through orphan drug designations, both in Europe, in the US, and in South Korea, which offers market exclusivity. And we also have a patent that has been granted in Europe, but is still pending in US and other key markets, which lasts until 37 approximately, around using our technology for treatment of bile duct cancer with gemcitabine. And of course, for an orphan disease like this, there is a premium price potential. And with regard to competition, what we've seen mostly of here is precision genes, small molecules, targeted treatments that are mainly either second line or towards targets present mainly in intrahepatic bile duct cancer. And there have been two approvals in that area recently. But those are really targeting only intrahepatic. Now, the exceptions from this are acelerin, which we talked about before, and also some immune checkpoint inhibitors, which is being developed, durvalumab and pembrolizumab, which are also being developed in a phase 3 study for this specific indication. The results that have been seen so far has been a little bit sort of both ways. Some failures, a recent failure in August, some bad results last year with one of these drugs. Excuse me. But now recently, the Ruvalumab in the phase three study reported a positive interim analysis. Now, this is a study which comprise not just our patient population, but also gallbladder population. We have the perihilal and the distal, but this also is gallbladder and it's intrahepatic. We know nothing about the results yet, so we don't know what the results are in total. We know that it's positive, but we don't know what about the results in different subgroups. And this has been differing quite a lot in earlier studies when you look at targeted treatments of different kinds. So we have to wait for these results before we can say how this will affect, whether it will affect the real study and to what extent and how. The study that we agreed with the regulatory authorities was to do a one-to-one randomized study between control and experimental. Control is standard of care today, which is gemcitabine plus cisplatin in up to eight cycles, and then adding onto in the experimental arm up to two treatments with FemaChem to enhance the effect of gemcitabine. And this is now then ongoing across 47 different clinical sites across three different continents. And you can see at the lower end here how this treatment is done. At the start of the cyclic treatment of cisplatin and also potentially if the investigator and the patient wants it, also a second treatment later in the cyclic treatment of cisplatin and gemocytobin. The status of that study is today that we have 47 sites currently open for patient enrollment, 32 sites in Europe, nine in Asia and six in the US. We have implemented a lot of different initiatives to try to recoup the COVID-19 cause delays to the study. And the most important of those being the increased number of sites, expanding the study to new areas and more sites, and also the protocol amendment to expand eligible patient population. And we clearly saw that these initiatives provided increased screening and increased enrollment into the study. But the level has been fluctuating during 2021. We didn't think that the pandemic would affect the study to the extent that it has for such a long time, but it continues to have an effect on our study. And the reason behind this, I think Amir will come more back to later in the presentation. Now we had, as I said, five patients enrolled during the third quarter, and we had three patients enrolled in October, and the total enrollment then is 30 patients into the study. We have a continued strong focus on recruitment, on enrollment of patients. We are emphasizing really regular trial management, but doing it in a boosted and powerful way. We have a lot of performance evaluation, motivation, and booster visits, and we replace sites where we don't think they are motivated enough or don't contribute sufficiently to the study. And as I said, more than 10% of the sites have actually been replaced so far in 2021. So looking forward, what are the endpoints, the milestones and the timelines? We have then an interim analysis where we look for objective response rate, so the response to the tumor of the treatment, and of course a secondary endpoint of overall survival, which is always important and the authorities will always look at. And then the final analysis, the primary endpoint there, is progression, free survival, and the secondary endpoint, overall survival. We had our first patients enrolled in May 19 in Asia in October 2020, in the US in April 21, and we are now enrolling patients then in three continents. We have established an independent data monitoring committee which will regularly look at this trial, and the first time is when we have eight patients that have undergone two FEMA chem treatments and have passed through a safety window, so you can look at whether it's safe to do two treatments. And that safety review is expected before the end of this year. The objective response rate is the endpoint, as I said, which will be looked at after 120 patients have been enrolled. That's the interim analysis, which is expected second half 23. And then the timing and the format for the study conclusion can be impacted, of course, on the outcome of the interim analysis. But it is expected approximately second half 24. So these are the broad terms, the study. And I will now hand over to our CMO, Chief Medical Officer, Amir Snapir. He is joining us from Finland, where he lives. So we have some new technical things that we are trying to, we hope will work well. So Amir, can you hear us? Yes, I can hear you very well. Can you hear me? Yes, we can. And we can see you as well now. Thank you.

Very good.

Next slide, please, Per.