PCI Biotech Holding ASA

Yes, good morning and welcome to PCI Biotech's Q1 presentation held here at Oslo Cancer Cluster Innovation Park. My name is Ronny Skogedal and I'm the CFO of the company. Unfortunately, I need to inform you that our CEO, Per Volde, is acute ill, so I need to take this presentation on short notice. That's of course unfortunate, but I will do my best. So, before we start with the presentation, please notice our important notice and disclaimer. At the end of the presentation, we will have a Q&A session, open both through a telephone conference facility, where you can dial in for questions, but you can also, as usual, post questions through the webcast console. we will start the Q&A sessions with the telephone conference facility. And you can find the details both in the slides and in the invite for the presentation. So first, a couple of words, intro words about PCI Biotech. We have an enabling technology, enabling intracellular delivery. We use this platform technology for three different programs. FEMA Chem, our lead program, now in pivotal phase with the release study. FEMA Vac, our therapeutic cancer vaccine program, completed phase one and recently published results in a scientific journal. And then the FEMA NAC program, our preclinical assets where we have a collaborative approach to try to bring this asset into the clinic. Very briefly about the mode of action of our technology. It's a triggered endosomal release technology where we have a molecule named Femaporphine which is designed to attach to the inside of the endosomal membranes inside cells. When we apply light, this molecule takes up the energy from the light, generates the photochemical reaction, destabilizes the endosomal membranes, and the trapped molecules are released into the cells. So that's why the intracellular delivery. And with this technology, we believe that we have the potential solution for key challenges for several modalities. For Femachem, we enhance the effect of gemcitabine for bile duct cancer. For Femavac, we enhance cellular immune response, important for therapeutic vaccines. And for the NAC program, we are providing a delivery solution, which is a major hurdle for nucleic acid-based therapeutics. Then, highlights for FEMA Chem. During Q1, we have seen increased screening and enrollment into the release study. And this is seen after implementation of the amended protocol and opening of sites in Asia. However, we do not expect to see the full effect of these optimization initiatives until the COVID-19 situation improves further. And in April, meaning after the balance sheet event, the first patient was enrolled into the release study in April. And going forward, we will continue with focus on enrollment into the release study, of course, but now the focus will be more on regular trial management, meaning performance evaluation and replacement of underperforming sites. And this process is already initiated, so we have already started to wind down underperforming sites. Both to save costs, but also to make sure that we focus our efforts towards sites that show real interest for the study. And the timelines are retained as previously communicated. For FEMAVAC, the successful phase one proof of concept study was in early January this year, published in a high impact immunological journal, Frontiers in Immunology. These data demonstrates FEMAVAC to enhance the immune response for peptide and protein based vaccines in healthy volunteers and we will come back to some of the the data there and the focus going forward for the vaccine program will be utilizing these published data in partnering efforts and also planning for a clinical proof of concept study in a disease setting then for FEMA NAC The encouraging data of enhanced delivery of mRNA for various medical application was presented in February at the UK state-based virtual conference focusing on RNA therapeutics. And another after balance sheet date event in May, a couple of days ago, we announced that we had entered into a preclinical research collaboration with a South Korean company named Olyx Pharmaceuticals, a leading developer of RNAi therapeutics. Then I will go more into the details for our lead program first. FEMA Chem Important here to notice that or to understand that this is a first-line treatment for an orphan indication We have a positive early clinical results from our phase one study We have had interactions with regulators both in US and Europe so the pathway to market is settled and the ongoing pivotal study with registrational intent is ongoing and we foresee to have approximately 50 sites open across US, Europe and Asia. Now the number of sites will now start to fluctuate from quarter quarter since we are implementing this trial management process with focusing on the high performing sites and the potential underperforming sites which do not show a real interest for the study will be one down yes So our technology here for bile duct cancer has an excellent fit with the medical need and the existing treatments for bile duct cancer patients. We have encouraging early results from the phase one study. The technology is easy to use. The illumination can be done through standard endoscopic methods. We are enhancing the recommended first-line chemotherapy gemcitabine and we boost the effect locally. So it's easy to understand the potential benefits with the treatment. We have orphan drug designations in both EU and US. The competition pipeline is limited. And the reason for that is that the competitors are mainly focusing on intrahepatic CCA, meaning bile duct cancer inside the liver, while we are focusing on extrahepatic bile duct cancer. That's due to the light application. And also competitors are not necessarily focusing on first-line treatment. And being an orphaned indication, there is a premium price potential. Here on this slide, I do not intend to go into details for this slide. I think most of this information is fairly well known. But here we have a map of the European sites, sorry the European countries we are active in and also US and in Asia, South Korea and Taiwan. So now we have by end April there were 46 sites open. one less than last quarter but as I said that's due to this management trial management procedures we have nine sites open in Asia and the first Asian patient was enrolled in October last year we have six sites open in the US and the first US patient was enrolled in April US has been difficult but We hope that we now with the first patient enrolled also can get up to speed in the US. And we have implemented several initiatives to recoup the COVID-19 delays and most important being increased number of sites also going into Asia, protocol amendments and to expand the eligibility criteria. So study progress going forward, as I said, we have seen increased screening and enrollment in first quarter, but we do expect to see even further increase when the COVID-19 situation improves. Focus going forward, regular trial management, replacement of underperforming sites, and also monitoring of the study specific risks meaning adherence to study procedures and eligibility criteria to make sure that we have a solid data package when we approach the authorities and as I said expected timelines for interim read retained as previously communicated Further, some endpoints, milestones, and timelines. I do not go into details here, but I can draw the attention to the center of the slides regarding the IDMC. We plan to have a seamless safety review by an independent data monitoring committee when eight patients have undergone two FEMA chem treatments, and we foresee that to happen in second half of 21. Then, FEMA-VAC. As I said, we have compelling preclinical results, particularly strong CD8 T-cell immune responses. We have successfully translated the technology into humans through the Healthy Volunteer Study, which has recently been published. And the platform is versatile, meaning that it can potentially be used with several modalities, including nucleic acid-based technologies. And the results from the phase one is well known, and I will just draw the attention to the highlights here. that we saw increased number of responders in the study, enhanced T-cell responses and improved T-cell functionality. So going forward for FEMA-AVAC, we are seeing or we are growing robust evidence with the phase one study now published in high impact journal. And we are actively exploring and preparing for a potential clinical proof of concept study for therapeutic vaccination. Both on the collaborative path, but also looking at opportunities we have for in-house development. And here we are also working with international experts and having considerations around how to take this further in the best possible way. And you can see further details around these considerations in the report. Then for FIMANAC. Here we are targeting to solve one of the major issues for nucleic acid based therapeutics, meaning the intracellular delivery issue. It's still a major challenge for this type class of drugs. We have compelling preclinical results. strong data and also we see that the FIMANAC technology works in synergy with several vehicles meaning other types of technologies to achieve the same intracellular delivery. We are addressing the major hurdle here and with FIMANAC we foresee that we are able to provide high payloads into the target cells. And here we have our collaborative approach, and we have several collaborations with players in the field. and most recently with a South Korean company. And the strategy here is to continue with a targeted business development approach for taking this asset into the clinic. And these collaborations provide important know-how for us and has also provided encouraging results. Currently we have five collaborations. And we see strong potential for further development of FEMA-NAC, not least within the field of mRNA, based on the recent successes mRNA-based therapeutics have had in the pandemic. So we actively center our efforts towards the most attractive FEMA-NAC opportunities, meaning that we also in-house look at what potential synergies we see with our potential collaborators. And for the compelling results, I'm not going into details on this slide, but I draw the attention to the figure here. And the figure shows fold increase of mRNA expression with FIMANAC. and with different applications. Here the first bar with intramuscular delivery with fema NAC close to 10 times fold increase. With intradermal application close to 30 times fold increase and with intratumoral meaning direct into the tumor close to 50 times fold increase with this application and that's why we see a strong potential for the technology here going forward and also the established collaborations show that the external world also show interest for the technology So, to a short summary of FEMA NAC with naked mRNA delivery. We have a local delivery technology, which is an asset deposited this way. And we can co-inject our molecule with mRNAs. And we can avoid systemic side effects by that. and the illumination can be done in the same procedure, and by the illumination, we target and restrict the mRNA effects to the illuminated areas. Since PCI is a platform technology, the clinical proven programs, meaning FEMA-Chem and FEMA-Vac, supports the application of the NAC platform as well we have ample safety data in humans both from systemic and by local administration and this is important for the next step by taking FEMA NAC into the clinic Yeah, I think that's the details I'm able to provide on this slide. Then some words about the collaboration recently established with Olix Pharmaceuticals. It's an extensive preclinical research collaboration with a leading developer of RNA therapeutics. We will combine our know-hows and technology platforms to explore synergies and the potential for further partnership. The partnership is governed by a research collaboration agreement and there are no monetary terms in this collaboration and there are no major financial commitments for PCI Biotech in this collaboration matter. But it's an important step and it's our first step into Asia, so that's also good for the interest of the technology in general terms. So the existing collaborations we have are listed here. And we continue to pursue new and value-adding collaboration opportunities. Then it is my usual slide, the finance slide. And in Q1, there are no major changes from previous quarters. we have a net change in cash during the period around 20 million NOC minus which is kind of the average we have had over the last year and more specifically also in the figures we had the very special situation in q1 last year with a actual net profit but that was due to exchange rate effects in on the bank deposits placed in euros So we still have a solid cash position here of 164 million NOC by end of March. Then, we have an overview of the recent key achievements and near-term milestones. In second half 2020, we enrolled the first Asian patient in October last year. We also worked hard with optimizing the study by optimizing the protocol and procedures and implement them at all sites. And the increased screening and enrollment we see in Q1 2021 is a direct result of this. work. And as I said, we also hope and expect to see further improvements as the COVID-19 impact on the study further improves. For FIMAvac, early January this year, phase one results were published in a scientific journal. And these data are now being used for partnering efforts. And also for FEMA NAC, we presented the results from previous collaborations at the scientific conference, UK-based virtual conference, focusing on our presentation, we're focusing on the mRNA delivery. And now in April this year for Femachem, we had the first patient enrolled in the release study, and we continue with our trial management procedures. And we now expect to see the IDMC review of safety for two Femachem treatments within second half of 2021. Then I think I have completed the presentation and we can open up for questions through the telephone conference. So please, moderator, if there are any questions out there.

Thank you, sir. Ladies and gentlemen, if you would like to ask a question, please signal by pressing star 1 on your phone keypad. If you're using a speakerphone, please make sure your mute function is turned off. Once again, if you would like to ask a question, please press star 1. Speakers, we have our first question from Adam Carlson at ABG Fundal Collier. Please go ahead, sir. Your line is open.

Hi, Ronnie. Thanks for taking my questions. I send my regards to Para. I hope it's nothing serious and he makes a speedy recovery. You've communicated that there would be a reshuffling of trial sites for the release study, closure of ineffective sites and so on. I was wondering whether you could give any more details on approximate numbers or roughly how many sites have been replaced because of a lack of recruitment. And separately, whether you can give an indication of the approximate proportion of currently open sites that have enrolled their first patients.