PCI Biotech Holding ASA

Yes, good morning, and welcome to PCI Biotech's Q4 2022 presentation. My name is Ronny Skugedal, and with me today are Anders Haugset, CSO, and Morten Lur, BD Manager. There will be questions and answers at the end of the presentation, and it will be possible to call in questions. If you want that, I have information about that here. It will also be possible to send in questions in writing via the webcast console. Please take a look at our Important Notice and Disclaimer. Let's go straight to the highlights for Q4. within FIMANAC with our project within dermatology and bioprocess. Within dermatology, the first step in our preclinical development of the platform is an external study where we want to demonstrate the delivery of nucleic acid in a skin model. This study has a reading in the course of the first half of 2023, as previously reported. The purpose of this study is that positive results from it will give us a basis or be a trigger for further collaboration and further development. Within Bioprosess, this project has also had a good development through Q4. We have failed the first patent for Bioprosess, and we have received positive initial external feedback on our application. This motivates us for further internal development of the project. Both to strengthen our position and for potential testers of a prototype, and to strengthen our IP. Both of these programs, Morten and Anders will come back to during the operational review. Inside Fimavac, our intratumoral immunotherapy, where we want to combine Fimavac with different immunotherapy combinations. Here we plan to file a new patent in Q1 about an undisclosed treatment combination. This program is also supported by the Research Council through a PhD candidate. So, corporate, with 57 million in the bank, we now have a financial runway towards the end of 2024. Release is considered to be almost finished. Less than 1 million kroner in expenses in 2023 is expected, and the down payment process is terminated, and the last The statement in that connection to the company will also be in Q1 2023. That was the highlights, very short. Then we will move on to the operational review, and I will give the floor to Anders Haugset first.

Good morning. I'm going to talk a little first about what we do within dermatology, and come back later also when it comes to intramural immunotherapy. When it comes to our activities within dermatology, the goal here is to develop a platform technology to deliver nucleic acids to the skin. There are many skin diseases where there is a great need for better treatment, and where nucleic acid treatment... Okay. What I tried to say is that our goal within dermatology is to develop a platform technology for the delivery of nucleic acids to the skin. There are many skin diseases where there is a great need for medicine and where these can potentially be treated with nucleic acid therapies. For example, chronic wounds, inflammatory diseases and various types of hereditary diseases. What is common for many of these is that what is wrong is that the cells in the sick area have bad signals. They are not able to perform the processes they should, so for example in a wound, you often have inflammation reactions instead of wound healing. These are typical problems that can be solved with nucleic acid therapies, because nucleic acids can reprogram cells in such a way that they perform the steps they should have done instead of being in a bad state. And there are many different principles here that are in early development, both clinical and preclinical, when it comes to nucleic acid therapy, for example, of wounds. It is immediately a big problem for all of these to get the nucleic acids delivered to the lesion you want to treat. What people typically do is to inject. You can do many injections around a wound, for example, but this is quite heavy wind. And especially when it comes to large skin surfaces, it is difficult to get that type of delivery. So what we want to do is to make a much simpler solution for this. We want to make a topical formulation, which is a cream or gel, for example, which contains a photosensitizer and a nucleic acid molecule. This can then just be smeared on the area you want to treat, and then it is lighted afterwards. Very simple. You don't need any advanced equipment here. You can use handheld lamps, as shown in this picture, and that will work very well. But you can also make more advanced solutions, of course. But this is very easy to do, and light and creams are used today in the treatment of many skin diseases. The first step in Our attempts here are to demonstrate that we are able to deliver mRNA in a wound model. This will be carried out by a leading contract research firm, which is an expert in this area and has developed many products based on topical formulations. The experiments here are based on what we have done before. We have shown many times earlier that we are able to increase the delivery of mRNA to mouse skin, as shown on the left here. We get an increase of 80-30 times the delivery of mRNA to mouse skin by injection. Instead of injection, we want to transfer this to a topical formulation and do it on human skin. The model here is that you take skin from patients who have had our skin areas operated. This can be kept alive for up to 14 days after it has been removed. And you stretch it out into a chamber, as shown in the right here, and can make a wound in this skin. And then we apply photosensitizer and mRNA on this wound and light it, and measure if we get an effect, if we are able to increase mRNA delivery. If this is not the case, we would like to proceed with a more therapeutic model. This can be done both in the same type of model as I showed in the previous slide, but it can also be done in animals, for example in mice. The goal here is not only to deliver nucleic acid to a wound, but to induce an effect that affects the wound healing. And if you look at the pictures at the bottom here, this is typically what a model looks like. You follow how fast a wound grows again. If you look from the top to the bottom here, you can see that from day 4 to day 7, wounds that have been treated with a type of treatment will grow again, while controls do not grow again. So this is also very easy to do and very easy to use PCI on. We can do exactly the same as we are shown in the previous slide, just drip on a solution that contains a nucleic acid and Fimaborphine or butter on a cream and light afterwards. So this is what we plan to do within dermatology at the moment. Of course, we primarily want to do this together with a partner when we have achieved good results in the first study, but we also have the opportunity to do this alone. Okay, that was this part of the presentation.

Good morning. In our bioprocess program, we focus on the production of virus vectors that are used for gene therapy. A type of medicine that has great potential, but is limited by challenging and very expensive production methods. In short, these methods are used to use living cells as factories of gene therapy. Today's production methods must be better for making enough viruses to treat new diseases and larger patient groups. And the reason we think that FIMA NAC has its place in this area is that we have in vitro, small-scale data that indicates that we can solve certain bottle caps in the production of gene therapy. And our goal is to contribute to maximizing... Oh, I'm sorry, I forgot to switch slides. I can take it short and new with this slide forward. In our bio-process program, we focus on large-scale production of gene therapy, which is a type of medicine that has great potential, but is limited by challenging and very expensive production methods. This is about using living cells as factories of gene therapy. Today's production methods must therefore be better for making enough viruses to treat new diseases and larger patient groups. The reason why we think that FIMANAC has its place in this area is that we have small-scale data that indicates that we can solve flat throat in the production of gene therapy. Our goal is to help maximize the exchange rate from these productions. Research and development within the bioprocess takes place internally, where the focus is to create proof-of-principle data. This resulted in 2022 in a submitted patent for the use of Fimannac in a specific step in the production of gene therapy. We also started dialogue with potential partners and received positive feedback on our application. We also see an interest in early prototype testing, i.e. alpha testing, given that certain in vitro data can be generated. Prototype testing at an early stage, i.e. alpha testing, is extremely important to get feedback from experts and potential customers on how the product works in their hands, This means that you can make adjustments at an early stage, and in the long term ensure that you develop something that works and that there is a need for in the market. Our focus in the future is therefore to further develop our application to enable prototype testing with external partners. Thank you, then I give the floor back to Anders.

Yes, then I will briefly talk about what we do within intratumoral immunotherapy. Intratumoral treatment is very well suited for PCI technologies, because we can inject photosensitizers and active substances into a tumor and light it locally. The point with intratumoral immunotherapy is what has been called treat locally, act globally. This means that you can give a treatment and induce an immune response in this tumor, which then afterwards, the immune cells that are induced will wander around in the body and also attack tumors that have not been treated, so that you can use a tumor in a way like your own vaccine and get an effect that can make a patient in principle healthy if this works as you want. As most people want to know, immunotherapy has in recent years revolutionized cancer treatment in many areas. But it is still the case that most patients respond poorly to immunotherapy, and there is a great need to make it work better. And what a lot of people are doing is developing new combination therapies, where you combine immunotherapy with other things, such as cells, immune-stimulating substances, and so on. The problem here is that if you inject all these different components in the same patient, the side effects will often increase drastically, so there is a strong limitation on what you can do if you are to use this in a normal way, that is, inject it into the bloodstream. This is completely different if you can do the treatment in tumors, because then you just give a low dose that works locally, and then you use this to induce an immune response that will have an effect on the entire patient. If you look at the curve, This slide shows that this treatment principle works with PCI. We have had mice where we have two tumors, one that we give a PCI treatment or a PCI vaccination in, and another that does not get treatment. And if you look at the red curves here, we see that both these tumors, both the treated and the untreated, had a very strong effect on tumor growth compared to the controls that go right in the opposite direction. So this principle works with vaccination, and what we have done now is also to try it out with other types of immunotherapy than vaccines. We try different principles here, also to identify what works best together with PCI. But here I have shown an example of an immunotherapy that is in clinical development, where we have given this immunotherapy together with PCI in in tumors. If you look at these curves, you can see that we have a fantastic effect of the PCI treatment in this case. The black curves here are untreated. The green ones are those who get immunotherapy without PCI, have no effect. While if we give PCI in combination with immunotherapy, we see that the tumor growth disappears completely, and that in this case 75% of the animals survived at the end of the experiment, while no one survived in the control groups. We are looking for patents. send a patent application for this, and we also develop this principle further, among other things with the help of a P&D approval from the Research Council. So this is an area that is very promising, we think. There are many types of this type of immunotherapy that are in clinical development, and it is a principle that has been recognized by many and more and more as a possible further development of cancer immunotherapy.

Thank you. Thank you, Anders and Morten. A little bit about finance. I mentioned it at the beginning that we have a cash position that takes us to the end of 2024. This gives the company a space to generate data that can take us new steps towards a possible commercialization of the technology. More details about the figures, apart from the fact that we have about 57 million kroner in the bank, are not covered today. Some thoughts on the future. We continue our pre-clinical development of the platform with a collaboration development-focused strategy. We work within dermatology, intratumorology, immunotherapy and bioprocess. For the first half of 2023, we have listed some milestones that can lay the foundation for our collaborative development plan. We will have a readout for our topical delivery in dermatology. We will further develop our bioprocess program internally. We will file a patent for intratumoral immunotherapy, and we will also file a patent for a reformulated approach for the fight against laksalus. Det var egentlig det vi hadde lyst å presentere for dere i dag. Så da hadde vi tenkt å åpne opp for spørsmål, og vi starter med noen eventuelle spørsmål via telefon. So please, moderator, you can open the lines now for questions.

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