PCI Biotech Holding ASA

Good morning, and welcome to PCI Biotech, first quarter 2022 presentation. My name is Per Valdai, I'm the CEO of PCI Biotech, and I have with me today also Ronis Kugudal, who is the CFO, and Amir Snapir, who is the CMO. After the presentation, we will have a Q&A session, which will be through both the teleconference and the webcast console. So please pay attention to the details here. If you want to ask a question, you need to call in and do this if you want to do it verbally. Otherwise, please use the webcast. Also, please pay attention to this important notice and disclaimer. So what we are going to review today, first to start with the highlights of the first quarter 22, and then an operational review, the clinical and preclinical programs, and then ending it with key financials and outlook before we have the question and answer session afterwards. So let me start by going through the highlights. So FIMAVAC is our lead program now, and this is progressing towards initiation of a phase two clinical proof of concept study. This study has a very good project readiness. We have established a group of international clinical experts that have helped us in designing the study and will provide clinical guidance and support the development and performance of the trial going forward. We are working on the preparation of a clinical trial application and also sourcing of all the study treatments. And the selection of clinical sites in the main countries in EU has started. We will come back to much more details about this and specifically Amir will go through a lot of the details around this study in the presentation later. With regard to FEMA-NUC, we are progressing a focused preclinical development plan. We are targeting this specific application, which is delivery of nucleic acid therapeutics into cells, to applications that are suited to the specific strengths of this PCI technology. We have in the first quarter also established a preclinical collaboration with the South Korean company MD Immune, who are developing innovative drug delivery technologies for modifying cellular and disease processes. And we'll come back to this program also with some further details. As you know, in the first quarter, we had to close Release, our lead program. It was closed to recruitment in January 22 due to changes in the competitive situation with results that was announced at the ESCO GI meeting in January. And the new information that came out at ASCO GI will render this trial challenging to complete and potentially also inadequate for approval. And so we had no other choice than to stop the trial. And now we have collected all the data and reviewed the data. And there is not sufficient data here to show differences between the different treatment arms. And therefore, we are now terminating the whole study as quickly as possible. And we are not going to follow up patients any further. And the last patient will leave the study in this month. Now, closing release as quickly as possible also means that we will not spend much more money on this, and we expect the future cash effect of up to 10 million NOC to close the study. On the corporate side, I will step down as CEO at the end of this month, and Ronny Sugardahl will take over as interim CEO effective 1st of June. The CBO, Ludovic Robin, will leave the company in May also this month. And the whole organization after release was closed for recruitment has been reduced by four full-time equivalents. And we have noticed periods of all of those ending during second quarter. This means that the financial runway with current commitment is now estimated to be towards the end of 2023. We have also, and I'm happy to announce that we have strengthened the scientific advisory committee. We have now included Professor Ernst Wagner at the Ludwig Maximilians Universität in Munich, and the Center of Nanoscience in Munich, which has had a long history long experience in delivery of nucleic acid therapeutics, and he also has some experience in working with the PCI technology. So he's a luminary in this area, and it will be important for us and for the progress of the FIMANAC program to have him in the scientific advisory committee. I would also like to thank Kjetil Taskeen who will leave the Scientific Advisory Committee. He has been with the company both as the Board of Directors and the Scientific Advisory Committee after that for a number of years and has contributed significantly to what we have achieved in BCI Biotech. And then just an overview of where we are now then. So we have two development programs that are based on the PCI technology platform. We call these Femavac, which is a vaccination technology for therapeutic cancer vaccines, and Femanac, which is a delivery technology for nucleic acid therapeutics, drugs that needs to get into cells to be effective, but have a real barrier of actually getting into cells. So PrimaVac is a clinical stage program. We have completed a healthy volunteer study, a phase one study, and we are now moving towards a clinical phase two study, a proof of concept study for this specific program. While FIMANAC is a preclinical program where we have established a number of collaborations and more of a collaborative program, although we now also have quite some internal research and development at the preclinical stage to target specific applications. So with this, we are going into, those were the highlights. So with this, now we are going into the operational review. And I will hand over to Amir, who will lead the presentation on PimaChem and PimaVac, the clinical parts. Amir.

Thank you, Paul. Next, please. There is not much to add on what Per mentioned earlier in the highlights about release. The clinical team is working hard to close the release as effective as possible to reduce costs and to complete the transfer of the focus to the planned FIMAVAC proof of concept study. All these facts that are listed here have been mentioned. So shifting to FIMAVAC program, I want to start with a recap of the science. behind the technology before talking about the planned proof-of-concept study in more details. The planned Femavac proof-of-concept study is based on the demonstrated capability of the technology to enhance the cytotoxic effect of the immune system, which is essential for effectiveness of therapeutic cancer vaccines. CD8 cells, called also cytotoxic T cells, are the preferred immune cells for targeting cancer, and they require MHC class 1 antigen presentation to be induced, which is the major hurdle in cancer vaccination. TimoVac platform overcomes this challenge by strongly enhancing MHC class 1 antigen presentation activating and inducing infiltration of cytotoxic T cells in tumors, leading to tumor cell killing. Following intradermal injection of the PCI vaccine, which is now depicted as one, step one, femoporphine and vaccine antigens are taken by antigen-presenting cells and co-localized to endosomes and lysosomes. With light activation of femoporphine, it triggers permeabilization of the endosomal and lysosomal membranes, releasing vaccine antigens into the cell cytosol, which is a critical step because the next step of enhanced success to antigens result in increased MHC class 1 antigen presentation, a critical step in the therapeutic vaccination of cancer. If you go next, please. The antigen-presenting cells then carry the vaccine antigen and migrate to lymph nodes, where they activate cytotoxic T cells, which then migrate to the tumor and infiltrate it. This is now depicted by five, six, seven, and eight steps. The activated cytotoxic T cells are able to recognize and attack the tumor cells. Next, please. The effectiveness of the PCI vaccination principle has been demonstrated in preclinical models. Here we show one where we use HPV tumor model with TC1 cells that are rapidly growing tumor cells. In this study, TC1 cells were inoculated an animal where they're either not treated or treated with femoporphine and HPV peptide antigens with the addition of poly-IC adjuvant. This was done on day 8, 13, and 22 after the tumor was established. The tumor in the untreated animal kept growing as seen here very quickly. and the experiment had to be stopped before day 30. In the animal treated with the PCI vaccination, which you see on the right, the vaccine adjuvant and the treatment with PCI vaccination, the tumor did not grow, and the animals finally became tumor-free, as seen by the zero volume of the tumor cells. Moreover, the animal became immune to re-challenge with these tumor cells, meaning that the immune system has developed a way to recognize these cancer cells and kill them before they establish a tumor. Next, please. The FEMAVAC technology was further investigated then in humans. in a phase one study where healthy subjects were given PCI vaccination. Subjects who received femoporphine in a dose of 12.5 microgram or higher had a significantly higher rate of immune response. The femoporphine dose of 12.5 microgram given intradermally with the vaccine components, which were the antigen and the adjuvant, They showed a good safety profile and was very well tolerated. The dose of Femaporphine was identified as a recommended phase two dose. The dose of 12.5 microgram was recommended as phase two dose. And this is the dose that we take forward to our proof of concept study. Recognizing the power of the Femavac platform to increase immune response, preliminary by enhancing cytotoxic T cell activation, we believe that PCI vaccination can improve the effectiveness of the immune system to fight tumor. If you go to next slide, please. And the basic idea is that immune checkpoint inhibitor are effective treating for tumor. But it means tumors that the immune system can see in a way. But unfortunately, most patients have tumors that are hidden or partially hidden from the immune system, so-called cold tumors. And these are then characterized by few T cells and lower infiltration of T cells into the tumor, immune suppressive cell present in the tumor, and poor response to immune checkpoint inhibitors. We believe that PCI vaccination is going to significantly increase cytotoxic T cells activation and infiltration into tumor. And by combining the vaccine with additional immunomodulation that aims to reduce suppressive immune cells and inhibit immune checkpoint, we can achieve a significantly better response treatment. Next, please. When we initiated the plans for the proof of concept study, we evaluated the building blocks of success of the FEMAVAC platform scientifically, clinically, and commercially. We recognized that a big challenge with the dominating immunotherapy market, many patients have limited response to checkpoint inhibitor. We recognize that this is an attractive opportunity space to leverage the FEMAVAC platform. We talked about the capability of FEMAVAC to sensitize what we believe is the capability to sensitize non-responding tumor to checkpoint inhibitors. We evaluated which indication, we evaluated several indications, and we looked for a high unmet medical need, commercial opportunity, and scientific rationale for studying this specific indication. We reviewed and evaluated different trial designs that can maximize the cost benefit from expensive clinical trials, and we engaged early in the process a top-level group of key opinion leaders to evaluate with us the plans, the clinical plans. We wanted that we develop a treatment concept that can be taken forward and is more ready not just to demonstrate proof of mechanism, but go and show clinical efficacy. And we wanted also that there is a way to expand the value that the platform can grow from this initial proof of concept study. Next, please. Following thorough evaluation of several different cancer indication, we consider that recurrent or metastatic head and neck squamous cell carcinoma is the best entry indication for evaluating the effectiveness and safety of the PCI vaccination. The reason is that the treatment with checkpoint immune checkpoint inhibitor is established and most patient would get this treatment. However, many patient are not going to respond to this treatment. It depends on the history of treatment and the, what are the treatment, what they are combined with, and what the stage of the disease, but it is about 60 to 70% of patients that receive these anti-PD-1 inhibitors, sorry, anti-PD-1 therapy, they will progress within six months. So there is high unmet medical need to convert these patients that progress and resensitize them for checkpoint inhibitors. The design, we ended up with a design that is optimized to explore efficacy of the PCI vaccination that is combined with immunomodulation in this target population. And we believe that we ended up with a study that is most cost-effective for the purpose or for the aim of the development. Next, please. The treatment in the study, this has been following much discussion. We plan to combine the PCI vaccine with an adjuvant like we have done in the past, in past studies. But this time, we want to add additional treatment that can take the response to a higher level, to maximize the response. The PCI treatments in this study are planned to include the PCI-V01, which is the PCI vaccine, which has femoporphine and a mix of peptide antigens that are relevant. These antigens are tumor-associated antigen presented on cancer cell surface. We are going to include in it also a CD4 helper T-cell stimulator peptide and a To this vaccine, we are going to add a vaccine adjuvant, Hiltonol, which is poly-IC. We have much data generated in combination with Hiltonol showing strong synergism between the two. To these two treatments, we are going to add immune checkpoint inhibitor, and this is to modulate the system helping the T cells attacking cancer cells. On top of this, at the beginning of the treatment, we plan to add additional immunomodulator. It is planned to be a specific chemotherapy to decrease immunosuppressive cells to enhance immunotherapy efficacy during the initial treatment cycle. So this is not going to be the treatment throughout the treatment period, but only through the priming period, when we initiate the immune response to the cancer box to the vaccine to the study vaccine. Next, please. This is just to bring all together what we plan to do. So the patient population are recurrent or metastatic head and neck squamous cell carcinoma patients progressing on pembrolizumab or nivolumab within six months of treatment. This is called primary progression. And this suggests that the patient have One of the reasons they progress, or in many of the patients, is that the tumor is just not seen by the immune system. So we consider that primary progression is a better starting point for the PCI vaccine. This patient can have history of pembrolizumab or nivolumab as monotherapy or with chemotherapy. And we also chose to have the HPV negative type of tumors. And the reason behind it is that there is greater unmet need and also for the HPV positive type of tumors, there are already several treatments in late stage development. And we believe that it's a much more difficult indication to get into at this point. We plan to study up to 20 patients and the treatment like was described in the previous slide, because there are some combination of treatment, we had to design the schedule in a way that we maximize the effect and we minimize the potential negative interaction, for example, with regard to safety or use of corticosteroids that are associated with other treatments that can potentially affect the vaccination, the effect of vaccination. So this has been carefully considered and designed, and we aim to follow on radiographic progression immune response in tissue and in blood, and of course, on safety. This is open study, and data are going to be accumulated as more and more patients are treated, and we will have, of course, a way to look into the safety and efficacy and immune response data, and we are able to discuss these internally and externally. Um, this is, uh, internal, uh, sorry, international multicenter study planned in eight to 12 clinical sites. We need to assess, uh, recruitment rate in, uh, different sites. And based on this, another factor select these sites. And after this, we will know better how many sites are going to be involved in the study. We are very happy with the core clinical investigators and external experts that we engaged into this program. They endorsed the study. They were actively involved in the planning. And they are going, some of them, are going to be also investigators in the study, which helps in the engagement of the investigators. And we hope that this is translated into better recruitment and better execution overall of the study because they've been part of planning the protocol. So there is a better streamline between the clinical sites and the protocol. And we plan to start the study in 2023. Next, please. So this is now where we are in the project readiness. So ongoing activities focusing on preparation of the clinical trial application. This is a big job involving several major documents that is under work currently. We are working on the CMC aspect. This is a study with several treatments, so there are much considerations and efforts need to be done to source the study treatments and first to manufacture and then sourcing the rest. And the study operations in a way started when we look or we evaluate clinical CROs to be involved in the study and starting to plan for the start of the study. Like I said, we are very happy with a group of international experts that were engaged in this program, and they are truly engaged and very responsive. We had very good meetings to evaluate the outline of the study and we are in very good progress working with them. And selection of sites, clinical sites for the study started in Europe, in Europe, major countries or bigger countries. Next, please. To summarize this proof of concept studies, is a focused opportunity that is scientifically solid, the plant study design, the treatment endorsed by top expert, and is well positioned to drive value, we believe. Solid foundation and scientific rationale, we have preclinical and clinical data supporting the anti-tumor activity in animal models and increase immune response in humans. Broad IP portfolio, covers protection of the vaccine technology in combination with immune checkpoint inhibitors for years. Entry indication has high unmet medical need and is perceived to have high likelihood of response to treatment. And again, a dedicated group of top-level clinical experts has been engaged, which we consider one of the biggest advantages where we are to the success of the study. Next, please. We plan to submit the clinical trial application in Q4 this year and enroll the first patient in Q1 2023, with top-line results available in first half of 2024. We are actively seeking partnership for the program, and as data accumulate in the study, good results are going to support this process. And I think that with this, Roni, I completed the cover of FIMAVAC program. Thank you so much, Amir.

Then I will take over and move into the FIMARvac. Before I do that, I would like to just say that the groundwork that Amir and the clinical team has done on this FIMARvac is really outstanding, really, really good work, laid a very good foundation to move this FIMARvac technology into a solid clinical proof of concept study. show hopefully the value in the clinical setting of this technology. So thank you, Amir. And then Femanac. For FIMANAC, we have a technology where we help nucleic acid therapeutics getting into cells because that is a real barrier. We have some really compelling preclinical results with strong data from oligonucleotides, smaller nucleotides to large molecules like mRNA. As I said, we are addressing what is considered a major hurdle for this class of drugs. to get sufficient of the amount of the nucleic acid therapeutics into cells for them to give the therapeutic advantage they are meant to give. And we are now focusing the development with targeting applications that are suited to the strength of the platform. And the strategy is then to build partnership in key areas. But we are still opportunistic and open with this. So whenever there is interest from the outside in our technology, we are open to collaborate to see whether there is any synergies that can be found. further development that can come out of those kind of collaborations. We have most recently now in Q1 2022 established a collaboration with MD Immune, which is a South Korean biotech company, who are developing other types of innovative drug delivery technologies that potentially can be combined with PCI to really produce good synergy and even better effects. We have determined now that the area we want to put focus on is dermatology. There's an excellent technological fit with dermatological diseases. We have seen substantial enhancement of intracellular nucleic acid delivery in skin with the studies that we have done preclinically. We also know that FEMA-NUC provides excellent spatial specificity of nucleotides, so it means that you don't have leakage to other areas, to off-target areas. You can actually restrict the entry to the specific area where you want this to happen. And we know that of course with dermatology it's easy illumination access and also it's possible to have topical applications and topical formulations done which means that you can use this without being very invasive at all. There's a large market and large opportunity space. A lot of companies developing nucleic acid therapeutics for dermatological applications. And we have currently also one collaboration in place with a company who is doing exactly this. This is another South Korean company called Olix. So this is a very good fit with the Femanac technology. So what we are then going to focus on is to develop a user-friendly and integrated and suitable application for dermatological diseases. And then the intent is we intend then to initiate the collaborative development of these integrated solutions, developing a topical formulation of Himalak and also a specific skin illumination device. And this can be applied across a number of different dermatology applications, which will expand the collaborative opportunity space within this focused area. So that is our plans for Firmanac going forward. We are still having a collaborative strategy on this, but we are focusing some internal work to more mature some specific applications to ready-to-use solutions in specific areas where we think it's best suited for our technology. And then we're done with the operational review, so we move over to corporate, key financials, and outlook before we go into the Q&A. And I will hand over to Jonny Skogedal to take over at this stage to do the rest of the presentation.

Thank you, Per. So then first corporate organizational changes. Clinical team reduced as a direct effect of the release trial. The CBO will leave in May and the CBO's main objective was to commercialize the FEMA CHEM program based on release. As Per mentioned earlier, he has decided to pursue new opportunities, and he will step down by the end of the month. And myself is appointed by the board as interim CEO effective 1st of June. The research and development team is fit for purpose now when release is put behind us soon and we will push hard for FEMA WAC. We have a highly skilled team with a diversified experience and they are highly motivated to achieve our objectives. And also, here is a list of conferences we are attending in the short term. LSX World Congress in London, a combined BD and investor conference, where we are in person as we speak. And the CSO Anders Hursk set is in Boston, in person at Tides, a FEMA NAC-focused event. where we also have a poster and we will have a virtual company presentation later in the month at ABG's Life Science Summit. Then key financial figures, with the changes we have now an estimated financial runway towards the end of next year. Release closure, estimated future cash effect of up to 10 million in cash for closure of the program and here I would like to give credit to the clinical team for all the hard efforts to make sure that we have a swift and cost-effective wind down of the study balancing our need or our wishes to gain results out of the study. But now since the follow-up of patients are to be ceased in May with the last patient leaving the study in May We are pushing hard and looking into even further efficiencies in the closure of the release trial, and hopefully we are able to reduce the cash effect as well. Organizational changes will impact in full from Q3, and preparations for the FEMA WAC study will continue while financing opportunities are being explored. Regarding the figures, public grants in the quarter slightly decreased from last year due to the BIA program ending in the summer 21. Net financial result fluctuates with exchange rate effects on bank deposits in euros. And we have a cash position of around 93 million at the end of the quarter. So Q1 cash flow has been on the same average level as 2021, and this is due to release being close to a normal operational month for Q1. And also remember that we had very good recruitment into the trial in Q4, also impacting the Q1 costs. And then Outlook. Of course, now FEMA-VAC is our lead program, so we are pushing hard to progress towards initiation of phase two, where we aim to convert cold tumors to hot, improve the response of ICIs, and thereby generate value. We have good project readiness, the clinical expert group, as Amir reviewed, and through this network we have been able to select or to recruit sites in major countries in Europe. So the objective now is to show the real value of our versatile vaccination technology. and generate partnering opportunities. For FEMA NAC, as Per reviewed, we are focusing on applications well suited for the PCI technology strengths. And we are starting with dermatology. And we are, of course, pursuing new collaborative opportunities and also work hard to convert the existing ones into more more into next steps. And for FEMA Chem, swift and cost effective closing, of course. And I can assure you that the team, clinical team and the whole company still push hard on this to put release behind us and minimize the costs. Then we are over to the Q&A session. And we can start with opening up for verbal questions. So monitor, please open up for any questions. Then we will start with some questions from the web. And here is a question for you, Amir. Can you elaborate a bit on the results seen from release? Is there not any differences between the treatment arms?

Yeah, I will answer this. So first, the first thing to see, to consider is the size of the data, the valuable data that we look at. We enrolled 41 patients and 34 patients have been treated. So we include 34 patients in the analysis. Not all of these patients provided radiographic progression data. They were included in the analysis, but the data set that actually provided information on progression-free survival and objective response rate is smaller than this. And this represents less than 20% of the patients what was planned, 20% of patient or events that were planned to provide power to assess different between the arms. Now, we did look whether there are some differences. So overall, in the two population, the effect was similar. But when we looked in the patient to receive, only in the patient to receive the PCI treatment, on average, there was a numerically greater effect in the biliary tract tumors that were exposed to illumination, meaning that because we allowed patients that to enroll into the study with lesions that are measurable, that we can measure radiographically, also the lesion could be in the liver, in the lungs, lymph nodes in the abdomen, everywhere. So what we looked at, we looked on those patients that had the lesion next to the bile duct that we treated and compared it to lesions in the same treatment arm that were further away, and there was numerically rather big difference between the effect on the lesion itself. So lesions that were exposed to illumination, all lesions were exposed to the same treatment because femoporphine and chemotherapy were given intravenously. But those that were exposed to the light, this is where femoporphine was activated. And these lesions that were exposed to light shrink more, numerically significantly more than other lesions. But this is a small look further into the data. And this is not something that we can in any way stand behind and build because the study was designed with effect between the arms on these endpoints. And this is only scientific interest whether the illumination shrink tumors more than without illumination. Hope this answered the question.

Thank you. And then we are over to FEMA WAC related questions. And here is one very specific one. What kind of chemotherapy are you planning to use?

So more information will be provided later. We are now finalizing. The last steps of putting the protocol together, and we are not going to give this information at this point, but it's going to be provided at earlier point. There are several considerations behind when we reveal what data, but at this point, we do not tell about the specific chemotherapy.

Okay, here is another one specific. What are the therapeutic peptides included in the PCI V01 vaccine?

So this falls under exactly the same response that I gave regarding the chemotherapy and the specific peptides, you know, like the sequence of the peptides is going to be revealed later from the same consideration. I can only say as we said in the presentation, that these are tumor antigens, and they are expressed commonly, very commonly, in head and neck cancer, in recurrent metastatic head and neck cancers, so that we expect these antigens to be relevant to all the patients that are enrolled into the study.

Thank you. And here is a question maybe for you Per. Will initiation of the new FEMA VAG study need to be proceeded by an equity issue or do you expect to initiate the start with the current funds?

So you do never initiate patient treatment in a clinical from ethical considerations until you have ensured that you have sufficient funds to actually complete the study. So we will not start treating patients until we know that we have funding to complete the study. But we can complete all the and do all the preparations towards initiation of the study at this stage.

Very good. And then it's more general question here. How is the Aterna collaboration going? And do you see any interests in the FIMA-VAC and or FIMA-NAC program?

Yes, I think we can clearly say that we see interest in both FIMANAK and FIMAVAK program, absolutely. And the ETHERNA collaboration is progressing. As these are confidential, the results that come out of this, we can't talk very specific about these collaborations and what we're doing in them, but it is progressing well and it is absolutely something that we are still focusing on. Specifically, intratumor treatment with the PCI technology, which is where we're collaborating with Etherna, is a very interesting area for PCI. Although it wasn't mentioned now specifically in this because we focused on the dermatology and the FIMAVAC opportunity for clinical for this quarterly presentation, it is still part of the focus of what we are doing preclinically in PCI.

Very good. Then maybe we can go back to the moderator to see if there are any questions from the telephone conference. Okay, then I think we have a covered all questions from the web and I will then take this opportunity to say thank you to Per for all your efforts for pci biotech over the years it's been a pleasure and good luck with your new for your new opportunities thank you and I would also like to say thank you to all the the hard work done by our PCI colleagues and also say good luck to those who are also seeking new opportunities outside of PCI biotech. And with that, I think we will say have a good day. Thank you.