Welcome to Targovax and the presentation of our fourth quarter results for 2022. My name is Erik Digman Wiklund, and I'm the CEO at Targovax. During 2022, we have made important progress on all of our R&D programs, and this sets us up for success in 2023. For the ONCOS-102 program, our lead clinical asset, we published promising phase 1 results in prestigious journals and scientific conferences. Based on these strong data, we're now preparing to set up a phase 2 trial to demonstrate and validate these data in a larger setting. This trial is called SOPHOS-213. Preparations are going forward according to plan, and we're planning to open up prestigious cancer centers in the USA and Europe later this year for enrollment of patients. Second, circular RNA. We've established a new cutting-edge circular RNA program from scratch.
We've hired the discoverer of circular RNA, Dr. Thomas B. Hansen . He is running this program for us. In just 12 months, we've achieved technical proof of concept for our vector delivery system. In addition, we have filed critical IP applications to carve out territory for Targovax in this space. Moreover, TG01 our KRAS cancer vaccine. Here we've enhanced the product format and we're bringing it back into the clinic in a creative way, where we use collaborative setups and external sources of funding in order to bring the program forward at low cost to Targovax. 2 externally sponsored trials are set to open, or are open and will soon enroll patients. In order to execute on these programs, we are relying on having external partners.
On the business development side, we've forged a strategic relationship with Aduro, who are supplying checkpoint inhibitors to several of our trials, both on ONCOS-102 and the TG vaccine. In addition, they're supplying us with a next-generation adjuvant QS-21 to boost immunogenicity of TG01. In order to run this internally, we've retooled the organization. We've hired key people in finance and in business development. Importantly, we built a new scientific team at the Karolinska Institutet in Stockholm, where we're running our circular RNA program. We're set up well. We're going to deliver in 2023. In order to achieve that, we need the finances in order. Let me hand over to Lubor Gaal, CFO, to give you an update on this front.
Thanks, Erik. I have the pleasure to present the fourth quarter results, as well as talking about the convertible bond financing with Atlas that we announced earlier this morning. Let me first talk to you about the fourth quarter results. Our spending in the fourth quarter reflects our strategy to support all our research areas, which Erik just explained, to advance efficiently to the next value inflection point. The investment reflects the initiation of the phase 2 study for ONCOS-102. It reflects the two clinical studies for TG01, one in Oslo and one in the USA. Of course, it reflects our investment into circular RNA platform that will be the engine of growth for Targovax going forward.
Overall, we spent NOK 30 million in the fourth quarter, which brings our cash balance to NOK 60 million at the end of fourth quarter. On the right-hand side, you can see our cap table. You can see that we spent NOK 30 million in the fourth quarter, bringing the balance to NOK 60 million. Our market cap remains around NOK 200 million, and our daily trading volume shows a healthy interest in the Targovax shares. Now let me switch the story and talk about the convertible bond financing from Atlas that we announced earlier this morning. Before I talk about the bond, let me explain a little bit the backdrop of the financing. 2022 was a tough year to raise money for public biotech companies, not just in Norway, but globally.
2022 showed drop about 70% in investments into global biotech companies. In Norway, that drop was 80%. As you can see, there were only 2 public biotech transaction in Norway in 2022. This reflects the lowest investment in Norwegian biotech companies for 5 years. Against this challenging backdrop, we were able to secure NOK 300 million financing from Atlas Capital Markets. Let me really give you a high-level overview of this convertible bond. The total amount, as we said, is up to NOK 300 million. We can call it in different tranches and over a period of 36 months. These tranches will be available to us every 3 months. What is really important that Targovax remains in control when and if we call those tranches.
We will call these tranches very carefully only when we actually need the resources to advance our research programs going forward. Why did we choose Atlas Capital Markets? Atlas Capital Markets is an experienced international investor that provides growth capital to biotech companies like Targovax. They invest globally, but with a focus in Europe. Atlas typically invest in companies which shows high potential for growth, and Atlas was specifically attracted to our strategy of supporting late-stage assets like ONCOS-102, but also investing heavily into novel platforms like circular RNA, which will be the platform for growth for Targovax. Atlas sees great growth potential in Targovax and wants to support us and give us the necessary resources to advance our research programs to the next value inflection point.
Now let me go back to the convertible bond and explain you a little bit more about how this will work. When we decide that we need more resources, we will call a tranche from Atlas Capital Markets. Atlas will then send us the cash, and it will be 90% of the nominal value that we call in that tranche. Once received the cash, we will issue a convertible bond to Atlas Capital Markets. Atlas will hold these convertible bonds until they decide that they want to convert them into shares. That can be at any day after the convertible bonds up to the 36 months in 2026.
Once they send a request to us that they want to convert the bond into shares, we'll issue a stock market notice to inform all our shareholders, how much they want to convert, what will be the price of the conversion, how many shares will we issue in response of that. There will be full transparency to you, our shareholders, and we'll keep you informed about the developments of this convertible bond. Of course, and then we can do this every three months, but as I said, we'll be very careful when to draw these convertible bonds, and we will only draw money when we need it to advance our research programs. Of course, this agreement is subject to your approval, our shareholders.
A EGM notice will go out shortly, and we expect that the EGM will happen in early March, where this EGM notice of course has much more details about these convertible bonds, but I'm happy to take any questions in our Q&A session to explain these convertible bonds in more details. With that, I hand back to our CEO, Erik.
With this financing, we now have access to the necessary capital to advance all our 3 R&D programs. Starting off, ONCOS-102, our lead clinical stage asset. We are setting up a phase 2 trial in melanoma, and this we're calling SOPHOS-213. To remind you, in phase 1, we demonstrated strong response rates. 35% is the best published response rate in this late stage patient population. It compares favorably to other companies that have published data in the same indication, and this gives us confidence to move the program forward. The plan now is to run a larger phase 2 trial to validate this data and combine with both CTLA-4 and PD-1 checkpoint inhibition, which we believe can boost the response rate even further.
With this, we've partnered with Aduro, who will supply their next generation checkpoint inhibitors. The trial is planned to be set up at prestigious cancer centers in the USA and in Europe in second quarter of this year. Let me explain how the trial works. It's a two-part trial. In the first part, we're going to try and increase dose of ONCOS-102. In the phase 1, we didn't see any safety signals. We saw an association between level of virus and the response rate. We believe by increasing the dose, we may also enhance the efficacy. We try the higher dose in the first part. Once that is confirmed to be safe, we plan to bring the high dose forward into part 2. What we're doing is, number 1, we combine with a PD-1 checkpoint inhibitor.
Number two, we combine with botensilimab, a second generation CTLA-4 from Aduro. It's really the third step, this cohort number four. This is the key. Here we wanna do the triple combination of ONCOS-102, PD-1, and CTLA-4. This triple we think has the potential to really boost the response rate up and beyond the 35% and establish ONCOS-102 as a class leader in PD-1 resistant melanoma. This study is designed to deal with several important aspects. Number one, we have been in dialogue with the regulatory authorities. We're answering here important regulatory questions to set the program up for subsequent registrational trials. We're doing our homework from a regulatory perspective. Secondly, we want to be able to out-license ONCOS-102 based on data from this trial.
We designed the trial with a size and combinations that make it attractive to potential partners in the future. We are convinced that both strategically and scientifically, this triple combination with the unique CTLA-4, second generation CTLA-4, has the potential to really generate class leading data and make us the leader in PD-1 resistant melanoma. That's the plan for ONCOS-102. SOPHOS-213 is the study. It will open later this year. On circular RNA, this is an emerging area of strong interest and growing interest in the pharmaceutical industry. The first mRNA product was approved only 2.5 years ago. Here on this graph we show you the sales for the top-selling drugs in 2022, and you can see 2 of the top 4 drugs actually are mRNA products.
They sold for more than $50 billion last year. Now, this is a special situation with the COVID vaccines, but it does show the therapeutic potential and the commercial value of these products and how they can be leveraged as, as drugs in the future. mRNA faces several issues. mRNA is unstable, it's immunogenic, it's difficult to deliver, and it's difficult to use as the therapeutic payload for solid tumors. We believe that circular RNA can solve many of these issues that are facing mRNA. Circular RNA was actually discovered by Targovax scientists, myself and the head of research at Targovax, Thomas Hansen, and we published the first paper on circular RNA back in 2011.
This discovery has now led to several companies setting up in the USA based on the discovery, which has now been advanced to a stage where you can use circular RNA as novel messenger RNAs that are more stable. This is also evidenced by a recent deal by Merck, who partnered with Orna Therapeutics in the USA for very significant financials for an early-stage preclinical program. Building on the circular RNA discovery, preclinical stage US biotechs have been able to attract very significant funding. We give you two examples here of Orna and Laronde. These are the two most famous circular RNA companies, and you can see they have raised several hundred million dollars in early stage round to build this platform into future potential therapeutics. What they are doing is synthetic circular RNA. They're effectively doing mRNA, just using circular RNA as the modality.
It's a synthetic circular RNA, and it's geared towards vaccines and gene therapy. That's the approach they are taking. At Targovax, we have a different angle to circular RNA. We have developed a vector system, which we call circAde. circVEC is a DNA-based system that we use to express the circular RNA. Our product is not the circular RNA itself, but the recipe for the cell or in the patient to make that circular RNA. This setup we can use to create multifunctional products that are highly versatile and have excellent stability. We have already established technical proof of concept, and we've filed critical patent applications to protect our technology. Using a vector system offers several advantages over traditional synthetic RNA approaches. Here we compare versus synthetic circRNA and synthetic mRNA on the table.
There are many aspects to discuss here, but I'd like to highlight two specific points. One, we have a delivery route to solid tumors. Currently, there are no other effective ways to get RNA-carrying therapeutic payloads into tumors. We already have a clinically validated system based on our clinical experience for how to do this, and we know we can do it, and we know how it performs over time. We're building on this to develop a solid tumor approach for circular RNA, which is unique as far as we know. Secondly, we're relying on manufacturing technology which is commercially available, robustly known, and we already have established, we already have clinical manufacturing ongoing. For circular RNA, manufacturing does not yet exist. This is a new therapeutic concept, no one's ever produced this at scale.
This will take time and resources to achieve. We believe this gives us a head start. Our aim is to be the first company into the clinic with a circular RNA therapeutic product in solid tumors. We have to aim to achieve that already in 2025, which would be a remarkable feat given we only started this program one year ago. To sum up, we're now set up for success in 2023. ONCOS-102 is ready to enter clinical phase 2 trial in combination with the PD-1 and CTLA-4. Second, our circular RNA program, here we're starting important in vivo work to validate our findings in the model system.
We believe with this data in hand and a robust IP portfolio, we should be able to start having business development discussions which could enable early partnering as soon as last quarter of this year or in 2024. On the KRAS program, 2 trials are open. They are ready to recruit patients. We expect this to get going very soon, and these are trials that are run with academic collaborators at low cost to Targovax, creating broad optionality for the future for the KRAS program. With that, I wrap up the formal part of our presentation, and we are happy to take questions from the audience, and I welcome Lubor back to join me on stage.
Thank you.
We got some questions on the, from the web. Congratulations on the financing. Just wondering why did you choose Atlas?
Very good question. We of course evaluated many different opportunities and options and we, through negotiations and we received many offers from interested parties. We compared those offers very carefully, the combination of the features that Atlas offered to us made them the preferred scenario. Of course, we also appreciate the background that Atlas has, an experienced investor supporting small biotech companies who have a large opportunity for growth and taking a long-term view and then of course offering us a large amount to advance all our research programs. It was a combination of many different factors and that made Atlas the most attractive option for us.
Yeah, just to reiterate that this is a specialist investor. This is what they do, these type of financing. They do a lot of them for biotech, we believe these were clearly the best terms we found out there.
Do you know if Atlas is going to be a long-term investor in the company, or are they going to sell their converted shares in the market when they are converted?
I would say both. I mean, clearly they provide this capital resources for us for the next three years, that makes them of course a long-term investor that will support our growth on the long term, and they see growth potential. They wouldn't have offered us such a long facility if they didn't believe in us long term. Clearly, they, once they've convert the convertible bond and they can hold convertible bonds for the entire 36 months period, once they will convert the bonds, they will then decide to trade those shares in a short period of time.
What is the restrictions for Atlas when it comes to selling Targovax shares in the market?
That was a very important point. I mean, first of all, of course, it was very important for us to stay in control of this convertible bond. Again, it's only we can call the bond, so we are in full control. The Atlas cannot force us to take any tranches or any convertible bonds, so we'll only draw from them when we need it. When they have the convertible bond fund turned into shares, they will trade very carefully not to impact our share price. They agreed to a limitation of 25% of the weekly trading volume, which I thought it was a very fair amount. Otherwise, there are no other really restrictions.
Thank you. We have a question on melanoma. What is the progress in melanoma phase 2 trial, the SOPHOS trial?
We are currently in discussions with the prestigious cancer centers, both in the US, USA and Europe. We are preparing to open the trial. It will probably be in the second quarter of this year. There are quite long bottlenecks, both regulatory-wise and at and at sites, post-COVID. It does take a while to get through the bureaucratic mill, to get things set up and ready for enrollment. We do anticipate that first patient should be dosed in the second quarter of this year.
There are a couple of questions on circular RNA. What is the potential value of circular RNA, and what kind of strategic options are you looking for in circular RNA?
Circular RNA is emerging as a new RNA therapeutic class of very high interest. It's difficult at this stage to put a number on what the value is. You can look at, for instance, a deal done by Merck. They were willing to invest $150 million upfront, plus $100 million of investment in RNA therapeutics to partner on the program, which really is very early stage. It's preclinical with some in vivo data. If you use that as a benchmark, I think that illustrates the potential of this modality. Now, we are still quite early in our process. We only worked on this for one year, but we're making important progress.
Our aim is to, of course, capitalize on this as we move forward and get partners to enable us to develop more broadly and show the platform potential of what we're trying to achieve.
Yeah, I think I would add that, you know, like, considering that the advantages that circular RNA offers over messenger RNA, you can see the big investment into the messenger RNA field, how many programs are in development. Circular RNA is supposed to be better than plain linear RNA. The potential is huge, but Erik is right, we can't put a number at this point in time.
To the strategic options question, when we talk to both investors and partners, we get a lot of interest for this, for the circular RNA program. This kind of early stage platform development attracts a different type of investor who are interested, who don't necessarily buy into listed shares. We are trying to structure ourselves and establish opportunities that enables us to tap into that source of capital as well.
In addition, of course, we are in discussions with pharma companies and other companies who are interested in circular RNA, and we're exploring, of course, with them how we could collaborate in the future on our platform and exploring different avenues for collaboration. There is interest also, of course, from the industry in working with us, but it will take some time to make that work.
Thank you. There are no further questions.
Thank you very much. With that, we wrap up our 4Q presentation, and don't hesitate to contact us if you have questions. Thank you.