Hello everybody and welcome to this webcast. It's the reason for us introducing two new biosimilar candidates to our portfolio and the initial development of these two products. My name is Martin. I'm the CEO of Xbrane Biopharma, and I have with me Siavash, our COO, and the head of our biosimilar program. We want to spend some time now to discuss our new portfolio. It will be a presentation of maybe 15, 20 minutes or so, and then we'll have a session of Q&A. Okay.
Just starting with a recap from our Capital Markets Day, which we held in May this year, there was quite some time to talk about the biosimilar market and with regards to attractiveness in the market, above all, the strong growth which is expected in this market coming years on the back of multiple large biological drugs losing their patent protection and being opened up for biosimilars. It's one of the fastest growing segments actually in the pharmaceutical market, and we believe it's a very good opportunity for us to tap into this market that opens up. We believe we are now well-positioned to address quite a few of these opportunities which comes up with regards to us having strong team in place.
54 employees now, and really having the competence required in-house to take programs from the start to regulatory approval. I think we are demonstrating that now with our lead program Xlucane, our Lucentis biosimilar. We have a strong platform technology, which we have spent quite some time to expand from E. coli to mammalian cells. We believe that this platform technology gives us an edge when it comes to yield in expression of proteins, which then is translated into competitive production cost. The new facility which we've established here in Solna with an expanded laboratory, with also the equipment required to conduct quite a few programs in parallel here.
We believe now we have kind of everything we need in place to accelerate the development of our portfolio. We put forward an ambition on the Capital Markets Day with regards to initiating at least one new biosimilar program per year and doing that in such a manner that we still shall be able to become cash flow positive towards the end of 2023 and beginning of 2024. On the back, of course, of expected income to be generated from our lead product, Xlucane, and also relying on a business model where we out-license or find commercialization partner at a rather early stage in these development programs, preferably in, let's say, late pre-clinical stage before we go into the clinic.
We can continue to do that, and I think we've demonstrated with our Xlucane program that we can do that. If we continue to do that with our upcoming programs, we believe we can reach a cash flow positive stage late 2023, beginning of 2024. That's our ambition and we stick with that ambition. We feel comfortable that we're going to be able to achieve it. This is just what I spoke a little bit about. I think we now have the platform in place with regards to technology, team and facility to accelerate the development of our portfolio. I think interesting on the platform technology side also is that we've been very active on the IP front.
We now have 9 approved patents and 13 pending patent applications. So it's not only that we have been active in expanding the platform and strengthening the platform, but also in protecting the platform from an IP perspective, which we're very, very pleased about. Okay. Then we spoke about target selection also at the Capital Markets Day, and that we have a good target selection process in place, which we have been working with for a couple of years, where we essentially look at the biological drugs which lose the patent protection in 7 years or so. That's just because we know it takes roughly 7 years for us to develop a biosimilar from start to regulatory approval.
It is important to be able to come to market roughly by the time of patent expiry of the originated product. That's kind of the first lens or first criteria that we put forward when we're selecting new targets to go for. Of course, technical feasibility. In a way, can we express this protein and can we get a competitive yield and thereby production cost on the back of our platform technology for this specific product? We know that our platform technology is better for some proteins than others. It's about assessing if we believe we shall have a meaningful competitive advantage when it comes to cost on one particular product. That's another lens or criteria we look at.
We like to work with products where there's a high unmet medical need due to high pricing and high costs of the drugs limiting the accessibility. We believe we can do something meaningful for the patient population in question in coming out with a biosimilar price at a lower level and then increasing accessibility. We want to work with products which have or at least are expected at peak to have above EUR 1 billion of annual sales. That's kind of the main criteria that we look at when we select products. Naturally speaking then, we are looking now at products with patent expiry between 2028 and 2030.
We've gone through the process in 2021, and we have now selected and decided to introduce biosimilar candidates to Darzalex and Keytruda in our portfolio. We're now starting cell line development on biosimilar candidates to these two products and we're going to run them through our process development or product development process. What this then becomes in combination with our Xdivane program, our Opdivo biosimilar candidate, is really an oncology biosimilar portfolio, these three products. You probably know Opdivo, a PD-1 inhibitor, developed by and commercialized by BMS and Keytruda, competing PD-1 inhibitor, commercialized by Merck.
They're both revolutionary in treatment of different kinds of cancers, multiple cancer indications they are approved for and proven to be efficacious. Revolutionary products in treatment of many cancers and but very expensive. We're talking about annual treatment costs which can go up to SEK 1 million a year. Very expensive treatments which of course also limits accessibility and also in certain regions and this is particularly true in the U.S. can lead to a concept called financial toxicity with essentially patients surviving cancer but having to face the debt accumulated throughout the treatment able to finance the treatment. There's an elevated risk of ending up in personal bankruptcy due to this.
There's a problem with the pricing and the cost of these products. That's what we can address in developing and ultimately introducing more cost-efficient biosimilars to the market. Darzalex, a product used in treatment of another cancer, multiple myeloma. Also there we have a problem with the treatment cost. We think that this forms a very attractive oncology portfolio for us to work on. I think from an out-licensing perspective for Ron, an opportunity for us to be able to actually now think more as finding a partner from a licensing perspective for a complete portfolio of products. I think that could be more effective way for us to be working. Okay.
Of course then these are products which can come to market towards the end of this decade. We're looking a long time ahead now. We also see changes in the biosimilar market underway. We are on the one hand an increased precision over time in analytical instruments and methods when it comes to the methods we use to analyze and compare our biosimilar candidate from structural perspective versus the reference product. Increased precision in these methods leads to that you can kind of be more certain about that you have a high similarity with regard to the structure of the protein and therefore there's a limited residual left with regards to potential differences. This actually has led.
This in combination with that research has been done looking at phase III trials conducted for biosimilars and the fact that most of them actually succeed or meet the primary endpoints on efficacy side and also show no meaningful differences on the safety end. Has kind of put the question on what's the scientific value we're adding in these phase III trials, which are rather extensive and costly, of course. Earlier this year actually, MHRA in the U.K., the regulatory authority in the U.K., came out with an update guideline with regards to biosimilars, where they open up for waiving the phase III.
Actually, opening up for approving biosimilars on the back of an extensive and precise comparative analytical assessment in combination with clinical PK/PD trial, pharmacokinetic and pharmacodynamic clinical trial. More or less what is done now as phase I for biosimilar candidates. We've seen this in the U.K. now, and we expect that this updated guidelines could also be the case going forward for EMA and FDA. We'll see if it happens in this decade or not, but we believe it will happen ultimately.
We believe that this is the course of action for this industry, and we're ultimately will be able to get approval of biosimilar on the back of competitive analytical assessment and more as a phase I trial or bioequivalence trial in combination with looking at some pharmacodynamic parameter. What does that then mean? We think that we are well-positioned in such a developing world. We believe that that focusing on low production cost on the back of a platform technology which gives an edge on a production cost is the right thing to do. We truly believe that we have an edge versus other developers on this. I think we need to invest further into that.
That shall be one of our core edges and one of our core competitive advantages, and I think it plays very well in this developing world. Also, to continue to be fast and cost-efficient in the development. What that means is to lead the industry in being able to waive phase III trials for our upcoming programs, and that shall be done on the back of world-leading analytical capabilities. That's what we're building here in Solna with regards to instrumentation, but also with regards to team and competencies. We really need to be best at that, because it will have very important consequences and impacts on our development timelines and the costs required or investments required into these developments. Then we need to remain, of course, cost-conscious and agile and flexible as we grow.
I believe we are that today. We continue to be that and focus on being cost-conscious in everything that we do. I think we're well-positioned, and we have the right competitive advantage for how we believe this world will develop going forward. Looking at our complete development portfolio, of course, you're very well aware of our Xlucane program, our biosimilar candidate, which is in the regulatory process with EMA. We're targeting Q1 next year for submission in the U.S. to FDA. We're looking forward towards approval towards the second half of next year, followed by a launch of the product via two partners, STADA and Valorum respectively.
Our Xcimzane program, our Cimzia biosimilar candidate, probably many of you saw that we partner up with AGC Biologics for scale-up and subsequent manufacturing for clinical batches. Yeah, so that's a process which we're now going through together with them. We also, as we've been talking about before, are trying to find a suitable commercialization partner for this program. I hope we will be able to get back during next year with an update and hopefully some positive news on that. I think this program is progressing according to plan, and it will be. It's still very exciting situation.
I think as far as we can tell, still, we are the only biosimilar candidate under development targeting Cimzia, and still it's a product with close to EUR 2 billion annual sales. Still a sizable progress. I think it opens up a very interesting commercial opportunity. Then we have our oncology portfolio with our biosimilar candidates, Opdivo, Keytruda, and Darzalex respectively, which now are in more early stage preclinical development, of course. I think it's a very exciting portfolio to be going for that come to market towards the end of the decade. I think that it's a portfolio we could be thinking about with regards to one deal with one commercialization partner who want to take this portfolio to market.
We stick to our ambition to initiate at least one new biosimilar development program annually. Now, this year, we start two. We're going to commit to one. It's dependent a little bit on when we see the actual patent expiries of the different products we're interested in and when do we need to start. Sometimes we need to shift a little bit so that maybe it comes to another year, maybe it becomes zero, but it should be at least on average one new program on an annual basis. That's what we commit to. I think that kind of ends the formal presentation and update, so to say. I want to then open up for potential questions.
Thank you. If you wish to ask a question, please dial 01 on your telephone keypads now to enter the queue. Once your name has been announced, you can ask your question. If you find it's answered before it's your turn to speak, you can dial 02 to cancel. Once again, that's 01 to ask a question or 02 if you need to cancel. Our first question comes from the line of Mattias Häggblom of Handelsbanken. Please go ahead. Your line is open.
Good morning. Thanks so much for taking my question. I had two. Curious to understand some of the recent issued IP. Does that mean that you now have new tools at hand that serves better the development of pembrolizumab rather than nivo? Or why would you know, could you expand otherwise, why have two PD-1s in development? And then secondly, sort of tied to that, I'm curious to hear what you make of the fact that Coherus, a leading biosimilar companies, has in-licensed a proprietary PD-1 antibody from China but has no biosimilar nivo or pembro in development, to my knowledge.
Yeah. Yeah, I can take the latter part of that question, and maybe Selva can take the first part. The assessment made is that we believe that the development of biosimilars to PD-1 is a more attractive proposition than developing a novel PD-1. We think there's a huge advantage in the concept of indication extrapolation that we're going to do clinical trial demonstrating equivalence in one indication, then get approval across all the indications versus the investments needed actually to take a novel PD-1 to market, and getting approval for all the respective indications that you otherwise would be having with the biosimilars. That's why we find it a more attractive proposition to be working at.
With regard to the IP front, I think we've done a lot when it comes to expanding into mammalian cells, and I think the patents we got approved during the year shows that. Maybe Siavash Bashiri can elaborate.
Yeah.
A little bit further.
No. I mean, we have seen from our experience with. First of all, I mean, both nivolumab and pembrolizumab are IgG4 antibodies in terms of amino acid sequence and structure. We have seen in our own past experience with nivo and the IP that we have developed for that, it will be well applicable for pembrolizumab. We have seen significant improvement in yields for nivo, and we believe that we can utilize this in the pembro project and have a competitive edge in terms of that product.
Good. I have one follow-up. I'm curious too. I read that there are more than 70 drug makers in China working on PD-1. To what extent does that come into the equation when you think about, you know, going for another PD-1 in development? I would expect some of them have ambitions outside China, but, you know, just curious how you tie that into the competitive landscape picture.
Well, we do believe at the end of the day, by the end of the decade or 2029 or so, still Opdivo and Keytruda will be the leading PD-1s on the market. We believe that it will be huge business opportunity for biosimilars on these two products. I think that we are well positioned to be a leading player in that emerging biosimilar market on the back of low production cost. We do believe that production cost and price will be important, and that's where we want to focus when it comes to our biosimilar development programs.
We are confident that we are going to be able to find a partner who wants to take these products to market as well, because they're just gonna be so sizable products. We know that many of the companies which we are working with are interested in this kind of product. Actually we believe that this process will be so big, it will be such a big market to address from a biosimilar perspective, and that's what we're focusing on.
Perfect. Thank you so much.
Thank you. Our next question comes from the line of Christophe Piguet of Kempen & Co. Please go ahead. Your line is open.
Hello. Good morning, everyone. I have two questions, if I may. Firstly, given the two new biosimilar development programs you announced today, how should we look at R&D expenses in the short term, given you initiate or launch two at the same time? How should we look at that? Will that go up in comparison to what you have shared at the CMD, mid this year?
No. I think that we run these programs in a very cost-efficient manner in the first phase of the development. It's really at the stage where, frankly speaking, Xcimzane program is now where really the investment goes up. That's when we move into commercial manufacturing site, that's when it really goes up from an investment perspective. Cell line development and pilot scale process development we do internally in a very cost-efficient manner.
Yeah. Okay. Clear. A bit out of the box question and follow-up on that. Let's say that in whatever time regulatory parties decide to eliminate phase III clinical trials for biosimilars, what would be the magnitude of cost savings in R&D expenses? As you stated, the most of the parts of the expense takes place as of phase III. What is the magnitude? It's significant, I suppose. It's more than 50%, no?
It is very
In that case scenario.
Yeah, it's very significant. I would probably say up to 50%, but probably say that, you would say save between 30%-50% of a given development budget of a biosimilar program if you would be able to waive the phase III.
Another follow-up, if I may. Not on today's news, but I noted that you shared that you plan to submit BLA at FDA in Q1 2022. That sounds like a delay compared to what has been communicated until today. What is the reason behind that?
Well, we communicated already in our Q3 report that we were to be submitting the BLA Q4 this year to Q1 next year. It's just due to the fact that we're working through the file and there are certain aspects of the file which need to be reworked for BLA with a greater level of detail and so on. It took a little bit longer time than maybe anticipated. We're working on it and we're going to be able to submit it in first quarter of next year.
Yeah. Yeah, you still foresee, let's say, U.S. approval in H2 of next year?
The regulatory process can take, I think, anything from 8-12 months in the U.S. We hope that we'll be able to get it in place before the end of next year.
Okay. Thank you, Martin.
Thank you. Our next question comes from the line of David Clement, who's a private investor. Please go ahead. Your line is open.
Yes. Hi, Martin and Siavash. Thanks for taking my question. I recently noted that your peer, Alvotech in Iceland, is getting listed in the U.S. They have a somewhat similar pipeline to yours, at least in the number of targets. However, their valuation is something like 8-10 times your valuation. They also have in-house manufacturing capability. My question is, how do you think about building up or acquiring this during the coming decade as your pipeline grows?
It's a valid and an interesting question. Of course, we want to focus on cost and having the lowest production cost. We believe we have a platform technology which provides high productivity, so to say, in expression of the proteins. Also the manufacturing side of the drug substance is something which we are looking into and have to look into during the coming decade and how we shall view that if we shall continue to work with the contract manufacturers like we do today or if there is a way for us to do that in a more cost-efficient manner. We're undergoing such an evaluation, and we're looking at that question.
No decision taken, but on the map, of course, and what we naturally have to be evaluating, given who we are, is, should we have our own manufacturing. If we would come to that conclusion, of course, the two routes of setting up something yourself or acquiring. It's a natural strategic question for us to ask ourselves and a question we have asked ourselves but not come to the answer on.
Okay. Yeah. Thanks. Makes sense. That was my question.
Thank you. Once again, if there are any further questions, please dial 01 on your telephone keypads now. Okay. As there are currently no further questions on the phone lines, I'll hand the call back to our speakers.
Okay. Excellent. We want to thank everybody for calling in and listening, and thanks for all the questions. We can close down this call and we'll. You'll hear back from us in a new year with hopefully more positive news.