Good afternoon. Thank you for coming to twenty nineteen UBS Healthcare Conference. The next presenter will be David Veatch from Vazelaya Pharmaceuticals. He's the CEO, and please welcome David.
Thank you very much, and good afternoon to everyone. I will try in the next twenty five minutes just to give you an overview of the company, our priorities and what the immediate future lies in store for Basilea Pharmaceutical. Just at a glance, the key high level summary, we were set up originally as an anti infective antibiotic developer when we were spun out from Roche in February. We went public in 2004 on the Swiss VI Stock Exchange. And, during the course of the last nineteen years, we have bought three products to market, all the way from research to market.
Two of these we have still in our portfolio today. That's an invasive fungal infection product and an antibiotic. And then we had another agent called Toctino, which was a hand eczema product, which we actually sold in 2012 to GSK Stifel. So that no longer is in our portfolio. However, that manifests itself in terms of the revenues you see, and I'll come back to that later in the presentation.
In terms of our pipeline, as I said, we have two now commercial stage assets, which are the top two on this graph. One, as I said, an invasive mold infection, invasive fungal infection drug, Cresemba, which is generating the majority of our revenues at the moment. So we are a revenue generating biotech company. And then the second agent on that slide, Zevtera, Mobilio, broad spectrum cephalosporin. And then behind that, in Phase onetwo, are our oncology products, which about ten years ago, we made the strategic decision to move away from just anti infectives into oncology.
And the result of that decision is shown on this slide in terms of the three clinical stage assets, and we have a number of assets behind that. I should say that these are these assets, these oncology assets are as a result of both internal and external, development. So two of those agents we licensed in from other companies, and one was a result of our own, R and D efforts. In terms of our commercial model for our commercial stage assets, we have a we don't have a Basilea presence around the world. We have commercial stage partners who basically commercialize our assets, the two assets, commercial stage assets on our behalf.
They either fall into a license partnership, which is where they manufacture the product and then commercialize it or distribution partners where we manufacture through our CMOs and then the partner commercializes. And you see here, we either have big global players like Pfizer or Astellas or we have strong, what we believe are strong regional players, to commercialize our assets, around the world. In terms of our partnerships, for Cresemba, our invasive mold infection drugs, our partnerships cover all the important markets for Cresemba. And then for Zevtera, our broad spectrum antibiotic, we have partnerships covering the major markets with the exception of one market, which is The U. S, and I'll explain what the plan is with regard to The U.
S. In a short while. In terms of the partnerships, how do we participate? We participate through royalties from the license partnerships. We participate through a transfer price for the distributor partnerships.
And then also, we have sales milestones. We have regulatory milestones and, upfronts, etcetera. And you see here on this slide, it alludes to the fact that we've already booked $245,000,000 of upfront and milestone payments so far, and there's about $1,100,000,000 of outstanding milestone payments due to us if we achieve and most of these are sales milestones, actually. And that's on top of the royalties and the transfer price structure. In terms of, just briefly then, a few moments on each asset, the invasive mold infection drug Cresemba, what I would say here is mold infections are having an incredibly high mortality rate.
These are in patients that are already very sick. Their immune system is compromised, so they can be a high dose intensive chemotherapy patient or solid organ transplant patient, for example, and then they get a fundal infection and the mortality rates, as you can see on this slide, are really quite high. And so this is serious, serious medicine area. In terms of how is Cresemba doing since it's been launched, these are the in market sales, so the IQVIA sales, for want of a better description. And you see here in sort of the third year of life for Cresemba, it's already achieving $160,000,000 of in market sales, most of that coming from The U.
S. At the moment, and that's our partner Astellas, who's commercializing in The U. S. And, the reason why The U. S.
Is quite dominant on that graph is because The U. S. The FDA approval was in front of the European approval. So it was launched about a year earlier in The U. S.
Than, in Europe. But here you can see Europe play an increasingly important part as we launch in new countries. And our partner for Europe and Asia Pacific is Pfizer, and they're doing a good job like Astellas in terms of helping us commercialize successfully, our invasive fungal infection drug, Cresemba. In terms of, what's the potential of Cresemba, I mean what this the box on the right just points out that the previous gold standard treatment for invasive aspergillosis, which is the main indication, voriconazole, achieved sales of just under $1,000,000,000 about $900,000,000 of sales. Now it's a bit less because it's genericized, and it has been genericized for the last few years actually.
So that sales ramp up I showed you on Cresemba was in an environment where the key competitor was generic. And you can see there, that's had very little impact in terms of the projection, the sales uptake at Cresemba. And the reason for that is because it's got a very strong profile, Cresemba. In the pivotal study, where it took on voriconazole, so it was a randomized controlled study, isoviconazole versus voriconazole, and, there was similar efficacy between the two agents but significantly better side effect profile for Cresemba. And that's one of the key drivers of use of the product combined with the fact that it's got a broader spectrum in terms of, use in more rarer molds And also, it's a more convenient, drug to use for physicians.
So the profile of the drug is strong, which is helping it lead to that uptake you saw on the previous slide. And as I said, this is really driving our revenue uptake at the moment. In terms of final comment on Cresemba, just at the bottom of this slide, you can see here exclusivity extends to 2027 for the brand in The U. S. And actually 2027 also in Europe as long as we compete, complete the pediatric program, which, for orphan drugs, you get two years of exclusivity, which takes you to 2027 in Europe as well as The U.
S. But even that is not the end of the story because obviously, we're working with our partners now on launching in other major markets like China and Japan and the exclusivity for those or the useful life of those compounds will extend beyond that period of 2027 in other markets. So Cresemba, that's all I was going to say on Cresemba. Then just switching gear to the next asset in our pipeline, Zevtura Mobilio, ceftobiprole, broad spectrum antibiotic with a cephalosporin safety profile, particular strong activity gram positive, staph aureus, but also MRSA as well as MSSA. And that is important because unlike for Cresemba, when you look at the sales potential of MRSA agents, like what we've done here is we've picked out the peak year sales of daptomycin and linezolid and looked at where the distribution of sales were by geography.
And unlike with Cresemba where many geographies are really critically important for the brand, for MRSA antibiotics, The U. A. Is pivotal, in terms of us launching in The U. S. And whilst we're commercialized in several markets around the world for Zevtera, we're not currently licensed in The U.
S. So actually, then the next question obviously is, well, what is the plan to get licensed in The U. S. And access this really important strategic market for an MRSA antibiotic? Well, the plan is that we have agreed with the, FDA, and we're currently carrying out two studies, one in skin infections and one in staph aureus bacteremia.
The skin study is recruiting very quickly as skin studies do, and, that should report out in the, second half of this year. And then the bacteremia study, actually, that takes a longer period of time to complete. We're projecting currently that will run into mid-twenty twenty one, and then that will, we would then potentially, with positive data, launch in The U. S. In 2022.
The benefits of this or two points to dwell on with this program. This Phase III program is funded to the tune of $128,000,000 effective from the U. S. Government, by BARDA. This is non dilutive funding, and that's about 70% of the cost of the program.
The Basilaya pays the other 30%. The U. S. Government through BARDA pays 70 percent of the cost of this program, and it's a program over about five years. And then in addition to that, the other important incentive that we have with regard to an antibiotic developer is this QIDP designation, which gives us ten years of exclusivity following the approval.
So this is independent of the patent situation. And, this would then run, all things successful, from 2022 to 02/1932. And this is when at the point at which ceftobiprole would start to have a meaningful impact on our revenues in addition to Cresemba, which is driving them at the moment. In terms of, just shifting gear to our pipeline products, So that's the commercial stage assets so far. The three oncology pipeline products, I'll just say a brief word about each of those.
Derazantinib, this was an in licensed compound from ArQule, a Boston based company, which we in licensed in April. This is our lead oncology compound in terms of progress. And this is actually quite interesting because if you so if you go back to this slide here, When we took over the compound, very much it had been progressing a story in interhepatic cholangiocarcinoma or bile duct cancer, and it had some interesting data, which in due diligence is one of the reasons why we like the compound. It had real positive clinical data in ICCA. But what we've been doing is we've been profiling the compound in the year that we've had the compound and looking at other opportunities and ways in which we can differentiate the compound from the other FGFR inhibitors that are in development.
Actually, just recently, one was licensed from, J and J and then there are a number of other FGFR inhibitors with another number of other companies that are in development. And what we see, and it's highlighted on this slide, is that we have what we believe is quite a unique property in terms of, activity against FGFR1, two and three, but also against CSF1R, which actually gives us potentially an advantage in certain situations versus the other FGFR inhibitors. I'll come back to that in a moment. I mean, it's culminated, as it says on this slide here, is that we're about to start a study in urothelial cancer working with Roche in terms of the combination of derazantinib and PD L1 Tecentriq in a study of urothelial cancer. And the rationale for that, I'll explain in just a second.
Another piece of interesting information that attracted us to this asset was the fact that FGFR aberrations of all sorts occur in many different tumor types. And currently, the most profiled areas are ICCA, bile duct cancer, and also bladder cancer, urothelial cancer here. But, as yet, what we don't know, and in many of the different tumor types, the extent to which, the FGFR is an oncogenic driver. We know they occur, but we don't know to what extent they're an oncogenic driver and that's what we're currently profiling preclinically with our R and D team in terms of, these different tumor types to understand where the compound may have a differentiated position and utility in other tumors as well as ICCA and urothelial cancer, which we're currently progressing. In terms of I touched on this, the data.
This is one piece of data. I've just pulled out one piece, but this was the classic waterfall plot looking at the patients with FGFR2 fusion aberrations in ICCA. And this is the tumor, what happened to the target lesion tumor volume. And you can just see by eyeballing it that actually, the patient more patients were getting a benefit from this in terms of the these were partial responses. And these were good responses, but didn't quite qualify at the thirty percent level to be a partial response, but so these are classified as stable disease.
But you can see many patients are getting a benefit, from the agent. What we announced earlier this year was the interim results from a registrational Phase II study, which is just shown at the bottom piece of this slide here. And, this was just it was encouraging for us because in a 29 evaluable patient group, we had an overall response rate of twenty one percent, which actually mirrored the data from the previous graph I just showed you. So this is an ongoing potentially registrational study in ICCA, which we'll report out fully in the middle of, next year, mid-twenty twenty. In terms of just go back a slide.
In terms of differentiation, which as I said is important for us because over the last year, as I alluded to, we've been spending a lot of time on trying to understand the compound and which way we can go and how we can differentiate from other FGFR's in development. This is I'm not going to go into the detail of this. This is just to say suffice to say that what's interesting is when you look at the different FGFR inhibitors in each of these little acronyms or different, FGFR inhibitor, and they've been studied, as I said, mostly in bile duct cancer and in bladder cancer here. And, what it just looks at is it looks as if from a side effect profile point of view, many of them have a sort of what we would call as more of a class like side effects. And then, there seem to be differences.
And this is not a comparative study saying, but this is just data from posters from abstracts at clinical meetings. And you can just see here that it seems to be that there are some specific side effects that occur with certain of these, FGFR inhibitors and not with, other ones. And then another point of differentiation, which I alluded to a moment ago, is this CSF1R activity. We carried out in house, an in vitro, kinase screen. And if we normalize the activity for FGFR2, where we know they all have activity and we look at the relative potency against other kinases, FGFR1, two, three, four and CSF1R, you can see here that derazantinib, our FGFR inhibitor, much sort of pretty much equipotent between FGFR123 and CSF1R, whereas the other, FGFR is in development, are not it's not the case.
So actually, it was this type of data that then we sat down with Roche and we shared the information because obviously the role of CSF-1R is quite well understood in terms of, potentially reprogramming immunosuppressive tumor infiltrated macrophages, which actually means that it could potentially improve the susceptibility to PD L1s. So actually, that's why Roche were happy to come into a collaboration with us in urothelial cancer, where interestingly, the high FGFR patients in urothelial cancer almost always are low PD L1 expressers. So that was, I think, the interest from Roche's point of view. And, we're just about to start the study. I'll just point out here, the middle of this year, we plan on starting the study as both in urothelial cancer, FGFR positive patients, as single agent, derazantinib, but also in combination with Tecentriq.
And, like I said, there is a scientific rationale behind it, which we believe we can own that others can't copy because they haven't got the physiological CSF1R, inhibition that we've got. In terms of just the other, very briefly, the, other two agencies earlier, so I'll spend only a couple of seconds on these. We have a this is our own R and D efforts. It's a destabilizing microtubule agent which actually can cross the blood brain barrier. And so not surprisingly, when we looked at preclinical models, there was really exciting data in glioblastoma models.
So actually, we've been this is the summary of the studies that are ongoing at the moment. And you can see here 've got a forty eight hour IV infusion schedule looking at the agent in patients with recurrent glioblastoma and also resistant ovarian cancer, and the data from that study will report out at the end of this year. Then we have a Phase I dose escalation all in, again, recurrent glioblastoma. And then we have a Phase I study in newly diagnosed glioblastoma patients, in collaboration with radiotherapy as well in collaboration with the adult brain tumor consortium here in The U. S.
And, that will take longer to recruit, enroll patients for. So there are the ongoing studies and the data readout points. And then if I just very briefly, the last of our assets, which again is fascinating from a preclinical position and data set. A pan RAF, we think it's a unique compound in development. There's no other pan RAF sarc kinase inhibitor profile like we've got here.
This was in licensed from a U. K. Consortium, including the, Wellcome Trust and the, Institute of Cancer Research. And you can see here that the concept here is that, it would target resistance mechanisms associated with approved BRAF inhibitors. We've completed a Phase I study to bring you up to date.
We studied a broad dosage range, but MTD was not, defined. And we're currently the issue with the study was that whilst it was good in terms of there was no, there was no untoward, issues in terms of safety, what we needed to do is improve the bioavailability. So that's what we're currently working on. We're looking at alternative formulations because the preclinical promise is there, but actually we need to get improve the bioavailability to get the drug into the body at the right level. And that's currently what we're focused on in terms of this agent.
And that brings you right up to speed, right up to date in terms of the assets, terms of how this all comes together in terms of the financial picture, of the company can be seen on this slide here, and it just needs one little word of explanation. So if you look at full year 2018 actuals, total revenue of about $133,000,000 $82,000,000 was from Quessemba and Zevtera revenues. This is our commercial stage assets. But when you look at our guidance for this year, it looks like we're flat in terms of total revenues. What should be borne in mind though is I alluded at the very beginning to the fact that we had some legacy revenue recognition when we sold our hand eczema product called Toptino, and that's the red piece on this bar here, and that ended last year.
So effectively, what we're doing as a company, we've replaced noncash generating revenues, which are here shown in red, which is about $24,000,000 last year. We've replaced that with more cash generating revenues from the growth of Cresemba and Zevtera. And as I said, this is mostly, at the moment, Cresemba rather than Zevtera. And then if you're wondering what the green piece is, this is the reimbursed, reimbursed costs we get from BARDA, The U. S.
Government. So the way that works is we spend the money. It's in our P and L. Then the U. S.
Government reimburses us for the cost of the development of ceftobiprole, and that's what the and we have to book it as revenues, other revenues. So that's what that is there. But you can see here, the picture is replacing noncash generating revenues with this blue bit is the strategically important bit. It's the increasing revenues from our commercial stage assets. And that's and then when you look at go back to the P and L, revenues then in the order of magnitude of 128,000,000 to $38,000,000 Zevtera, Cresemba growing nicely from 2018 to 2019 here.
And then operating loss at a similar level to last year, which shows you that the expense base is pretty constant. But obviously, our cash burn starts to go down significantly because of this replacement of non cash generating to cash generating revenues. And then that's just pointed out that we had CHF $223,000,000, which is the same in dollars really, at the end of twenty eighteen. And so we're financed to deliver, the key value inflection points which we have coming, which on my last slide are shown here. So this is a summary of hopefully, it makes sense from what I've said in terms of these are assets that have value inflection points coming up in the next sort of eighteen months.
We've got the top line results from the skin study, the first of those two Phase III studies for ceftobiprole. Derazantinib, we have, like I said, the urothelial cancer study starting here. And then we get the readout from the bile duct cancer and the urothelial cancer study here. We also have another cohort in the ICCA study, which is the non FGFR2 fusion group of patients just to try again, try and broaden the utility, from the current, trial set, which is more FGFR2 fusion only patients. And then, as I said, one hundred one thousand five fifty three, this is the microtubule stabilizing agent, which actually has key data readouts at the end of this year.
So that's all going on in terms of clinical development pipeline. And then at the same time, obviously, we have a real focus on supporting our partners to commercialize and maximize the revenues from our commercial stage assets. So think so thank you for your attention.