Ladies and gentlemen, welcome to the Basilea Pharmaceutica Full Year Results 2024 Conference Call and Live Webcast. I'm Sandra, the Chorus call operator. I would like to remind you that all participants have been placed in listen-only mode, and the conference is being recorded. The presentation will be followed by a Q&A session. You can register for questions at any time by pressing star and one on your telephone. For operator assistance, please press star and zero. The conference must not be recorded for publication or broadcast. At this time, it's my pleasure to hand over to David Veitch, Chief Executive Officer. Please go ahead, sir.
Thank you, Sandra. Hello, I'm David Veitch, CEO of Basilea, and I would like to welcome you to our conference call and webcast, reviewing our financial results and key achievements for the full year 2024, as well as highlighting our key future value drivers. For further detailed information, please see the ad hoc announcement issued this morning and also our annual report. Both these documents are available on our website at basilea.com. I'd like to mention that this call contains forward-looking statements. Joining me on our call today are Adesh Kaul, our Chief Financial Officer, and Dr. Marc Engelhardt, our Chief Medical Officer. I'd like to start with our key achievements in 2024, starting with currently our most important commercial product, Cresemba, our antifungal for invasive mold infections.
Cresemba continues to perform very well, as demonstrated by the 20% increase of global in-market sales to more than $500 million, according to the latest available data for the 12-month period to September 2024. This continued strong performance drives our 30% year-on-year increase in Cresemba and Zevtera-related revenue. We also report a very strong financial performance for 2024. Compared to 2023, we tripled our operating profit and reported a five-fold increase in operating cash flow, as well as ending the year with a strong cash position and net cash. In addition, we have been able to secure significant non-dilutive funding for our research and development projects. We also made significant progress in our portfolio. The FDA approves Zevtera in the U.S. for a broad range of indications, and we have announced Innoviva Specialty Therapeutics, or IST, as our partner for the commercialization of Zevtera in the U.S.
For Cresemba, we received the approval in Europe for use in pediatric patients, with Cresemba gaining two additional years of market exclusivity. For our next lead product, the antifungal fosmanogepix, we initiated the first of the two phase 3 studies aiming at a broad label for treating both yeast and mold infections. Furthermore, we strengthened our portfolio by acquiring a preclinical stage antibiotic program from a novel class, the LptA inhibitors, which target Gram-negative bacteria, and we recently nominated one of the acquired compounds, BAL2420, as a drug candidate, which we're now progressing towards clinical studies. When we look now at our portfolio, we can see that we have a balanced mix of already commercialized brands and compounds in the clinical and preclinical stages.
Cresemba remains our main revenue driver, but we expect to see stronger contributions from Zevtera following its recent approval and partnering in the U.S., where it has market exclusivity until 2034. Since October 2023, we have significantly expanded our anti-infective pipeline with fosmanogepix, the antifungal BAL2062, and the LptA inhibitor antibiotic BAL2420. These are all making good progress. Fosmanogepix, which has moved into phase three, has the potential to ultimately replace Cresemba, and we are looking forward to the start of the second phase three study in mold infections. We had also acquired an evaluation license for a fourth compound, the endolysin antibiotic tonabacase. However, after thorough preclinical evaluation, we've decided to not pursue its development as it did not meet our stringent risk-return criteria.
Going forward, as we continue to see attractive market opportunities that could be addressed with novel therapies, we will aim to access additional assets to expand our pipeline in our focus areas of antifungals and antibacterials. Our focus is to in-license or acquire assets between late preclinical stage and the end of clinical phase two. In summary, with our current pipeline, we are positioning ourselves as a leading anti-infectious company, advancing anti-infective drugs from research through clinical development to commercial success. I'll now hand over to Adesh.
Thank you, David. I'd like to start with an overview of our business model before turning to an update on the commercial performance of Cresemba, a key driver of our strong set of financials. I will then highlight some of the key financial figures that we published today. I'd like to mention that all figures I refer to are in Swiss francs unless specifically stated otherwise. We have successfully established a profitable business model which is optimized to overcome the economic challenges in the anti-infectious area. Research-focused companies often lack the financial strength, organizational resources, or capabilities to advance their drug candidates beyond the early stages of clinical development on their own. While large pharma companies are open to commercialize new anti-infectives, they are reluctant to make R&D investments in antibacterials and antifungals.
We are therefore able to fill a gap in the value chain by in-licensing or acquiring the most promising drug candidates in our space and creating value by advancing them through clinical development. While doing this, we focus on generating the data required to support a differentiated commercial positioning in the future. We can often reduce the required level of investment for taking our drug candidates to the market by accessing non-dilutive funding. Through partnering with experienced partners, we operate a lean and low-risk commercialization model. We participate in the commercial success of our brands primarily through royalties, milestone payments, and product sales, which generate the cash flow for repeating the value creation cycle. Through our partnering model, we have global reach. Cresemba is currently marketed in 75 countries and Zevtera in 20 countries. In total, our partnerships cover more than 100 countries.
We can take a look at the performance of our antifungal Cresemba to see how a successful global brand can be established by working with regional and local champions. Our partners have been able to generate $533 million in a 12-month period to the end of September 2024. Ten years after launch, this is still a remarkable 20% increase year-on-year and makes Cresemba the largest branded antifungal for invasive fungal infections worldwide. We see continued significant growth potential for the brand going forward, especially with increasing contributions from China and Japan, where Cresemba was launched more recently. Turning now to our second commercialized brand, Zevtera. As seen with daptomycin, the U.S. is the most important commercial opportunity for branded anti-MRSA hospital antibiotics, representing about 90% of the market. Hence, in 2025, a key milestone for Zevtera is the launch in the U.S. by our commercialization partner, IST.
We have established several operational work streams that are jointly preparing for launch, which is planned for mid-year. Initial launch material has already been manufactured, and field force training is in preparation to name just two key activities. Before turning to our 2024 financials, I would like to remind you of the significant non-dilutive R&D funding that we have been able to secure last year. One of the major achievements was the execution of the BARDA Other Transaction Agreement, or OTA, which provides up to $268 million for the development of novel antifungals and antibiotics. The way this works is that we get reimbursed for R&D expenses agreed with BARDA, and we expect that this could offset up to 60% of the total development cost for the clinical programs included in the OTA. $29 million have already been granted and assigned to Fosmanogepix and BAL2062.
However, what is special about OTAs is that BARDA and Basilea can jointly decide to move candidates into and out of the portfolio based on product performance, technical risk, and program-specific needs. This flexibility results in significant time, effort, and cost savings to both partners. In addition, we were awarded a grant of initially up to $0.9 million from CARB-X to support early preclinical activities for the LptA inhibitor program. Following successful nomination of BAL2420 as a drug candidate, we were awarded an additional $7.3 million for CARB-X in December 2024. Our ability to consistently access non-dilutive funding underscores the value of our R&D pipeline. Moving now to financials. 2024 has been an outstanding year for Basilea, marking our third consecutive year of reporting a net profit and positive operating cash flows. Total revenue grew by 32% to $208.5 million.
Cresemba and Zevtera-related revenue increased by 30% year-on-year to $194.9 million, driven by the strong in-market sales of Cresemba, which generated royalties of $96.7 million, which is a 23% increase year-on-year. Milestones in our prompt payments too increased to $40.4 million compared to $33.5 million in 2023. Cost of product sold increased to $38.7 million, reflecting the significant increase in product revenue. Research and development and SG&A expenses together amounted to $108.6 million. Overall, this resulted in an operating profit of $61.2 million, three times the operating profit of the previous year. Based on our sustained profitability and positive midterm financial outlook, we recognized deferred tax assets of $17.3 million in 2024. This one-time gain contributed to a net profit of $77.6 million. In addition, we now report a net cash position at year-end amounting to $28.6 million after a net financial debt in previous years.
Cash flows from operating activities have jumped to $74.4 million for the full year 2024, which is a five-fold increase over full year 2023. Besides investing into the expansion and progression of our pipeline, we have used the cash flows from our commercial business to strengthen our balance sheet. Since January 2022, we have significantly reduced our debt by $124 million in a completely non-dilutive way so that our only remaining debt is our $97 million convertible bond, which will mature in mid-2027. For 2025, we expect continued growth in total revenue to approximately $220 million, driven by a 14% increase in royalty income to $110 million and by reimbursements from BARDA and CARB-X, which we report under other revenue. These reimbursements help us to offset the expected 14% increase in R&D expenses reflected in the continued investment in our portfolio, including running two phase three studies with fosmanogepix.
SG&A expenses are expected to increase in a low single-digit percentage range. Overall, this should allow us to maintain a high level of operating profit of approximately $62 million. A final word on tax impact. While we expect no material cash outflow related to income taxes thanks to the use of tax loss carry forwards, a 12% income tax rate will be reflected in the 2025 net profit, in contrast to a $17.3 million one-time gain from the recognition of deferred tax assets in 2024. Finally, I would like to give a little bit more granularity on the Cresemba and Zevtera-related revenue in order to provide more context for our financial guidance. We expect to see continued strong double-digit growth in royalty income, reflecting the continued strong underlying demand for Cresemba in key markets and first contributions from Zevtera in the U.S.
While we expect increased product sales to our distribution partners, product revenue overall is expected to decrease temporarily due to the previously announced decrease in product supply to Pfizer, which is the result of the successful transfer of the majority of manufacturing responsibilities to our partner. On a full-year basis, we expect milestone payments to revert back to the average range of the last several years of approximately $33 million. Finally, there is deferred revenue from past upfront payments in the amount of $1.6 million that will be reported under contract revenue in 2025. I will now hand over to Marc for the portfolio update.
Thank you, Adesh. As mentioned, we have significantly expanded our portfolio since October 2023. Fosmanogepix is now the key compound in our development pipeline and has the potential to become our next lead commercial product and the value driver in the midterm. The urgent and unmet medical needs for developing new treatment options for patients with invasive fungal infections is evident when looking at the high mortality rates that have remained at about 25%-50% or higher over the last decade in invasive yeast and mold infections. Considering the often severely immunosuppressed patients who require antifungals, new agents are urgently needed to help patients to better overcome the critical phases in their disease.
Fosmanogepix holds a lot of promise in this fight against invasive fungal infections due to its new mode of action, broad-spectrum activity, and the wide tissue distribution into the body compartments that are relevant for fungal infections. It also has a favorable drug-drug interaction profile with low cytochrome P450 inhibition. So Fosmanogepix is clearly differentiated against existing antifungals and other novel compounds in development. If we can successfully develop it, it could have an important place in the therapy of fungal infections. Last year, we initiated a phase three study with Fosmanogepix in patients with candidemia and invasive candidiasis. We are now preparing a second phase three study in patients with mold infections, which is expected to be initiated in the second quarter this year. Fosmanogepix is the product of the active compound manogepix. Manogepix inhibits the GPI-anchored wall transfer protein 1, or GWT1, in the fungal cell.
This is a completely different mechanism of action compared to all other antifungal drugs. manogepix leads to a lack of anchoring elements for important cell wall proteins such as mannoproteins. The depletion of these proteins on the outer fungal cell wall causes multiple and unique effects that make the fungal cells less pathogenic and less invasive and results in fungal cell death. The spectrum of Fosmanogepix includes multi-drug-resistant fungal species, essentially covering all fungi that the WHO has included in their list of critical priority pathogens. We believe that among the currently approved antifungals or those in clinical development, Fosmanogepix has the broadest coverage against fungi that are relevant for invasive fungal infections in humans. The FDA has acknowledged Fosmanogepix's potent broad-spectrum activity and granted it fast track and orphan drug designations for seven separate indications. In addition, it has received QIDP designations.
Because fosmanogepix is available IV and oral with a high oral bioavailability, it can be used in both inpatient and outpatient settings. The first phase 3 study is already ongoing. It is a double-blind non-inferiority study in candidemia and invasive candidiasis. This study will include approximately 450 patients randomized to initial intravenous therapy with fosmanogepix or caspofungin. The study includes an oral step-down option to fosmanogepix in the fosmanogepix group and to fluconazole in the caspofungin group. The primary endpoint for the FDA is 30-day survival, and for the EMA is overall response at the end of study treatment. We anticipate starting a second phase 3 study in invasive mold infections in the second quarter of 2025. This study will include a total of approximately 200 patients.
Patients will be enrolled in an open-label randomized portion comparing Fosmanogepix with the respective best available therapies for several cohorts of patients with invasive mold infections. In addition, patients requiring salvage therapy will be enrolled in a separate cohort. If successful, this phase three program will provide a comprehensive data set supporting broad use of Fosmanogepix in yeast and mold infection as primary therapy and as a salvage therapy option. Fosmanogepix is also available via expanded access for patients with serious or life-threatening invasive fungal infections and no other available treatment options. To date, more than 230 patients received Fosmanogepix via expanded access in the USA and in several other countries. This includes patients with a broad range of fungal diseases, including invasive fusariosis, invasive aspergillosis, Lomentospora or Scedosporium infections, mucormycosis, other rare mold infections, and patients with Candida infections and with coccidioidomycosis.
There was an increasing number of cases following the Matamoros Fusarium meningitis outbreak in the U.S. and Mexico in 2023. This fungal outbreak has garnered significant media attention, including publications in the New England Journal of Medicine and other journals, underscoring how new unapproved drugs can emerge as life-saving therapy options. The outbreak of Fusarium meningitis occurred at two clinics in Matamoros, Mexico, affecting patients mostly from the U.S. who had undergone aesthetic surgery procedures with epidural anesthesia. Primarily young and previously healthy individuals drawn to medical tourism suffered severe neurological and cerebrovascular injuries due to the infection. The Fusarium strain proved resistant to all available antifungal agents except for Manogepix, which led the CDC to formally recommend the use of Fosmanogepix, which is remarkable as it was in Phase II development at the time.
The additional Fosmanogepix led to favorable clinical outcomes in patients previously failing on approved antifungals, with a clear reduction in the in-hospital mortality from about 65% with standard of care treatment alone to less than 20% once Fosmanogepix was added. Moving to our second clinical asset, BAL2062 is a first-in-class cyclic hexapeptide antifungal targeting patients with invasive aspergillosis. Our plan aims at positioning BAL2062 as a first-line intravenous treatment with the potential to deliver superior efficacy to standard of care. It has FDA QIDP, orphan drug and fast track designation for invasive aspergillosis. It has a new mode of action as it is actively transported into fungal cells through the siderophore iron transporter one or SIT1, which is not present in mammalian cells. BAL2062 does not show any cross-resistance with marketed antifungal agents.
One of the key attributes of this compound is its potent and rapid fungicidal activity against Aspergillus species, shown in preclinical studies, with the potential to provide superior efficacy in invasive aspergillosis. It is active against azole and amphotericin B-resistant Aspergillus species and has a low propensity for drug-drug interactions. We are currently conducting preclinical profiling studies to define the optimal positioning and the most efficient clinical development path for this asset. If successfully completed, we expect to start the phase two program in 2026. Turning to Tonabacase. Tonabacase is a bactericidal endolysin. We had initially acquired an evaluation license for Tonabacase in October 2023. As already mentioned by David, after thorough preclinical evaluation, we have decided not to further pursue its development as it did not meet the stringent criteria that Basilea applies when making portfolio decisions to move into phase two or phase three development.
However, we remain interested in this space and continue to look at novel modalities that could provide superior outcomes in infections caused by Gram-positive bacteria. Finally, moving to the LptA inhibitor BAL2420. LptA inhibitors are a new approach to the treatment of infections caused by Gram-negative bacteria, and we acquired the rights to this preclinical program in January 2024. We believe that this new class of antibacterials has the potential to become a new important treatment option for infections caused by Enterobacteriaceae, including carbapenem-resistant isolates. This includes bacteria such as E. coli and Klebsiella pneumoniae, which are the most frequent pathogens causing Gram-negative bloodstream infections. The compounds have a new mode of action by inhibiting LptA, which is a part of the lipopolysaccharide transport bridge in Gram-negative bacteria, hence resulting in a loss of integrity of the outer cell membrane.
High potency and rapid bactericidal activity have been shown in vitro and in vivo, and no cross-resistance has been observed to other antibiotic classes. Based on our preclinical work in 2024, we have successfully nominated one compound, BAL2420, as drug candidate and are now progressing to the start of a first-in-human clinical study, which is expected in mid-2026. I will now turn over to David.
Thank you, Marc. Let me close with a quick summary and outlook. We reported very strong financial results for 2024 and have guided for continued healthy profitability in 2025. We are also looking forward to the U.S. launch of Zevtera this year, and our focus is on supporting our partner, IST, in the launch preparations. At the same time, we are progressing our clinical and preclinical assets through research and development. Specifically, we plan to initiate the second phase three study with fosmanogepix for the treatment of mold infections in the second quarter. We will keep on assessing further opportunities to complement our pipeline with promising assets. This will be associated with increased investment into research and development, but this will also be significantly offset by non-dilutive funding.
As Adesh and Marc highlighted, a well-filled, balanced pipeline will bring us closer towards our goal to be a leading provider of anti-infective medicines. Thank you for your attention, and we'll now open the line for your questions.
We will now begin the question and answer session. Anyone who wishes to ask a question may press star and one on the telephone. You will hear a tone to confirm that you have entered the queue. If you wish to remove yourself from the question queue, you may press star and two. Questions on the phone are requested to disable the loudspeaker mode and eventually turn off the volume of the webcast while asking a question. Anyone with a question may press star and one at this time. Our first question comes from Brian White from Calvine. Please go ahead.
Yes, good afternoon. Thanks for taking my question. The first one's on the partnership with Zevtera and IST. We obviously spoke to quite a number of companies during the partnering period, and I wondered what it was that convinced you that they were the best partner for Zevtera and if there was any comfort they were able to give you during discussions about their commitment to the molecule itself. And then secondly, just thinking about, I mean, I don't know if this is relevant or not, but Marc's comments about the expanded access, and obviously very familiar with how helpful this can be, especially with investigational products. But is there a risk that if we have a lot of expanded access, that recruitment into the phase three program may be affected, or is that just a theoretical risk and nothing to worry about? Thanks.
Okay. Hi, Brian. Thanks very much for your questions. Actually, I think myself and Adesh will comment on your first one, then Marc will come back on the EAP question. So in terms of IST, I mean, I think from my perspective, one of the key attributes of IST is that they are an experienced seller, commercializer of antibiotics in the U.S. They're actively selling Eravacycline, sulbactam-durlobactam. So they've got two other that I know that they're commercializing now, and one of them was very recently launched, so in the last year. So actually, they have got sort of contemporary experience of commercializing antibacterials in the U.S. market. So they know all about how to get market access, how to support with medical affairs activities, and the salesforce sort of targeting and training and approach to be successful with commercializing antibacterials.
So for me, from that perspective, they're an ideal partner. And so far, since we announced the partnership in December, things are going very well. We're in close collaboration, as I think Adesh alluded to in his words earlier, that we're working with them closely on the pre-launch planning so that we can hit this launch date of the middle of the year. But do you want to add anything, Adesh?
I would just build on that. So the reason, the other reasons why we felt that IST would be a really good fit is that when we look at their portfolio, their portfolio has critical mass from our perspective, but it's highly complementary to the profile of Zevtera. So it fits perfectly with the profiles of the drugs that they have in their portfolio so far. I think also the long-term commitment, just to remind you, the way that our partnerships are structured are that we participate over the lifetime of the product. And then especially for products in our space, usually value creation is more skewed towards the second half of the life cycle of a product. So having conviction in the long-term, in a long-term commitment of a partner is something that is also important to us.
So these were two additional reasons why we felt that IST would be actually a good fit for us.
And then maybe Marc, you could come back on the question about the fosmanogepix EAP and would it potentially be taking patients from the phase three studies?
Yeah, thank you, Brian. I mean, I'd like to start that this is an exceptional program with a really high demand, which reflects the high unmet medical need. For the clinical trial, there's really nothing to worry about it. The larger part in the clinical trial is primary therapy, and that is not the population that qualifies for the expanded access because these are patients who have no other treatment options, so they've already gone through a primary therapy. There is a salvage cohort, but when the study starts, patients from the expanded access would be channeled into the salvage cohort, which is somewhat smaller than the primary therapy cohort in the study.
I think on the positive side, across the world, we have more than 100 centers that are now familiar with the drug, and most of them convinced about the value of it and the efficacy, and they will be very motivated to contribute to the study.
Okay, thanks, Marc.
The next question comes from Jyoti Prakash from Edison Group. Please go ahead.
Hi, thank you for taking my questions. So my first question is on Cresemba. 20% YY growth in mature markets such as the U.S. is very encouraging. Just want to understand if there are any specific drivers for this and how much of this growth is coming from the pediatric label expansion. Is it related to the pricing or more on the volume side?
Yeah, hi, thank you for the question. I think I'll take that. I mean, I think essentially wherever you are in the world in terms of the launch sort of curve for Cresemba, it's very much a sort of market share gain story. So it's not growing because of market growth. It's growing because the market share growth. So actually, even in the U.S., where it's been incredibly successful, and it's the class market leader in volume terms, it's still sort of 20%-25% vis-à-vis voriconazole, the previous gold standard. So actually, and then in the launch markets, it's got just so significant potential, which is why I think we comment quite often about China, Japan, and Asia-Pac having big potential because they're so early in the curve.
But in every market, it's basically a market share penetration game because of the profile of the product rather than sort of market growth. And actually, your comment about pediatrics is interesting because I think where the pediatrics is happening, apart from bringing this product to a vulnerable population that hadn't previously been indicated for the drug, in absolute sort of cash terms, the pediatric opportunity is very small. But in a market like, and I think Adesh alluded to this, in the U.S., where it's sort of nine, 10 years old, it gives the field force and the medical affairs team something new to talk about for the product. So I think having the pediatric indication gives a whole new sort of energy to the organization, which helps for the growth of the product per se, not just in the pediatric population, but also the adult population.
Thanks. That's really helpful. My second question is on Zevtera. It looks like the initial commercial focus is on SAB, whereas the drug has been approved for three indications. So when can we expect the commercial push for the other two indications as well?
Yeah, this is Marc Engelhardt. I can answer this. So SAB, certainly, also when we designed the program, was clearly the indication with the highest unmet medical need. There's very limited treatment options that cover both MSSA and MRSA, and there's no approved beta-lactam in this space. So it clearly is differentiated in the SAB indication. There's more, I think, competition in the other indications, ABSSSI and CABP. But the medical need will be distributed. Some physicians will perceive the primary need in SAB, but there is need in community-acquired pneumonia too and in ABSSSI. And then SAB is associated with these two diseases. So we believe going to the market with this really broad labeling, including a pediatric indication and CUP, will just help with bringing this drug into practice.
While SAB, as I said, is the highest medical need, I think the other indications just contribute to giving this drug penetration into the market.
Thanks a lot. No further questions from my side.
Thank you.
The next question comes from Ram Selvaraju from H.C. Wainwright. Please go ahead.
Thanks very much for taking my questions. These are both, in a sense, related to the antifungal outlook, the long-term outlook. I was wondering if, A, you could comment on what you expect the dynamics and cadence to be of potential generic erosion of Cresemba once the product eventually loses exclusivity. If you anticipate that this will be more pronounced in specific territories, if so, in which ones? And if there are specific sub-geographical market features that would automatically lend themselves to an expectation that generic erosion would proceed more gradually. And then the second part of my question relates to phase 3 enrollment in the Fosmanogepix Pivotal Program. If there are any specific initiatives or strategies that you might undertake in order to accelerate enrollment, and if so, when you might expect to see the impact of such strategies should you elect to undertake them. Thank you.
Yeah, thanks, Ram, for the questions. I mean, I think let me Adesh might jump in as well, but your question one about the Cresemba shape of the sort of Cresemba curve after exclusivity loss. I think what we've gone on record saying previously, which we believe, is that your question is a good one because there are certainly different markets that will sort of evolve the Cresemba sales at different rates. And what we believe is that in the U.S. and in Europe, from 2028, the product will decline. The steepness of that will be for the U.S. and for Europe will be reasonably. I mean, we've got analogs we look at in terms of Voriconazole and other antifungals or other hospital-based products that have lost exclusivity. And there is a distinct reduction in sales in 2028 and beyond in the U.S. and Europe.
but there are other markets, like for example, Japan, which by that time, we believe, could be quite a meaningful market where the exclusivity runs into the 2030s. so actually, that market will have exclusivity to beyond 2028. and then there's China, which looking at I mean, China is in quite a dynamic situation in terms of the sort of environment in China. but historically, the use of branded Western-originated products tends to not proceed with the same decline after exclusivity loss as in the U.S. and Europe. so we think China could be a flatter decline than Europe and the U.S. and like I said, other markets could continue growing. so the net of all this is that we believe there will be a peak in sales in 2027, and then the product will start to decline in 2028 and beyond.
But our sort of description is that this will be more of a cone shape than a cliff, which some products have depending on the dynamics of the product in the market they're operating in. But hopefully, that sort of answers a bit about how we think about the evolution of Cresemba post-2027. In terms of your second question on the phase three enrollment and what are we doing to accelerate it and the trend in enrollment, maybe Marc, you could take that.
Yeah, sure. So we are making good progress in the invasive candidiasis candidemia study in initiating sites and advancing enrollment. I think we have the experience from the isavuconazole phase 3 program where we conducted mold as well as candidemia studies. And so one of the key things that we have done while developing the protocols was to get feedback from sites and investigators on the protocol to try and minimize any stipulations that could be obstacles for the enrollment. So that optimization we've done early on. And then for the operational conduct, I think there's slight differences between the candidemia study and the invasive mold study. So candidemia study is more sites, and then we have to really understand the workflows in the respective clinics and keep a constant engagement with these sites to prioritize the enrollment.
So that's the strategy that we know works and also works in this case. And for invasive mold infections, really a smaller number of sites, but these are investigators and opinion leaders that we work with for more than a decade, and they are highly motivated to bring a product like fosmanogepix with a broad spectrum, the tissue penetration, and the efficacy that's also reflected in the high numbers in the expanded access program forward. So there are slightly different strategies. It starts with minimizing obstacles for enrollment in clinical development, and then on the operational level, slight differences on how we optimize candidemia and how we optimize mold studies.
Okay, that's very helpful. Just one last question with respect to the R&D direction of the company. I just wanted to clarify whether you remain interested in the broader disease areas in which Tonabacase would have been applicable and not in the drug class to which Tonabacase belonged, or if you remain interested in the endolysin drug class still, even though you have elected not to move forward with Tonabacase.
Maybe I'll take this, Ram. I would say the answer to both is yes. In the sense of we are broadly looking at any kind of modalities, and that includes actually potentially also endolysins. I think we have also learned quite a lot from the evaluation work that we have been doing on Tonabacase. Secondly, we absolutely believe that there is an unmet medical need in the gram-positive space, and we remain interested in solutions that would help us to address that specific need.
Thank you.
Thanks.
The next question comes from Xian Deng from Pareto Securities. Please go ahead.
Hi, good afternoon, and congrats with the progress. Just one question from me. So with your cash position continuing to strengthen, which I guess gives you a good position to further advance the pipeline through acquisition or in-licensing, could you provide some more flavors on the progress and maybe what kind of drug profile that would best fit in your criteria? Thank you.
Thanks, so for the time being, we continue to see significant opportunities in the antibacterial and antifungal space, and that actually with all kinds of different modalities. Stage-wise, just as a reminder, based on the function basically of our business model, we are focused on opportunities or assets that are in late preclinical development up to phase two development, so that's sort of the range we're looking at. I think that should actually, I suppose, answer your question, so yes, absolutely, we are looking at opportunities. We're seeing also market opportunities in our space, and we are agnostic with respect to modalities.
Okay, thank you.
As a reminder, if you wish to register for a question, please press star followed by one. The next question comes from Thomas Maeder from Baader Helvea. Please go ahead.
Hi, thank you for taking my question, and thank you for the presentation. I just have one question quickly. First of all, on Fosmanogepix, just as a recap as well. So with the second phase 3 study that's set to initiate by the half of the year, I just wanted to kind of get a quick recap on the timeline, whether it was fair to assume that we'd still be able to anticipate a commercial launch by, say, end of 2028-2029. And on top of that, I'd love to know what kind of geographical sales states you'd envision for the compound and also what kind of key KPIs, so to say, you would want to get for potential partners in the key areas.
Okay, hi, Thomas. Thanks for the question. I mean, I think in terms of the fosmanogepix, maybe Marc, you could comment on the.
Yeah, I think we are on track with the timeline. So I think the time frame you suggested, we're comfortable with that time frame. So we don't anticipate a major delay, and we anticipate that both studies will be completed around the same time.
And then maybe to the second part of your question, maybe to start out with, in response to your question, just to remind you that Pfizer still holds the right of first negotiation on a global basis for the drug. So from a partnering perspective, geographic split, I'd say that's sort of the starting point. From a commercial opportunity perspective, probably the best way to look at the geographic spread is to look at Cresemba or just the antifungal market in general. So we believe it's truly a global opportunity with probably the US also reflecting again about 25% of the opportunity, Europe, a little bit more than that, China, maybe in the range of 20%, Japan, 5%, and the remainder spread over Latin America, MENA region, and so on.
So we have no reason to believe that it would be fundamentally different from what we have been seeing for Cresemba. And then on the financial, I suppose KPIs, you mean term-wise, here also, it's of course premature to discuss about what exactly the terms may look like. But just generally speaking, again, our business model is that we are willing to share into the commercial, let's say, risk and opportunity of our drugs. And that means whatever partnership we would envisage from today's perspective, at least, would be in a way that we participate over the entire lifetime of the product through, again, the combination of royalties, milestones, potentially also product sales, depending on whether it's more regional or a global partnership, which would allow us to have this appropriate participation.
Probably just to throw in one extra point, on this distribution that Adesh said for the geographic spread of potential Fosmanogepix sales being similar to Cresemba, that obviously differentiates it from the MRSA market, which is why we've consistently said that for Zevtera, the big opportunity is the U.S., because when you look at other analogs for MRSA drugs, it's the complete opposite of what he's just said for antifungals. It's much more biased towards a U.S. opportunity. But just to differentiate that point, probably.
Thank you. And I might just quickly bounce on that if we still have some time and about Zevtera as well. So obviously, with the U.S. market making up at least 80% of sales potential and the current climate about pricing pressures in the U.S., has it had any impact on your forecasting and other potential risks that you envision for the compound there?
Maybe that's again something that I could take. First, a disclaimer, pricing market access is sort of the responsibility of our partner, IST. Therefore, we will not be directly involved beyond what is legally possible to be involved in. However, I would also say that we have, I think, for antibiotics, there is a generally accepted range where novel antibiotics are being priced, basically. We have no reason to believe that anything in that perception has changed so far. Secondly, you may have seen that we have actually NTAP, so new technology add-on payment for Zevtera, which should also, in the initial years, sort of mitigate any impact from a pricing perspective, from the perspective of hospitals. Generally speaking, we have no reason to change our projections about how well the drug could do in the U.S. based on recent discussions on the pricing environment.
That's perfect. Thank you for clarifying. That's it from my side. Thank you again.
Thank you.
Ladies and gentlemen, that was the last question. I would now like to turn the conference back over to David Veitch for any closing remarks.
Thank you for your questions, and thank you for your attention, and enjoy the rest of your day. Thank you very much.
Ladies and gentlemen, the conference is now over. Thank you for choosing Chorus Call, and thank you for participating in the Basilea Pharmaceutica Full-Year Results 2024 Conference Call. You may now disconnect your lines. Goodbye.