Welcome, everybody, to our new webinar on the first year 2024 results. This is an exciting day for us, following the announcement of today, that we issued this morning in a press release. We have announced and communicated that we have reached a new agreement with Sun Pharma for the global commercialization of Nidlegy, of Fibromun, and we will expand on that during the presentation. We also have other exciting results to share coming up from the chemistry team with the new OncoACP3 ligand. We have collected the first imaging in patients, which look very, very exciting and much better than other PSMA ligands that are currently used now. As always, on the call, we have Professor Dario Neri, our CEO, Dr. Laura Baldi, our CFO, and myself.
We will give a presentation which lasts around thirty minutes, which is being recorded, and as always, this will be followed by a Q&A session, which is not recorded. Without further ado, we hand over the stage to Professor Dario Neri, who will start off with the presentation.
Thanks a lot, Emanuele, and welcome everybody. As always, we start with a forward-looking statement, and then we take the opportunity to present that the Philogen group is actually a Swiss Italian company. Whenever you see this green color, characteristic of Philogen, we make reference to an antibody pipeline, which is growing in number and also in development. We have a fully owned daughter company called Philochem, that focuses on small molecule targeting agents, and this Philochem company is based in Zurich, and both Philogen and Philochem together aim at targeting tumors and other conditions with ultra-selective targeting agents. We are listed on the Italian Stock Exchange, and over the years, we have collaborated with many pharmaceutical companies.
The approach that is really common, both for the antibody products and for the small molecule products, is that we take payloads of proven therapeutic benefit, for example, drugs, radionuclides, a lot of work with cytokines, and we fuse them to ligands that selectively go to the site of disease. These ligands are antibody fragments when the payload is a cytokine or a small organic molecule when the payload is small, such as a drug or a radionuclide. In both cases, these ligands are discovered from proprietary encoded chemical libraries or antibody libraries that we have developed over the years, and they represent the discovery engine of the group. So we take payloads of proven activity, we make them better. The opportunity of ligand-based pharmacodelivery is well explained in this slide. You see a gradient of targeting performance results in cancer patients with different molecular entities.
At the very left, you see a patient with mesothelioma, so the tumor is somewhere around the lungs. The patient received docetaxel, standard chemotherapeutic agent, labeled with carbon-11, and basically, the nuclear medicine tells you that this poison goes everywhere in the body except to the tumor. There is no preferential uptake in the tumor at different time points, and you see a very strong uptake in liver, spleen, feces, urine. Again, confirming that there is no chemical reason why a chemotherapeutic agent should preferentially localize to the tumor, and it doesn't. Now, antibodies are very fashionable in IgG format, but actually, they are not very good targeting agents. You look here at a patient with metastatic colorectal cancer, who had received an anti-FAP antibody that was radiolabeled. At seven days, you see some accumulation in the tumor, but this is not really fantastic.
We get better results with antibody fragments. Here you see one of our antibodies called L19, at twenty-four hours with a very nice preferential accumulation in liver mets of breast cancer. I think you get tumor to ratios, tumor to organ ratios of about ten to one, and this is as good as it gets with antibodies, and it's useful, as you will see. But the world record of selectivity can be achieved when we have ultra-high affinity, small ligands that bind to targets with antibody-like affinity, but being small, they go to the target much better. And you see a patient with metastatic breast cancer. At one hour, you see already everything you need to see. The primary tumor in one breast, the many bone mets, the liver mets, and the rest of the body is clean.
The mission of our company is to achieve selectivity of therapy by means of selective localization of our targeted drugs. You see that the pipeline is growing and is advancing. We had previously announced the partnership with Sun Pharma in Europe, Australia, and New Zealand for Nidlegy dermat oncology program that we will present again. Today, we have announced a global deal with Sun Pharma for Fibromun, and Emanuele will expand on this drug that is initially developed in soft tissue sarcoma and glioblastoma. I will then expand on certain developments in the chemistry field, which are really exciting, and we trust that you will like the results. Let me start with Nidlegy. Nidlegy is a product that originally was intended for the treatment of melanoma, Stage 3 melanoma, but also Stage 4 melanoma.
but we have later expanded the clinical investigations also to other non-melanoma skin tumors, like basal cell carcinoma and squamous cell carcinoma of the skin. You see that the incidence of melanoma is high, and for BCC and SCC, it's even higher, and we will expand on the clinical results in a split second. Nidlegy is a combination of two active ingredients called L19-IL2 and L19-TNF. In these products, the L19 antibody, specific to EDB fibronectin, is used to anchor interleukin two or tumor necrosis factor at the tumor site. We mix the two products before administration. The product enjoys a Combipack authorization by the EMA, and this is the only product that we give intralesionally because we treat the skin tumors.
Now, I'll be short about the development activities in melanoma, because basically, we have previously announced that the phase III trial in Europe had reached the primary endpoint, recurrence-free survival compared to the control group. The clinical data were presented at ASCO on May third. In parallel, there is a similar trial which is also developing in the United States. We have already treated 104 of the target of 186 patients. A pre-BLA meeting is planned, and we foresee that the phase III results will be used to complement the European data and hopefully get full approval in the United States. We have a partnership agreement with Sun Pharma that I've mentioned before, and in addition, we have also started a U.S. trial in Stage 4 patients in combination with the PD-1 blocker, pembrolizumab.
We take the opportunity of this webinar to show you some updates in the field of non-melanoma skin cancer as well. We are running two phase II clinical trials, in the first one that was started in the DUNCAN trial, we have already treated 65 out of the 72 patients that were intended for the study. The first results have been published this year, and you see patients with very nasty lesions in the face that responded with complete remission upon intralesional administration of the drug, which appears to be very safe and efficacious, with a response, complete response rate, according to BCC-like RECIST criteria of approximately 50%. As mentioned, the second phase II trial, INTRINSIC, is also ongoing.
The product is also studied in both DUNCAN and INTRINSIC trials in squamous cell carcinoma in high-risk lesions of the face, and you see how patients could enjoy a complete and durable response following administration of Nidlegy. Typically, the responses show up two, three months after the onset of therapy, and they reported the complete response rate is also very high compared to approved agents in the same indication. We are also starting to observe complete responses in Kaposi sarcoma. This is a smaller indication with about 2000 new cases per year in the United States. But you see the photographs of two patients with different types of lesions at baseline, one with very extensive lesions, the other one with more localized lesions.
But you can see that basically, two, three months after treatment, the patients enjoyed the complete responses, which are still ongoing. So these are two complete responses out of three patients, which have been treated, so we are encouraged by the fact that, activity is also being observed in other indications. So in summary, and then I will hand over to Emanuele, we have promising results with Nidlegy, not only in melanoma but also in non-melanoma skin cancer. For non-melanoma skin cancer, our, advisory board with global key opinion leaders have advised us that the best initial positioning for Nidlegy may be in third line BCC and second line SCC. This does not exclude that additional trials will be run, and these trials in the last line setting do not require a huge number of patients, and that's why we are actively pursuing those objectives.
So with this, I hand over to Emanuele, who will guide us through the developments in Fibro.
Thank you, Dario. You remember that with Fibromun, we're tackling two huge unmet medical needs, soft tissue sarcoma at the advanced or metastatic stage, and glioblastoma. Just as one slide as a recap, you remember glioblastoma is the most malignant primary brain tumor. There are about fifteen thousand new cases every year, only in the U.S., there are even more in Europe. And unfortunately, at present, the mortality rate is virtually 100%. Patients with recurring disease live, let's say, around eight months. This is the median overall survival, which has been published in many trials. The situation in soft tissue sarcoma is also very grim. We're speaking about here thirteen thousand six hundred new cases every year in the U.S. You have to imagine that 50% of them are metastatic, and also at that metastatic stage, the mortality rate also reaches almost 100%.
Here, the median overall survival is about 12 months. The Fibromun is one of the two active ingredients of Nidlegy. We have the antibody here in green, that brings selectively the TNF, which is the anti-cancer payload at the site of disease. The product is given for systemic application by intravenous infusion. We have orphan drug status, both in the STS and GBM, both in Europe and in the U.S., and we have shown that the tumor, tumor uptake is excellent, with also excellent tumor to organ ratios in different organs, and this morning, we announced the new strategic, licensing agreement with Sun Pharma, which expands, compared to the one we have already with Nidlegy. It has been pretty exciting for us, first because the two teams already on Nidlegy works very well together. The two companies have synergistic backgrounds.
They're very strong in discovery, and they're very strong in commercialization, and Sun Pharma is a company in extremely good health. Just to give you a few numbers, the number of employees has grown from 38,000 last year to more than 41,000 new employees this year. The market cap has virtually doubled since last year. The company has a global footprint, operates in more than 100 countries. The revenues are around $6 billion every year. And they have a clear commitment to now also commercialize the specialty products. And, you know, as a last note, Nidlegy contains TNF, which is also the product of Fibromun, so it makes a lot of sense to collaborate with one company on both products.
As a duty, Sun Pharma and rights, Sun Pharma will have the global commercialization rights and duties in all indications, and we also have the duties to complete the ongoing trials in both soft tissue sarcoma and glioblastoma. Together, we will expand also in other indications. The post-commercialization economics are pretty exciting for us. There's a split of 45 for us and 55 for Sun ratio in terms of basically sales and royalties. We will take care of the production, and they will take care of the commercialization aspects. Other terms were not disclosed in the press release. With regards to the glioblastoma programs, you remember they started in Switzerland a few years ago, and now they have a global footprint, so in Europe and U.S.
The trial GLIOSUN, ongoing in newly diagnosed patients, is basically finishing phase I part, and we should be able to present the initial data of the phase I very soon, and then at the next webinar. I will expand on the GLIOSTAR trial in patients of first progression. This is the most advanced trial we have, and it's ongoing in Europe. Also, the GLIOSTELLA study started very fast in the U.S., in patients, basically, with last-line glioblastoma. With only one center, we have more than 10 patients. Now we're expanding the number of centers, and also on that, we should be able to provide the initial data in the next webinar.
With regards to the GLIOSTAR study, we presented already several times the exciting phase I data published in Science Translational Medicine, where a good proportion of patients went into almost virtually near complete remission, long lasting, something that is never seen with lomustine alone, especially in recurrent glioblastoma. Now, the phase II part is randomized, it started last year. You see patients receive either lomustine as standard of care, or the combination in the experimental arm, and we look at overall survival as primary endpoint. From the graph on the right, you see that the enrollment rate continues to be very fast. We already treated 104 patients out of 158 to be enrolled as per protocol.
We expect that to be completed, I mean, the enrollment to be completed by April next year, and the trial readout is expected by the end, let's say, of 2025 . In soft tissue sarcoma, we also have three studies with powerful potential. The phase III, ongoing in Europe in the first line setting, has completed enrollment. We now are waiting for events to mature. You see from this graph, we treated two additional patients. This is allowed in, basically by the protocol, and this is something which is common in virtually all powerful studies. We communicated also last time that we passed successfully the first interim analysis, which gives us hope for the readout of the study, which is expected, around the end, of the year or beginning of next year.
We have also an ongoing study in the U.S., on which we will keep you updated, but the phase II in Europe, which is randomized, last time was also quite advanced, more advanced, and we are only missing eight patients for the completion of the enrollment. Since these patients have advanced disease, those are last line patients, we expect also the completion of the enrollment to happen around the beginning of next year or end of this year. This is something which is pretty exciting for us, because aside from Nidlegy, in which we have submitted a marketing authorization application to EMA, we've started a dialogue with FDA.
We now are expecting these new trials in sarcoma with Fibromun to read out very soon, and this will be basically the new drug that for which we will ask for a marketing authorization application, then it's a successful readout of the trials.
I'm glad also to give you an update about some aspects of the chemistry pipeline, which are very exciting. First of all, I'll start with celebration. Our head of chemistry, Samuele Cazzamalli, has won the 2024 Medicinal Chemist in Industry Award, which is probably the most prestigious medicinal chemistry award of the European Federation of Medicinal Chemistry. Basically, having Philogen as a small, medium-sized biotech company, winning over other larger companies in terms of innovation potential, fills us, of course, with pride. But what is important is also the quality of the products, and we come immediately to them.
You remember from the presentation before, that really the vision is to capitalize as much as possible with state-of-the-art antibodies, but whenever we are able to make ultra-high affinity small ligands, the targeting results are fantastic, both macroscopically, but also at the microscopic level in terms of the ability to homogeneously reach the tumor cells within the neoplastic mass. Now, we have a number of programs which are ongoing, and we have different modalities. Using our DNA-encoded chemical library technology, we discover the ligands, we optimize the ligands, and then we can choose between different payloads, radionuclides, drug conjugates, and other type of conjugates. Again, for the sake of simplicity, today, I will focus only on clinical results with radionuclides and drug conjugates.
We have at least five targets with validated targeting performance in humans, and today I will focus on FAP and on ACP3, and I'll start with fibroblast activation protein. When we look at the programs with radiopharmaceuticals, we are active both in imaging and in therapy. In imaging, we have successfully imaged more than 200 patients in collaboration with our clinical partners using the gallium-68 version of OncoFAP. A phase I trial, sponsored by Philogen, has been successfully completed with accurate dosimetry, and now the duty of development sits with Blue Earth Diagnostics, a company of the Bracco Group. In therapy, we have already successfully treated the first three patients with lutetium-177 OncoFAP-23. The phase I trial has been approved by authorities, and the patients have received up to three doses, which were well tolerated up to 200 millicuries.
We think that this very initial data are a good starting point for the development of the program. I would like to focus a little bit also on non-radioactive conjugates for therapy, and specifically illustrate our OncoFAP-GlyPro-MMAE product. This product is very attractive, because FAP is not only a target for the OncoFAP moiety, here depicted in blue. FAP, in molar excess at the tumor site, is also a protease, and so you can imagine that while you target FAP in the tumor, a neighboring molecule will cleave the linker that contains the GlyPro linker, and will set free a potent payload, such as monomethyl auristatin E.
So this is the theory, and in practice, after successful animal studies that we have published in Clinical Cancer Research, we have launched a phase I study in animal patients, and you see that the design was to escalate the dose from 3.5 mg per meter square, up to 10 mg per meter square, with the possibility to expand at this dose, and one dog per dose level, and once a week for four weeks with complete examination by CT scan and hematology. So we learn a lot, actually, in patients which are quite large in mass and have spontaneous tumors. And we have already actually seen that the treatment is well tolerated up to 10 mg per meter square, so we may even go higher with the dose.
We have started to record objective responses that were confirmed by this CT scan in very difficult to treat tumors, and I would like to show you one example. You see both the photograph but also the CT scan of a dog called Coco with a sarcoma. You see it in the scan here, and basically, after four injections, the mass was substantially reduced, as you can see from the pictures. The protocol unfortunately did not allow at the time for retreatment, so waiting several months, and not being able to give OncoFAP again, the tumor grew back, and it became enormous. You can see that this was a tumor of 15 cm of diameter.
So we treated again with 10 mg per square meter of OncoFAP-GlyPro-MMAE, and you can see that in just four weeks, the tumor mass was substantially reduced, and you can see it both in the photograph and in the CT scan. So when we see this type of activity in vivo, we are optimistic that similar results may be possible in human patients. Now, I want to finish with ACP3, a target for prostate cancer that I had introduced in the past at the preclinical level, and I'm very glad to show you how this program continues. The product is developed for metastatic prostate cancer, and the field of prostate cancer therapy is really dominated by a different target called PSMA, prostate-specific membrane antigen. And there are radiopharmaceuticals on the market that sell a lot.
For example, for imaging, the best-selling product is Pylarify, that has reached now sales over $1 billion per year, and this is Amgen's product. Pluvicto is a Novartis product for therapy, where the radionuclide is lutetium-177, and you can see that the product is already estimated to sell more than $1.5 billion per year. So this is a market that cumulatively is greater than $2.5 billion. Now, if we look at therapy, Novartis successfully demonstrated that Pluvicto could extend the median progression-free survival in the VISION trial, but also, unfortunately, if you see, when you wait 18-20 months, basically almost all patients progress, and it's very difficult that Pluvicto may be a curative option for these patients.
And the problem is you cannot give higher doses because there are some liabilities associated with target antigen PSMA. So with PSMA targeting agents, not only with Pluvicto, you see invariably an uptake, a durable uptake in the kidney, an uptake in salivary glands, in lacrimal glands, and if you go up with the dose, then there would be unacceptable toxicities in these organs. So the way to outperform the PSMA targeting agents is to go for a different target, an acid phosphatase called ACP3. You see a panel of normal organs stained with both targets, PSMA and ACP3. If you see brown, it means that the target is present in normal organs.
You see that PSMA has a number of liabilities in kidney, in the GI tract, and even in the salivary glands, whereas ACP3 is completely clean in all organs, exception made for prostate, which is not an issue for prostate cancer patients. ACP3 is cleaner than PSMA. Now, when we look at tumors, a first study revealed that in some patients, you look at serial sections from the same patient. In some patients, both PSMA and ACP3 are good. You see it from this brown staining. But in many patients, ACP3 is good and PSMA is very weak or even absent, and ACP3 is always positive. We contracted out a larger study to the University of Pisa, and you continue to see much of the same.
So serial sections stained with ACP3 or PSMA, and the pathologist included a score where red is very positive. This is also red. I'm sorry, it's a type of the presentation, but this is red. You can see it from the brown staining. And ACP3 is almost always red, so score three, whereas PSMA is often very weak or even with undetectable antigen. And this is in different types of Gleason scores for the patients, and much of the same in the next slide. So if you put it all together, ACP3 in this study, in this independent study, was a top scorer, so strongly expressed in 34 out of 39 samples, whereas PSMA was top score only in 23% of the specimens. And this, I think, provides a strong motivation to develop.
Now, we discovered OncoACP3 thanks to our DEL technology, and what you see here is percent injected dose per gram in tumor and in different organs at different time points, going from two hours to 72 hours. The uptake in normal organs, including kidney and salivary glands, is extremely low, but the uptake in tumor is very high, starting at about 70% injected dose per gram and not even reaching 50% after 72 hours. In mouse studies, we could cure mice at doses that were about factor 10 lower than what used for other radiopharmaceuticals, and we have initial clinical data obtained in collaboration with the University Hospital Münster, Professor Schäfers and Professor Backhaus. You see here a couple of patients that were imaged both with a standard PSMA agent and with our ACP3.
We show you one example with fluorine-18 and an example with gallium-68, and the story is very similar. The PSMA targeting agent, as expected, has uptake in salivary glands, lacrimal glands, GI tract, here even liver and kidney. Whereas the background is very clean already at one hour for OncoACP3, and you see all the metastases that you could see with PSMA, plus other metastases that were not suspected. Here, this is a comparison based on gallium-68, and again, it's very clear that OncoACP3 gives a much better profile, both in terms of uptake in the metastatic lesions, these black spots that you see, and very clean organs already at one hour after injection. Very high SUV max values, and it's clear that for therapeutic interventions, this will tolerate a therapeutic radionuclide better than a PSMA.
So, some bold statements. The PSMA market is about $3 billion per year, growing. PSMA has liabilities in normal organs that ACP3 does not have, plus ACP3 is more abundant than PSMA. In imaging, ACP3 performs better than PSMA, and this opens therapeutic options, for example, the use of alpha emitters that have curative potential. We have strong and fresh IP position on ACP3, and we believe that ACP3 has the potential to take a big portion on, of the PSMA market, potentially most of it, because the comparison until now is clearly in favor of ACP3. I briefly go through the last slide, which are the financials, and our Chief Financial Officer, Dr. Laura Baldi, is available in case you have additional questions.
So the results of the first half of the year are for low revenues, EUR 1.7 million , which are lower compared to last year, but these revenues are variable for our company, because we don't have products on the market yet. We don't have a steady stream of revenues. In terms of operating expenses, we are at EUR 16.9 million for half a year. This is an increase compared to the corresponding period last year, because we have accelerated clinical trials, and we have expanded manufacturing activities. So for the first months, the EBITDA and the net results correspond to a loss of about EUR 15 million .
The financial position as of the end of June was with a liquidity of EUR 64 million , and the cash burn is still limited for a company of our size, especially if you look at the programs. If you subtract the money which is allocated to the lease of facilities for a number of years, this would correspond to a positive net cash position of still EUR 50 million . Still, based on the evolutions of our business and some of the results that we have disclosed and that we will disclose, we expect that financials will be very positive at the end of the year, and this is a statement that we can make firmly, and for this reason, we conclude here a webinar that hopefully has shared with you many positive results.
As always, we are glad to open the discussion session, which is not recorded. Again, if you have specific questions for the financial part, they should be addressed to Laura.
Recording stopped.
Okay. As I start with the usual... I think Andrea Arniani wants to speak, so I'll let him-
We have five questions, and maybe we go in a row. We start with Andrea Arniani. You are on mute, so we would need,
Could be that the hand was raised by mistake also, so if we wait ten seconds if-
We wait 10 seconds to see if Andrea Arniani has a question. If yes, you should please unmute your mic, and if this is not the case, then we go to the second in the list. That would be Vanessa McCann.
Vanessa, you should be able to speak in case you raised your hand, on purpose.
So if you want to unmute, you can. And if this is not the case,
Then we ask, Clémence.
Then we ask Clémence. Yes.
Clémence?
Yeah. Can you hear me?
Yes.
Okay, perfect. Thanks for the update, and congratulations for your partnership. Great news. I just had a question on that first. Just to get a sense of the split of expenses, post-approval, when you say you'll handle production and they will handle commercialization, should we understand that they will bear all marketing costs, and you will bear the COGS, or will it be split 45, 55 after commercialization? And the second one, more general, is there any reason why they went for a global partnership for Fibromun, whereas they went for sort of a more local one with Nidlegy?
Okay, so the situation is very clear. Let me start with the geography. We started with a European focus for Nidlegy. It was the first partnership. It made sense to go in Europe, Australia, and New Zealand, because these are countries with very high incidence of melanoma. The incidence of melanoma is very different in different countries, and it's not excluded that we may expand the Nidlegy agreement to other countries in which we do development, namely the United States. But I think at the time, it made sense to start like that, and over the years, we have started really to appreciate the qualities of Sun Pharma. It's a great partner, and it's a privilege to work with Sun Pharma.
When it comes to glioblastoma and soft tissue sarcoma, these are indications which unfortunately impact on people, irrespective of the color of the skin, and the incidence of these conditions is pretty homogenous at the global level. If the products prove to be efficacious, these products need to be offered on a global basis, because basically, as of today, there are no efficacious treatments in the settings that we are investigating. So it made sense from the very beginning to look for a global agreement and to be able to offer the products as broadly as we could. Now, in terms of who does what, it's clear that we have always produced the product. We are the originator of the product.
The product is given at low dose, on average one milligram per patient, and so we will continue to do the manufacturing at our cost, and Sun Pharma is responsible for commercialization, and also commercialization has many expenses, and I cannot expand more than this, because the press release that you have read is quite limited. We are pleased of the collaboration, and there is a very clear statement about the split of economics.
Okay. Perfect. Makes sense. Thank you. And just a quick one in non-melanoma skin cancer. So last time, we're talking about a readout in 2026, accounting for one year of recruitment and three to six months follow-up. Now, the study are not launched yet, but I think we can expect a launch soon. Is that timing still doable, and will it be only in Europe, or will you expand centers in the U.S. as well?
Yes. No, I think the timelines are confirmed. Time will tell, but in our projections, the timelines are confirmed. I think we have demonstrated with Duncan and Intrinsic that we could treat the patients that we had planned according to the estimated timelines. The clear commitment is to do the development in BCC and in SCC at the global level, so both in Europe and the United States, again, because the incidence of high risk BCC and high risk SCC is similar in Europe and in the United States.
Okay, perfect. Thank you so much.
Thanks a lot, Clemence. Then, it's Rajan.
Hi. Can you hear me?
Yes.
Hi. Thanks for taking my question. Just a couple of follow-ups on timelines and on the new Sun Pharma agreement. So maybe just on the Sun Pharma agreement, I know that you're kind of limited in what you've disclosed so far, but just wondering if there are any. Is there an upfront due to Philogen from Sun in line with the deal, and then if there will be milestones on a forward from here? That's question number one. And then secondly, just on Nidlegy and melanoma, just wondering when you expect to have the pre-BLA meeting with the U.S. FDA. Is that likely to be a 2024 event, or will that now be 2025?
And then maybe just following up on the previous question, the BCC and SCC trials for Nidlegy, when should we expect data from those?
Okay, so there are three questions, and I hope I can take all of them. You know, the press release is very limited, and I will not add much, but I've made a quite strong statement at the end of my presentation that we are very confident that the economics this year, not only because of the new deal but also because of other activities, will be very good. And so I think all we have to do is to wait and see also what the future disclosures are. And the agreements in this field often include different components, but they will be revealed as time goes by in our financial statements. Now, the pre-BLA meeting, basically, we are at filing, and so whether it happens at the end of the year or at the beginning of next year, we'll see.
It depends also on the dates that we get, but basically, we have done the preparatory work, and we intend to use the opportunity to address not only the pre-BLA activities but also introduce the non-melanoma skin cancer activities, because, as mentioned to Clemence, we have the interest to execute the next trials on a global scale. Now, the last question related to the situation with the U.S. trials in melanoma. We have two trials. We have the Neo-DREAM trial, where we have treated 104 out of the target of 186 patients, so we still believe that the trial has the potential to read out, probably around 2026.
The trial in Stage 4 melanoma in combination with pembrolizumab has also started recruitment, and so, over time, we will see, you know, if we can meet the timelines. As always, we keep you informed at regular webbys.
Thank you.
Now, when you ask about the BCC and SCC, when do we expect the data? Of course, in these phase II clinical trials, the data read out continuously. These are non-controlled trials, as all the products that have been approved in these indications. So they show over time, and you may have seen that we report the complete response rate in this setting. We had important information from the authorities, for example, that RECIST-like BCC criteria are an acceptable standard, and complete response rate is an acceptable endpoint for the trial. So I think we have clarity about what we have to do, but in addition to DUNCAN and INTRINSIC, we now have to run these last trials, and then I think also the package of dataset will be large enough.
Thanks. Sorry, if I could just follow up on those phase III trials or the next trials, the pivotal for BCC and SCC. In terms of kind of timing, when do you expect to initiate those?
2025, for sure. We had initially entertained the idea to go in first line, but we have received very clear guidance from the authorities that if you go in first line, for example, in BCC, you have to compare to Hedgehog inhibitors. In second line, you have to compare to PD-1 blockers, which is a possibility, and I don't want to exclude it in the future. But we see a big request for the drug. A lot of patients really do not tolerate Hedgehog inhibitors because of horrible side effects, and a lot of patients do not want to be treated with PD-1 blockers, or if they do, they get out of the study. So there are clear opportunities in third line BCC, where there is no therapeutic alternative, and this calls for a single arm trial.
The same is true in SCC post PD-1 failure. This is essentially what we have decided to do, also supported by the recommendation of the investigators. The request for the drug is very big because you can imagine SCC is a disease that kills. BCC does not kill, but is a disfiguring disease. More and more often at our clinical centers, patients even ask to skip surgery when it's disfiguring, because the results are very nice, and I think they're documented in our publications.
Okay, thank you very much.
Thanks, Raj.
Thank you, Raj. Walter, you should be able to speak now.
Can you hear me?
Yes.
Okay, thank you. My question mainly regards to the Stage 3 melanoma treated with Nidlegy. And especially my question regards two elements. The first one is, probably you touched on during the presentation, but I didn't write it. So if it's late, can you repeat it to me, whether or what is your strategy in U.S., so the application in U.S.? First one. And second one on the commercialization in U.S., if you end up or come to a decision on the commercialization to the U.S. geography. Thank you very much.
Yes. These are good questions. The strategy is very clear. In Europe, we have filed for the marketing authorization application, and the process is ongoing. In the United States, the pre-BLA meeting will serve to clarify one issue. The U.S. authorities may accept the European data and may decide to work on European data to give conditional approval to be confirmed by the U.S. results, or they may decide that European data are not appropriate for a conditional approval, and they want to see the American data for full approval, hopefully. This is entirely their decision. They have said it from the beginning. They told us that when we have the European data, we should go to them and present the data, and that's exactly what we are doing.
So we don't know what the FDA will decide, but the pre-BLA meeting is certainly important for that purpose. And then the commercialization, I've mentioned it, and I'm glad to repeat it, that we have active discussions looking at possibilities to have also Nidlegy commercialized in other territories, but these discussions are ongoing, and as always, we communicate if and when such deals are reached. At this moment in time for Nidlegy, the only agreement which is in place is with Sun Pharma, and it covers Europe, Australia, and New Zealand.
Just to follow up on the first question. So you expect FDA feEDBack by the end of this year, or we will expect it by the end of 2025?
It's a process, so we have to file, and we are doing it now, the Pre-BLA meeting, and we have waited a little bit because we wanted to make sure that we present both the consolidated melanoma data but also non-melanoma skin cancer data. Then FDA offers a meeting, and whether it's at the end of 2024 or at the very beginning of 2025 remains to be seen. It also depends on the calendar which they offer. And then usually the way it works is you file an application providing data, they digest the data, then they make a preliminary summary, and then they give the final summary. So it's a process which takes a few months, and so we are in the middle of the process.
Thank you.
Then we have last question from Isacco Brambilla.
Hi, everybody. Hope you can hear me well. Couple of questions from my side. The first one is quite high level, so if you can elaborate on the pipeline in terms of news flow you should share, say, by the beginning of the year or the next six month. Second question is more specific on the small molecule platform. So it looks like you are increasingly thrilled on the potential of ACP3. Could you give us a sense of the time frame for trials related to this small molecule, just to have an idea, three, five, 10 years, which is your ambition here?
Yes. No, thanks a lot, Isacco. Now, in terms of news flow, some news have already come out, of course. So if we look at the future, the very next steps will be the readout of the Fibromun trials. As mentioned, with FIBROSARC, we have completed recruitment, so, you know, the time is driven by the events, anything between December and probably April next year. We don't know precisely, but the events, once we reach the target number of events, we will unblind the data, and we will look at the result. And this is true for first line, soft tissue sarcoma and, third line, soft tissue sarcoma. We will announce, very soon, as mentioned by Emanuele, the phase I results in, first-line glioblastoma, so the GLIOSUN trial.
This data are not blinded, so we are looking at them, and we are excited by what we have seen, but we want to give a comprehensive vision at the next meeting, and then, of course, there is the regulatory update about the Nidlegy programs, so this, in terms of antibodies, I would say these are the most important steps. Of course, completion of recruitment in GLIOSTAR, and eventually readout at the end of 2025 is also an important milestone. Now, in terms of small molecules, you have seen that we pursue actively both radiopharmaceuticals and non-radioactive products. In the field of radiopharmaceuticals, we have already a partnership with Bracco, or better, with Blue Earth Diagnostics, which is part of the Bracco Group, for OncoFAP imaging.
I think it's very clear that ACP3, FAP, and even Carbonic Anhydrase IX, a third target on which we are active in the clinic and which we have not presented today, they represent attractive targets, both for in-house development and for partnering. We have the financial capabilities to run those programs independently, but it may also be that if we find the right partner, we partner the radiopharmaceuticals. So this is another field in which there will be a news flow, because you can imagine, we study with our partners four patients per week by imaging with ACP3, and soon, we will start treating those patients also for therapy. So this is also an element of news flow that we expect in the coming weeks and months. When we look at the non-radioactive pipeline, I made clear statement about OncoFAP-GlyPro-MMAE.
It's a product which has the ability to shrink huge tumors in dogs. So the next step is to take it to the clinic in patients. And we have other components of the small molecule-targeted therapeutics which have not yet been disclosed or have only partially been disclosed in the literature, but they will be disclosed in the coming months. And, for this reason, I think the news flow should be a rich news flow, for good or for bad, both for antibody products and for small molecule therapeutics. The last topic is: What is the vision? The vision is always the same. If products are good enough, move them to completion of pivotal trials alone or with partners. If products are not good enough, we have a sufficiently rich pipeline that we can kill the one or the other program and focus on what looks promising.
We are data-driven, we are honest about the data, and the data drive our developments, for good or for bad. It's clear that ACP3 is particularly attractive. I think the data speak for themselves, and I hope that you share our excitement. We always thought it would be the same when we looked at the mice, but looking now at the superiority of ACP3 over PSMA in the clinic is very, very satisfactory.
Thank you, Isacco. So, with this, if there are no additional questions, we thank you for your time, for your attention, and as always, we are available for one-to-one calls, so reach out to us directly in case you want to have a call with the management. Thank you very much, and have a nice rest of the day. Bye-bye.