Welcome everybody to this new webinar, and thank you for joining us today. As always, we have our CEO, Dario Neri, and our CFO, Laura Baldi, and myself, that will provide an update on our latest clinical developments and financial results as of first half 2026. The presentation is being recorded and will be followed by a Q&A session, which is not recorded. As we have a busy agenda with 48 slides, without further ado, I hand over the stage to Dario Neri to start the presentation. Over to you.
Thanks a lot, Emanuele. The first slides are very well known to you. We are a Swiss-Italian biotech company listed on the stock exchange in Italy, and you see that the three locations in Siena, in Milan, and in Zurich, they are all important for the company, and we are indeed expanding them. Today, I'm calling from the Zurich operations. We continue to be active in ligand-based pharmacodelivery. We have at present clinical operations with drugs, with radionuclides, with immunological modulators. We are expanding beyond cytokines, and these payloads are delivered to the site of disease by means of targeting agents, which are nothing but molecules that bind to markers of pathology, and these ligands can be antibody fragments or small organic molecules. The quest is a quest for selectivity. We see really a gradient of selectivity from left to right, looking at patients with cancer that receive radioactive drugs.
We see that conventional chemotherapy, for example, docetaxel, goes everywhere except to the tumor in this mesothelioma patient. Liver, spleen, feces, urine, but no preferential uptake in the mesothelioma. With monoclonal antibodies, the situation doesn't get much better. We get much better with antibody fragments. This is one of our patients with liver mets of breast cancer. And when we have small ligands with antibody-like affinity, two accessible targets. This is really the world record of targeting. You see 60 minutes post-injection, a patient with metastatic breast cancer, every lesion. So the primary tumor, the bone and liver mets are clearly visible. Our pipeline has grown both horizontally and vertically. We have more products, more indications, more studies. The studies which have been completed are indicated in blue. The new studies launched in 2026 are indicated in red.
As always, we'll go through the products and tell you what's relevant for late stage and for early stage products. And I will give the presentation together with Emanuele, as usual. Nidlegy is our most advanced product. It's a cocktail of two immunocytokines with an EMA combination pack authorization. We give it intralesionally because we treat, so far, mainly skin cancer patients, and we have focused both in melanoma and non-melanoma skin cancer. We had previously presented the European data of the pivotal trial, 256 patients in locally advanced melanoma. Two arms are receiving surgery as standard of care, and our treatment arm with Nidlegy in the neoadjuvant setting, followed by surgery with recurrence-free survival as primary endpoint.
I'll show you the updated data that have just been published in the Journal of Clinical Oncology. It's nice to mention that an expanded access program, managed by our partner, Sun Pharma, has treated some 330 patients in about two years in France and in Germany. We are very delighted to see the adoption of the product. This is the primary endpoint of the study, recurrence-free survival as a function of time. We have just published in the Journal of Clinical Oncology the 36-month, basically, monitoring of the data that confirmed the very nice separation of the Nidlegy arm from the control arm with good hazard ratio and p-value. In terms of company operations, you see that we have done everything we promised to do.
We had scientific advice with the German authorities, scientific advice with the FDA, which has defined a very clear path for a possible approval in the U.S., pending successful outcome of the U.S. trial. Pre-submission meeting with rapporteurs and submission at the EMA on July 23rd. We are awaiting the first feedbacks from Europe that may come in November or December this year, with a procedure that hopefully will be completed next year. In 2028, we expect the completion of the U.S. trial, and I'll tell you more about it. It's really a sister trial compared to the pivotal trial. It's called NeoDREAM, and we have agreed with American authorities that we would treat 240 patients, and you see we have already treated 184 patients. So we are approaching the completion of the trial.
This speed up in the trial has been possible, because we really dedicated a lot of energy to activate the new sites in the U.S. and in Europe. You see the situation in 2024, and you see the situation in 2026 with the involved centers, and the sites in activation are indicated in red. Here, a big thank to our team. You remember that we are as passionate for melanoma as for non-melanoma skin cancer. Also, the non-melanoma skin cancer data have been published. In 2025, a first report, and now really the complete set for the phase II trial called DUNCAN, has just been accepted, and it's in press in the Journal of Clinical Oncology, in which we document this beautiful, complete, durable responses observed in patients with basal cell carcinoma and also in squamous cell carcinoma. These are pictures of patients who enjoy a durable benefit.
You see 52 weeks follow-up for different types of BCC in different parts of the body. This last slide is, again, to remind us that the benefit extends to other tumor. For example, merkel cell carcinoma, you see a big lesion here in the neck that is converted into a necrotic scab within two weeks, and then the skin is perfect by week 12 for a patient with squamous cell carcinoma. Even smaller lesions like this lesion in the lip that would have required disfiguring surgery with amputation of about 2 cm of lip. You see a perfect cosmetic and functional outcome at week 52. So we like the product very much, and we have a vision also in non-melanoma skin cancer.
We have launched three global trials with registration potential. There is a fourth one, which has just been submitted, again, with a global intent, Europe and U.S.. If I go slowly, we are going in squamous cell carcinoma in second- line, so post-PD-1 failure, 92 patients. In last- line, basal cell carcinoma, again, 92 patients. A trial which has been asked by the U.S. FDA, in which we will treat between 60 and 180 patients with BCC, depending on different steps of the protocol. We have submitted the DUNCAN-2 trial, that is a head-to-head competition against the current standard of care, which is a hedgehog inhibitor. Again, we go in a randomized trial, first-line BCC patients, with the plan to treat 180 patients.
In short, we continue to believe that Nidlegy has transformational potential as a broadly applicable dermato- oncology drug, and we are making progress with our trials. With this, I hand over to Emanuele. Yes, there is a last slide that, of course, is also important. It's something we know, but it's good to repeat it. These are indications, unfortunately, with many, many patients. If we look at Europe and U.S., for locally advanced melanoma, we are talking about around 23,000 new cases per year. Whereas if we look at locally advanced basal cell carcinoma and locally advanced squamous cell carcinoma, the numbers are even greater. We see it from the many requests for compassionate treatment and also from the early access program that there is a need for efficacious drugs that treat patients locally and so are also better tolerated.
With this, I hand over to Emanuele, who will guide us through Fibromun and also very exciting results for dodekin, an antibody-cytokine fusion that we have not described in the recent past, but on which we have made considerable clinical progress.
Thank you, Dario. We start with Fibromun, that is partnered with Sun Pharma, that is currently investigated for the treatment of soft tissue sarcoma and glioblastoma. Both indications targeted with Fibromun represent areas of huge unmet medical needs. In the United States, we have about 15,000 new cases per year in terms of glioblastoma, with more than 10,000 reported deaths annually. For soft tissue sarcoma, we have about 13,600 new cases every year, with more than 5,000 deaths annually. In the past, unfortunately for neither indications, there have been really big progresses in the pharmaceutical field. Fibromun is based on L19TNF. L19 targets EDB fibronectin, a well-characterized marker of the tumor extracellular matrix. When fused to TNF, we aim at selectively delivering the payload at the site of disease, limiting the exposure to healthy organs.
TNF is a very important cytokine with immunostimulatory and cytotoxic properties that we aim at exploiting via the targeted delivery approach that Dario mentioned before. L19TNF is given by intravenous infusion, and at this moment is meant for the treatment of solid tumors such as sarcomas and glioblastomas. In one slide here, we provide a concise update on the developments in both indications. Starting with soft tissue sarcoma first- line, we have completed the first phase III study called FIBROSARC. The primary endpoint was progression-free survival. What we had observed is a strong signal in terms of overall survival in a subgroup of patients, representing approximately 70% of the patient population of the study.
If you look at the graph, we went from 13.6 months in blue in the control arm to 21 months, you see in red, in the treatment arm, with a hazard ratio of 0.57. Based on these findings, we are now devising new potential phase III studies called FIBROSARC-2, with the overall survival as primary endpoint in that subgroup of patients where we saw the signal in FIBROSARC, and now there is a current alignment with both FDA and EMA. In parallel, we also have a study in the U.S. called FIBROSARC US. It is a phase II-B clinical trial in which we enrolled 87 out of 158 patients with metastatic leiomyosarcoma. So this is slightly different compared to the one investigated in the two first studies, and the primary endpoint is progression-free survival.
On the right, you see the updates on glioblastoma, where we are active both in first- and last- line setting. With GLIOSUN running in first- line, we have a phase I/II-B study. We have completed the first part with 18 patients and launched, in the last few months, the part two that foresees 30 patients, and this was aligned with the FDA. That part two is expected to be completed in 2027, after which we will reach out again to FDA before launching the phase II-B part. So really keeping a constant dialogue with authorities. In the last line setting, you remember the GLIOSTELLA phase II study. The primary endpoints were actually safety plus the 12-month overall survival rate. The last patient was enrolled in September 2025, so the 12-month rate ends this September, so this month.
We now need a few weeks to clean the data and run the analysis in order to be presented at the upcoming webinars. Moving back to the dodekin, so the pipeline, I would like now to focus on dodekin, which is another important component of our antibody portfolio, which is being investigated for the treatment of various solid tumors. For dodekin, in this case, the payload is interleukin-12, also called directly, simply IL-12, a key mediator of antitumor immunity, and that has been for long regarded as a very promising cytokine for cancer immunotherapy. Here, IL-12 is still fused to L19, the L19 antibody targeting EDB, which is expressed in various solid tumors. You see five different examples of cancers, from breast to pancreas, in five different patients. You see EDB expression you always find it in brown.
The pan-tumoral expression of the antigen gives also a very broad applicability of dodekin across different indications. The interest in IL-12 is also reflected in recent, very substantial transactions that have been reported over the last years. Here, we report two of them, one between Bristol Myers Squibb and Dragonfly Therapeutics, and the other between Gilead and Xilio Therapeutics, in which you see a significant upfront and milestone payment that were foreseen in these agreements. Dodekin is now investigating a phase I clinical trial. We have completed the dose escalation part. We went from 0.1 mcg/kg all over to 12 mcg/kg , and this is the dose that's been selected for the dose expansion part currently ongoing in 20 patients with various solid tumors. The clinical results which are emerging are promising.
We have seen, for example, a patient with a heavily pretreated disease, so metastatic mucosal melanoma. You see here a liver metastasis. This is a FDG scan. The lesion here eats a lot of glucose. That's why it lights up so much. But after two months or four months of treatment, you see that the tumor is basically dead, and that's why it doesn't eat any glucose anymore. So in that case, we saw a strong metabolic complete response. As a next step, what we want to do, based on our experience with dodekin, is that this drug has a dose-dependent antitumor effect. So we want to go higher than 12 mcg/kg by applying our patented technology called intraCORP.
In this slide, we have a simplified explanation on how this intraCORP technology works, but it's much more detailed in the papers that you see at the bottom of the slide. This is a classical, let's say, PK profile in blood, in tumor of our immunocytokines. You see the concentration of the drug as a function of the time. You see normally, the concentration of the drug in blood is highest soon after the infusion, and it drops quite rapidly, while thanks to the L19 antibody, we have a build-up over time in the tumor. With immunocytokines, the toxicity anomalies observed shortly after the infusions and are reversible, and as soon as the concentrations in blood drop below a certain threshold, here indicated as toxicity threshold, the adverse events fade away.
What we want to do is to use an intracellular signaling inhibitor, namely ruxolitinib, to transiently mask the activity of IL-12 for only a short time when its blood concentrations are the highest without impacting on the antitumor efficacy as the inhibitor gets cleared. This only works with ligand-based delivery. If you have a non-targeted approach like the one described below of Dragonfly Therapeutics, this wouldn't work because you wouldn't see a build-up in the tumor. The first clinical trial has been just started also with another L19 fusion called Darleukin, and we're now planning the second study also with dodekin, and we plan the submission in the coming weeks.
Also, the vision, as you see, is to continue to innovate antibody cytokine fusions with a couple of twists. First of all, the observation that FDG-PET is a very good methodology to detect early responses, especially when you are then left only with a necrotic scab, which no longer it is obviously tumor because it is no longer live tumor, and also the implementation of our patented intraCORP technology. We will present updates also in the upcoming webinars. Now, when we come to the small molecule pipeline depicted in blue because it corresponds to the fully owned, the Philochem, daughter company of Philogen.
We go again through the principle that for certain targeting applications, small ligands are even more efficient than antibodies, both macroscopically in terms of their ability to localize to the tumor, and also microscopically in terms of their ability to reach every single tumor cell, here depicted with a green ex vivo fluorescence microscopy study. The pipeline starts with discovery of ligands, typically from our DNA-encoded chemical libraries. We confirm the targeting ability of the best molecules, and then we functionalize them by attaching a radionuclide or a cytotoxic drug, or even immunostimulatory agents. We have all these programs in the clinic at this moment in time. Today we focus on three targets called FAP, fibroblast activation protein, CA9, carbonic anhydrase IX, and ACP3, an acidic phosphatase. We will show you clinical data.
But we have, as you will see, more radiopharmaceuticals moving to the clinic in 2027, and I have a dedicated slide later today. You see already from these pictures, not only the structures of our molecules, but also the fantastic selectivity observed in patients just 60 minutes after intravenous administration. Let us start with FAP. You know that the product is partnered with Blue Earth Diagnostics, a company of the Bracco Group. We had already treated more than 500 patients. BED has now started a phase II clinical trial. Here you see the number, and again, information on this trial are provided by the Bracco Group because they hold an exclusive license for imaging applications. We have kept all rights for radionuclide therapy applications. We have launched Philogen's sponsored phase I clinical trial.
Again, those patients not only want to know that they have lesions, but they want to receive therapeutic radionuclides like lutetium- 177. The trial has started, and from these three exemplary patients that we show, I think you can see the exquisite selectivity of OncoFAP in reaching the metastatic tumor lesions in different indications. We have also a promising non-radioactive FAP-based therapeutic called OncoFAP-GlyPro-MMAE or OncoFAP-GlyDotin. You see the modular structure of this product. You see the OncoFAP moiety in blue that targets FAP. FAP is not only a target, but also a protease that cleaves after Gly-Pro, glycine and proline. So you see that we have put glycine and proline in the linker, and then we have monomethyl auristatin E as a very well-established potent cytotoxic payload. We had previously reported on the nice experience in animal patients, clinical trial in animal patients, namely dogs with spontaneous tumors.
This is one of these patients with a 15-cm sarcoma that received the four injections of the product, and you see that 28 days later, the mass of the tumor has substantially shrunk. You look at the hematology of all the treated patients, the treatment is really very well tolerated with really no sign of hematological toxicity or other types of toxicities in the investigated dose depicted here to the left. The beauty is that the data are published, and if you go to the publication, you see a 1:1 correspondence between performance and immunohistochemistry. In patients with high FAP expression, you see this type of performance. If the tumors are negative for the antigen, then the performance is worse. We have completed the GMP production of the active pharmaceutical ingredient. We have completed safety tox studies, and first-in-human studies are expected in 2027.
We are obviously very excited because FAP is a good target for many tumors with nuclear medicine validation, and this data in animal patients are a good basis for the clinic. The second target that we would like to describe is carbonic anhydrase IX, and we have, again, a ligand called OncoCAIX. Kidney cancer is actually an important type of oncological disease. In this graph, you see the incidence and the mortality of different cancer types, and you see that actually kidney cancer is unfortunately pretty high in terms of mortality per 100,000 persons per year. Among kidney cancers, clear cell renal cell carcinoma accounts for about 80% of renal cell carcinoma cases, and it's really, unfortunately, in many cases, a deadly disease.
There is a need to distinguish between clear cell renal cell carcinoma and benign kidney lesions because about 30% of renal masses are surgically removed, in a way, even though they may not be aggressive tumors. So in a way, we want to avoid this unnecessary surgery and also provide a reliable diagnosis to the clinical centers. CA9 is the target for clear cell carcinoma. Telix has already published a phase III clinical trial with 300 patients showing good results, but since they used an antibody to image patients with kidney cancer, they had to observe patients for several days, and possibly this methodology delivers a high amount of radioactivity because antibodies circulate in vivo very long. Our OncoCAIX gives a very confident detection of kidney masses already after one hour with excellent discrimination against the normal kidney.
You see residual uptake also in stomach and intestine, but this has no impact on the diagnostic performance. When you have a patient with heavily metastatic disease like this third patient that you see in the slide, you can really appreciate the potential of the drug, not only for the detection of the primary tumor, but also for staging applications. The phase I clinical trial has been run in Italy and coordinated by Arturo Chiti and Paola Erba, and data have been presented. It's nice to confront these two situations. A patient with a mass in the kidney, which was a CA9 positive clear cell renal cell carcinoma indicated by this red arrow. Already after 10 minutes, you see very confidently the presence of the lesion and the negative control if you want a patient with a benign kidney mass.
At no moment in time you see the yellow arrow, a detection of a mass in the PET experiment. We like the product very much, and we are committed to moving the product towards phase III clinical trials. We have completed phase I testing. We are making progress with GMP manufacturing and cold kit development. By the end of the year, we will have a meeting with the U.S. FDA to discuss the registration path for the product that is expected to start in 2027. You know that imaging trials are faster than therapy trials. Of course, we have ACP3 that we will discuss in a split second, and of course, more products coming to the clinical next year. If we look at the PSMA market of radiopharmaceuticals in prostate cancer, you see imaging products like Illuccix and PYLARIFY, and you see therapy products like PLUVICTO.
There were cumulative sales in 2025, greater than $3.5 billion, probably around that $4 billion, growing, as you can see. There is an opportunity to do better than PSMA. We always like to show the slide that the European Association of Nuclear Medicine chose to start the congress with a smiling ACP3 and maybe an angry PSMA. We think that ACP3 is an interesting contribution, and you know that we announced last year the licensing of OncoACP3 to RayzeBio, a company of Bristol Myers Squibb, both for imaging and for therapeutic applications. If we use the new Bristol Myers Squibb names, which are indicated here, these products are being developed as a therapeutic and as a diagnostic agent. Of course, if you have more questions, you should address them to RayzeBio, which is the new owner of the product.
The financials for the deal with upfront payment, milestone payments, and also royalties are indicated in this slide. We will bring new products to the clinic next year, but there is a dedicated slide. I want to show two last slides on science to say that all these developments are possible because we invest in discovery technologies. Everything starts with the ability to discover ligands. You know that we have practiced antibody phage display technology for more than three decades by now, and also we mentioned how DEL technology has delivered products for the targeting of FAP, CA9, ACP3, and more targets. We have established by now very large phage display libraries of cyclic peptides containing more than 200 billion candidates.
We have recently established successfully mRNA display of cyclic peptides and modified peptides, and we have been successful also in applying artificial intelligence tools for the discovery of other types of protein binders. Different methodologies give us the binders with which we implement our discovery platform. Again, in addition to the late-stage trials that were mentioned before, I am pleased to confirm that in 2027, we expect the start of at least four new molecules in the clinic. OncoFAP-GlyDotin for various FAP-positive tumor types, so a small molecule drug conjugate that has been tested in dogs until now. Two new radiopharmaceuticals, which are not disclosed today, but we will present them when they yield the first clinical data. The preclinical data are very promising.
We have a second-generation IL-2 based immunocytokine called F8-IL2 with intraCORP technology that we believe will move us ahead in the field of cytokine-based therapeutics. The last slide is really a comparison of important financial figures, in 2024, 2025, 2026, always looking at the first half of the year. If we look at the cash, we went from EUR 64 million in 2024 to EUR 100 million in 2025 to more than EUR 300 million in 2026. We have a very good cash position, as you can see. The operating costs have grown moderately, so to a stage that we can afford. There, of course, will be future revenues from contracts that we have in place. When they come, of course, we will communicate them. With this, the presentation finishes. It's basically almost 3:40 P.M.
We stop the recording, and we can start the Q&A session, which is not recorded. We see that Clémence and Isacco have questions. Maybe Clémence, you want to start?
Yes. Hi. Thanks for the presentation, and congrats on the progress. Two questions on my side. The first one is on BCC combination. Could you clarify the development strategy? Because you describe the study as pivotal, but unlike the other three studies, the pipeline slide do not label it at having registrational potential. Just wondering whether it could support a regulatory filing or if it's more like a dose component section study. That's the first.
It's a good question. It's an important trial for the following reason. In squamous cell carcinoma, we have the second-line trial. In BCC, we have the third-line trial. But the difference between the U.S. FDA and the European situation is the following one. In Europe, we have a combi pack authorization, which means European, EMA, has accepted that the combination of L19-IL2 and L19-TNF at the dose that we use is one product and is handled as one product. The U.S. FDA formally requires that whenever you go with combinations, you have to demonstrate the contribution of each agent. So it's not a dose-finding study, but it's a contribution of each component.
The trial foresees that we treat patients with L19-IL2, with L19-TNF, or with a cocktail of the two cytokines, and it can stop at different stages depending on the signals which are generated. I consider it of registration potential because we treat many patients with BCC that are underserved by other modalities. As always, when we have data, we go back to the FDA not only for the confirmation that the combination of the two active ingredients is better, but also to show the data that we have. On top, in first- line, the race is against the hedgehog inhibitors, and that's why we are launching DUNCAN-2.
Okay. That's very clear. Thank you very much. Just maybe a broader question because across all your program, there are several ongoing regulatory interaction. Could you maybe give us some idea of where you would say you have clear alignment with the agency and where there is maybe more regulatory uncertainty?
Yeah, it's a very fair question. I will give a long answer because we have gone through many different meetings. If I look at Nidlegy in melanoma, in Europe, we are at the marketing authorization application, so the next one to speak will be EMA. But in the U.S., we have aligned about the number of patients, the statistical design, the endpoints for the NeoDREAM trial, so the phase III clinical trial. So I feel that we have complete alignment with the FDA about the design of the trial and the requirements for registration. For non-melanoma skin cancer, we have formally asked for a scientific advice on the different indications, and I think that, again, we have clarity in first-, second-, and third- line.
When we go to Fibromun, the soft tissue sarcoma results that have emerged from the FIBROSARC Europe study have been discussed and have been presented, and we in a harmonized parallel scientific advice procedure with Europe and U.S. authorities. And it has been clear that a registration will require a second trial with overall survival as endpoint. In parallel, the glioblastoma programs we have in writing the outcome of parallel harmonized scientific advice procedure with Europe and the United States. When we go to dodekin, this is new stuff. This is really emerging potent data of activity, and so dodekin has not yet been discussed with authorities in terms of path to registration. When it comes to the radiopharmaceuticals, again, the Bracco Group will speak for FAP, the BMS Group will speak for ACP3.
For OncoCAIX, we have submitted a request and the documentation for a Type C meeting, and by December, we should hopefully have the blessing on our development plan for the phase III trial. I have covered a lot of ground, and I stop here and listen.
That was super clear. Thank you, both of you. That is it on my side.
Thanks a lot, Clémence. Isacco? Isacco, we cannot hear you. I see the hand raised, Isacco. We cannot hear-
Can you hear me now?
Excellent.
Okay, apologies. Apologies for the issue. Three questions on my side. I will go one by one, if it is okay for you. First question is on, non-melanoma trials. Just if you can share a bit more color on the timetable you have in mind for the completion of the different registrational trials.
Yes. The three trials which are ongoing, they have to be considered one by one. The squamous cell carcinoma trial second- line is the easiest to execute because it is 92 patients, and basically, after PD-1 blockade, there is no other agent. At this moment in time, we expect to be able to recruit it by 2028, but time will tell. As always, you know that you have seen it for NeoDREAM. When we make progress, we tell you really webinar after webinar where we stand, but our timelines are so. For the third-line basal cell carcinoma, we will see, unfortunately, because in third- line, patients are more difficult to treat. And we have never really focused on third- line so far. I do not like to make a prediction.
I can only tell you that we watch the recruitment and having opened good centers like MD Anderson in the U.S. and also many European centers, I think we will be able to recruit by 2028, 2029, but we can be more specific once the trial has made sufficient progress. For BCC combination, this is something where we will have the answer very, very soon. But as indicated, the trial could stop already after 60 patients. That would be 20 per arm, or depending on the protocol, it could go all the way up to 180 patients. And the last one is a first-line trial, DUNCAN, that we have submitted, so DUNCAN-2. The trial will start in 2027 with Odomzo as comparator, and we need to treat 180 patients. I believe that we may need between two and three years to finish that particular trial.
Thanks, Dario. Super clear. Second question is more on strategy on your side. With OncoACP3, you opted for an early-stage partnership. From the presentation on OncoCAIX, looks to me you look confident to go alone. Is it a correct understanding or—
Yes
I do not know. Okay.
No, maybe I will be more specific. I think OncoCAIX is really a good imaging agent. I am biased, of course, and you have to judge with your own brain, but I think the pictures speak for themselves, and also the data presented by the Chiti group are very nice. I can say that we have multiple companies that have actually approached us for a possible licensing of the product. Never say never. But what I have learned is that it is extremely important, at least for moving the product to development, for key development. Little by little, we have gained these capabilities, and then when we have them in-house, we like to move product with Philogen quality, Philochem quality, and also with Philochem speed.
This is something that will certainly enter the clinic very soon, and then we will decide really based on the offer, if it is worth partnering or if it is worth thinking of bringing the product all the way to the market ourself. Sorry, long answer. I know you have more questions.
No. Makes sense. Thanks for this. A similar comment maybe on interleukin . Just curious to know if you are keen to go alone or maybe a partnership would make sense.
I honestly think whenever you bring these products and you see activity, you dream to have the next immune oncology drug. We feel that the road to interleukin-12 therapeutics has been a difficult road. Some 30 years ago, actually, interleukin-12 was first brought to the clinic as a known targeted agent. Roche and other companies studied it. They saw some responses, but also they didn't manage toxicity, and interleukin-12 was sort of forgotten. We were the first group to publish that you can deliver interleukin-12 with antibodies, Nature Biotechnology 2002, and we have really spent 20 years perfecting the molecule. We have seen molecules go to the clinic and fail. We mentioned some of them. At this moment in time, we really go one step at a time.
The goal of the phase I trial was to see if we could see activity and also pharmacodynamic evidence of activity in patients. This evidence is here. We have a technology, intraCORP, to go up to the dose, and we know from animal studies that the more you give, the better it is. Your question is, what do we do next? What we do, certainly, is we want to establish very clear evidence of efficacy in the clinic with intraCORP technology, and this will happen within the next 18 months. The plan for the next 18 months is to collect documentation of solid evidence of durable activity in last- line patients. Then, of course, it's always the same decision. If we find good partnering opportunities, we will partner.
If we think that the development of the company allows us to go further ourself, possibly all the way to the market, we know that we can do it because we have brought other products to the completion of phase III. We are not in a hurry to partner because actually we are doing very well with money. But we are in a hurry to provide a clinical proof of principle, which is solid. Until now, no company could show solidly that they could exploit interleukin-12 therapeutics. We believe we will be the first, actually, to formally prove this.
Okay. Final question is more on modeling and the second alpha outlook. Over the past years, we have seen Philogen consistently staying above breakeven, while first half had around EUR 20 million EBITDA loss. Without commenting on single milestones, of course, but it is reasonable to assume some stronger support from the top line before the end of the year, or should we expect a similar pace of cash burn in the second semester?
Yeah, appreciate the question. Of course, you know that our revenues are not continuous revenues. They are associated with milestone payments for contracts that we have already signed or new licensing agreements. I cannot make a forward-looking statement. I can only tell you that as a CEO, I feel very comfortably with the cash situation that we have and with the cash that we expect in the near future. Unfortunately, I cannot be more specific, but you know that at regular times, we publish our financial statements, and I can tell you that I am very relaxed about the financial position of the company. I am not relaxed about trials because we are never fast as we should, and this is what keeps us busy at the moment, not the expectation of payments which are due and that will come.
Okay. Thanks, Dario.
Thank you. Then we see-
Talia
Talia has also questions.
Can you hear me?
Yes.
Hi. Hello. I am Talia Biran, and I am from the United States. I am the former president of Oncolys USA. I was very impressed by your presentation, your strategy, your pipeline. I have a question. You mentioned that enrollment, and you said it again, U.S. site activation and enrollment is a very important execution priority for your programs. As the U.S. portfolio expands and your discussion with FDA Type C meeting is planned the end of the year, do you envision building additional clinical and operational capability in the U.S., or you are planning on primarily managing those activities through the existing global organization and partners you have?
It is a good question. Until now, we have operated well, and we continue to operate well in leading clinical centers. You have seen in the slides how many centers we have opened in the United States. With our headquarters in Europe, plus with CROs, so contract research organizations, which are crucially important for our operations in the United States. I do not exclude the possibility to start headquarters also in the United States since our presence in the U.S. is growing. Certainly, we are able to execute the programs that we have discussed with the current operations and with the help of CROs.
Thank you very much.
Thank you. There is, I think, a last question from Cesare, and maybe Clémence has additional questions.
Yeah. Sorry, just a quick one since there is a couple of minutes left. I was just thinking about the intraCORP technology. Since it can be combined to reduce toxicity, could you see it as a sort of platform technology where you would license the technology for other companies that are having issues with good drug but poor tolerability?
No, absolutely. This is a general technology. It is a platform, and luckily, we have a very good and strong patent. The requirement, though, is that the active principle is targeted. It really works because you keep your payload at the site of disease forever, basically, and you cancel toxicity for the first few hours. So whenever there is a payload which is delivered, intraCORP will be useful. We have shown it for interleukin-12, for interleukin-2, for TNF, and I think it is a smart concept. If we manage to partner and if companies understand that this is an elegant solution to the activity on demand problem, I think this will be a nice partnering opportunity for us.
Perfect. Thank you.
Thanks a lot, Clémence. Then there is a last question from Cesare Colombo, I think.
Okay. Thank you. My question is related to Nidlegy because, we read in August the publication with the last, I suppose it was Journal of Clinical Oncology, about the recent data for Nidlegy. A few days after the publication, there was a lot of news flow related to Moderna melanoma vaccine. I know they are two different things, but please, if you can help us try to understand the difference. The end market is always melanoma. Can you help us try to understand the difference between Nidlegy and
Moderna.
Yes. Thank you.
If you want, you could even put Replimune because there was a, if you want, a surprising, or maybe not surprising, approval by the FDA. Slowly I go through these different points. For us, the Journal of Clinical Oncology publication was very important because it showed, with 36 months follow-up, the durability of the benefit, and not only in terms of primary endpoint, but also in terms of secondary endpoints and other parameters. I think it provided the confidence to us and also to the investigators community, and I have seen it presented at multiple meetings. I think it gave us the confidence to go ahead again, not only with the European resubmission, but also with speeding up with American trials. What is the Moderna situation?
Moderna has a vaccination approach in combination with anti-PD-1 treatment of Merck in so-called Stage II and Stage IV melanoma. It is not yet approved. There was a lot of publicity, but actually the Moderna approach is not yet approved. We focus on Stage III disease. They focus in Stage II and Stage IV. Let us make clarity. What is Stage III melanoma? Stage III melanoma is melanoma which is metastatic in skin, in lymph nodes, but has not yet spread to visceral organs. Stage IV melanoma is metastatic melanoma that has reached visceral organs, that has reached internal organs. These are different indications. We are happy with our neoadjuvant treatment. We believe we provide benefit to patients, and this is our focus. What is Moderna trying to do? What is Replimune trying to do? Let us start from Replimune because this is easier.
Replimune goes to ultra late patients, so last patients with Stage IV disease, so with metastatic disease. They go in the post-PD-1 setting. They give intralesionally an oncolytic virus, and they have shown that a proportion of patients is benefiting from the treatment. With a trial with about 100 patients, they got approval. What is Moderna trying to do? Moderna proposes the following strategy. Let us suppose I am a patient with Stage II or Stage IV melanoma. I get surgery. Moderna takes my tumor. They basically process it. They sequence it. They find the mutations, maybe of my tumor, and they prepare a personalized vaccine for me, which a few months later, they send back to me so that I will start using the vaccine together with anti-PD-1 treatment. It is a long procedure. It is a personalized procedure. It is an expensive procedure.
Time will tell if it gets approval or not, but we hope, of course, that it benefits patients. Again, it is Stage II melanoma and Stage IV melanoma, whereas we are focusing primarily, at least with our pivotal trials, in Stage III melanoma.
Thank you.
Well, okay, sure.
Okay. Thank you very much, everybody. With this, we can close the event. Thank you for attending. If you have any questions, we are always available, so please reach out to us directly by email. Bye.