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, 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, and 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 to accessible targets, this is really the world record of targeting.

You see 60 minutes post-injection a patient with metastatic breast cancer, every lesion, 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; and as always, we'll go through the products and tell you what's relevant for late-stage and for early-stage products.

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 combi-pack authorization. We give it intralesionally because we treat, so far, mainly skin cancer patients, and we have focus 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: arm 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, but 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, and 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 confirm the very nice separation of the Nidlegy arm from the control arm with good hazard ratio, p-value.

In terms of company operations, you see that we have done everything we promised to do. We had scientific advice with German authorities, scientific advice with FDA, which has defined a very clear path for a possible approval in the US pending successful outcome of the US trial, pre-submission meeting with rapporteurs, and submission at EMA on July 23rd, and 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 US trial, and I'll tell you more about it. It's really a sister trial compared to the pivotal trial.

It's called Neo-Dream, and we have agreed with American authorities that we would treat 240 patients, and you see we have already treated 184 patients, we are approaching the completion of the trial, and this speedup in the trial has been possible because we really dedicated a lot of energy to activate new sites in the US 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, and 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 2 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, and this last slide is again to remind us that the benefit extends to other tumors. 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, and even smaller lesions like this lesion in the lip that would have required disfiguring surgery with amputation of about 2 centimeters of lip, you see a perfect cosmetic and functional outcome at week 52.

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, and there is a fourth one which has just been submitted, again with a global intent, Europe and US.

If I go slowly, we are going in squamous cell carcinoma in second line, post-PD-1 failure, 92 patients; in last line basal cell carcinoma, again 92 patients; a trial which has been asked by the US FDA in which we will treat between 60 and 180 patients with BCC, depending on different steps of the protocol; and 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, and again we go in a randomized trial, first line BCC patients, with a 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.

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 US, 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 L19-TNF. L19 targets ED-B fibronectin, a well-characterized marker of the tumor extracellular matrix, and 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 potent cytokine with immunostimulatory and cytotoxic properties that we aim at exploiting via the targeted delivery approach that also Dario mentioned before. L19-TNF 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 a first Phase 3 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 patient 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 a new potential Phase 3 studies called FibroSarc-2 with overall survival as primary endpoint in that subgroup of patient 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 US called FibroSarc-US. It's a Phase 2b clinical trial in which we enrolled 87 out of 158 patients with metastatic leiomyosarcoma.

This is slightly different compared to the one investigated in these two first studies, and the primary endpoint is progression-free survival. On the right, you see the updates on glioblastoma.

We are active both in first and last line setting. With Gliosan running in first line, we have a Phase 1/2/2b 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 FDA. That part two is expected to be completed in 2027, after which we will reach out again to FDA before launching the Phase 2b part, we're really keeping a constant dialogue with authorities.

In the last line setting, remember the GLIOSTEL, a Phase 2 study, the primary endpoints were actually safety plus 12 the 12-month overall survival rate. The last patient was enrolled in September 2025, the 12 months rate end in this September, this month.

We'll 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 to the pipeline, I'd 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 ED-B, which is expressed in various solid tumors.

Here you see five different examples of of cancers, from breast to pancreas, in five different patients. You see ED-B expression is always you always find it in brown, and 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 the 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, and the other between Gilead and Xilio, in which you see a significant upfront and milestone payments that were foreseen in these agreements.

Dodekin is now in investigated in a Phase 1 clinical trial. We have completed the dose-escalation part.

We went from 0.1 microgram per gig all over to 12 microgram per gig, 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've seen, for example, a patient with heavily pretreated disease, metastatic mucosal melanoma. You see here a liver metastasis.

This 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.

In that case, we saw a strong metabolic complete response. As a next step, what we want to do is, based on our experience with Dodekin, is that this drug has a dose-dependent antitumor effect, we want to go higher than 12 microgram per gig by applying our patented technology called Intracork.

In this slide, we have a simplified explanation on how this Intracork technology works, but it's much more detailed in the in the papers that you see at the bottom of the slide. This a classical, let's say, PK profile in blood and tumor of 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 normally is 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 signal 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, that this wouldn't work because you wouldn't see a buildup in the tumor.

The first clinical trial has just been just started also with another L19 L19 fusion called Darleukin, and we're now planning the second study also with with Dodekin, and we plan the submission in the in the upcoming weeks.

The vision is, as you see, to continue to innovate antibody-cytokine fusions with a couple of twists. 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 is obviously tumor because it's no longer live tumor, and also the implementation of our patented Intracork 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 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 confirmed 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, CAIX, carbonic anhydrase IX, and ACP3, an acidic phosphatase, and we'll 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's start with FAP.

That the product is partnered with Bracco Diagnostics, a company of the Bracco Group. We had already treated more than 500 patients.

Bracco has now started a Phase 2 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-sponsored Phase 1 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-Gly-Pro-MMAE or OncoFAP-glidotin. 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, 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, a clinical trial in animal patients, namely dogs with spontaneous tumors. This is one of these patients with a 15-centimeter sarcoma that received four injections of the product, and you see that 28 days later the mass of the tumor has substantially shrunk, and 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 one-to-one 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, and so in a way we want to avoid this unnecessary surgery and also provide a reliable diagnosis to the clinical centers. CAIX is the target for clear cell carcinoma.

Telix has already published a Phase 3 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, and 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 1 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 CAIX-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, and 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 3 clinical trials.

We have completed Phase 1 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 US FDA to discuss the registration path for the product that is expected to start in 2027, and 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 clinic also 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 $4 billion, growing, as you can see, and 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, and 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, and 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.

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, CAIX, 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'm pleased to confirm that in 2027, we expect the start of at least four new molecules in the clinic: OncoFAP-glidotin for various FAP-positive tumor types, 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 yielded the first clinical data, the preclinical data are very, very promising; and we have a second generation of IL-2-based immunocytokine called F8-IL2 with Intracork 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 64 million in 2024, to 100 million in 2025, to more than 300 million in 2026. We have a very good cash position, as you can see, and the operating costs have grown moderately, to a stage that we can afford, and there, of course, will be future revenues from contracts that we have in place, and when they come, of course, we will communicate them.

With this, the presentation finishes. It's basically almost 3:40.

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 Comb.

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. The difference between the US 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 US FDA formally requires that whenever you go with combinations, you have to demonstrate the contribution of each agent. 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 the 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 Hedgehog inhibitors, and that's why we are launching DUNCAN-2.

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?

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, the next one to speak will be EMA.

In the US, we have aligned about the number of patients, the statistical design, the endpoints for the Neo-Dream trial, the Phase 3 clinical trial, 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, the 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 US 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 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 3 trial.

I've covered a lot of ground, and I stop here and listen. No,

that was super clear. Thank you, both of you.

That's it on my side.

Thanks a lot, Clémence. Isacco?

Isacco, we cannot hear you. I see the hand raised.

Now we can hear you.

Can you hear me now? Okay.

Apologies for the issue. Three questions on my side.

We'll go one by one, if it's 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. They have to be considered one by one.

The squamous cell carcinoma trial second line is the easiest to execute, because it's 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 Neo-Dream, when we make progress, we tell you really webinar after webinar where we stand. 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 don't 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 US 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 Comb, this is something where we will have the answer very, very soon.

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. The last one is a first line trial, DUNCAN, that we have submitted, 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 I don't know, okay.

No, maybe I'll be more specific. I think OncoCAIX is really a good imaging agent.

I'm 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 companies, multiple companies that have actually approached us for a possible in-licensing of the product, and so never say never.

What I've learned is that it's extremely important, at least for moving the product to development, for kit development, little by little, we have gained these capabilities. Then when we have them in-house, we like to move product with 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's worth partnering or if it's worth thinking of bringing the product all the way to the market ourselves. Sorry, long answer.

I know you have more questions.

No, no, no. Makes sense and thanks for this.

A similar comment maybe on Dodekin, just curious to know if you are keen to go alone, or maybe a partnership could

I honestly think whenever you bring these products and you see activity, you dream to have the next immuno-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 non-targeted agent. Roche and other companies studied it.

They saw some responses, but also they didn't manage toxicity, and so 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 the time. The goal of the Phase 1 trial was to see if we could see activity and also pharmacodynamic evidence of activity in patients, and this evidence is here.

We have a technology, Intracork, 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 Intracork technology, and this will happen within the next 18 months. The plan for the next 18 months is to collect a 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 ourselves, possibly all the way to the market, I think we know that we can do it because we have brought other products to the completion of Phase 3. 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.

Final question is more on modeling and the second half outlook. Over the past years, we have seen Philogen consistently staying above breakeven, while first half had an around €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?

I 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'm 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.

Thanks, Dario.

Thank you. Talia.

Then we see Talia has also questions.

Can you hear me?

Yes. Okay.

Hi, hello. I'm Talia Biran, and I'm from the United States.

I am the former president of Oncolys USA. I was very impressed by your presentation, your strategy, your pipeline, but I have a question.

You mentioned that enrollment, and you said it again, US site activation and enrollment is a very important execution priority for your programs, and as the US 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 US, or you are planning on primarily managing those activities through the existing global organization and partners you have?

It's a good question, and 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, contract research organizations, which are crucially important for our operations in the United States.

I don't exclude the possibility to start headquarters also in the United States since our presence in the US is growing, but 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. Then there is, I think, a last question from Cesare, and maybe Clémence has additional questions.

Sorry, just a quick one since there's a couple minutes left. I was just thinking about the Intracork 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's 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.

Whenever there is a payload which is delivered, Intracork will be useful. We have shown it for interleukin-12, for interleukin-2, for TNF, and I think it's 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 would 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.

Thank you. My question is related to Nidlegy, because we read in August the publication with the last, I suppose it was Journal of Oncology about the recent data for Nidlegy.

A few days after the publication, we saw the, 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, 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, if you want, a surprising or maybe not surprising approval by the FDA. Very 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've 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.

Now, what is the Moderna situation? Moderna has an approach, a vaccination approach in combination with anti-PD-1 treatment of Merck in so-called Stage II and Stage IV melanoma.

It's 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's 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 the 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's start from Replimune because this is easier.

Replimune goes to ultra-late patients, last patients with Stage IV disease, 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.

Now, what is Moderna trying to do? Moderna proposes the following strategy.

Let's 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's a long procedure. It's a personalized procedure.

It's an expensive procedure. Time will tell if it gets approval or not, but we hope, of course, that it benefits patients.

Again, 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.

Thank you very much, everybody. With this, we can close the event, and thank you for attending, and if you have any questions, we are always available, please reach out to us directly by email.

Bye-bye.