I would like to welcome everybody to our latest webinar. Today, we will focus on the latest scientific and financial results as of the first semester of 2023. As always, on the call, we have Professor Dario Neri, our CEO and Chief Scientific Officer, and Dr. Laura Baldi, our CFO, and myself, as investor relations. We will give a presentation of about 30-40 minutes, which is being recorded, and this will be followed by a Q&A session, which is not recorded. To ask questions, as always, please raise your hand using the platform, or just type the question on the chat and we'll be able to answer live. With this, I hand over the stage to Dario, who will present the introduction in Nidlegy. I will then take over for Fibromun.
Dario will take over again for OncoFAP, and Laura Baldi will finish off with the financial slides. Having this, please, Dario.
Thanks a lot, Emanuele, and it's a pleasure to meet you again for this update. First of all, for those who are new to this webinar series and want to know more about Philogen and Philochem. Philogen is the mother company listed on the Italian Stock Exchange with two industrial headquarters in Siena. Philochem is a fully owned daughter company located near Zurich, in this blue building, where especially discovery activities and certain small molecule therapeutics are developed. Collectively, the Philogen group works, as you will see, on ligand-based pharmacodelivery activity, and we have or we have had a number of industrial collaborations over the years, and just in the recent past, we announced collaborations with Bracco, Google, Sun Pharma, Merck, IBSA, and hopefully there will be more to come. A quick update about GMP production, which is very important.
On one hand, we were inspected by authorities for the Montarioso production facility, and this received an extension for the next period of GMP production. We were very pleased. But importantly, we have had the MED inspection of our GMP manufacturing facility in Rosia, the second facility, which is designed for commercial activities, and the inspection went very well. And a second API inspection is expected in October. That should complete the, the procedure, but you see pictures in operation of our cell expansion, 200-liter fermenter, downstream processing, fill and finish, really in a facility which is state-of-the-art in terms of quality, instrumentation, and size. Now, again, a look at the pipeline. As always, we will focus on Nidlegy and Fibromun, which are our most advanced products.
We have a number of programs, typically partnered with other companies that we don't cover in these webinars, and we will cover also the chemical activities, which are really exploding in a positive sense, as you will see from the slide. So really updates on Nidlegy on melanoma and non-melanoma skin cancers. Then Emanuele will follow up on Fibromun, and you see a number of trials, which are either phase III trials or phase II trials with registration potential. Now, if we focus on Nidlegy, as always, it's a dermato-oncology product. It's the only product that we give intralesionally because we are treating skin conditions. However, we treat locally, we act globally. As we had the opportunity to publish and present in the past, we have found that these two active ingredients, L19IL2 and L19TNF, potently synergize.
The green moiety, it's the L19 antibody moiety that anchors the product in the tumor, whereas the interleukin two moiety in blue and the tumor necrosis factor moiety in orange, red, are potent immunomodulators that activate the immune system against the tumor. We have an EMA CombiPack authorization for the use of this product, and, which is an important regulatory milestone, and we focus both on melanoma and non-melanoma skin cancer, and to be more specific, I'll show data for both indications. Last webinar, we announced, a commercial agreement for the distribution of Nidlegy Europe, Australia, New Zealand, with Sun Pharma. Sun Pharma is a leader in dermato-oncology . We are really pleased to have Sun Pharma as a partner.
They are also very present in dermato-oncology as they market Odomzo in basal cell carcinoma, and the economics of this term were communicated in a previous webinar. Now, again, we focus mainly in Stage IIIB/C melanoma, which means melanoma, which is metastatic, has reached the skin, the lymph nodes, but has not yet spread to visceral organs. And after seeing activity in Stage IIIB/C melanoma, we have started using Nidlegy in basal cell carcinoma at high risk, as well as dangerous squamous cell carcinomas and other tumors. And you will see, as always, an update of what has been accomplished. So this is an important slide because we had previously announced the completion of enrollment for our phase III trial, whose design is depicted in the slide. You see that patients are randomized 1:1. They are typically patients relapsing with the disease.
One half receives surgery, which is the standard of care, sometimes followed by immune checkpoint inhibitors, and the treatment arm receives Nidlegy once a week for four weeks, and then surgery if it's needed, to render all patients with no evidence of disease, and the primary endpoint is relapse-free survival. The trial had successfully passed two interim analysis. You see the geographies of trials and centers, which participate in this effort in Europe and in the United States. It's really a global effort, with 22 sites for the European trial, 33 sites for the U.S. trial. The news is that the events have been reached, so 95 out of 95 events. This is what we are told by the centralized independent central review procedure, which in a blinded fashion, is actually organizing and documenting the results.
And within the next couple of weeks, probably 1-2 weeks, we will receive an important binary communication, whether the primary endpoint of the study has been met or not. So these are very important pieces of information, which should become available in the next 1-2 weeks. So please stay tuned. Now, while I cannot show the results of the phase III trials, and they will be communicated in a dedicated press release once the central review board has finished its activity, I can communicate results of the phase II trials, which are running in basal cell carcinoma, but also in other tumors. Let me start.
Basal cell carcinoma is the most common tumor on earth, is actually a disease which affects, for example, alone in the United States, 4 million new cases per year, with an incidence which is growing because the tumor is sun-driven, and about 1% of such patients are high-risk BCC patients. The disease is highly disfiguring, as you will see, and the three approved drugs for high-risk BCC, which are Libtayo, Odomzo, and Erivedge, have a low complete response rate, and this is clearly what we are trying to improve. But let me mention, and you will see a couple of examples, that we have activity now also in other conditions. While BCC is a disfiguring disease, squamous cell carcinoma is actually a tumor that kills. It actually kills more than melanoma.
So really, the expectations for Nidlegy are not only in melanoma, but also in other skin cancer conditions. The trials which are ongoing are called DANCAN and INTRINSIC. You see the European countries in which the trials are working, and you see also the centers. We are also about to start a clinical trial in the United States because we see really the development of this product on a global basis. Again, simple program, which means we inject up to four times our Nidlegy in the lesion, and you will see the benefit for the patients. All other products in this indication have been approved after non-controlled phase II clinical trials based on overall response rate. So we see this as an opportunity also for the development of Nidlegy.
Now, this is a picture which has been presented before, and still it's very impressive. You see a patient in St. Gallen with our colleagues, Professor Cozzio, Flatz, and Dr. Wagner. This patient was candidate to disfiguring surgery with amputation of the nose, and you see how the treatment is very effective, not only in removing the tumors, but actually favoring a complete formation of the skin. From the biopsy, you see the tumor in red before treatment and the complete disappearance, so a pathological complete response at two months. And of course, encouraged by these results, we want to show a few more. A young lady with a tumor at tip of the nose, which was again, candidate to disfiguring surgery, and you see how the nose looks like after basically two months and a half, just perfect.
Again, the biopsy confirms a complete pathological response. One more patient, again, in St. Gallen, with a heavy mass in the cheek, which would have required disruptive surgery, and again, a good healing of the tumor, documented by biopsies. And again, in brown, you see the presence of the tumor before treatment, and it disappears at two months and a half. One more patient, 85 years old, again, to document that the treatment is well tolerated. The patient was candidate for surgical removal of this portion of the ear, and if you follow the disease over time, you have a complete formation of normal ear, really, with no detectable disease, and again, pathological complete response at day 72, and these responses are durable.
Patient, 78 years old, with a large tumor in the scalp, and at day 36, actually, the tumor is gone. Pathological complete response. The blood that you see comes from the biopsies. One more example of a really diffuse basal cell carcinoma that, again, would have required the disruptive and disfiguring surgery in the face. Again, complete response confirmed by four punch biopsies. This is an example of patients with multiple lesions of BCC, so lesions of basal cell carcinoma in multiple parts of the body, again, with pathological complete response. Again, showing that I think we have a good opportunity to treat these patients.
This is an ugly picture of a patient with a really nasty, locally advanced basal cell carcinoma next to the ear, and the improvement of the lesion is clear, even though the response is still ongoing, and so we will show you more pictures at the next webinar. I want to finish this series showing again examples of a patient with cutaneous squamous cell carcinoma. As mentioned, this is a disease that actually kills, and it kills more than melanoma. You see really a very nice response, which is, at present, a partial response, clinical at week eight, and typically the responses, the complete responses come at a later time point.
So this is one of examples of patients with other skin lesions that make us believe that Nidlegy has the potential to be a broadly applicable dermato-oncology drug in melanoma and beyond. And with this, I hand over to Emanuele for the description of Fibromun. He has really accompanied the development of Fibromun in glioblastoma, and you will see an update on the clinical activities in soft tissue sarcoma and glioblastoma. Emanuele?
Thank you very much, Dario. I'm glad to provide an update on the ongoing activities with Fibromun. You may remember, we're tackling two notoriously deadly conditions like glioblastoma and metastatic soft tissue sarcoma. Glioblastoma is the most common and aggressive primary brain tumor, and unfortunately, 50% of the patients die from diagnosis within 14.6 months. Those patients are typically treated with radiochemotherapy as frontline therapy, and they all recur, and at recurrence, they typically receive Avastin or Lomustine in second line. Soft tissue sarcomas, when they become metastatic, they become very difficult to treat. Patients receive doxorubicin at the beginning. They progress typically in 4.6 months, and then they receive different treatments in second line, and in third line, they get dacarbazine.
Here, the objective, as said also during the previous webinars, is to add Fibromun on top of the standard of care and try to do better than the standard of care alone. You may. You remember this picture from the slides presented by Dario. So we basically deliver TNF payload selectively at the site of disease by means of the nineteen antibody depicted in green. The product here is given by intravenous infusion, so it's for systemic application, and we've published in several peer-reviewed scientific journals that the L19TNF localizes selectively at the site of disease, sparing healthy tissues. A quick update on the glioblastoma programs. With the glioblastoma program started now in 2017 in collaboration with Prof. Weller and Dr.
Weiss at the University Hospital Zurich, and currently running two pivotal programs, one in first line and one in second line, in combination with Lomustine. You see, this is a phase I/II study. We completed the phase I, those escalation parts, with 15 patients, and I will give you an update in the next slide on the MRI scans. Now, since June 2023, we started the phase II randomized part with 158 patients, and see, the randomization is one to one, meaning that 50% of the patients get Lomustine, and the other 50% get the treatment. They go in the treatment arm and get the, the combination. And we look at the difference in terms of overall survival between the two arms.
You see, we are now opening up to 15 centers in different European geographies, and you see we already have 7 patients within few months with the only two centers, and now we are opening up to 15 centers. So you see here the expected prediction of the enrollment rate over the next few years. An update here of the phase I part of this study. You may remember the treatment lasts nine months, then patients are followed up. If you give Lomustine alone, you may expect an overall survival of eight months, so patient die within these timelines. Patient two was one of these cases.
It was an unfortunate patient that basically had COVID infection, could not receive the combo treatment, and you see that at six weeks, the lesion indicated by the red arrow increased by 350% in terms of tumor volume. Whereas patient number one that received the combination treatment, at nine months, you see the primary lesion was gone. See - 98% of tumor shrinkage, long lasting for, let's say, at least 18 months. At month 21, there was a new lesion at a different geography of the brain compared to the first, where the first lesion was. And now this patient resumed treatment under compassionate use, the so-called individual treatment attempt, and the lesion shrunk again by more than 60%. So it's quite impressive, considering that typically these patients unfortunately die within eight months.
Also, patient number three, see there is long-lasting major objective response, is now -98% at 27 months. Also, patient four, five, and six are benefiting, and this data have been published in Science Translational Medicine last May 2023. In soft tissue sarcoma, we have three ongoing studies: a phase II- B study in the U.S. in first-line patients, a phase II- B, phase II study in combo with dacarbazine in last line patients, and the most advanced one is this one in bold, a phase III European study in combination with doxorubicin. In first-line patients, we need to treat 118 patients, which are randomized to receive doxorubicin alone or the combination. Then here we look at progression-free survival as primary endpoint.
You see here that we are almost in line with the, basically in line with the predicted enrollment rate, you see, which is in blue, and the actual enrollment rate is in green. We opened 20 centers in, in, five different countries. We have 78 patients out of 118 patients to be treated. So to summarize, I think we're pretty. We're pretty excited about the, the progress of the programs. As if you think in, back in, at the time of the IPO, we didn't have the BCC data. We weren't so close to the melanoma readouts in Europe. We didn't have the glioblastoma data, and also we didn't have 20 centers in soft tissue sarcoma, and we didn't have the OncoFAP that is going to be presented by Dario, to which I hand over the stage again.
So we're really excited to see the progress of the pipeline, and as mentioned, while we see already nice results that we are very proud of in phase II studies, an important milestone will be the readout of the phase III trial. Now, if we focus on chemistry, we want to give you a glimpse of what we believe, could be the next area of expansion of our activities. We will focus on FAP, Fibroblast Activation Protein, but this is only one of the targets, as you will see, on which we are generating results. The big picture and the big question is the following: We come from a situation in which most pharmaceutical companies like to use full IgGs, so full antibodies for pharmacodelivery activities.
We have been the first company, and so far, the only company, that has constantly compared the performance of full antibodies with antibody fragments and even with small organic ligands, to ask, "What is the best agent for pharmacodelivery?" The results clearly show that especially for small payloads, the small ligands are the preferred delivery vehicle. Let me explain what I mean. In a paper that we published already in JACS 2018, we were looking at the microscopic level about the localization of tumor-homing antibodies and tumor-homing small ligands within the tumor mass. Tumor cells are in blue; the localization of the product is in green. You see that the antibodies can only give you a patchy uptake, typically in perivascular structures, and similar findings have been published by Genentech and other companies.
Again, highlighting that antibodies, if they are used in IgG format, they are big, they extravasate slowly, and they target badly. Now, with small organic ligands, the small molecules extravasate rapidly, and you see a uniform green staining of the tumor that suggests that the molecules are much faster and better at getting out of blood vessels and reaching the tumor cells. Also, at the macroscopic level, the comparison is clearly in favor of the small ligands. Here you see two patients from published clinical data, imaged with ligands to Fibroblast Activation Protein, FAP. With a full IgG, the tumor is visible, but the contrast is not fantastic, whereas with the small molecule, you get an excellent, contrast, tumor-to-organ ratio of 20 to 1 or better, as early as one hour, while you need several days to get this picture with the antibody.
So at least the good and selective localization in the tumor, you see the primary tumor in the breast, the bone metastasis, the liver mets, suggest that if we can deliver payloads to the site of disease, we are doing something good for imaging and for therapy. Now, we discover these ligands using our DNA-encoded chemical libraries. That's an area in which we have performed pioneering work. And once we have ligands, small organic ligands, two good targets, we can equip them with radionuclides for imaging or therapy with linker drug payloads. If you want, we can think about anti-inflammatory drugs, immunomodulatory drugs, CAR-T approaches. We are active in all these areas. We have published in these areas, but for the sake of simplicity, I will focus on these two programs because they have a clinical relevance, which is immediate. So let's start with radionuclides.
We have previously reported the fact that FAP is a very important target for multiple tumor types. In German centers where OncoFAP is used routinely, 5-10 patients per week receive OncoFAP, often as a problem solver for imaging needs. And if you focus, for example, in breast cancer, you can distinguish locally advanced tumors from heavily metastatic tumors, but also other type of malignancies are nicely imaged with FAP ligands. There is work recently published on a molecule that now belongs to Novartis, in which a ligand called FAP-2286, equipped with a therapeutic radionuclide, was mediating a rapid response. You see a patient with lung cancer before and after treatment, and of course, there is the wish to have even better targeting agents than the one described in this slide.
To keep a long story short, if we look at long time points, so one, two, three, four days after injection, the molecule that looks so good for imaging is washed away from the tumor. But our therapeutic candidate, called OncoFAP-23, actually stays on the tumor for a longer period of time with an exquisite specificity over normal tissues. In our hands, these are the results obtained with the molecule that was originally developed by Clovis and which is now licensed to Novartis. And in our hands, that molecule goes away from the tumor and has higher kidney levels, so time will tell what is the clinical performance, but this is the molecule that we have chosen for therapy. So patients who have a positive FAP scan, they become eligible for radionuclide therapeutic intervention. In mice, the best molecule for targeting is also the best molecule for therapy.
Now, therapy here was performed at an ultra-low dose of radioactivity, 5 megabecquerel, which is about 20 times lower than what you would normally use in the mouse. We can cure tumor-bearing mice with this medication, and as you will see, a clinical trial is about to start. Let me be more precise. We have completed GMP manufacturing at Senn, a Swiss partner, for the production of these small organic molecules. We have completed central labeling procedures with our partner, Seibersdorf, in Austria. So we label with lutetium-177 at the central location that can ship the drug globally. You see a number of clinical centers in Italy, in Germany, in the U.K., and probably in other countries, who will participate in this phase I/ II clinical developments.
Importantly, the trial will select patients based on a positive scan, but will treat either patients in monotherapy with lutetium-177 OncoFAP-23, or in a combination with L19IL2 immunocytokine. Now, one last slide to touch on the drug conjugates. At present, antibody drug conjugates are a huge component of the pharmaceutical market, but we believe that the future is in small molecule drug conjugates rather than antibody drug conjugates. Our first candidate that will go to the clinic is OncoFAP-GlyPro-MMAE. So in blue, you see the OncoFAP moiety that homes to the tumor. In green, you see a spectacular opportunity offered by FAP. FAP is not only a target expressed in the tumor, it's also an enzyme that cleaves GlyPro. So immediate after targeting, we can have cleavage of the linker and release of the potent payload called monomethyl auristatin E.
This data have been published in many publications, including a recent Clinical Cancer Research paper. This complicated slide monitors the release of MMAE over time in the tumor. You see that at 24 hours, the blue bar shows an excellent selectivity in tumors over normal tissues, and this works both with cellular models of FAP expression, but also with stromal models of scarce FAP expression. We have completed phase II of a program in animal patients, which means dogs with spontaneous tumors, and the therapy part is about to start in collaboration with the University of Milan in Italy. Which means that while the GMP manufacturing for clinical use is progressing, we have the opportunity to learn about the activity of OncoFAP-GlyPro-MMAE in animal patients with FAP-positive tumors. And, FAP is only the beginning of what we can do with ligand-based pharmacodelivery.
We have previously shown the ability to target carbonic anhydrase nine at sites of hypoxia and in renal cell carcinoma, both for imaging and therapy. Prostate-specific membrane antigen is a good target for prostate cancer. Somatostatin receptor two is a good target for neuroendocrine tumors, and we have recently discovered, against a very important undisclosed target, new ligands with ultra-high affinity, 100 picomolar dissociation constant or lower, using our DNA-encoded chemical library. So I think there is a bright future for Philogen and for Philochem, and we actually will invest more in these activities. With this, I hand over to our Chief Financial Officer, Dr. Laura Baldi, who will tell us about two last slides on the financial results.
Yes, thank you, Dario. Just two slides to comment on the group's key economic and financial figures as of 30 June 2023. The group reports on the top line of the income statement, consolidated revenues of EUR 22.5 million, an increase of more than 10% compared to the first half of 2022 revenues. These revenues are almost entirely attributable to revenues from contract with customer, approximately 96%, and to a minor extent, to other income as operating grants. The first half of 2023 was characterized by substantial payment related to contract, to new contract and existing contract with third party. At the present, revenues still remain the nature of known constant revenues linked to the achievement of milestone or upfront payment of new contract.
With the signing of this contract, the group is structuring itself to market product once approval are received. At that stage, revenues will become more stable and recurring, as now. Although the company is not yet a product company, it has nevertheless demonstrated that it is able to generate value from multiple assets, and to carry out its research and development program and clinical trial projects. Before we turn into the cost analysis, it should be noted that the operating cost amounted to EUR 13.9 million at the end of the first half.
This cost include a personnel cost of about EUR 9 million and clinical cost, sorry, personnel cost of EUR 6 million and clinical cost of approximately the same value, EUR 6 million, and the remaining part are production cost. The operating costs increased by 25% compared to the previous half quarter of last year, confirming the continuing investment in clinical trial that are increased of 30% and the corporate organization, the personnel costs are increased of more than 16%. But you can see the group closed the half year with an EBITDA of EUR 8.6 million, in line more or less with the previous year, and an EBIT of EUR 6.9 million.
The depreciation and amortization, so no monetary cost, increased by 36.5% due to the full commissioning of the new GMP site. Finally, the company continues to invest in plant maintenance. In the first quarter, the CapEx is EUR 1.5 million. If we move to the net financial position, we can see that it is up by more than EUR 8 million compared to the beginning of the year. And in the next slide, we will see a bridge composition of the breakdown of increasing and decreasing of this financial position. The cash position confirm, while balancing a prudent management, as well as, a good level of capitalization to continue the activities and the program, the strategy of the company.
In the next slide, we summarize in a graphic way the net financial position evolution. We start the year with a net financial position of EUR 70.4 million and liquidity of EUR 86.2 million. We increased in this quarter, in this half part of the year, EUR 22.6 million of new proceeds. The operating expenses incurred has been EUR 13.2 million, as I said before. 1.5 million is CapEx, and 1.2 million is the liquidity absorption for the buyback program. And then we had EUR 1.4 million of other financial items.
So at the end of the first half, the group has the liquidity of EUR 94.3 million, plus EUR 6 million of tax credit, so more or less a liquidity of EUR 100 million, and then a net financial position of 79.1. We remember that the group, the financial liability of the group is largely linked to the accounting treatment of lease liabilities, and the amount is EUR 15.2 million. So from my side, that is the key figures of the first half, and I thank you, and hand over again to Emanuele.
Thank you very much, Laura. With this, we hand over the formal presentation, and we open the floor to potential questions and comments.