Chief Medical Officer Zbigniew Zasłona, the Chief Scientific Officer, and Sławomir Broniarek, Chief Financial Officer. The meeting has been planned for around one and a half hours. First, we will discuss the presentation, and then we will hold a Q&A session. Please write your questions in the chat. The presentation has already been made available at the company's website in the For Investors tab. Now I give the floor to Martin.
Hello, ladies and gentlemen. I would like to welcome you at yet another webinar where we present the report, this time for 2024. We have decided not to hold the meeting yesterday because some of the information might have been considered a joke. We decided to present it on a different date in full seriousness, to present to you what we have managed to achieve in 2024 and what we have done so far in 2025.
This presentation will be focusing on two of our main assets, those which have the greatest weight in terms of the company's value and which also are most cost-generating. OATD01, the GUIDE study in patients with sarcoidosis, and OATD02, the phase I trial in oncological cancer patients with solid tumors. We will present a quick update regarding the preclinical products, and we will also tell you a little about the plans for further development of our pipeline. Currently, as you can see, we are actively developing four different projects, two of them in the clinical stage. Some of the projects in our pipeline have been temporarily suspended, however, like OSP21, but we are not giving up on it, given what Zbigniew will tell you soon, and the projects regarding mRNA targets.
Now I will give the floor to Piotr so that he can tell you a bit more about the progress in our flagship phase two project, patients with lung sarcoidosis.
The GUIDE study is in the phase of accurate recruitment. The study was launched much earlier in terms of approval in the United States than in the U.K., and finally in the EU. The majority of the study sites is active, but not all of them. At the moment, we have approximately 15 sites activated with the ongoing patient enrollment. They already have patients either in screening or already enrolled in the study. The recruitment, the enrollment has been sped up at the end of last year, and we tried to make the enrollment easier for the sites and to make the study more visible for the study community, so doctors, pulmonologists, and patients themselves. Over the last four months, we've been enrolling intensively. We have now two-digit numbers of patients in the study. Last sites are awaiting their full launch.
Like such as communicated earlier, we considered two additional countries, and we decided in favor of one country in the EU, which would be much easier since the EU has already an ongoing study of OATD01. This is the Netherlands. This is something we communicated before; we targeted the country from the beginning, but it had a premed competitive study. The sites were not interested in other competing studies, but now they are much interested in joining our study. One activity that we've undertaken is a certain modification of the study protocol so as to make the enrollment easier in terms of the enrollment and exclusion criteria, and also at the level of the procedures themselves.
The burden of the procedure for the site or for the patient, the modification of the study protocol is currently under assessment at the competent authorities, and we are expecting that in May, if there are no questions from the bioethical committees, we should be able to implement the modification in full. However, those modifications do not intervene in the study matter and in the population. The population will continue to be homogenous, so we're not stopping the enrollment. The enrollment is going on according to the current protocol. In the coming days, also, we are going to provide further support, further boost. We plan to resubmit to the NIH for the grant for the American part of the study. As to our activities in different fields to boost the enrollment, we decided to put them all in one slide.
I've mentioned already the study protocol amendment, also some on-site visits by our medical team, myself included in the study centers. Most of them we've already visited, but we still plan to visit the last ones so as to talk with doctors to discuss any problems or potential problems and how we can help in the subject matter-related issues or also purely logistical or organizational issues. Also, as a non-standard activity, we organize an expert seminar for pulmonologists, practitioners that practice in the area surrounding the study sites so that can refer their patients to the sites. The first seminar took place in February in Philadelphia in cooperation with Temple University, where we have our study site, and further seminars are planned in Europe.
Another activity that we are planning is one addressed at the medical community so that the community of pulmonologists is aware of our study, that it is being talked about during meetings on lung sarcoidosis, during medical conferences. All the conferences that you can see in the slide have been or are going to be attended by our team, by our researchers. Our researchers are present there as well, and we are holding meetings with them. Finally, an information campaign, including direct advertising, of course, within the limits of bioethics and national regulations. The campaign is now boosted. It is relaunched, especially in the United States. We have extended our cooperation with the Foundation for Sarcoidosis Research that, together with us, is now launching its campaign in the social media together with other elements that we are relaunching, such as patient-facing leaflets and wall posters.
This is provided by the teams of the research sites so that our study is more visible for patients. We are also approaching patient advocacy groups. As we have already communicated, we will not be reiterating some of the subsequent slides. The next indication where we have been putting a lot of effort in, both the scientific and the medical teams, is MASH. Metabolic dysfunction-associated steatohepatitis, also referred to as MASH. We perceive this as an indication, as already mentioned on many occasions. It is as attractive as sarcoidosis as a target for various scientific reasons, also clinical reasons, which I will tell you about in a moment, but also from a purely market perspective. It is a completely different market, a different specificity, and also an unmet medical need. It still remains an unmet medical need across the world. Martin, would you like to comment?
You've seen this slide on many occasions. The players in this market are the same, remain the same. There are big players, and there are several smaller companies or mid-sized companies with which we have been in talks as well, which are also interested in entering this metabolic area, in particular MASH. The number of potential partners is on the rise. So far, only one drug has received marketing authorization, but it is a trailblazer. It's building the pathway for subsequent molecules, which definitely will receive marketing authorization as well. In most cases, 90% or more, these are programs related to the GLP-1 antagonist. There are a lot of those studies carried out. Most of them focus on obesity, but there are also studies which address MASH as well.
We are operating in a completely different area, a different target, which potentially is complementary to the metabolic action, which are reduced by GLP-1 antagonists by addressing both the chronic inflammation, which results in fibrosis of the liver, as Piotr will elaborate on in a moment. We have results of both our in-house results, of course, in vitro studies, which indicate that inhibition of kynureninase makes sense and is a valid therapeutic target. This is also confirmed by data from external studies. We also have seen this in various publications. This is an example from other academics in South Korea. They are conducting research on kynureninase 1, with MASH being the therapeutic target. Their results are the same, are similar, that indeed this target makes sense. Also, the background knowledge is also in favor of continuing these trials.
Also, the data, other Omnic or other data, all this can be used, and we do use it. Zbigniew would like to add something.
Also, data from trials, either ex vivo or on clinical matters, so taken from or also the kynureninase in the plasma as a biomarker. I will not be discussing the details. If anyone is interested in the details, you can see the references to the publications and go more in depth. All the research indicates that on the one hand, the expression of kynureninases correlates with the degree of advancement of the disease and the lower or more broadly obesity, as indicated here in the clinical materials. Also a slide which we like to present. I'm sure a lot of you have already had the chance to see it.
This is the indirect evidence on clinical material proving that reduced or eliminated activity of kynureninases not only has a protective effect against contracting the disease, so developing MASH, but also has a protective effect when it comes to progression of the disease. To sum up this short summary, because most of you have already seen these slides and we've already discussed this at length, to sum up, we have a lot of results of preclinical translational genetic research results, which are indicative of the fact that the role of HIF-1 is of key importance for the progression and development of the disease. Lack of that activity has at least a protective effect. We are actually also counting on therapeutic effects. We will strive to prove this by starting a phase two clinical trial conducted on MASH patients.
We are carrying out a number of various actions preparatory, preparing us for the trial. We are also submitting grant applications to achieve the funds to do so. That way, before we actually enter into an agreement with the potential partner, we are ready for analysis of biomarkers and analysis of the disease itself and the role of our target, as well as the target protocol for the trial, which will be based on biopsies, given the results mentioned by Piotr. Summing up, a huge potential. Unfortunately, with the company's current setting, we are unable to do this alone. We need a partner because of our current resources and finances. Therefore, our main objective right now is entering into an agreement with a partner who will support us, especially in the area of finances.
Because when it comes to human resources, we think that in cooperation with a CRO, we are able to manage it very well. Here, we have clear outlines, unlike with sarcoidosis where we face a blue ocean situation and where the indications for endpoints are only being developed now. That is my short input. I am giving the floor back to Piotr.
Our second clinical program, which is OATD02, solid tumors and for colorectal cancer and other cancer patients, for those patients that have, for those who were the doctor or the patient and the patient decided they want to continue, the study is enrolling very well. There is no problem with that.
Currently, we are during a pause in enrollment because after reaching the 20 milligrams per day dose and after looking at pharmacokinetic and pharmacodynamic data and also from the perspective of the safety data, which we are since the beginning have not observed any toxicity effects that would limit the dose. We keep increasing. There was no need to reverse, which is, of course, not acceptable and typical for such a scheme. After the first patient received the 20 milligram per day dose, we looked at the data. We also consulted with the safety review committee and according to its recommendation, we recruited patients. All the patients were reviewed for DLT for four weeks. The data was analyzed. The data was assessed as consistent of the second trio of patients after the first trio of patients.
There are no safety precautions and no safety concerns that would limit the dose. We decided to escalate the dose more aggressively, as it is said. According to the data, we presented this proposal to the external committee that supported our intention to amend the protocol. We amended the protocol in the beginning of this year. The study protocol was submitted to competent authorities, and now it is under assessment. We expect that at the end of this month, if there are no reservations on the part of the authorities, we are expecting an approval for the continuation of the study with the increased dose. A dose that is going to be higher than the dose so far. We are not yet disclosing the dose because it is not yet certain.
The regulator has a final say, but this is going to be the assumption. The Boeing scheme determines the fact that the number of patients is not going to change. The time of the study, the timeline, is going to be prolonged by several, like a dozen, weeks because of this pause that we are having now. This was for the clinical studies. Now, preclinical pipeline. Yes, you can see reduced pipeline, so a shorter time. To sum up, the most advanced protein targeting programs, we have the USP7. We are at the advanced lead stage where we are currently conducting the toxicology study. As a reminder, this is a result of some of the drugs similar to drugs that inhibited MDM2 and stabilized P53. We demonstrated in vivo efficacy for four compounds.
We have a very good pharmacological understanding of the USP7 behavior in cancer. We are now discussing with Piotr on how to enter the clinic in an optimal manner. Lymphoma is one of the potential indications. However, at the moment, there is no room in the clinic to develop it. With the other challenges, we are waiting for the development of OATD01-02. At the moment, there are no other companies that are as advanced as we are in the USP7. Some of the compounds we've created are also now covered with patent protection. USP7 is not yet a full-speed program, but we proved genetically that USP7 inhibits phosphorylation of process. It is a very attractive target. Even though the program is at an early stage, we are going to try to apply for grants to be able also to relaunch USP21.
As to mRNA, it's a two-track approach. We on one hand have means to develop the platform. We hope for the cascade to be consistent to be able to apply at least with two tests the effect on mRNA. We are developing this both internally and externally in cooperation with scientific centers and CROs. Also, we have two mRNA targets that we treat as early-stage programs that if the conditions are favorable, are going to enter our pipeline as well.
Thank you, Zbigniew. Thank you to Piotr, because he talked about slides, and I will now use a few slides to present the figures with which we closed 2024. I would like to draw your attention to a few figures. A few of them have been put into brackets.
That's because for the first time, we could create a consolidated financial statement of our company because we have this branch in the United States, and they had an actual impact on our statements, as you can see in the difference in the revenue, where you can see a difference, where we can see the amount of the grant, which was mentioned and discussed by Zbigniew. He didn't mention the grant, but thanks to that additional financing, we were able to effectively finance most of all that study and the animal model in this project. This was very cost-effective. That's why I'm drawing your attention to this. That's why we also have a visible impact of the grant from NIH. The rest is from the NIH.
Here, it's worth to mention that even though this amount is lower than last year, we'd like to point your attention that in 2023, we had the revenue which applied to a program which was closed down related to the transaction with Galapagos, where we had to pay the last installments. Here, this revenue from the grant, that's for the grant regarding mRNA, which is a good signal because since the previous quarter, we were informing you about some problems with capitalizing the applications. At the end of last year, we achieved PLN 1,200,000, and then also a grant for PLN 600,000. We've managed to unblock this source of financing, and we have been experiencing increased flows. Now we have around PLN 42 million of co-financing. We still have around PLN 30 million to use as part of this grant.
What I wanted to underline as part of the top line, even though it's not a specific amount, the amount indicated in the other, this is a discount which we received, so a relief that we received for our employees. This is something which we will be continuing in the subsequent years. When it comes to our cost position, the costs, they are lower, but I'd like to draw your attention to the amount of the motivation program. It was settled on a single occasion. It's not a cash position, so we only presented it in the area of costs, and this increased our capital, which can be seen on the graphs to the right side of this slide. If we were to deduct, eliminate this motivation program from those costs, you can see that we've made sure that these costs are lower than last year.
Basically, each line, you can see exactly 15% of difference, including the early programs mentioned by Zbigniew. This reduced the pipeline, which translated into reduced costs, again, by 15%. As a consequence, the result, the total result, you can see that the net loss is greater, but keeping in mind the motivation program, I would like to point your attention that the actual loss is lower, also because we had lower revenues, which is the result of the funds that we have. Moving into the right-hand side of this slide, you can observe how those actions taken on specific projects translated into specific figures. You can see how much we spent on clinical trials. That's PLN 18 million. The company reduced its cash position, but when it comes to the liabilities, we can see an increased the capital increase, which took place at the end of 2024.
If you look also below, you can see that this capital increase has been taken into account in the capital amount because it was registered on Christmas Eve 2024. However, as it was registered in 2025 officially, you can see that there is a slight increase, but the position has not changed significantly. This is good information because we can see that this is a stable position. Now to sum up our expenses in general, when we compare 2024 and 2023, please notice that we also reduced some things. 2024 was characterized by lower dynamics of expenses compared to 2023. In total, that is around 25%. In different items, you can see you can wonder why in clinical programs we have such a decrease because there we have around 40%.
This results from the fact that 2023 was the time of huge investments where we invested in a lot of our investigation sites, which resulted in a lot of investments. Now, as we are increasing the enrollment rates, those expenses will now be on the rise as well. In 2024, we had lower expenses on the early programs and also lower administrative burden. The reduced pipeline also resulted in the manpower rates and the employment rates. At the end of the year, we had 102 employees. Year on year, that was a reduction by around 10%, but we are still keeping the same proportion of the scientific staff with a PhD. That's over 50% still.
What I want you to, the key takeaway, what I want you to remember is that the increasing of the capital, at the beginning, that was PLN 48 million, and at the end of March, that's PLN 40 million. These funds will allow us to carry out our planned actions until the end of the year and the beginning of 2026. Here, I also would like to propose a slide that shows our position in terms of grants. We have the mRNA platform grant, the only active grant, which is now fed with the payment from PARP. We use its benefits. As we've already informed you, one of our programs, the OATD01 application was rejected. We didn't obtain the funding. Also, the NIH application is going to be resubmitted really soon, where we expect the early Q3 of this year to provide a positive decision.
We've also submitted, resubmitted a grant, an application for an mRNA development program grant, where we submitted it on the 28th of March to the National Center for Research and Development, NCBR, and we will know the results in the third quarter of 2025. Just to inform you, unfortunately, our application for the project OATD-01 for MASH to create an in vivo model was unfortunately rejected by the NCBR. This is all as to grants. As far as our plans are concerned, they amount to PLN 105 million. They are related to the clinic. As to the mRNA, it's approximately PLN 20 million. The other early programs are around PLN 15 million. General and administrative expenses also approximately PLN 20 million, with the PLN 105 million as a total amount. Where are we going to look for funding?
Surely, we are going to look for grants and subsidies in mRNA and also the grants I have already mentioned when discussing the previous slide. The other sources is typical for our biotech industry. I would love to be able to tell you that it is going to be funds from partnering agreements, but also we are expecting some of the increase in capital that we would want to use, and we would like to use those sources as well. A very short summary that will cover both the year 2024 and the beginning of 2025. In total, it covers four different meetings and events, conferences with bilateral talks held between our company and potential partners. All of those conferences, starting from BioEurope Spring in Barcelona, and the main asset that is under discussion is OATD-01.
In the Q&A session, we'll be happy to provide more detailed information on the nature of advancement of those talks and the division of interest by external partners in our program. Surely, as I mentioned already, OATD01 is dominating those negotiations and for various indications based on this ongoing study in lung sarcoidosis in the GUIDE study, as well as as a second possibility, but similar in the amounts, the MASH indication for the same molecule. Those meetings amounted to some 100 instances, and they mostly concerned in 70% OATD01, either open meetings or confidential meetings. The other area, similar in numbers of meetings, was OATD02 and mRNA. The last conference this year also included some meetings on USP7.
In terms of the probability and time to transaction, the frontrunner is definitely in terms of the potential agreement and the time of signing is OATD01. We are going to provide a summary in a minute, but the highest priority for now is the fastest possible signing of the agreement and also signing an agreement for the MASH indication because we are aware of the lifetime of the patent, and we want to use the potential of the molecule. The development of study will, of course, increase the costs, but it diminishes the risk since it is an opportunity to show the mechanism of action and effectiveness. The different organ, but the same mechanism. There is actually the opportunities are greater in MASH than they are actually in sarcoidosis, but the sarcoidosis will provide a size of data once it is available after the second phase study.
The MASH data for now come from various models, including animal models and others that try to mimic the steatohepatitis of liver and also because there are no standards in the market as to the preclinical models of this disease.
Therefore, our model became a standard, but that was just one of the models. There is a lot of data from patients, as we often mentioned. This is one of the biomarkers for the disease progression. We are currently in the process of submitting a publication which indicates that this is not just a correlation, but there is a cause-and-effect relation that the kinolytic activity is the result, is the source of the disease progression. There are indications that this should work. When it comes to the data volume and the amount of data from patients, it's much greater in the case of MASH.
I will not be saying much more about this right now because I'm expecting a lot of questions about it in the Q&A sessions. Now I will move on to the summary of this rather brief presentation. That's by design. We wanted to reduce the time spent on the presentation to leave more time for a discussion with you because all those areas which we've discussed is where we have progress. We have a dynamics in the number of randomized patients and those in the screening, but we don't have breakthrough information which we could communicate to you compared to our previous meeting. When it comes to this OATD01 and OATD02 has been discussed by Piotr at length. When it comes to the early stage studies, also including AI, as already mentioned, we have resubmitted a grant application. It was valued very highly.
It was, as I call, the second best result when it comes to the expert appraisal of the project. However, we did not receive the grant because we did not prepare the prohibitory rule which the institution set up for subcontractors. We have decided that the most effective way of getting the grant would be resubmission rather than an appeal. We are counting on the fact that since the appraisal of the project was so high and the requirements in the institution have changed, our chances are quite significant to obtain this grant.
It would help us in the development of our early programs where these tools are particularly intensely utilized, both in the mRNA platform and other programs like USP7, which has been suspended for now, USP21, sorry for this mistake, and USP7, which has not been suspended, and will help us select the drug candidate after the non-GLP toxicity studies. Non-GLP studies will present us with the scope of potential doses and the safety requirements, which would allow us to safely nominate it and start the preclinical stage. In those early programs, we are actively striving towards cooperation and early partnering. Here, the talks on USP7 have been maintained on the US Bio. Also, one of the targets in our mRNA platform seems to be very attractive. It is in the cancer area, and here we are also holding talks with potential partners.
Obviously, the overarching objective is entering into an agreement which has been long awaited by both us and you, our shareholders. We are holding more and more negotiations and talks. They have been progressing, and that is why we are counting on it coming to fruition this year, regardless of when the partial and final readings in the Guide study are available. In the mRNA area, as already mentioned, we are also in talks with various potential partners, and they might lead to entering into a partnership agreement on the development of the program and nominating a leading molecule and thus a clinical candidate. We are also striving to achieve funds wherever possible, both from public funds, both in Poland and abroad, and also from private funds, also in the form of option agreements or partnership agreements. Thank you for your attention.
Now we will be happy to answer any questions you might have. I am happy that Piotr will be the main person to answer your questions as he might have the most interesting information for US shareholders.
Thank you for this presentation. Moving on to the questions. We have the first question regarding finances.
I will break this down into chunks. How much cash does the company have at the end of the year? I understand that the net amount is before the inflow from the issue. Yes. Is it more the June 2026 in terms of or January? If it is not possible to finalize any partnering agreement, when will it be necessary to make the issue?
We will decide based on the development of the clinical programs and the partnering talks.
What are the cash needs for the year 2025-2026 in order to continue all the ongoing projects in not a reduced scale?
It was an amount of PLN 105 million, which we now need to be able to conduct and continue our projects in an unchanged state.
Another question is on the Guide study. The current pace of enrollment does not meet probably the expectations of the board. What are your expectations as to the results of the activities that you have proposed, and what is your backup plan if the enrollment fails to speed up? Do you think that the market conditions could be more favorable, such as, for example, completion of other studies in sarcoidosis?
Starting from the end, there are currently no studies that are competing for the resources, that are competing for the assets at the CROs and not at the patient level at least.
We have not identified any study that would be competing for patients at the moment. However, there is at least one study, the Spasantria study, that is conducted in several sites, shared sites with our studies. This can be competitive in some terms, but it is not a dominating sort of impact. Answering to your question on when are we going to perceive the effects, we are seeing them already. We see a simple causal relationship between the amount of invested effort in a given site and the increase in the pace of enrollment. The best example is the United States, where that were approved at the earliest time, and we could start early.
Currently, the United States has more than 50% of our total enrollment, which is not typical because typically the United States are usually not a leader in terms of enrollment of patients. We can see a very direct relationship between our efforts to the actual enrollment numbers, especially that the European sites have not yet been initiated in full or active. Now we've started to pay a lot more attention to the European sites, and we're expecting a situation that is more typical of the global clinical studies that Europe will show its power. In the end, we expect that there are going to be more European patients than American ones.
Thank you. One more question on the pace of enrollment. Let me read the whole. The current enrollment rate, three for patients a month, obviously this regards to OATD-01.
At this pace, the recruitment and observation, so follow-up, gives interim results at mid-2026. What are the options for increasing this pace? When does the company plan to publish interim results starting from the end?
We cannot publish full results as we won't see them. These are the rules of the double-blind or blinded trials. Regarding the results regarding the primary endpoint and the safety, this will be seen only by our independent external monitoring committee. In line with the rules of the game, which apply and have applied for years across the world, and in line with our protocol, what we get as the sponsor are recommendations. Recommendations of what the results that have been seen so far are positive from our perspective. That is, give us the chance of seeing the drug being effective or not, or efficacious.
Something which we cannot exclude is that maybe the placebo arm would be more efficacious than the study drug. Obviously, we've had such cases in the history of research in the world. From the perspective of those two data sets, recommendations on whether the study should be continued or not, so efficacy and safety, but we will not see the actual figures in the form which would allow us to publish this data. This would violate the fundaments of the principles of carrying out research and the idea of blinding the study. As to the first part of the question, I understand that this is a certain assumption that we have the three for patients a month pace. The enrollment pace is on the rise constantly.
The sites which are carrying out enrollment are at various advancement stages when it comes to the learning curve, which is typical for clinical trials. Also, from the perspective that we are adding on new sites and a new country, which we've mentioned, we expect the enrollment curve to become more and more steep than it is currently. We are not extrapolating it linearly when we are forecasting the full enrollment of patients and carrying out the clinical trials on the patients in the number which would allow for an interim analysis.
One more question regarding enrollment for OATD01. How many patients, when it comes to %, do not successfully pass the screening? What are the main reasons, and how has this % changed over time?
Does the company know whether these percentages are similar for studies carried out on rare diseases which were carried out by your CRO, Sinbeck?
We did not go in depth on such data. This would not really be that useful because each protocol and each set of enrollment criteria impacts the screening failure %. The % of patients who fail to be enrolled, the % currently is relatively high, which is indicative of the learning curve. Approximately, every second patient who starts the screening is in the end randomized into the trial and receives the treatment. It is quite high. Obviously, in the medical team, in the team of medical monitors, this issue is always the area where we educate, where we discuss regarding specific patients.
We are anticipating that this % of this negative decision to enroll will be reduced, which is typical for the rising learning curve in various sites.
Piotr gets a little bit of rest. A question regarding partnering OATD01 and MASH. How many partners are you in talks with? How advanced these talks are? Do you estimate the agreement to be weeks or months away? What is the profile of the interested parties? Is it big pharma or is it smaller entities? A question whether Madrigal, whether you perceive Madrigal to be biotech or a mid-sized pharma.
I'm not sure I remembered all parts of this complex question, but maybe let's take it one by one. I will be reminding you of any ones that you might have missed.
Before I answer this complex question, just let me give you a short summary or maybe supplement what Piotr just said. We have been observing a significant correlation between the actions that we've been taking, the many hour-long meetings in sites in the U.S. and the U.K., because it's clear that the states recruit the best, and the U.K. is right behind them. I think that this is meaningful. The time we spend on those meetings and the trips by plane that we do makes sense. It makes a difference. We will see it give fruit in the weeks to come, but this correlates. The time we've invested in talking with the sites will provide us with benefits. When it comes to the advancement stage of the talks, they are at different stages of development or engagement.
Some have been ongoing for several months now, and probably at the next bio-international in the United States. That might be the first anniversary of these talks. They are at a different advancement stage than the ones which we've initiated at the previous Bio-Europe or Bio-Europe Spring in Milan. We are also observing new trends when it comes to the entities with which we've been in talks, because I think this was also a part of the question. It is clear that there is this global trend when it comes to the partnering market, that big pharma is quite reserved and hesitant when it comes to entering into projects before the phase two results have been read. The big preference is larger transactions at later stages with lower risk of failure.
When it comes to the larger biotech companies with which we've been talking, this tolerance for risk, this appetite for risk is a bit greater, definitely greater. This is offset, because the numbers, the value of the transactions would be lower. Something which has been shown by the last Bio-Europe in Milan are mid-sized companies between $1 billion and a few billion US dollar value, where the dominating area is the regional or global sale of generics, but they are also more prone to enter into innovative areas. At least 10 meetings in the last Bio-Europe were with companies of this profile. It is a different type of partnering because their main objective and the main element of their partnering is financing of further development of the studies.
They don't always have the internal competencies to develop innovative drugs, but they have a certain market reach on the continent or even internationally, and they want to increase their portfolio by adding innovative products. There are more and more companies like these, and the financing capacities of such companies are greater than for smaller biotechs, even those which are listed and well-valued. Still, such companies, in terms of cash flow, it's different. The companies dealing with generics have more stable inflows. This is an interesting area for us, which we are exploring, and the talks are at different advancement stages. These talks started at different events, the last ones at the last Bio-Europe. I don't want to make specific forecasts because all of them are subject to significant uncertainty.
I think that when it comes to this estimating the probability of when that can happen, we are counting on the second half of this year, the final readings, even in the Guide study, because with MASH in 2026, this is something we will not have, even if we were to start this trial this year. The positive results of the Guide study will definitely increase the number of potential partners and also might make big pharma entities interested, as they are interested in both the target and the indications which we are developing. We anticipate they will join the discussion, so to speak. On the other hand, we also have this scenario that we will finish with sarcoidosis, and we will develop MASH with a different partner, and big pharma will approach us in the subsequent year. It's difficult to make forecasts to us.
As already mentioned, the most important objective is starting the MASH trial as soon as possible and to have a very dynamic acceleration of patient enrollment, because the recruitment enrollment itself might not have such a huge impact, although it is a positive occurrence. Reaching these even unblinded interim results, reaching that stage is also a potential value inflection point, which will increase the probability of a transaction and will improve the parameters of a potential transaction. This was a lengthy answer, but I'm sure I missed some of the parts of the complex question.
There was also an additional question with how many companies, in terms of MASH, you are currently in talks, but it's a similar question. There was also a question about how you classify Madrigal.
When it comes to Madrigal, despite the fact that they have a drug with a marketing authorization, I would classify it as a biotech company, given the scale of their sales and the area where this molecule was authorized, that is, in the US, and the fact that currently it is a company is a one-product company. It is more an entity for a specific product. Not really a biotech rather than a mid-sized pharma. With which companies from the slides regarding MASH are you in talks? With several, that's all I can say. The talks are also at different intensity stages. As already mentioned, some companies insist on seeing the second phase results. Most of them insist on that. Some of them we are no longer talking with at this stage. There are some with whom we talk. We are currently talking.
I think that the likelihood of entering into an agreement is more far away than in the case of mid-sized companies or biotechs.
Thank you very much. Going further, another question on MASH. Have your potential partners in the bio conference, were they expecting the company to conduct, to have conducted drug-to-drug interaction with Resmetirom or Romer, or maybe a company or other entities have conducted such combined drug studies? Also the studies on the efficacy or effectiveness in animal models, in animals.
A quick answer to the first questions is no. Let me now give the floor to Piotr so that he can reply in terms of the DDI results with Resmiteron, because the second reply is also that we have not conducted any such studies in the clinical context, and whether your potential partners require them.
No, they did not require that.
It would be too early for that. When conducting second phase or third phase trial, this is the time to respond to the question of potential drug-to-drug interactions, such as with Prednisilin. This is not only potentially Resmetirom , but if so, it would be more sensible to test Resmiteron interaction, but it is not something that you start your partnering talks with. It is not a key element. You can imagine a situation where we have an unexpectedly unfavorable interaction between one or the other drug. It is not a situation that can block preclinic development of OATD01, because it's not that we have a standard of care in MASH established in Europe, which would be decisive here, because we, of course, had to conduct DDI with Pirfenidone.
The standard of care is one thing, because these are the guidelines of scientific societies that are not directly influential on the presence of drugs in the market, but the second thing is centralized guidelines in the EU that have their own dynamics. I confirm what you have said.
A question about partnering in MASH. How should we understand co-development? Would upfront be rather symbolic, or can it be the mentioned PLN 100 million? Would the partner fund the entire cost of the MASH study? What are your assumptions?
Again, it's a complex question. Returning to our priorities, for the moment, the most important element in terms of the company's strategy is the fastest possible launch of the study.
If we are talking strictly about the co-development structure, which is less standard than the typical license or option to license and taking over the rights by the partner, undoubtedly, the initial payments are lower than in the case of a license, especially one signed at a certain stage of advancement of the project. The main contribution of the partner is to fund the study, so the actual study. The company retains more rights than in the case of the license, where the company obtains payment and some milestones and some royalties, but is no longer the owner, so does not participate or participates in the potential revenue to a much lower level.
Whereas in the case of co-development, it can be a bigger share of the pie, but you cannot expect very high initial payments in the case of if the IP rights are not entirely transferred to the partner. This is one thing or the other, but the structures that we are discussing with different partners are multiple, and they have to be actually adapted to the partner's priorities. Our priority is for us to be able to finish the Guide study as soon as possible, to begin the MASH study as soon as possible. We also would like to have a high share in the potential big success, but the upfront payments and milestones are important, but they are secondary to the timeline. Time is money, and each day has its value, and starting as fast as possible is our highest priority now.
You said a molecule appealed against the negative decision regarding the grant for the KAIT trial. What's the status of the situation, and what are the possible solutions?
Indeed, as you might remember, the appeal was submitted by ABM. We are currently waiting on information. Unfortunately, we do not know the date of the hearing. We are still waiting on that.
A short question regarding YKL-40. How can you comment on the project? Is there no chance for reactivation?
There is a chance for another new partnering. A more extended answer is that we would like to avoid a situation. We are observing interest, but we would like to avoid a situation which took place with Ocean Biomedical, of which we've informed you. We are more cautious in our talks.
When from the formal and financial situation, everything will be in order, there is a chance that we try partnering in this regard again. However, when it comes to the financial aspects, I would not expect much larger parameters given the stage of development of that molecule.
Now, OATD02. I will combine two different questions because they have the similar objective. What are the conclusions of adding the next three patients on the 20-milligram doses? Have you managed to see greater correlation for the parameters in terms of safety and efficacy? With the 40 milligrams, have you seen any signs of efficacy?
The data from the three additional patients are quite consistent with the results for the first three patients. That was the aim of adding the additional three patients.
To see whether the results that we have been observing, they were not the same as modeled on animal models, whether they are reproducible or whether they are incidental. Generally, we are seeing a similar significant consistency in all six patients, and hence our decision to take a more aggressive approach and to scale up. Yes, we are observing a correlation. Obviously, it's difficult to say about a linear dynamic when we are talking about such a small patient sample. With the 20 mg per day arm, on the one hand, it is not usually practiced to go into details on the figures about what works good in an ongoing clinical trial. However, since the beginning, since this is the key component which impacts whether the dose will be escalated, we have been informing about the key parameter, so DLT. Here we have not been observing any.
As it is with clinical pharmacology trials, with efficacy somewhere in the background, because that's how we can define the first-in-humans trials, we have to look at all those parameters as a whole. When it comes to pharmacodynamic data compared to the previous arms and compared to the pharmacokinetic exposition for the given group, in this case, the one with the largest dose, and based on data on the safety, that is when we take the decision on how to move forward. That is whether to modify the previous protocol. Not the change of the study design itself, the number of patients, but just the number of doses which we see we can in a justified manner, justified by pharmacokinetics, and in a safe manner that we can or even should increase the dose.
When it comes to the efficacy, if it is something which obviously excites everyone in such developments, in particular in cancer trials, that is the fact that this is somewhere in the background. This should not determine the decisions on searching for the final largest dose or the range of doses where we will feel confident that we can continue the drug development process. Data on the efficacy are paradoxically, at this stage, the least important ones. Obviously, from individual participants, they are the most important, but when it comes to decision-making at this stage, they are not the most important type of data.
One more question for OATD02. According to the company, the decision to have a large escalation of the dose can draw more attention of the sector to OATD02, given the low toxicity of the drug, so no significant adverse effects.
This could provide more area for increasing efficacy. Obviously, we use medical aspects as the motivator and not that we become more attractive.
Could you repeat the question? Whether this question on significant escalation of the dose, something which will draw attention of the sector, I imagine what is meant is whether partners will be more interested. Can this be a signal that if the drug, if the compound has been characterized by low toxicity, then maybe such escalation of the dose could give larger options for increasing efficacy? This obviously depends on the width of the therapeutic window. On the one hand, we are limited by safety measures, and on the other hand, the efficacy. Here, the question mentioned that there are no side effects, no adverse effects.
As already mentioned, at the general level, we are communicating that we are not noticing any DLT. However, we should not interpret it as absolutely no adverse effects. In every clinical trial, not just cancer clinical trials, there are some adverse effects viewed by the investigator. Obviously, we are building this safety database and database of adverse reactions. This is the case for every trial, and we have been observing some. Please do not extrapolate to this stage. There is no DLT. When it comes to the decision on dose escalation, the toxicity level, which has been included in the study design, the level for the first four cycles of treatment determines whether DLT has been observed. No DLT has been observed, and this is what we are communicating to clarify why we have decided to escalate the dose.
Let me just add a short summary because Piotr is speaking very technically, very scientifically. Let me tell you something from the business perspective. If we have talks for OATD02, if with the dose escalation, we're not seeing DLT, but we see the level of arginine impact, then it will surely influence the continuation or reinitiation of certain talks, which would then translate directly into the potential therapeutic window. The fact of escalation does not change much, but the effect of escalation can have an impact.
Another question on USP7. Can you tell us when this program could start phase one if the funding is available?
Let me try because if, as Zbigniew said, or Martin, we are the older results are positive and the candidate nomination are for mid-year, then knowing ourselves, we need at least one or two years to conduct us through the CNC talks in the GCP standards. This is 12-24 months. From the point of view of our strategy and business development, as Zbigniew mentioned in the beginning of the presentation, we're actively looking for a partner for that molecule. It is a molecule that is more advanced than YKL-40, but it is at the same time very impressive. It gives very good in vivo results for different molecules, for different models. I think it is ready to be sold in the preclinic stage.
If our internal resources dedicated to several assets are not enough to put it through the GLP and scale up in GNP, we are going to try and combine this molecule sooner or later. This is the sort of cooperation that we continue to consider. We also are still considering different types of application. When talking with Avicenna, we think about oral dosing, but we are also working on the alternative formulation on an injection or extra intestinal application.
What perspective do you see for the small RNA partnering or maybe big mRNA partnering agreement?
I think that a big mRNA partnering agreement in that regard, we need to show more advanced products and send more data, but we can see interest, especially in one of our early internal projects for a target that we are not yet disclosing due to the level of advancement of this research. If we are talking about a small-scale agreement, we can see a potential even in the next months to come. Surely the data that we can observe internally, especially in the combination with one well-known drug, is very, very good. The molecule is early, so it needs to be optimized to be developed further, but the potential is there.
I can also add that we are carrying out a lot of studies on the cellular level, and this is the system on which we are working and a system which is probably reflected in various types of deals mentioned by Martin.
Thank you for that. One more question regarding OATD02. The cancer indication, what means that a few trials have finished rollover? Does it mean that the time of follow-up has been limited in the protocol, or was it limited by the disease progression?
The rollover study is not infinite. Its objective is to allow access, in this case, in Poland, patients' access to a molecule. It's also referred to as compassionate use. After the clinical trial, if this is the objective, especially since in Poland, simpler models, so simply compassionate use, ordinary compassionate use, is, as many companies realize, not really realistic.
There is no legal framework for that. Both us and many other sponsors had to up the bar. We had to create for this specific purpose a full-blown formal clinical trial to allow such compassionate use. Patients in the rollover study obviously continue until a certain point until there is disease progression, and at that point, the investigator comes to the conclusion that continuing with this treatment using OATD02 is pointless, or a patient reaches the end of the trial. That is another question. What if the patient is doing so well, but it reaches the end of the rollover study? Like every such trial, it cannot be open-ended. It cannot be indefinite. Of course, we kept in mind scenarios where if a certain patient was to be close to the end of the rollover study, we would be amending it.
We would amend it as soon as possible to allow for extending this period. We considered this timeline realistic, but there was an option to potentially extend it. So far, there has not been a situation like this. We have not seen a patient who could and would like to go outside of that rollover study. So far, no such patient.
We have two similar questions, which I will ask in a second. In 2025, can we expect in 2025 results of the clinical trials, which would increase the commercialization potential? Another question regarding OATD01. Are there parties interested in entering into a transaction before the interim results?
Yes. That is the short answer. This depends on the specific partner. I think that I have already outlined the profile of the entities with whom we are in talks who are ready to invest at such an early stage.
These are larger biotech companies or areas or mid-size companies. There is some potential for one or two big pharma companies, but as a rule, they are definitely preferring to wait and see until the readings of the second phase study.
With the first group of entities, yes. With the big pharma entities, quite unlikely. Other partners are more likely. The two events that might be game changers for OATD02, if with a larger dose, we see a larger PD effect with no toxicity. This is this inflection point. This is the one element. Another element is the directions of the interim readings, which we can expect in autumn. This will give us an answer to the question of whether we're good, whether it's quite disappointing, or it's really bad.
This will have a realistic, tangible impact, even if we are unable to disseminate this information until the end of the trial.
A question about chitinized platform and backups. Is another compound in the freezer? Is anything going on in this project? It is in the freezer,
yes. We want to see the general result before we start to invest in another molecule because we want to use the funds reasonably and optimally. We would first start and develop USP7 until we can see if we validated the target and the efficacy of our molecule, of the lead molecule, so leading molecule, which is OATD01. It is not a priority now, but we are thinking of it in the context of second generation and patent.
We want to develop the AI tools in that direction because always a molecule that is in a clinic but can reach the market in some perspective, that's always a valuable asset. For now, as to the preclinic development in the formal GLP toxicology, we're not taking that into account before we actually see the results of the OATD01.
Also, questions about partnering. By a potential partnering with biotech companies, do you understand joint venture and then joint sales of the final pharma partner? In March, do you see you have enough competence in metabolic diseases to be able to conduct a JV with a purely financial partner?
I will allow Piotr to respond to the question more broadly, but for myself, this area, this field is well described in terms of expectations as to endpoints and elements of the study.
We are going to follow the same path as in sarcoidosis. We are going to cooperate with key opinion leaders like the ones that we've approached already. These are going to be some experts, well-internationally recognized experts in MASH. It is not that we ourselves are going to do all the thinking. It is key opinion leaders. We've talked with some seven CROs that also have experience in conducting studies in that area. So far, we only have one drug in the market, but those CROs have experience and competence in that regard. Yes, we feel up to the task. I confirm.
Of course, by operating with a CRO and with this great team that we have, although we do not have as many people as we would like, and with a lot of experience thanks to the clinical trial development in the MASH indication being located in Poland, in Central European Europe, from the operating side, we have no doubts that if we had to do it by ourselves, had or wanted to do it by ourselves in cooperation with a CRO, we could do that. When it comes to the expert aspect, so the right design of such a clinical trial, the situation is as mentioned by Martin. The situation is just, as a sponsor, we would never do it on our own. Please note, have a look at the case of pulmonary sarcoidosis, where our team also did not really have too much experience and competencies in that area.
We acquired this competence, and we are doing well. Paradoxically, MASH is a simpler type of development when it comes to determining the pathway, primary and secondary endpoints, because there's not just a lot of significance of research body, but also we have the American FDA involved. We can also carry it out in Poland. The first part of the question, if you could give a brief answer to remind you, by potential partnering, do you understand a possible joint venture and sale to a later stage to the big pharma? To the second part, yes, because both us and maybe the partner, if it's not a deep-pocket company, they will not be able to carry out effectively a large-scale pre-registration clinical trial in MASH.
As to the joint venture, this is a rather complex issue in terms of the operating aspects, as we are a public company. Here we could come across more complications. Obviously, we are considering this potential scenario, but this is not our first choice. Sure. To sum up, a little bit of politics. What impact on your trial, the pace and cost of enrollment and achieving grants can Trump policy have? You made me scared. I was afraid we were going to talk about Polish politics. When it comes to American politics, first of all, we can't really impact that in any way. I think Trump looks a little bit as if he had MASH himself. That could be of help to us. It's not John Dees. Secondly, we are observing reductions in all areas related to government and public aspects.
When it comes to the processing of issues with NIH itself, we have not been observing any questions. The pre-Trump and the pre-Trump era and currently. I think that our area, our activity is on a low significance level when it comes to politics. Does the current situation help? Not really, because there is some chaos, some disorganization. There is a lot of change. This is definitely not helping. Will this actually impact whether we get the grant or not? I think that at this stage, it is rather marginal. It might have only a slight impact, if at all, unless something goes really wrong and NIH operating capacity will go completely bust. This grant has already been recommended. We just did not make the cut-off. There were too little funds.
Now, I don't know if they have the same amount of funds, more or less, but most definitely, we have put a lot of effort into addressing all the doubts or any things that might have required clarification by the reviewers when we were resubmitting. So our options are strong. Do we get the grant? We don't know. Given what's happening in the states, in the public administration scene, this is hard to assess for us. Thank you, obviously. We have actually reached the end of our designated time some time ago, actually.
We will be finishing up today. I would like to thank you for all the answers that you have given to the questions and the presentations you held. We'd like to help our guests for tuning in. We recommend you to go back to this recording. It will be available on our YouTube channel.
The presentation is already available on the company's website in the For Investors tab. Thank you so much, and we wish you a very pleasant day. Thank you. Bye.