Herantis Pharma Oyj

Good morning and welcome to Herantys Pharma's full year 2025 results webcast and business update. My name is Antti Vuolanto. I'm the CEO and together with me, I have here CFO Tuuna Kuole. During the webcast, we will review the key highlights of the past year and provide you an update of the business and R&D. After the presentation, We have a Q&A session and you are welcome to submit questions throughout the webcast. With that, let's get started. And first, the necessary forward-looking statements and then a short introduction. Reminder of what Herantys Pharma is, and then we go into the last year's highlights. So Herantys Pharma, we are a clinical stage public company listed here in Nasdaq First North Growth Market Finland. And with our lead asset, HER96, we aim to stop the progression of Parkinson's disease by protecting protecting dopamine neurons from further degeneration and also support their functional restoration. We have just also announced that we have completed a phase one program. We have solid safety data. We have shown efficient brain penetration. We have strong biomarker data showing biological response in Parkinson's patients. and basically we are ready to start a phase two efficacy signal finding trial so uh just a reminder what her 96 is it is a first in class peptide targeting key drivers of parkinson's disease specifically modulation of the unfolded protein response pathway, so proteostasis, and we have also shown a robust impact on mitochondrial function as well. HER96 design is based on a protein, a neurotrophic factor called CDNF or cerebral dopamine neurotrophic factor. And we have shown in preclinical setting protein in terms of protection of the neurons and supporting the neurons for functional recovery. R96, we do have a disease modifying and symptomatic potential based on preclinical studies and earlier studies with the CDNF protein, so we can slow or even halt the neuron degeneration in midbrain, which is relevant for Parkinson's disease. As already mentioned, we have a biological validation with the biomarker data from Parkinson's patients. We have robustly confirmed the brain penetration after the subcutaneous administration. So we believe that we have all the ingredients that HER96 can really be a game-changing therapy that could really stop the progression of the Parkinson's disease, which currently is not possible. So there is an unmet clinical need in the disease. The current treatments, can treat the symptoms, but not the disease itself. And many patients don't get a symptomatic benefit or they might have significant side effects. And also the effectiveness of the current treatments declined over time when the disease progresses on the background, always regardless of the current treatments. And of course, As a consequence of that, there is a huge market potential for HER96. Parkinson's News Today is an organization who has evaluated the estimated economic impact of Parkinson's disease globally. is around 277 billion US dollars annually. So it's a huge impact on societies. It's forecasted that therapeutic market in PD will grow to 13 billion US dollars by 2033. This is from global data. And there are also estimates that from the currently approximately 10 million patients until 2050, there will be 25 million patients. So we are in the middle of a very large unmet clinical need, and we want to be among the first ones to really address this. So this was the short introduction to Herantys, and let's go into the highlights of 2025. So I'll start this with the business highlights. So a year ago in February 25, we announced that we successfully completed a directed share issue. We raised 5.2 million and that was obviously used for finalizing the phase 1b and being able to deliver the great data. We announced the top-line data from the Phase 1b trial with Parkinson's disease patients in October. The trial met its all primary and secondary endpoints, so we demonstrated very nice safety profile and also the robust brain penetration in the Parkinson's patient's brain. In November, we announced that we have completed a six-month preclinical toxicology study with HER96, and this is, of course, a major milestone towards to be ready for phase two trial as this kind of a long-term preclinical tox study is a prerequisite for starting a long phase two efficacy trial. And right after the reporting period, we also have provided Actually, a lot of good news. So, in early days in January, we reported the biomarker data showing that we have a very clear evidence of biological response to HER96 exposure in Parkinson's disease patients. In early February, we announced a directed share issue. We raised 4.2 million euros. Further in February, we announced that we have been selected for 8 million Horizon Europe grant that will be used for supporting the conduct of the phase two clinical trial. But let's go into the financial figures and Tuuna will go through those.

Thank you. So full year 2025 compared to last year, the total operating expenses, they went to the same level, but the difference you can see on the last slide is that in 2024, we had the ACA accelerated grant program, which ended now in 2025, so we got more grant in 2024 compared to 2025. We are spending the money on most of the money goes directly to the science. We spent it on finalizing the phase 1b trial. We also preparing for the phase 2 and the development of biomarkers is also a big part of the costs. And then last year we raised money in February 2025 and we had finance expenses relating to that. And we are continuing the focus on investor relation and partnering activities. So when it comes to the cash, we ended the year with 2.6 million in the bank compared to 2.1 in 2024. Right after we closed the books, we had a successful fundraising and raised gross 4.2 million. With the cash we have as of today, it takes us into Q1, 227. So to be able to start the phase two clinical trial, we need to raise more money. So for the financial position, just going through some of the balance items for 2025, if you look into the balance sheet, you see that the long-term debt increased from 2.1 million in 2024 to 3.4 in 2025, and that is due to the research funding which we are receiving from Michael J. Fox and Parkinson's UK. This is very good money that we have spent now on the Phase 1B. We had a temporary negative equity by the end of the year of 1.7, but that went positive when we raised the money in February. And as Antti mentioned, for the financial events, we had the successful fundraising, and also we were selected for the $8 million grant from Horizon, which is going to be spent on running the Phase 2 trial. So that's really good that we have the cash coming in.

Very good. Thank you. And let's move on with the short business update. So, as mentioned, we have completed the Phase 1 program. Just a small, short recap of what the Phase 1 program told us and what will be the next steps. So, the Phase 1A clinical trial that we completed a couple of years ago was a single ascending dose study in healthy individuals and we also had elderly individuals there too to take cerebrospinal fluid samples to show the brain penetration profile of HER96. And the main findings were very good safety and tolerability profile of the single dose. We demonstrate the efficient brain penetration in elderly healthy individuals. And the brain penetration was in a way very much aligned with the preclinical findings we had reported earlier. And we also have very favorable pharmacokinetic profile considering the administration. And now we completed a phase 1B clinical trial where we first had a couple of additional elderly individuals for single administration to complete some of the pharmacokinetic work. And then we had... Parkinson's patients in two cohort or two dose levels, 200 and 300 milligram doses and placebo patients as well. And these patients received active, or they received HER96 or placebo treatment for four weeks, two administrations per week. And the main findings we continue to see, good safety and tolerability profile in Parkinson's patients. We established the pharmacokinetics in the cerebrospinal fluid in these patients, and of course, then we have this biological response in biomarker analysis, which I will also provide some more insights here and recap of the webinar that we held early January. About the safety profile. Here is a very high level summary of the systemic safety findings from patients or healthy individuals receiving HER96 dosing. So basically on the systemic level, we didn't see any treatment. emerged adverse events, no serious adverse events, no dose-limiting toxicities, and we didn't reach, obviously, the maximum tolerated dose, and this was very much aligned with the preclinical studies. The main incidents that we saw was related to the injection site. They were mild and transient and self-resolving. So exactly aligned with preclinical findings, and this is, of course, very good. And then the second part of the results is obviously the HER96 presence in the cerebrospinal fluid. And this data summarizes what we learned from the Parkinson's patients in the phase 1b with 200 milligram dose, we ended up close to 100 nanograms per ml with 300 milligram dose close to 150 nanogram grams per ml. And again, this is very much aligned with the preclinical data and these levels are comparable to those levels that we have seen in preclinical settings. to provide the maximum efficacy in those models. So we believe that 300 milligram dose will be a very good dose for going forward with phase two. And it is also supported by the biomarker data. and just a short recap of what did we see in the biomarker data and just a reminder that we analyzed different sample types with different technologies but the main comparison was the chains that we observed when we compared the before dosing sample of the last dose compared to the before dosing sample of the first dose. So, a cumulative effect of four weeks exposure to HER96. So, we had samples from CSF. So, demonstrating what happens in the CNS, central nervous system. And there we showed an effect on proteostasis and oxidative stress and inflammation. So basically really closely related to unfolded protein response pathway and then mitochondrial function as well. Then we had samples that is called neuronal enriched extracellular vehicles. So particles that comes from the central nervous system. The sample is taken from the blood. So we can't for sure say that all the signals come from the CNS, but maybe maturity of that. And again, we see changes in mitochondrial functions and also inflammation very much aligned with the mechanism of action. And then from plasma and blood, we also saw changes in proteostasis and in mitochondrial functions. So this, multiple layers of data showing very concordant results across different sample types, different location or where we derive the samples shows that there is a very clear biological response and this is a true response in Parkinson's patients and the response is aligned with the mechanism of action. So if I summarize on one slide what we see. At the baseline, Parkinson's patients, they have chronically activated unfolded protein response pathway. So there is a dysfunction of proteostasis, there is also lower activity of mitochondrial function. So mitochondria are the energy factors of the cell, and there is elevated oxidative stress. So overall, the stress level is high, and the viability functionality is low. After her 96 dosing, we see elevation of proteostasis activity. We see elevation of mitochondrial function activity. we see a decrease in oxidative stress. So we have decreased the stress and increased the viability functionality. And then of course, the very good question is, as this is the data from the first month, what happens after a longer treatment period. And we, of course, believe and hope that it will result in symptomatic improvement and disease modification. And this is, of course, the purpose of running the Phase 2 trial, to demonstrate this in Parkinson's patients, which would then allow going forward with the commercialization path. So if I summarize where we are with HER96, we believe that we have reduced development risk based on the very successful phase 1B trial. We have established very nice safety profile, confirmed brain penetration. We have biomarker confirmed biological activity. So we believe that we have much reduced translational risk. We are ready for phase two. So we are planning a signal-seeking proof of concept efficacy trial in approximately 100 early-stage Parkinson's patients. It will be a multicenter European study if we run that ourselves. And we are currently nearing the confirmation of the study design. It's not completely ready yet, but we, of course, will inform the market when we are ready to do so. HER96 is very much differentiated asset. So it's a first in class molecule. We are addressing unfolded protein response pathway as the only company in clinical development. With that, we target the core drivers of Parkinson's pathology. And we really have designed from the beginning the asset to really modify or stop the progression of the disease. And, of course, what we are currently doing, we are looking at the different routes and options, how we can execute the phase two, and we are in discussions with strategic partners. discussions in discussions with investors we also confirmed the 8 million eu horizon grant that will will support the conduct of the study and we are also looking at different non-dilutive opportunities there might act also be but of course we will inform the market as soon as we have anything material on on this resourcing of the phase two efficacy trial. I want to highlight the strong external validation and financial support that we have for HER96 Parkinson's UK, the Michael J. Fox Foundation, they have or they did finance the majority of the Phase 1b clinical trial with almost 4 million research financing. And we obviously continue to discuss with them how they could support the conduct of the Phase 2. We have also had very strong support from the European Union. We completed a biomarker development program of 2.5 million grants. That was completed a year ago, approximately a year ago. We have secured 15 million investment commitment from EIC fund, from which we have now utilized 4.2 million. So over 10 million still exist in that commitment. And we just announced 8 million grants. Support for the phase two trial. So we have been quite successful in achieving these This validation and I have to highlight that All of these financiers and the financing it's like really competitive vehicles and Opportunities so we have been really happy that our science and the commercial potential has been evaluated to be really strong among these organizations. So as a summary, we believe that HER96 is potentially game-chasing therapy that could become the first disease-modifying treatment for Parkinson's disease. We have huge market opportunity. We are backed by a long research, robust external validation, and one thing that I didn't address yet is that the broad functionality of HER96 in the basic biology of aging cells improving the tolerance against different stress factors. may open wide therapeutic opportunities in other neurodegenerative disorders or even beyond CNS indications. By this words, I think we will end the business update and we are ready to start the Q&A session.

Yeah, and we have received questions and you can just continue sending in questions via the webcast. The first one is can you provide an update of your phase two plans and when do you expect to initiate it?

Yes, so as I mentioned we are currently in a way finalizing the study design so we are also In addition to that, considering regulatory preparations, should we have regulatory discussions on the protocol, what we can say is that we are planning a double-blind, placebo-controlled, randomized efficacy and safety trial. in early stage Parkinson's patients. And we are engaged with several European really top notch investigators also within that EU consortium that won the grant. And also of course the recent fundraise, 4 million helps us to prepare for the phase two and also gives us the freedom to really find out the right financial ways of resourcing the phase two. And as mentioned, the trial will be most likely conducted within Europe if we run that ourselves. However, we are making sure that we are also open regulatory-wise to be able to open trial sites elsewhere, for example, in the US, if there is a need, for example, if there is a partner or there is an investor who would have an incentive to open up a site also elsewhere than in Europe.

Good. Next one is regarding the Horizon grant and congratulations with that. How will this impact the company on a strategic point of view and also from a financial point of view?

Yeah, of course, eight millions for conduct of phase two. It decreases the capital need for running the phase two with full amount. It is, of course, also very beneficial for our shareholders as that's non-dilutive. So I think that's great. But in addition to that, of course, Horizon EU grants, they are really competitive grants vehicles. And being selected for the grant shows that, first of all, we have great science, but we also have great commercial opportunities there. And that, in a way, brings a quality stamp as we were winning this grant.

Good. Next one is... Based on your current cash position and the benefits from the grant, what additional capital do you need and will be required to be able to start the Phase 2 trial? Maybe I can just take that one. As you know, we raised 4.2 million in February, and that will help us now kind of continuing the preparation for the Phase 2 trial. we got the Horizon grant of 8 million and that is earmarked the phase two. So of course that is helping us a lot for that one. But in addition, we think we need, of course we haven't, the final design of the trial is not ready yet, but we think in the range between 20 and 25 million is needed as an additional capital on top of this to fully fund the trial and also the ongoing operation during the trial period. Next one, is the phase 1B biomarker data good enough to secure a partner agreement?

Well, that's a very good question. Of course, the full phase 1, like, data package that we have, the safety data, the pharmacokinetic data, and also the biomarker data, it's a great package, and when we have discussed this package with the within the partnering discussions or with other stakeholders like the patient organizations or informed investors, everybody congratulated. You could not get much more within a phase one clinical program. However, it might not be appropriate to start speculating about exactly whether this could trigger a partnering agreement or not, because there are many different kinds of pharmaceutical companies they have different objectives and there might be different like deal structures that that we investigate so of course we will inform the market as soon as there is something material but before we have any anything material we can't speculate too much yeah next questions congratulations with the 225 progress

The Phase 1b biomarker analysis showed modulation of various PD-related pathways. How will these biomarker findings inform endpoint selection and patient stratification for the Phase 2?

Yes, of course, we are really happy that we have seen changes in the core pathways, including the proteostasis and mitochondrial function. Maybe for patient selection, the challenge is that how we can exploit that data when we are screening the patients. And we believe that we need to select early stage patients. And in phase two, we need to carefully design what is the primary endpoint and then select the patients in such a way that they show characteristics that are measured by the primary endpoint. So that's the focus there. Good.

I think there was no more questions. So maybe some closing remarks. I think just from my side, we see that we have a really strong external validation over science during 2025. So I think the future looks good. What do you think?

Yeah, I fully agree. So I think 2025 was a very successful year. We were able to complete a fairly large clinical trial within the time and the budget, which is not for certain in clinical development. The data is great. We have a very good momentum. We have got really good feedback. And now we just need to go forward and beyond and ensure that we can run the phase two clinical trial. And of course, within phase two trial, providing the first efficacy signal, that's the trial where potentially the value creation is quickest among the, let's say, clinical studies. So we look really forward, positively forward for this year and what this year will bring, and we hope to be able to update the market about the future development related to finalizing the phase two clinical plan and then also how we resource the trial within due course. So thank you for joining us today. Thank you for submitting the questions and I hope you will follow us intimately going forward. Thank you.