Welcome to Herantis Pharma 2023 report webinar. My name is Antti Vuolanto. I'm the CEO of Herantis. Together with me we have CFO Tone Kvåle in the studio. During this webinar I will present first of all why we are so enthusiastic about our lead candidate HER-096. Then we go through last year's figures followed by a questions and answers session. During this webinar or throughout this webinar you are able to submit questions for the Q&A session. Then we have the necessary forward-looking statements. Not going through them too detailed but let's go into Herantis. Herantis Pharma we are a listed company from Helsinki, Finland. Established already 15 years ago. During these years we have been mainly concentrating on developing disease-modifying treatments for Parkinson's disease. And now our lead asset HER-096 is a small engineered peptide molecule that has a very unique mechanism of action derived from a previously studied CDNF. But now we have been able to capture that in the small molecule which allows us to use subcutaneous injection as an easy route of administration. And this actually we have now demonstrated during last year when we completed a Phase 1a clinical study. First of all we presented a good safety profile but we also demonstrated efficient blood-brain barrier penetration. And together with the very strong preclinical data that we have this is of course a very nice starting point for further clinical development. And as we have already mentioned many times before the ambition of the company is to engage with a partner before starting a Phase 2 program with HER-096. But let's go through first why we are so enthusiastic about HER-096 and what is the capacity of HER-096 to act as a disease-modifying treatment for Parkinson's disease. So the normal function of the dopaminergic neurons is summarized in this slide. So in the middle you see the functional dopaminergic neuron. It produces dopamine, the small dots there below the neuron. It's a neurotransmitter that then is received by another neuron controlling further the normal motor function. And surrounding the dopaminergic neurons you see microglial cells, which role is to monitor the environment and keep the environment suitable for the dopaminergic neuron. And in normal states they are in a way inactivated. However in Parkinson's disease the dopaminergic neurons degenerate in the midbrain in a place called Substantia nigra. And what happens there? First of all there is a chronic neuronal stress in a cell organelle called endoplasmic reticulum. And the stress is actually caused by accumulation of misfolded proteins. And that results in turn in a chronic activation of a pathway called unfolded protein response pathway which is very important for us because that's the target pathway, the main target pathway for HER96. So in addition to the stress it's very much linked to a process called proteostasis which is the key mechanism in a cell controlling the synthesis, folding and degradation of proteins, the main building blocks of cells. And the failure of the proteostasis results in accumulation of toxic alpha-synuclein aggregates which are very harmful for the neuron but also for the environment of the neuron. And in addition to that the microglial cells are activated. They try to signal to the neuron that the environment is not favorable and they secrete pro-inflammatory cytokines. In the normal states that could be positive but in the chronic stage it's harmful for the neuron. Actually these three items, the stress, the accumulation of toxic alpha-synuclein aggregates and the neuroinflammation, they cause a vicious cycle in which all of these three components strengthen each other and make the life of the neuron even worse. That results in decreased dopamine production and that in turn results in movement disorder. When this process continues the dopaminergic neuron degenerates and eventually loses its ability to produce dopamine and eventually it will cause the death of the neuron. But with HER-096 what we have shown in preclinical settings is that we can break down this vicious cycle. How we do that is that HER-096's target is the unfolded protein response pathway. If you remember from the last slide it is chronically activated in degenerating dopaminergic neurons. However when we treat those neurons with HER-096 we can inactivate the UPR and normalize the function. We also address the amount of toxic alpha-synuclein aggregates. We can decrease the amount substantially. We can also alleviate the neuroinflammation. So basically breaking down the vicious cycle. We have shown in preclinical settings that we can normalize the dopamine production in the dopaminergic neurons which in turn means that we are able to normalize the motor functions. Many of you have seen earlier the nice mice video showing clearly that yes we have a clear effect on the motor functions. So basically using HER-096 we can change the degenerating dopaminergic neuron into a functional dopaminergic neuron. And thereby we can normalize the motor function and stop the progression of Parkinson's disease. We are really extremely happy about the great preclinical data that really demonstrates all the effects that I showed here. This makes us very enthusiastic about the potential of HER-096 in the treatment of Parkinson's disease. If you look at the status of the HER-096 program in addition to the preclinical data, so if you look at the manufacturing side, HER-096 is a synthetic molecule. We have already scaled the manufacturing in a large scale. As a synthetic process it's very straightforward. We are currently manufacturing a GMP product for the Phase 1b clinical study that we expect to start later this year. We are currently doing some formulation work to even decrease the volume of injection going forward. With preclinical toxicology studies we have done a one-month tox study. We are continuing the toxicology program towards the end of the year to enable later on a Phase 2 program. In clinical settings we have completed a Phase 1a clinical study. We are aiming to start a Phase 1b clinical study later this year. What I want to highlight is the patenting situation. We are very strong there as we have a composition of matter patent filed only four years ago with HER-096. Let's go into the 2023 report. About the business highlights. The Phase 1a clinical study that we conducted last year even ahead of time in October, we reported the top-line data that demonstrated a very favorable safety and tolerability profile. We demonstrated also very good pharmacokinetic properties, especially the significant HER-096 concentration in CSF, so demonstrating the blood-brain barrier penetration after the subcutaneous injection. So basically this shows that we have a very good starting point for further clinical development. We also were able to strengthen the financing position. We started the European Innovation Council Accelerator Grant Program or Project. In May we secured the financing for that in April EUR 2.5 million grant funding. We signed a term sheet with EIC Fund during the summer that allows us to raise EUR 15 million of equity from EIC Fund going forward. We were really happy that we were able to complete a direct share issue of EUR 4.5 million in December and also welcoming EIC Fund as a new investor and shareholder of the company. We also were able to strengthen the equity of the company during the autumn as Business Finland waived off some of the R&D loans that they have granted to Herantis for the development of CDNF. So all in all a very successful year 2023, providing us a very good starting point for this year and further development of the company. There are some events after the reporting period. So basically the science team is currently during this week presenting at the AD/PD conference in Lisbon. So for the first time they will present the Phase 1a clinical study results to a scientific audience. And they are also presenting preclinical data of HER-096. And there we also provide some new data on the potential of HER-096 for regeneration of stressed neurons. And then Tone will present the figures. Yes, thank you Antti. So for 2023 we actually ended up with a profit. And that is due to the cost-saving measure that we implemented during 2022, and also an extraordinary item. As you can see on the left side of the slide here, we have operating income of EUR 5.3 million in 2023. Most of that stems from the Business Finland waving off the development loan, as Antti mentioned, of EUR 4.5 million. In addition you also remember that we got the grant from the European Innovation Council last year, and 0.8 of that is also booked here in the other operating income box there. Then in the middle there you see the OPEX by item. The total operating expenses have been reduced with 37% compared to 2022. Mainly due to that we have reduced headcounts, and also that we are now focusing all the resources we have on developing of HER-096. So we ended up with EUR 280,000 in profit, and that's a huge improvement compared to last year. The explanation you see on the left, in addition to that, I want to mention that we also completed the bankruptcy proceeding from one of our subsidiaries, Laurantis. In the financial items you can find that we got EUR 607,000 in there as a finance income. That also helped for the profit and loss. During the year then we have been strengthening our equity position. Cash position by the end of last year was EUR 5.5 million. In addition to the cash we also have placed close to EUR 1 million, invested in short-term fixed income security. That comes on top of the EUR 5.5 million there as you can see. Cash flow from the operating activities ended at -EUR 4.6 million compared to -EUR 8.9 million last year. The significant improvement there is related to cost-saving measurements. I said positive equity EUR 4.7 million compared to a negative equity last year. Strengthening due to the waiving of the Business Finland loan, but also we had the successful fundraising in December last year of EUR 4.5 million. Okay, thank you. For this year we have clearly three milestones. All of them are related to the phase 1b clinical study. First of all we will submit a clinical trial application during the first half of this year. We will have the trial application approved during the second half. We aim to start the treatment of the first Parkinson's patients, in the phase 1b clinical study in the second half of this year. One of the topics that we have been discussing a lot, and what has been asked from us, is of course seeking the partner for HER-096 development going forward. That's as mentioned in the beginning, that's one of the biggest ambitions of the company, to engage a development partner. If we look at the process for having a partner on board, we believe that we have been able to substantially increase the value of the company and increase the value of HER-096 during the past years. So just a reminder that before HER-096 we studied the CDNF protein. So we gained preclinical and clinical experience with the same target mechanism in Parkinson's disease in patients. And we have been able to utilize that expertise in the development of HER-096 and also justifying the effects of HER-096 with discussions with pharma partners. And it's only four years ago since we filed the global patents of HER-096 we have been able to establish manufacturing which is straightforward. We have been able to demonstrate a preclinical evidence of disease modification with HER-096. Last year we were able to demonstrate the delivery of HER-096 in human brain after subcutaneous administration. When we go forward we have significant opportunities in further development of HER-096 in Parkinson's disease and in other neurodegenerative diseases. With the partnering discussions with the pharma companies, we are constantly, in a way, advertising and telling them this story. We are getting very good attention from them. Of course it's very difficult for us to define a certain time frame when we could close a deal with a partner. But that's clearly one of the most active things that the company is currently doing. What kind of an investment opportunity Herantis is? Let's, if we start with the market. The Parkinson's disease treatment market is rapidly growing. During this year the market size is approximately $5 billion. But it's estimated that it will grow up to $12 billion by 2030. We want to be part of that growth. That growth will be driven by the by the development of disease-modifying treatments such as HER96. We believe that HER96 is among the best candidates to become a disease-modifying treatment or even treatment that can stop the progression of the disease. The problem is that truly the currently available treatments may not slow down or stop the progression of the disease. So regardless of the current treatments the disease always progresses. There is a high unmet clinical need. We believe that our solution is really unique. We are addressing very in a very broad way of the pathology behind Parkinson's disease. We believe that that's a reason why we have a very good opportunity to really affect the disease progression. And so far the evidence that we have been able to collect, starting from the previous work with the CDNF, through the great effects that we have seen with HER-096 in preclinical settings, now transforming into human data with the blood-brain barrier penetration, we believe that we are among the best candidates in Parkinson's disease and also potentially in other neurodegenerative diseases going forward. So, this slide summarizes what we have. But I would like to thank our great team, our partners that we work with, our shareholders and especially our healthy volunteers that have participated in phase 1a clinical study during 2023. It was a very successful year and, as I said, very nice starting point for this year. And this ends the webinar or the presentation part of the webinar. And now we can go into questions and answers session. Yes, so I will ask the questions. We have one question here. Are you satisfied with Herantis' performance during the year? You mentioned it already but can you say more? So basically I'm extremely happy about the milestones that we achieved during the last year. Both the clinical study that we were able to conduct during the last year and the results demonstrating the safety and blood-brain barrier penetration of HER-096 in human. Of course great starting point for further clinical development. But also strengthening the financial position. The environment wasn't really friendly for a small biotech during the last year. But we were able to secure the financing from EIC Fund. We were able to complete the financing round in December. I think we did a very good job last year. Yes. Next question. You reported promising preclinical data this week. Can you say more about that? I think you also mentioned that but maybe... Yeah, so basically the team is currently in AD/PD conference in Lisbon—which is the biggest annual conference on Alzheimer's and Parkinson's disease. And there we have some fresh preclinical data on the potential of HER-096 to regenerate stressed neurons. Of course strengthening the preclinical package. And that's of course important going forward. Next question. What can we expect from the phase 1b clinical trial? And why can't you go directly to phase 2? Now that's a very good question. So we need to remember that the phase 1a that we conducted last year—was a single-dose study in healthy volunteers. And now the next step logically is to start dosings with Parkinson's patients. And we need to do multiple doses there—to demonstrate the safety and tolerability in the patient population—before we can go into longer studies. So that's definitely the aim and a very necessary step in the regulatory path going forward. Thank you. Next question. When will you be able to report the outcome from the phase 1b trial? Yeah, so the current plan is that the first administrations in phase 1b will start during this year, so during the second half of this year. And we believe that the data will be ready to be released by the end of 2025. Yeah. Next question. Can you comment on the cash runway? And I guess I can comment on that. Yes, please. We have funding into Q2 2025. Next question. Can you use biomarkers in phase 1b? Yeah, that's one of the very important objectives also in phase 1b. So we have done good or great biomarker work already with the CDNF clinical study earlier. And now we continue that with the preclinical studies with HER96 and clinical study the phase 1a with HER96. And we have identified several candidates of biomarkers. And we will continue this work in phase 1b. And this is a very important preparation going forward towards the phase 2 clinical study. So that's one of the important items for phase 1b to have as much information about the biomarkers as we can. Good. I think that was the last question. If any have other questions you can send that to you have your email address is there or you can send it to the investor relations email after this meeting. Oh, here's one more. Are you looking for Parkinson's patients volunteers for the phase 1b work? Yes, so as soon as all the practicalities are completed, then of course as I mentioned we will have in phase 1b also Parkinson's patients treated and of course we need to then have volunteers in for that study. Yeah, we should also maybe mention that we are running the trial in Finland only. Yeah, so we are just running this as I said at the same site, as we did the phase 1a study. Yeah. Good. That was all questions, so... Okay, so thank you for joining this webinar. I hope that we were able to to present you what we are doing and with all the good questions. I hope that you have now a good view on the potential of the company. And so thank you for joining and I wish you a very nice day.