This meeting is being recorded. Herantis Pharma's R&D update webinar. This is Gabriela Ortega, investor relations for Herantis, and I will be the moderator for today's call. Please note this call is being recorded, and for the duration of the call, your lines will be on listen only. Presenting today is CEO, Antti Vuolanto, CSO, Henri Huttunen, and clinical consultant, Charlotte Videbæk. CFO, Tone Kvåle will join the call for the Q&A portion. You can type your questions in the Q&A section on the webinar dashboard. Questions will be taken in the order they are received. Additionally, during today's webinar, management may make forward-looking statements that involve known and unknown risks, uncertainties, and other important factors beyond the company's control that could cause the company's actual results, performance, or achievements to be materially different from the expected results, performance, or achievements expressed or implied by such forward-looking statements. These statements are subject to risks and uncertainties that could cause actual results to differ materially from those contained in the forward-looking statements. Actual results and the timing of certain events may differ materially from the results implied or timing predicted by such forward-looking statements, and the reported results should not be considered as an indication of future performance. Please note that these forward-looking statements made during this webinar speak only as of today's date, and the company undertakes no obligation to update them to reflect subsequent events or circumstances other than those required by law. This webinar is being recorded and will be available soon on Herantis Pharma's website under the header News and Events and the subheader Company Live Presentations. With these formalities out of the way, I'd now like to turn the call over to our CEO. Antti, you may begin. Thank you, and welcome to our R&D webinar. The today's topics that we will cover is we will go through the key achievements during last year. We will give you an update about HER-096 development, the key data that we have currently from the preclinical studies. We will give you update on biomarker and clinical development that is more towards the future. We will update you also about the CDNF, the parent molecule, data and development there. Then we will definitely discuss about the development strategy for this year and what are the main milestones. At the end of the webinar, we will have a Q&A session. Herantis, what we aim to do, we simply aim to develop a disease-modifying therapy to address the unmet clinical need in Parkinson's. This is something that the whole Parkinson's disease field has been looking for decades to generate a drug that can really stop the progression of the disease and stabilize the patients at the early stage of the disease before the onset of severe symptoms. Our lead asset, HER-096, is something that we strongly believe that it has all the characteristics that it really can become the first disease-modifying therapy for Parkinson's disease. It combines a really unique mechanism of action and easy route of administration, two key points that we believe will take HER-096 forward. During this year, on a high level, our aim is to demonstrate the safety and blood-brain barrier penetration of HER-096 in clinical settings. During this year, we expect to complete the Phase 1a study and report the top-line data by the end of the year. As a recap, Herantis is a Finnish company. We are listed both in Helsinki and Stockholm. However, we are currently in the process of delisting from Stockholm, where the last trading date will be 31st of January this year. We have a compact but very experienced team of 10 employees. Six of us have a PhD. We work mainly through our supplier and partner network for, let's say, practical aspects of the work. All the laboratory research services are outsourced. We also have very experienced board that gives us a good support for our daily operations here. Then, I want to highlight our scientific advisory board that truly combines the expertise both from the academia and industry related to Parkinson's disease. Why we believe that HER-096 is a perfect drug candidate for Parkinson's disease? First of all, the mechanism of action is really unique. We have designed that based on the active side of a protein called CDNF. That is a well-known unfolded protein response modulator, meaning that it can stabilize the functions of neurons, it can restore the proteostasis, and it also can reduce the neuroinflammation in the target-- around the target tissue. It is also a synthetic molecule, so basically the manufacturing, the practical aspects of that are very compelling compared to many biological drugs that are currently in development. We do have very strong preclinical evidence that Henri, our CSO, will go through soon. During last year, we have been able to complete the toxicology studies, filing the clinical trial application. As I said, during this year, we will run the clinical study. If we go through the key achievements during 2022 last year, we were able to finalize the Blood-brain barrier penetration studies in with dog data. We have data from several animal species, everything is very encouraging. We have efficient brain penetration. We were able to submit the clinical trial application, meaning that we have completed sufficiently enough the toxicology package. We have great preclinical proof of concept, and we have manufacturing campaign completed for clinical studies. What was really good news for us in December, as we announced that we obtained, or we were selected as one of the receivers of European Innovation Council's Accelerator funding. Basically, we participated in a October call together with over 1,000 European companies across different industries, and we were among the 78 companies that obtained the funding. A funding that we currently are negotiating with our discussion with European Innovation Council to sign the grant agreement and then further go into discussions about the equity component of the financing. That financing will be used for advancing HER-096 clinical development beyond this year's phase 1a study. There I would like to give the word to Henri, who will continue providing you update on HER-096 data. Good. Thank you, Antti. We'll begin the R&D section by looking at recent events in HER-096 development, our lead asset, HER-096. First, I would just like to use a few minutes to walk you through the scientific rationale why we believe that HER-096 is a great candidate for disease-modifying therapy in Parkinson's. Common forms of neurodegenerative diseases share several common features at the molecular level. The diseases are often a result from a complex interplay between genetic factors and environmental factors. However, these diseases have been studied for decades, and it seems that there are certain common features, such as disrupted proteostasis, accumulation of misfolded, aggregated proteins in the brain tissue. And that's typical for practically all neurodegenerative diseases. This has been associated with several other features of the disease. Of course, death and degeneration of certain populations of neurons, for example, dopamine neurons are the ones to primarily degenerate in Parkinson's. There are also various other features related to the protein aggregation, various stress responses that cells will trigger because of this abnormal situation, and also inflammatory processes as already referred to by Antti. At Herantis, we have been particularly interested in the endoplasmic reticulum stress-related cellular responses. There's in the literature a lot of evidence suggesting from multiple on multiple levels that the ER stress and the main cellular response to ER stress called Unfolded Protein Response pathway is chronically and abnormally activated in the brain tissue of Parkinson's patients. It's also been similar findings have been reported from Alzheimer's or ALS, Huntington's, and other similar diseases. In Parkinson's, as shown here by the two images from a brain tissue from Parkinson's patients, the blue color here is the abnormal forms of aggregated alpha-synuclein protein. The red dots here are actually markers of abnormal UPR unfolded protein response pathway activation. Both phosphorylated form of IRE1 alpha receptor and PERK receptor are clearly highly activated at the regions where alpha-synuclein aggregates can be found. Thirdly, there's been several reports over the past decade or so showing that ER stress modulation by various pharmacological approaches can actually have prominent therapeutic effects in preclinical models of these diseases. Now, with CDNF, the parent protein of HER-096, we are targeting the unfolded protein response pathway. Very importantly, it is tightly connected to the disruption and maintenance of proteostasis in the cells, how the cells respond to the aggregation problem. It is also tightly connected to inflammatory processes on multiple via multiple molecular mechanisms. Importantly, by targeting a single mechanism is unlikely to result in best possible disease-modifying effects. We believe that by breaking this vicious cycle composed of these three elements, the disruption of proteostasis and the unfolded protein response activation and the inflammatory signaling or abnormal signals from glial cells, chronically activated glial cells. Disruption of this vicious cycle is something that we intend to do with HER-096. We believe that this is a really good and potential way to break down or improve the pathological situation in the brain. HER-096 then does this? CDNF has been shown to bind directly to a protein in the cells called GRP78. GRP78 is a major regulator of the unfolded protein response pathway, as shown here by this graph. The UPR pathway is composed of three parallel arms, signaling arms called IRE1, PERK, and ATF6. Together, the signals from these three arms actually constitute the unfolded protein response. While this mechanism aims to restore the homeostasis and is typically transiently activating the brain, the abnormal protein pathology as seen in neurodegenerative diseases can actually result in chronic and abnormal state of activity of the UPR. Again, by direct molecular interaction between the GRP78 protein, CDNF modulates and down-regulates the abnormal activation of UPR. HER-096 was developed based on this interface between CDNF and GRP78. The blue area here indicates the region of CDNF protein that corresponds to the HER-096 molecular structure. We have introduced some chemical modifications into this peptide, and these chemical modifications make this peptidic drug much more stable in terms of metabolic processes in the body and much more drug-like than a native peptide would be. To summarize, the therapeutic hypothesis for HER-096 is as follows. Similar to its parent protein, CDNF, HER-096 promotes neuronal survival and also functional recovery under prolonged stress conditions. These effects are typically based on a multimodal mechanism that involves reduced endoplasmic reticulum stress, reduced accumulation and toxicity of misfolded protein aggregates, and also reduced inflammatory activity in the affected brain area. This appears to be a hit-and-run mechanism, so successful therapeutic modulation of these pathways does not require constant presence of HER-096 in the brain. In our preclinical studies, we actually typically administer HER-096 a couple of times a week with very good results. Now, the important differentiating factor between CDNF and HER-096 is not only the size, it's also the fact that HER-096 can overcome the blood-brain barrier challenge. As you may know, the brain is protected from systemic circulation, blood circulation by a so-called blood-brain barrier. About 95% of all pharmaceuticals cannot pass the BBB. This is why, for example, the recombinant CDNF protein that we've developed for Parkinson's was administered with an intracranial drug delivery device, which is a cumbersome way to deliver a therapeutic into the brain for the patient suffering from chronic disease. This is why we developed HER-096. HER-096 is administered to patients via subcutaneous injection. With a small needle, couple of millimeters under their surface of the skin. From there, the molecule is absorbed by small capillaries, and it enters systemic circulation. This allows then HER-096 to get in contact with the brain tissue, and there appears to be a transport mechanism for HER-096 at the blood-brain barrier, which allows the HER-096 molecules to go through this barrier. Next, I will show you a little bit of pharmacokinetic data. We're here, we have tested how the body, first in animals here, how the body actually metabolizes and gets rid of the compound after dosing. Here on the left you can see data from rats. These are healthy, normal young rats, which have been given a single subcutaneous injection of HER-096, and then we have collected plasma and followed the HER-096 levels in plasma. As the graph shows, we have a rather expected profile for a compound like HER-096. The compound itself is very stable against proteolytic processing. Plasma proteases themselves do not really touch HER-096. We know that in both rats and dogs, which have been the main species for our preclinical work, HER-096 is mainly eliminated by renal excretion, by a kidney. It comes to urine in unchanged form. The plasma half-life after subcutaneous injection is about, as shown here, less than half an hour in rats. Here, where you can see the rat data, we have a little bit longer plasma half-life. However, the single dose pharmacokinetic profile is quite similar in both species. Next, we've tested penetration of HER-096 through the blood-brain barrier. Here we've injected again a single bolus subcutaneously, and then we collected plasma and cerebrospinal fluid samples from the animals. As you can see, the gray curve here being the plasma and blue being the cerebrospinal fluid, we have an extended half-life in the central nervous system. When the compound gets to the brain and the cerebrospinal fluid, it stays there for a little bit longer time as compared to plasma. The ratio of exposures, of brain exposure to the plasma exposure is about 20%, we are reaching roughly 100 nanograms or a little more per ml with a 10 milligram per kilo dose. This is very much above the minimum required therapeutic levels, which are about 1 nanogram per ml. Similar study in dogs, again, with 10 milligram per kilo subcutaneous bolus, showed rather similar effects or behavior. We have here, about 5 times longer half-life in cerebrospinal fluid as compared to plasma, and we are again reaching close to 100 nanogram level, Cmax levels in the CSF. This is quite promising and certainly supports the idea of using the compound with subcutaneous delivery. Next, we also performed a somewhat slightly different pharmacokinetic study. Here we used dual microdialysis. We collected continuously plasma from jugular vein and brain interstitial fluid, so the extracellular fluid of the brain tissue, by placing small microdialysis probes in the striatum, in the midbrain and in the jugular vein. Again, after single subcutaneous bolus, we have very similar profile here. We have the exposure ratio at about 20%, and we are reaching more than 100 nanogram per ml levels in the brain interstitial fluid. Again, the brain half-life is longer than compared to plasma. Based on the pharmacokinetic data, we then moved on to test the compound in an animal model related to Parkinson's. Here we're using a model developed by our long-term partner at Neuro-Sys from France. And this model is based on aged animals, and we believe this is very important as Parkinson's obviously it is a disease that typically presents in elderly individuals. Here in this model, we inject alpha-synuclein aggregates into the substantia nigra, which is the brain area where the dopamine neurons are located in the brain. We treat the animals with every second day, we give them an injection with a drug called Conduritol B epoxide, and this is a drug that inhibits an important lysosomal enzyme. This mimics certain forms of Parkinson's in the sense that the lysosomal dysfunction is thought to feed forward the alpha-synuclein aggregation pathology. We're trying to mimic the neuropathology of Parkinson's in an animal model as far as we can. One important feature of this animal model is that it results in progressive neurodegeneration as compared to toxin-based models which were used in the field of Parkinson's research for many decades. These models typically are a single hit model and the neurodegeneration is not in a similar way progressive as we have in this model. After a few weeks after induction of the pathology, we have about 50% loss of dopamine neurons as shown here in the top lay row of images. At the same time, in the same brain area, we also have a significant neuroinflammation, here indicated by activation marker of microglial cells. These are the, in a way, brain monocytes or macrophage type cells. And also we hear the green standing here shows that there is a very significant induction of Endoplasmic Reticulum stress in this brain area. Importantly, the progressive nature of the model is shown here. Many important markers that we are following here are inversely correlating with the dopamine neuron level here. In the end, the... in this model, in this time frame that we're studying, we have the condition stabilized to about 50% loss of neurons. The data that I'm going to show in the next few slides, we have administered HER-096 subcutaneously three times a week, starting at the same time with the pathology induction. We've also done studies where we do a delayed start and do a longer treatment, but in the interest of time and scope of this seminar, I won't go into all the details. We'll just show you some examples on how HER-096 modifies certain readouts in this model. In this first slide, the first graph shows number of dopamine neurons in the Substantia nigra in this model. The wide bar here is control animals without the alpha-synuclein pathology. The red bar is the group of animals with induced alpha-synuclein pathology and vehicle or placebo injections. Again, you can see that we're close to 50% loss here with dopamine neuron numbers. The blue groups are animals or groups treated with HER-096, either once weekly or three times a week. As you can see, both groups actually show significant neuroprotection of dopamine neurons, three times a week being somewhat better than the once weekly. In the same brain area, same model, we followed alpha-synuclein aggregates, and you can see that there's a very significant induction of alpha-synuclein pathology in the brain, which can be very nicely reduced by HER-096 injections. On the right-hand side, you can see neuroinflammation, we're again following here microglial cell activation, HER-096 treatment can very nicely bring down this inflammatory activity. In the next slide, I'll show you target pathway engagement. Here we're administering the drug peripherally, it's important to show that we're actually affecting the target pathway in the target brain area. Again, this is a slightly different study design, a different study. Here we have a three times a week injection, either at 1 or 10 mg per kilo, you can see that the 10 mg per kilo gives again a very nice neuroprotection. Dopamine neurons are nearly 50% higher in number as compared to the vehicle group. When we look at the UPR marker, we're here looking at phosphorylated form of the IRE1 receptor, which indicates activation states for this receptor. IRE1 is clearly activated in the model animals receiving placebo vehicle injections. In the animals receiving HER-096, we have a very nice nearly 90% reduction of IRE1 activity. Very similar effect can be seen when we look at ATF6. ATF6 operates in a slightly different manner. It's proteolytically cleaved, and the active fragment of ATF6 localizes into the nucleus of the cells where it works as a transcription factor. Here we are measuring the nuclear localized ATF6, and as you can see, HER-096 very nicely takes down the activity of ATF6 pathway as well. Here, this video in this slide first is a normal aged mouse walking the bar walking test, having really no trouble crossing this narrow bar. Here is an alpha-synuclein model animal. Very clearly you can see that the animal is struggling with motor function, motor coordination. The hind limbs are not really doing what they're supposed to be doing, and it's balancing the body with the tail. The bottom animal is the alpha-synuclein model animal treated with HER-096 for four weeks. Very clearly we have improvement in motor function, motor coordination of this animal. This is quantized in terms of time to cross the bar and still number of slips on the bar. Next, I will move on to preclinical toxicology. Here, I will just very briefly summarize what we've done. We have completed the toxicology program in rats and beagle dogs. In this slide, we summarize the data on the basically the studies completed with rats. In summary, subcutaneous daily repeated subcutaneous HER-096 injections did not reveal any systemic toxicities at the dose levels tested. The no observed adverse effect level was 175 milligrams per kilo of day, which was the highest tested dose. Looking at the injection site, there were some local findings, so this is quite typical for an injectable product. When you keep injecting the drug in the same site, repeatedly, it's understandable that you can see signs of hemorrhages and fibrosis, scleroses, and recovery from the injection wound itself. We also completed a respiratory safety study with a plethysmography in conscious rats, which didn't show any abnormalities. In dogs, we've completed maximum tolerated dose and 7-day dose range finding studies, and a 28-day repeated dose study with safety pharmacology, endpoints toxicokinetics, and 14-day recovery. Here, very similar to the rat toxicology, we didn't see any signs of systemic toxicities at the tested dose levels. However, we did observe some local adverse events, effects at the injection site. None of these findings are something that would prevent us moving with this administration route to clinical studies. The NOAEL, in rats and dogs when converted to corresponding human doses, here the table shows that, looking at safety margin, to the planned starting dose in humans, we have about 150 to 170-fold safety margin. As compared to planned maximum dose in human study, we have about five to six-fold safety margin. Conclusions from the non-clinical pharmacology and toxicology studies are here. Clearly, HER-096 can penetrate the Blood-brain barrier in multiple animal species. In the alpha-synuclein mouse model, we have clear evidence of target pathway modulation, neuroprotection, reduced neuroinflammation, and improvement of motor symptoms. Overall, the preclinical data is very well aligned with the known features of CDNF biology and our therapeutic hypothesis. The conducted toxicology studies did not reveal any significant systemic toxicities and we have a actually a very good safety profile to continue with subcutaneous HER-096. We will move on to clinical development and biomarkers, I would ask Charlotte Videbæk to take over the clinical part. Thank you. I have started my video, but I don't see myself, so sorry about that. Thank you for letting me go through the phase 1a. Based on these very encouraging data that we have seen preclinically, both for efficacy and safety and toxicology, we have planned a clinical trial where we have three key objectives. Key is to show safety and tolerability within the dose range that is relevant for the continuation of the program. Very important for us to show the important blood-brain barrier penetration to differentiate from the CDNF program. Lastly, we'll also do some exploratory biomarker work. The study is simple. We start with healthy young males, and we go up with the different dose levels from the lowest... from below the minimal effective dose, and then going up, so that we are in a significant range where we're looking for. After that, we move a little bit down in dose, and then we look in the elderly and older population for the CSF penetration to secure that we have an effective dose also in the CSF. We have submitted the CTA in December, and the first patient visit is expected here in the first half of 2023, and we expect to get results within six months of the study. Thank you, Charlotte Videbæk. Next, we'll talk a little bit on our biomarker program, and we'll start from here. As you may know, biomarkers are an very important part of drug development, particularly when moving from preclinical to clinical studies, it is important to carry on biomarker development and this helps the clinical development in many ways. We can find better ways, improved ways to monitor and optimize the treatment response. We can identify patients who are most likely to benefit from treatment, et cetera, et cetera. Overall, biomarkers typically reduce the cost and increase the likelihood of success in clinical trials. With CDNF, in the CDNF Phase 1 clinical study, using the intracranial administration, we collected a large body of data on biomarkers. The challenge typically is that if you dose a therapeutic, and then you look at clinical readouts, there's quite a large gap of unknowns happening between the dosing and the clinical readouts. Typically in Parkinson's trial, we would be using something like a Unified Parkinson's Disease Rating Scale, UPDRS, for looking at patients' motor symptoms and other symptoms. However, we don't really know what happens in between. This applies both in terms of time, but also in terms of levels of effect. From molecules to cells to tissues, symptoms. It is very important that we develop tools to follow the response to the drug and treatment as we go forward. In Parkinson's, typically, image and brain imaging is used to follow changes in the brain, and this is something that we're keen on doing also with the HER-096 development when going forward. We have some encouraging data from dopamine transporter PET imaging from the CDNF trial, which could be considered a readout for restorative changes in the brain, for example, how the regeneration of dopamine processes dopamine neuron-related axons and their sprouting that takes place in the brain. Another important way to bridge this gap is looking at fluid-based biomarkers. Here, the cerebrospinal fluid serves as an important matrix to study. In the CDNF study, we collected cerebrospinal fluids from the subjects, two hours after the end of drug infusion, and we've learned a great deal from this data. First of all, there are markers that seem to be related to the mechanism of action of CDNF. The markers appear to indicate that there may be two different type of responses in the brain tissue. One related to the improved proteostasis in neurons, and one related to a glial cell response. I'll just very briefly here show you data, some biomarker data from the CDNF Phase one clinical study, which still remains to be published. The clinical trial report we expect to come out fairly shortly. It's currently in review in revised form. In this clinical study, we administered CDNF once monthly intracranially. Importantly, for the first six-month part of the study, we had also patients or a group receiving placebo infusions. This placebo group converted to active treatment after six months treatment. We collected biomarkers, CSF biomarker samples at baseline before treatment at six months and at 12 months. From this data, there's a couple of interesting findings I would like to highlight in today's presentation. Today, I won't be able to disclose the identities of these biomarkers. I will refer to biomarker A, B, and C. However, what's important here is that when looking at all these three markers, and if you look at the groups shown in blue and green, you can see that from baseline to six months, when the patients in the blue and green groups have been receiving CDNF, we have a clear increase of biomarker A, B, and C. The relative increase, of course, varying a little bit. Very, very importantly, if you look at the gray group in the bottom here, during the placebo infusion period, we had absolutely no change. However, these subjects who received placebo infusions then converted to active CDNF, and after that, there seemed to be a very nice increase similar to the blue and green groups. This indicates that this is a true biological response to the treatment. Looking at the correlations of CDNF levels in the cerebrospinal fluid and the biomarker levels, we also found very nice correlation between these biomarkers and the therapeutic itself. Importantly, we work with these biomarkers, and we've shown pre-clinically that they also respond to HER-096, which is of course expected as we're targeting the same pathways in the brain. These are not the same molecules, this is not a given. These biomarkers will play an important role in our development, particularly when moving on beyond the healthy volunteer phase 1a study, when we plan to incorporate biomarkers in the next studies to be conducted in Parkinson's patients. I will give the word to Antti, who will walk you through or review or re-brief the CDNF development and talk about the development strategy. Yes. Thank you, Henri. Just as a high-level recap of our development timeline. It's only just over two years ago when the company completed the CDNF phase one clinical study and decided that the company needs to explore alternative administration routes for CDNF. Although the data from the study were good, and the route of administration intracranial was considered to be not optimal for commercialization of the compound. In only two years ago, we made that decision and started to look at preparation of nano-form CDNF and also starting to develop intranasal formulation and then characterization of the intranasal administration routes. At the same time, we were still quite early two years ago in HER-096 development. We still... At that time, we didn't have selected HER-096 as the lead candidate, which took place May 2021, so less than two years ago. During this, or since May 2021, the company has really been very effectively advancing the HER-096 program. one year ago, we decided that actually HER-096 characteristics and the data that we have had already then were so good that the company's strategy was to shift it towards focusing only on HER-096 as it has all the benefits that we have been discussing here today. If you just briefly mention or go through the intranasal CDNF development on actually the data from that program was very good. We were able to develop an intranasal formulation. We were able to combine that formulation with a delivery device. Using that formulation device combination, we were able to demonstrate that it is possible to reach therapeutic concentrations of CDNF in the brain. We were also able to successfully prepare CDNF nanoparticles. However, as already mentioned many times, HER-096 provides such major advantages like blood-brain barrier penetration, longer patent protection life, easier manufacturing. We decided that HER-096 will be the lead candidate. We will concentrate on that development. Now as we are preparing for the first clinical study, we strongly believe that this decision has been exactly the right one. I also want to highlight a bit on CDNF research that has been taken place outside of Herantis. There is a continuous accumulation of the data for CDNF biology, and it's used in different indications. This strongly supports also our development with HER-096, as we are talking about the same mechanism. We know that during this year there will be even further literature available for the biology. Of course, Herantis as a company, we are committed to publish also our great data with HER-096 as soon as the feasible. You might know, the scientific publication process takes time, and we are in a good position there as well. What is the strategy for Herantis? It's quite straightforward. During this year, we will create value in the clinical study of HER-096 to be able to demonstrate how we can shift from the great preclinical data and evidence to humans. At the same time, we recognize that to develop a disease-modifying drug for Parkinson's disease, it is a long process. It requires resources. We are really actively now working towards partnering. We have very active discussions with a number of potential companies, partnering companies with relates to HER-096. During this year, we expect to have the regulatory approval for the phase 1 clinical study during the first half of the year. We will start the study, also, soon after we have the regulatory approval, and we also expect that we will have the first preclinical publication on HER-096 during the first half. Towards the end of the year, we are committed to deliver the top line data of the phase 1a study. Evidence of the safety and also blood-brain barrier penetration in humans that we believe is a big milestone, translating the preclinical data into humans and giving us a very good stepping stone for further clinical development with then studies with Parkinson's patients. This is basically the update that we wish to have today, and now we are ready for the Q&A session. Gabriela, please, take the word from here. Thank you, Antti. At this time, we will now start the Q&A portion of the call. As a reminder, you can type your questions in the Q&A section on the webinar dashboard. Questions will be taken in the order that they are received. First question: Can you explain more about the European Innovation Council grant and the equity you communicated to the market in December 2022? Yes. Basically, the company applied for EIC Accelerator financing in October. That financing application or the project application, we define that the company wishes to continue with the clinical development preparation of further clinical studies and conduct of further studies. The EIC Accelerator model is that they provide a grant and then the opportunity to negotiate about equity from EIC. How the process actually goes is that during this spring, we will prepare the grant agreement together with EIC. Once that has been signed, we can progress forward with negotiations about the equity part. As a principle, the equity part is then or the equity, EIC equity is then provided to the company whenever the company is raising funds for its development. Of course, we will inform much more, we'll inform in detail once we have completed the preparation of the grant agreement and once we are ready to start the discussions about the equity part. Thank you, Antti. The next question is could HER-096 be targeted to a wider range of aging-related diseases and degeneration? Henri, maybe you'll take this one. Thank you. If we think about the target pathway of HER-096, it's well known that it's expressed ubiquitously in the, in the body. It's not limited to dopamine neurons, or any kind of neurons actually. In that sense, there's a lot of opportunities potentially. Of course, importantly, there's a large body of evidence and literature showing that the deregulated UPR pathway and endoplasmic reticulum stress is involved in a large number of chronic diseases, particularly, CNS diseases. There's, there's a scientific rationale there. Thirdly, there are many groups, and particularly I would like to mention Professor Mart Saarma's group at the University of Helsinki, who have been for years working with, different, animal models or different diseases. Also, Professor Mikko Airavaara from the same university has been actively working for example, in stroke models. We know that CDNF and related molecules like HER-096, MANF and so on, have great therapeutic potential much beyond Parkinson's disease. Herantis being a small company, we are fully focused on Parkinson's treatment, but we are very much following and interested in also other types of opportunities in the field. Thank you, Henri. The next question is what is Herantis' biomarker strategy? Henri, I think that's also for you. We strongly believe in a multimodal strategy, as I tried to explain in that graph with the timeline. It is important that we follow fluid-based biomarkers, but we don't believe that that provides or that's a be all, end all answer for biomarker questions. Brain imaging obviously very interesting and important for brain disease. Particularly in the field of Parkinson's, there is now a number of technologies based on, you know, wearable devices that collect continuously data, and particularly, of course, Parkinson's is a movement disorder. These type of devices can be very useful for support in clinical development, and these are called nowadays digital biomarkers. We believe that our strategy is we'll be building on three types of biomarkers: fluid-based biomarkers, imaging biomarkers, and digital biomarkers. Thanks. Wonderful. Thank you, Henri. Another question is how de-risked is the phase 1 trial with HER-096, in your view, given the previous CDNF trial? Charlotte, could you take this one? Yes, I would like to do that. I think the key point with the HER-096 phase 1 trial, that is to show that we are different. We have a lot of support from our animal data, showing good blood-brain barrier penetration, both in mouse and in dog and rat. I'm very confident that we will get CSF exposure and brain exposure. The problem with the CDNF program was actually to get the CDNF into the brain. Despite the Cell-Gide device used in CDNF trial, we already had interesting findings there. I think this is a very exciting pathway that we are moving along now and de-risking. Wonderful. Thank you, Charlotte. We have another question. Can you comment on the recent news flow within Parkinson's? Anything significant that impacts Herantis? Maybe I'll take this one. Basically, there has been some recent news about drug development in Parkinson's. As a company, Herantis won't comment too much on what the others are doing in the space. However, on a high level, I would say that the unmet clinical need for Parkinson's disease modification remains the same, and we are not expecting to see any significant effect on this, based on the news. However, last year, there was really positive news within the Alzheimer's drug development, disease-modifying drug development. I would say that the overall sentiment in neurodegeneration is that we are now closer than ever towards developing truly disease-modifying drugs for these diseases. This will be a great news for all the patients that are really needing new types of therapies. Thank you, Antti. Another question is, if the 2023 milestones will be successful, what would happen after that? Is it already dependent on finding a bigger partner? As I explained, we are currently working towards finding a partner, development partner to take with us and the program forward. There is no proof of success for this as the partnering discussions takes time. It takes that we have a partner that has the exact right view with us, and we have the right timing there. We are definitely not dependent on a partnering deal. We have clear plans how we would like to continue from the phase 1a data subject, of course, the phase 1a data that we have towards the end of the year. I want to mention that the getting the EIC financing or the opportunity to negotiate about the financing, I think that also provides us likely a little bit more freedom to design further studies. We are currently not ready to disclose the details of what we have in mind currently after the Phase 1a, so I think we will comment those more precisely once we know the data from this year's clinical study. Thank you. Another question: how do you select your patients for the studies? Charlotte, maybe you take this one. I think this first trial remains in healthy volunteers to show the safety and tolerability in healthy volunteers and Blood-brain barrier passage. For the studies to come, I mean, when we go into a patient, we're looking into the key thing. You need to get patients that are so early that they will benefit significantly from the treatment and that you can protect further progression. There's no yet definition exactly what patients will go into the future trials, but that will come, of course, later. We'll also see on exploratory biomarker work that we do in healthy volunteers, if that will give us any additional news. Thank you so much, Charlotte. Last question: Do you have any idea about the likely timescale for clinical trials involving early onset Parkinson's patients? Yeah. As explained earlier, we would not right now comment on the further clinical plans beyond the Phase 1a. Let's first analyze or conduct the study, analyze the data, and then I guess would be the right time for the company to comment how the further development goes and what are the timescales and schedules there. Wonderful. Thank you. With that, we would like to conclude the Q&A section of this call. I'll turn the call over back to Antti for closing remarks. Yes. Thank you, Gabriela. Thank you for listening, Herantis R&D webinar. I hope that we were able to provide you a comprehensive view of what we have been doing, why we are so enthusiastic about HER-096, what is going to happen during this year. I would like to encourage you to contact me or the company if you have any additional questions or comments. By this, I hope you a great day. Thank you. Thank you for joining.