Herantis Pharma Oyj (HRTIS) Earnings Call Transcript & Summary

Hello, everyone. This is Pekka Simula from Herantis with my colleagues, Henri and Antti. And it's about 1 minute to noon, so noon Helsinki Time, so let's give everyone 0.5 minute more to join if they are very punctual, like people in the Nordics often are. So just a second and then we will get formally started. So I believe now we can get started. So welcome, everyone, to this first-ever virtual Capital Markets Day of Herantis Pharma. These are very unusual times and unusual times call for unusual actions. So of course, we would much prefer to meet investors and analysts face to face. But on the other hand, it's wonderful that we have these technologies that allow doing this. So after having to cancel several meetings, we can actually communicate on the company via these virtual means. So my name is Pekka Simula. I'm the CEO for Herantis Pharma. And today with this -- with me in this webinar, I have my colleagues, Henri and Antti. I guess you could briefly introduce yourselves, too.

Okay. Maybe I'll start. So I'm Antti Vuolanto, COO at Herantis, taking care of, for example, the clinical programs, especially the Lymfactin program.

Hello, everyone. My name is Henri Huttunen, and I'm the Chief Scientific Officer of the company and involved in mostly in the CDNF-related projects. xCDNF is, of course, a very important new project in the company where I spend a lot of time business.

Thank you, gentlemen. And now I will start to share my presentation -- or our presentation. And obviously, as you can see, we are responsibly located separately. So also, Herantis is responsibly now making sure that we are in our separate locations. So let me just pull up my screen. So hopefully, you can all see the presentation and we'll get to it, so our Capital Markets Day webcast of Herantis Pharma. The usual disclaimer, obviously, we are a public company, and no one should make any investment decisions based on this presentation alone, so there's a lot of other materials that you should familiarize yourselves as well. And always, please keep in mind that drug development is a high-risk endeavor so it always should be considered a higher-risk investment than many traditional investments. But our company, we're all about breaking the boundaries of standard therapeutic approaches. So we aim at breakthroughs in unmet clinical needs. And this is really the big differentiator compared to many traditional drug development programs, where you aim at or people aim at just alleviating the symptoms. And our target indications at the moment are Parkinson's disease, an incurable brain disease that progresses from the first symptoms that include tremors and muscle stiffness, to worse and worse motor symptoms and also nonmotor symptoms. And in Parkinson's disease, the known drugs only alleviate the motor symptoms. They do not stop the disease from progression. And our other target currently is secondary lymphedema, probably not as well-known disease as Parkinson's disease but nevertheless a very common and also a huge impact on the quality of life. One picture tells you more than 1,000 words. So the women here is suffering from breast cancer-associated lymphedema. So as a consequence of her breast cancer treatments, the lymphatic system has been -- caused damage that has caused the lymph to start to accumulate in the other arm. As you can see, the affected arm is about twice the volume of the healthy arm. So as you can see, it's a huge impact on the quality of life. It's a painful, deforming, disfiguring disease. And there aren't any efficacious therapies for secondary lymphedema. And just some facts of these diseases. So Parkinson's is the second-most common neurodegenerative disease after Alzheimer's, estimated up to 10 million patients in the world. And it's also a very significant societal cost. So it was estimated almost a decade ago in the U.S. that if there was a treatment that could stop disease progression, it would save the society almost $0.5 million per patient. And the same applies to lymphedema. It's estimated that there are about 140 million patients with secondary lymphedema in the world. And in the U.S., it's been estimated that the annual treatment of Breast Cancer Associated Lymphedema costs between $10,000 and $20,000 every year for the rest of the lives of the patient. So again, it's a very expensive societal cost in addition to the human suffering. And that's really what we are fighting. So when we are targeting disease-modifying treatments, not just symptomatic treatments, we fight both the human suffering and the societal costs associated with these diseases. And jumping to CDNF, our first clinical program for the treatment of Parkinson's disease. The approach really is to protect and restore the dopaminergic neurons in the brain. So the underlying cause of Parkinson's disease is that the dopaminergic neurons die in a specific region in the brain and this causes the worsening symptoms. Obviously, as the disease progresses, more and more of these dopaminergic neurons continue to die and the symptoms grow worse and worse. And our approach really here is uniquely to try to help those neurons stay alive and even, to some extent, to restore their function. And excitingly, CDNF functions through several different mechanisms and I'd like to emphasize 2. So number one here indicates the endoplasmic reticulum, and so-called ER stress is associated with many neurodegenerative diseases, not just Parkinson's disease, and causes the neuronal death. And CDNF can very potently help the neurons cope with ER stress. It can help them -- protect them from ER stress and prevent them from dying due to ER stress. And also very importantly, in Parkinson's disease, number three indicates the alpha-synuclein aggregation. So that's one of the hallmarks of Parkinson's disease that the alpha-synuclein particles start to aggregate, causing toxic aggregates in the brains. And CDNF can directly inhibit this oligomerization, so it can also directly attack these alpha-synuclein aggregates, which is very exciting in Parkinson's disease. So this was the scientific basis for the program. And currently, we are already in a clinical stage but jumping back 1 step. So first, we had to do the preclinical studies. And maybe the most important preclinical study done to date was done in a nonhuman primate model of Parkinson's disease, a very severe disease model. So if you look at the panel on the left here, you see this is a slice of the brains of those monkeys, an image from the brains of those monkeys. And the dark staining here indicates the dopaminergic neurons. So as you can see, there's very little dark remaining. Almost all of the dopaminergic neurons have been lost in these monkeys with Parkinsonism or a lesion causing Parkinsonism. And these animals were then treated 3x, 3 monthly doses with our CDNF, the neuroprotective and neurorestorative drug compound. And as you can see in the panel on the right, this resulted in a significant restoration of the dopaminergic function, so much more viable dopaminergic neurons. And these monkeys are also very ataxic. They are, of course, suffering very much from the Parkinsonism. But the CDNF treatment, the results in the dopaminergic function correlated very nicely in the improvement of motor symptoms of the monkeys. And for the first time in the world, we also see an improvement in the nonmotor symptoms in this monkey model of Parkinson's disease. So a very exciting preclinical background to the work. And all of that has enabled us to proceed to the first clinical study in Parkinson's disease. And this -- and even having this study funded by the European Union, thanks to being based on leading science and a great potential to advance clinical practices. So CDNF is currently in a Phase I/II clinical study at leading European university hospitals. We have the great pleasure to work with Lund University Hospital and Karolinska University Hospital in Sweden, both renowned Parkinson's centers; and Helsinki University Hospital in Finland, the leading university hospital in Finland. The clinical study has been fully recruited, and it's -- even though it's a first-in-human study, we've also been able to do it as a placebo-controlled study, so we can already, in this first study, compare CDNF against placebo. And very excitingly, just last month, we reported the first initial results after the first 6-month treatment, suggesting that CDNF is safe. That's, of course, always the primary endpoint in a first-in-human study but also that we saw encouraging biological responses in some patients. So while the treatments continue, it's a very exciting situation to look forward to receiving more data. And the current conclusions from this ongoing clinical study, so after the first 6 months of treatment are, as said, CDNF is safe and well tolerated in these patients with advanced Parkinson's disease. But most excitingly, this study uses an imaging modality and DAT-PET imaging as a surrogate biomarker for disease progression. So this is an imaging modality that can kind of show the dopaminergic function in the brains, and it's actually being used to show the progression of Parkinson's disease. So it's known that in these Parkinson's patients, if you take this kind of a DAT-PET image every year, you see a constant decrease in the DAT-PET signal in the images, approximately 10% every year. So now when we looked at these patients after the first half year of treatment and we had the baseline PET image and then we imaged them again 6 months later, the assumption was that these patients would have lost maybe 5% more of their DAT-PET signal because of the disease continuing to progress. And very excitingly, we saw in one CDNF dose group, we saw 60% of the patients in that dose group having DAT-PET response and a couple of patients having a significant PET response. So we're talking about order of magnitude 40% or 50% increase in the DAT-PET signal. And if you keep in mind that the average decline is 10% every year, and suddenly, we see an improvement of 40% or 50%, that's really significant and exciting. Of course, this is still early days. This is still the first readout in the first-ever clinical study with CDNF. So we are very much looking forward to the next readout, which we expect in the third quarter of the year. At that point, we will have had all patients go through the 12-month treatment period and we will have much more results. And in the meantime, we're also waiting for more readouts in other endpoints such as alpha-synuclein in the brains of the patient. So it's a very rich clinical study, a huge amount of data being collected and very exciting to look forward to the next readout. And this, of course, takes us to the planning of the next steps. So we have already started to plan a Phase II study. And this slide intends to explain why we would want to do this in as early-stage Parkinson's disease patients as possible. So if you look at the top-left picture saying untreated, the dark blue curve there shows the expected amount of dopaminergic neurons left in the brain of the patients. So this is just a hypothetical simulation of a patient. It's known that when the first motor symptoms appear, maybe 5 years down the disease progression, the patient will already have lost maybe more than half of the dopaminergic neurons. Our brains are just so adaptive that the motor symptoms only begin once the loss is quite significant. And then obviously, the decline continues as time goes by, so 5 years later, 10 years later, there will be less and less of dopaminergic neurons. And at the same time, the clinical symptoms grow worse and worse. So the darker blue dotted line there, as it indicates, there's estimated approximately a linear increase in the UPDRS score, which is UPDRS part III score, which is a motor score of the symptoms of Parkinson's disease. So as you can see, that continues to grow and grow and grow as the disease progresses. And now we're dealing with patients who have an average 10 years of disease history. So they maybe actually have 15 years of the disease, but their first motor symptoms were recorded about 10 years ago. And that's corresponding to the top-right picture. So if you start this kind of a treatment that intends to protect and, to some extent, restore the dopaminergic neurons, there are very little of those dopaminergic neurons remaining when you start the treatment. So it's, of course, great if you can stop disease progression but you will still end up with a relatively high UPDRS score. So it's not possible at this stage to significantly reduce the symptoms anymore because the disease has progressed so far. And this is very exciting to see signals of efficacy in a PET imaging at this stage, suggesting that we can maybe restore 40% or 50% or increase the dopaminergic neurons by 40% or 50%. But if there aren't many of those neurons left, of course, that doesn't result in a significant clinical outcome. So if we can start treating patients with 5 years -- who have 5 years of symptoms, like in the picture in the lower-left corner, that already makes a big difference because then you could maybe reach 30%, 40% of viable dopaminergic neurons compared to a healthy person. And that could keep the symptoms of Parkinson's disease really mild, almost to the level where they were when the disease was diagnosed in the first place. Or if you'd go even earlier, so if you start treatment 2 years after symptom onset, a treatment like this could hypothetically even turn it into an almost symptomless chronic disease that's fully managed. And that's, of course, our target. I mean, there are a lot of treatments that try to alleviate the motor symptoms, and they can maybe improve your UPDRS score by 10 points. But in the long run, that just doesn't help because the disease keeps progressing. So this is how we significantly differentiate ourselves from most other Parkinson's disease gains. In the current clinical study, CDNF is administered directly in the brains of the patients. So CDNF, just like many other CNS drugs, has the challenge that it doesn't penetrate the blood-brain barrier. You can't administer it, for instance, by an oral pill because it will never end up in the brains in sufficient amounts. And that's why we are using this sophisticated medical device that's first implanted in the patients and then used throughout the clinical study for the monthly doses of CDNF. And it's well suited for Parkinson's disease because it's known exactly where the CDNF doses need to go to treat the dopaminergic neurons. But obviously, if we'd like to treat patients who just have had the disease for a couple of months, they have just been diagnosed, they will probably be hesitant on going through a surgical procedure to start a medical treatment. It's very different if you're thinking about patients who had the disease for 3 years or 5 years, which would still be great patients. But if we want to go all the way to the very early-stage patients, this, of course, would be a challenge. And therefore, we are very excited about the next-generation CDNF, or xCDNF as we call it. So we have shown that there are certain fragments of the CDNF, the mother protein, if you will, that retain its biological activity. So they do exactly all the same good things on dopaminergic neuron survival as CDNF does but they also penetrate the blood-brain barrier. And based on the current data, we believe that this could be administered much easily -- much more easily without this kind of a medical device. And Henri, there's continuous exciting progress with the xCDNF lead optimization program, but I'm sure you'd be happy to share a couple of updates even though this is mainly still confidential work.

Absolutely. Thank you, Pekka. So the xCDNF program, as mentioned by Pekka, is based on an active fragment, a peptide fragment of the CDNF protein. And peptides themselves are not very good drug molecules so we have taken these peptides as a starting point and then started chemically modifying these peptides into the novel compounds that are more metabolically stable, meaning that they can, to some degree, resist the proteolytic and metabolic processes in the human body that would eventually degrade these compounds, obviously then resulting in the loss of activity. So we have now -- we are in a stage of lead optimization, where we have multiple compounds that we call leads. They are promising compounds. They have potent effects, as shown in the top-right corner image. This is an in-vitro model where we use cultured neurons and glial cells and treat them with a toxin to mimic the pathology that happens in the Parkinson's disease patient brain. And as you can see, the difference between the orange bar, which is the disease state, and the dark blue bar, where the xCDNF compound -- lead compound has been added, there is a complete restoration and rescue of these neurons by the xCDNF compound. And very importantly, in this single graph, we also show that when we block the known receptor molecule, the molecule that mediates the effects of the CDNF protein, we can completely block the effect of the xCDNF lead compound as well. And this is very important in drug development. It's important to be able to show target engagement and to understand the mechanism of action for any new compounds. So this data very clearly shows that xCDNF compounds are acting and protecting cells via exactly the same mechanism as the parent protein does. And we have also been able to maintain the important blood-brain barrier penetration properties with these xCDNF lead compounds. So on the bottom right, you see a curve where the xCDNF lead compound has been intravenously administered in a healthy rat. And we are actually measuring, in this study, brain concentrations of -- we're collecting brain interstitial fluid in living animals via a very sophisticated device. And we can thus measure the concentration of our compound in the brain tissue in a living animal. And as you can see, within about 30 minutes after intravenous administration, we reach a peak level in the brain, and then the levels slowly decline up to 3 to 4 hours with a half-life of about 1.5 hours. And this is a very, very encouraging piece of data, showing that we can actually reach so-called pharmacologically active levels of these compounds in the brain after peripheral delivery. So this is really highlighting the exciting concept of xCDNF. So we can deliver the compounds like insulin, for example, an injection into the peripheral tissue, and then we can actually have the compounds traveling to the brain where they could do their protective actions. And finally, it's also important to keep in mind that very exciting developments in the clinical study of CDNF are also very important for the xCDNF program because they derisk this project quite significantly. So we are engaging with the same mechanisms, which means that if we see good effects in patients with the parent protein, it's quite likely that we would see similar effects also with the xCDNF compounds when we get to the stage of testing them in the clinic. So over the past 1.5 years, we've been very happy to see continuous accumulation of new data in this project. And we are actually very excited and hope to take this forward as soon as possible. So Antti, I think you will walk us through the Lymfactin development next.

Yes. Thank you, Henri. And Antti, would you like to go next or shall I continue with the first slides with Lymfactin?

Maybe you could start and then I can fill with the Phase III plans.

Happy to do so. So Lymfactin gene therapy, so jumping from Parkinson's and our CDNF program to Lymfactin for the treatment of secondary lymphedema. And again, we are aiming at truly a disease-modifying treatment, and again, we are harnessing the natural human mechanisms in doing so. In Parkinson's, it's a natural protein that whose role in the body is to help keep our neurons alive and restore them. And in lymphedema, it's a protein called VEGF-C, whose role in our body is a natural human protein, whose role in the body is to grow new lymphatic vessels. So quite obviously, if lymphedema is caused by a problem in the lymph flow, in the circulation of lymph in our body because of damage caused to the lymphatic vessels or the lymphatic system, it's quite clear that mechanistically, regrowing lymphatic vessels could be a natural treatment. And this is shown -- the way our Lymfactin gene therapy works is shown in these pictures. So the green lines in the picture show lymphatic vessels. And as you can see, there is a cut through some of the lymphatic vessels, preventing lymph to flowing at it's supposed to. And in that damaged area, we will inject our Lymfactin gene therapy. It's a simple vector that's carrying the human transgene for VEGF-C. So it will result in a local expression of VEGF-C in the damaged area or at the injection site, and that will result in growth or sprouting of these small lymphatic capillaries in that area. And then they will eventually mature into functional collecting lymphatic vessels, as shown very nicely in our preclinical development program. So it really aims at reconstituting the lymphatic system and kind of return the flow of lymph as it should. And as this slide shows currently in the development, we are in a Phase II study. We've called it AdeLE. The Phase II study is also a full recruitment -- fully recruited, just like our Parkinson's study and we have already treated all patients. So we have 39 patients with breast cancer associated lymphedema. And in this study, we have taken the approach that Lymfactin is administered as an adjunct to a surgical procedure, lymph node transplantation surgery, in which these patients who are suffering from lymphedema are tried to be helped with a surgical procedure where their own lymph nodes harvested from a donor site, for instance, in the lower abdominal area. And then those lymph nodes of their own are transplanted in the axilla. And this is an approach that's relatively commonly used in European countries and the U.S. as a treatment for lymphedema patients because they don't really have any other good treatment options. But the challenge with these surgeries is that even the best microsurgeon cannot connect the lymphatic vessels because they are invisible to the eye. So this still requires the body to grow new lymphatic vessels in the damaged area even though the lymph nodes are now available. So it's a perfect setting for our clinical proof of concept and a first target market for our Lymfactin. These patients will have lymph nodes in place after the surgery. But it's known that the typical problem with the surgery is that those lymph nodes are not connected well because of the lack of lymphatic vessels. So if we can grow new lymphatic vessels in that area, we can make a significant difference and a significant improvement in the efficacy of the surgery. And this clinical study is now, as I said, in its blended follow-up period or treatments completed. We have 5 excellent university hospitals in Sweden and Finland involved. And this is following on the footsteps of an earlier Phase I study, where we did exactly the same thing, exactly the same kind of patients to ensure that the treatment of Lymfactin is safe and well tolerated. But very nicely in the Phase I study, we have also seen promising signals of efficacy in signs and symptoms of breast cancer associated lymphedema, of course, keeping in mind that this Phase I study was an open-label study. There was no randomization. There was no placebo control, so it should not be considered any kind of proof of concept. And that proof of concept, we expect to see from this Phase II study so it's exciting times now. We're looking forward to having the readout from this study after the 12-month blinded follow-up. And we have estimated that we'll announce the results in the first quarter of next year. And this has taken us to already starting to plan a pivotal Phase III study. And Antti, you have been heading this program so everyone would certainly be interested in an update.

Yes. So as Pekka told, we will get the top line data from the Phase II study in about a year. And this will mean that we will have a busy year ahead of us in the preparation of the pivotal Phase III clinical study. The target indication in the Phase III will be the same that we have studied in Phase II and Phase I, so a single-dose Lymfactin administered as an adjunct to lymph node transplantation surgery. Very likely, we will randomize the patients 1:1 in Lymfactin and placebo groups. The size of the study depends on the Phase II results so we cannot speculate at this time how many patients we will include. The clinical sites will reside in the U.S. and in several European countries. And we have decided that we will have a clear U.S. focus in the Phase III study. Currently, we assume that the patient treatment can start in 2022 as we expect that it will take at least a year to prepare all the practical items for the Phase III when we have obtained the Phase II data, subject that the Phase II data is positive. And how we will then spend the year that we have now ahead of us? So of course, we need to continue the Phase III protocol development, discuss with the investigators about all the details. We need to take into account some national differences in the surgical procedures and align these into a protocol that is applicable both in the U.S. and in Europe. At the same time, we need to prepare ourselves for market access, so assess the Lymfactin value proposal and compare that to payer requirements. And here, we have a clear U.S. focus so we wish to understand how we will position ourselves and what kind of value we can create in the health care system in the U.S. And of course, one important item is the regulatory discussions, both with the FDA in the U.S. and in selected European national regulatory authorities, in order to ensure that once -- if everything goes well and we are able to submit a clinical trial application somewhere mid-next year, the process will be then smooth, and all the regulatory authorities are informed about our progress and our aim to start a pivotal Phase III study. And of course, 1 major item is that we need to be able to supply the drug into the Phase III study and later on also for the commercial market. So we are currently developing a commercial scale manufacturing process for Lymfactin and also improving the usability of Lymfactin as a single-use preparation for the surgical process. So as a summary, we really aim to have as rapid progress to a pivotal Phase III study if that is supported by the Phase II results that we will get in a year.

Thanks, Antti. And of course, very exciting that a product like this could be taken all the way to the market by a company like Herantis, at least in key markets such as in the United States. So we're not talking about a huge Phase III program. We're talking about a Phase III program that could definitely be executed by Herantis on our own. So it's very interesting to see how things proceed. There was actually 1 question from the audience, thank you very much, related to Lymfactin. So there's a question on whether we could describe the -- or what we could say about the general progression of adoption of the lymph node transfers as a stand-alone therapy. This is still -- the surgical procedure has still been, over the past years, something that's done by specialists, which, of course, in a way, is good for us because this is our first target indication and we intend to commercialize it on our own. It makes it much easier for us that we only have to target selected specialist hospitals in each country and will not require a significant sales force. Of course, we believe that if we can show in this clinical study that the combination of the surgery and Lymfactin is clearly efficacious compared to just the surgery alone, that should also increase the interest in increasing the number of surgeries because today, there is still surprisingly limited amount of published information on the efficacy of the surgery alone. And there's actually quite some skepticism that the surgery alone does not help these patients too much, which probably is true. So we believe that it really requires something like Lymfactin on the side. And to continue, another question on what if this was a stand-alone treatment? That's, of course, the interesting next step. If we can show in this first clinical study that Lymfactin is active and clinically relevantly creates new lymphatic vessels, then there's a lot of interest in jumping to the next step and trying Lymfactin as a stand-alone treatment in selected forms of lymphedema, not with any surgical procedure or with some very simple surgical procedure, but just use Lymfactin to grow new lymphatic vessels to help lymphedema patients. But we haven't speculated upon a possible efficacy yet in the public. We have had discussions with clinical -- some key opinion leaders and clinicians on the possible first target for this but we haven't disclosed any plans yet to the market. We believe that it's first important that we establish a clinical proof of concept in this ongoing Phase II study. And there was also a question on how many patients we expect in pivotal Phase III study. As Antti said, that depends very much about on the results in the ongoing Phase II study, how big a difference, if any, we see between Lymfactin and placebo. But the current speculation is that it would be some hundreds of patients. So moving forward then, just a word on lymphedema. It is a very unknown disease. But fortunately, over the past years, its awareness has increased significantly. And the patient advocacy group LE&RN, Lymphatic Education and Research Network, has significantly contributed to this, and it's growing as we speak. And they have great spokespersons. The Hollywood superstar Kathy Bates here is one of them. She herself has breast cancer associated lymphedema. And fortunately, she has been brave enough to speak about this openly and encourage everyone else to do so, to stop demanding better treatments because it's ridiculous that we have such a horrible disease without any good treatments. And it's a very exciting time also, from that viewpoint, to be developing something like Lymfactin because for decades, this has been a very neglected space. And at the moment, there really aren't any serious competing drug development programs to Lymfactin, just a couple of other drug development programs in the early stage in the whole Lymfactin space. So it's a very open market, just waiting for someone to take the market. So that concludes the update on our Lymfactin program, very exciting times really in both programs. And of course, under the current situation under the coronavirus pandemic, everyone is wondering how companies are doing, how they are impacted by the outbreak and how this will impact their outlook. And we are really in a fortunate position as we are working largely as the traditional virtual biotech modus operandi. So it's very natural for us to be working distantly. Of course, we'd much prefer seeing our colleagues every day at the office. But right now, basically, everyone is working from their own home offices or distant locations. Responsibly, we are keeping our employees in separate locations, and this really doesn't impact our daily operations at all. We are very used to this. We have, of course, done some practices. It's been a great practice that we have this virtual morning coffee. We previously had it 3 times a week to make sure that we remain connected with those who are traveling or working from their distant offices anyway. Now we do that every day during this pandemic because everyone is in that same situation. As you can see, here is a screen capture of a real virtual morning coffee meeting of ours. It's just 15 minutes of discussing this and that, not necessarily work related, just to ensure that everyone is doing well and everyone is -- everyone remains in good spirits. It's been great to see that everyone is doing fine and being able to cope with the situation very well. So this is something that I can highly recommend to anyone in the same situation. Video conferences are very easy to arrange. And even if it may seem odd at first, after a couple of times, it begins to feel very normal, and you really start to feel that you are present to the other person much better than you would just on the phone. But talking about our company, the big picture, we have really been fortunate to have completed almost all clinical treatments in the clinical studies of ours. Everyone understands that also, drug development will be hit hard now that hospitals are struggling to cope with coronavirus patients. And obviously, people are recommended not to go unnecessarily to certain hospitals so that they don't increase the risk of contracting the virus themselves. It's -- we are really happy to have already completed all treatments in the Lymfactin study, so we really don't expect any impact from this pandemic on the Lymfactin study. We're just now in the Phase II randomized follow-up period that will last for 12 months. And also in the Parkinson's study, all patients have completed the first 6 months of the treatment, and most patients have already completed also the second 6-month treatment period. We have -- at the end of this month, we will have only 3 patients with doses -- CDNF doses remaining. And there will, of course, be some impact. I mean, for instance, we just learned that in Stockholm, the PET center of Karolinska Institutet will start to focus on critical patients only. And clinical studies are, of course, not critical. So this will mean that some of our patients who would have follow-up PET imaging in the next 1 or 2 months will probably have those rescheduled to a later time. But we're still talking about only some data points so even that is not expected to have any measurable impact on the results of our clinical studies. And of course, we're also really happy to have just raised funding in December. Under the current market, companies who don't have a sufficient financial runway would be in a very tough situation. And we really have to say we are fortunate. Of course, no one foresaw this epidemic 3 months ago, so I'm not embarrassed to say that we are very lucky. And I'm really feeling for those companies who were not as lucky and are now suffering. But of course, I'm very happy for our team, our shareholders and our employees that we're all safe and sound and the company is in a strong position at the moment. And regarding the other activities of the company, Henri and Antti also already told you about the Lymfactin Phase III preparations and the xCDNF development. Of course, we are collaborating with numerous subcontractors everywhere in the world. And obviously, many of those will be affected one way or the other by the epidemic. So I'm sure that there will be certain subprojects in 1 or 2 of these bigger programs that will be delayed by a month or 2 because of this. But again, we don't expect to have -- that to have any material impact on anything essential and definitely not on our outlook and guidance for next year. So those both remain unchanged, thanks to having a sufficient financial runway, too. So the company continues to discuss collaboration opportunities with the potential partners. And the main objectives for 2020, the Parkinson's study readouts are not affected. And also, the Lymfactin target, being Phase II readout first quarter next year, is not affected. There was actually a question also related to the partnering discussions about what we can share with our partners at this stage and whether this outbreak impacts those discussions. Again, we are really lucky to have -- and it's not a surprise to anyone that companies like ours have this kind of partnering discussions. And having already continued such discussions for a relatively long period of time, having met those key people physically, in many cases, already several times, we are in a situation where that all can easily continue digitally. As you know, in drug development, the data rooms that would be open to the most interesting partners, they are virtual anyway, they are just digital, so that's not impacted by any way. And video conferences, teleconferences has been our modus operandi in international discussions anyway. So I can say that the pandemic has any impact at the moment on our ongoing partnering discussions. And of course, the continued work, like Henri's recent very exciting results, new results from the xCDNF program, of course, those are results that we can continue to share with our partners under a confidentiality agreement, so it really is not affected any way by this situation. So just to summarize before jumping to some further questions. CDNF and Lymfactin are in placebo-controlled studies and they aim at true disease modification. That's really the differentiation of our assets to many other drug development programs, that we really want to fight the disease at its root cause, not just target its symptoms. Lymfactin in a Phase II study, CDNF in a Phase I/II study, both randomized placebo-controlled, both studies fully recruited and almost all patient treatments completed. So that's really us in a nutshell. I always want to also emphasize that our work is based on renowned scientific work. This comes from great scientists who have hundreds of publications under their belts. And the work related to our CDNF and Lymfactin programs has been published in the most impactful scientific journals, Science and Nature. And that covers really the presentation. Thank you very much for your attention.

There are a couple of more questions received from the audience so let us try to cover those as well. A very understandable question in the CDNF study, where we mentioned that in 1 dose group, we have 60% DAT-PET responses, 60% of patients have DAT-PET responses after 6 months of treatment. And the obvious question is, was that the high-dose or the low-dose CDNF? Again, this clinical study continues to be blinded to the investigators, also the PET investigators. So we have taken a very clear-cut decision that we are not disclosing any further details to anyone without a confidentiality agreement so that we do not cause any risk to the possible objectivity of the investigators as the study is still ongoing. And also a question about the Parkinson's Phase II study design, if we can publish or disclose any details on that. So at the moment, unfortunately, we are not sharing any further details. As said, we are going to have discussions with the authorities to reach as early-stage Parkinson's patients as possible. As explained in the presentation, we believe that this kind of treatment will best serve patients who have as much dopaminergic neurons left as possible. So that's going to be the key factor. Also in Parkinson's disease, it's important to remember that the disease itself is very heterogeneous. Every patient is very individual. So in a study like this where we have recruited 17 patients, you can never expect to see any statistical significance because each patient is an individual. They have their individual rate of progression and so forth. So going forward, our target is also to have very well-characterized Parkinson patients as to reduce the kind of deviations that you have from having very heterogeneous patients. And -- but of course, no real details can be revealed at this stage. And let's see if -- then there's a question actually on the xCDNF. How efficient was the blood-brain barrier penetration in the rat model? And what's the targeted dosing frequency for humans? I think this is still early speculation, but Henri, would you like to say a sentence or 2 on the BBB penetration efficacy or efficiency?

Well, at the moment, we actually don't have that data yet because we are still investigating how effectively the device can actually collect the compound from the brain tissue. So we already see nanogram per ml levels in the brain tissue, which is in the range of pharmacologically active compound. It could be that it's actually a little bit more, depending a little bit on how effectively the device can recover the compound from the brain tissue. This is under investigation. We will probably have more information within a few weeks. But importantly, I think we're talking about a range of some, let's say, maximum 20% -- 15%, 20% would be probably an optimal case. Non-optimized peptides showed around 1% of injected dose penetration in the early studies. So this gives you a little bit of a ballpark where we are. Dosing frequency, that's actually a very interesting question and relates also to the mechanism of action of CDNF and xCDNF. For now, we haven't formally investigated that yet, but we know from CDNF studies already that we don't need a continuous presence of the compound in the subject or in the brain. So for example, in the CDNF clinical study, we are dosing once monthly. And now if we're dealing with the similar type of pharmacology, we probably are looking at intermittent dosing regimen for xCDNF as well. It could be a couple of times a week or even daily, but probably not something like multiple times a day because of the similarity in the pharmacology of these 2 compounds.

Thank you, Henri. And just to remind everyone, when Henri is here talking about the device in this preclinical study, so that's just the device we use for collecting the samples so to see how much these healthy animals actually have xCDNF entering their brains. So eventually, a device will not be needed if this is taken to clinical use.

And it is not the same or similar device that's being used for administration of CDNF. It is a completely different type, a microdialysis type of device that's being used.

Exactly. And as Henri pointed out, very exciting improvement that if we start from 1% BBB penetrating peptides and now we're significantly talking about a higher percentage, keeping in mind that already with this, let's say, quite poorly penetrating peptides, we did see -- we did reach a preclinical proof of concept in animal models of Parkinson's disease. So this is a very exciting improvement, of course, combined with the signal of efficacy of the mother compound that we are getting in the ongoing clinical study. And there was a question on the -- how the pandemic affects our business now. I believe that was covered already. Then we've been asked about our cash situation at the moment. We just have reported quite recently our figures for the past year. End of last year, we had approximately EUR 6 million in cash. And of course, as obvious also from this presentation, we have completed all the patient treatments in the Lymfactin study so that reduces our cash burn significantly. The Parkinson's study is predominantly funded by the European Union. And also there, only just some last doses remain to be administered. So we have -- we are in a fortunate position where we can control our cash burn much easier than we could maybe a year ago. So we have just our team, a dozen people working on these projects and then the Phase III preparations, Phase II preparations, xCDNF development with subcontractors. And if the corona situation pandemic, for instance, would seem to prolong and suggest that the market -- the capital market will not wake up in the next couple of quarters, then we would just slow things down. Of course, we don't hope that to happen. We believe that things will look much brighter again in the fall after the summer. Companies like Herantis will be able to go fundraising. And of course, we also are in discussions with potential partners on our programs, which could also change the situation. But still, things have not changed from the past when we have said that we expect our current cash to take us through the first quarter next year. So we have a very healthy runway for a drug development company under these circumstances. I believe that covers all the questions we have received and we've taken an hour of your time. Very much -- thank you very much for everyone's attention.

There is actually 1 additional question that has came. So the question are, are we or any academic collaborator currently looking at or planning to look at CDNF in other diseases than Parkinson's, for example, ALS?

Excellent question. Based on the mechanisms of CDNF, it's known that it could well be suited for also other neurodegenerative diseases, not just Parkinson's. And in our communication, we have always reminded that we have not yet selected the target indication for xCDNF. So even the xCDNF compounds could target something else. So definitely, we are looking at other neurodegenerative diseases, too. And definitely, we know that there are partners who are also interested in other neurodegenerative diseases as potential targets for CDNF. Whether that could be ALS or Huntington's disease or Alzheimer's or even stroke, where there was a very exciting data published recently, we have not disclosed to the public, so we are obviously keeping our eyes on different possibilities.

And Pekka, maybe good to also add that fortunately, there is academic research activities in this area. For example, the team at the University of Helsinki with their German collaborators are actively working on CDNF in ALS. So it doesn't mean -- if we are not actively working on it right now, it doesn't mean that we have forgotten ALS completely. It just means that we have focused our current resources on other activities. And fortunately, there are other people who are actively working on ALS development.

Very true.

That's a good point. Thank you, Henri. So I think now we've covered everything, we've taken an hour of your time. Thank you very much for everyone's attention. It seems we had several dozens of people in the audience. Thanks for your time. And the webcast will be also shared on our website in the near future, so also new audiences will be able to see it. Thank you very much. Thanks, Henri and Antti, and wish you all a great day.