Herantis Pharma Oyj (HRTIS) Earnings Call Transcript & Summary

[Operator Instructions] Presenting today is CEO, Antti Vuolanto; and CSO, Henri Huttunen; CFO. Tone Kvale, will join the call for the Q&A portion. [Operator Instructions] Additionally, today's webinar, management may make forward-looking statements that involve known and unknown risks, uncertainties and 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 these forward-looking statements made during today's call 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. Like I said, this webinar is being recorded and will be available soon on Herantis Pharma's website under the header, News and Events and the sub-header company live presentations. With these formalities out of the way, I'd like to turn the call over to our CEO. Antti, you may begin.

Thank you, Julie. It is a great pleasure to be here today. We have announced today the top line results of the Phase 1a clinical study trial. And we are very happy that the trial met both the primary and secondary endpoints, and we believe that this provides a solid basis for further development. But we will explain you the data in more details during the course of this webinar. So maybe starting with the basic facts about Herantis. So we are a listed company from Helsinki, Finland. We developed disease-modifying treatment to address the unmet clinical need in Parkinson's disease and also potentially other neurodegenerative diseases. We have now conducted the Phase 1a clinical trial with our lead asset, HER-096. That is a small engineered peptidomimetic molecule that combines a unique mechanism of action with the ability to use patient-friendly subcutaneous injection as the route of administration. So just a reminder about HER-096, that we believe is -- and as we call it, as a perfect drug candidate for Parkinson's disease. So it's a synthetic molecule that has been designed based on CDNF protein that the company has studied earlier. We have been able to capture the activity of the CDNF protein into the smaller peptidomimetic compound. So we are able to modulate a process called unfolded protein response pathway. And this is truly unique. No one else has such a compound that is addressing this pathway for Parkinson's disease treatment. So we aim to reduce sales press and thereby slow down or stop the progression of the disease. And combining this with the patient-friendly subcutaneous administration, we believe that we have a very valuable drug candidate in our development pipeline. So what we expect to achieve with HER-096 in Parkinson's disease treatment. Of course, as we have said, this is a disease modifying treatment. So long term, we aim to slow down or even stop the progression of the mid brain neuron degeneration at the early stage of the disease, but we believe that we can also have symptomatic improvement and that's very much what we have seen in preclinical studies. We also know that subcutaneous administration from 1 to 3 times per week, which is very patient-friendly way of administering would be sufficient for HER-096. And if we look at the market opportunities, so currently, there are approximately 10 million Parkinson's patients globally. The current Parkinson's disease pharmaceutical market size is approximately $5 billion. And we expect that the market size will grow like double within the next 5 years. A summary of the top line data is that the study met its primary and secondary endpoints. So with subcutaneous single injections, it had overall good safety and tolerability profile. And the pharmacokinetic data showed that after subcutaneous administration of HER-096, we had a quick absorption of HER-096 into plasma. We had linear pharmacokinetics across all the dose groups and HER-096 was efficiently delivered into the cerebrospinal fluid, so in the central nervous system in humans. And if you look at the outline, what are the next steps. So we aim to set up a Phase 1b clinical trial to demonstrate the safety and tolerability of multiple repeatedly subcutaneous dosing of HER-096 in Parkinson's disease patients, we foresee that such a study could be started during the next year. We are also doing other preparations for Phase 2 clinical study. And we explore -- also, we would like to explore the potential of HER-096 in other indications as well. I think we might have a challenge with showing the slides. So to set the scene where we are at the drug development currently. So the drug development process is divided into 2 main parts: one being the nonclinical development. So that we have completed with HER-096, including selection lead optimization and all the safety and efficacy data that are required in preclinical settings. Then when we go forward, we have normally 3 phases of clinical development, starting with safety going to signs of efficacy in Phase 2 and then finally in Phase 3, proving the efficacy in provided population. Now if we look at HER-096, there in Phase 1a study, we have shown or demonstrated the safety of the single dose in healthy subjects, and we have also demonstrated a blood-brain barrier penetration in healthy subjects. With HER-096, we want to run a Phase 1b clinical study to show the safety of multiple doses in Parkinson's patient population. We want to also study the pharmacokinetics in Parkinson's patients. And as we are aiming at establishing also biomarkers, the patient population would be optimal for the Phase 1b. And doing that in Phase 1b would allow us to derisk the development that Phase 2 study later on where the purpose would be demonstrating of the -- or having the proof of concept also with efficacy endpoints. So maybe Henri, you will take us through the details of the Phase 1a study and the results.

Thank you, Antti. And apologies, it looks like Zoom has a little problem showing the slides as in the full-screen mode, so we'll have to deal with edit mode here. So going into the Phase 1a study. This is -- first and foremost, this is a first-in-human trial with HER-096. It was a double-blind placebo-controlled study with a single ascending dose of HER-096 subcutaneously given to healthy subjects. We recruited a total of 60 healthy subjects in this study, 48 in Part 1 in the dose escalation cohort and 12 in Part 2, where we studied elderly individuals in a smaller setting. So in the Part 1, healthy male individuals were recruited, aged 20 to 45. We started with 10-milligram dose. Each dose cohort had 2 placebos and 6 receiving active drug. After completion of each dose cohort, the data was assessed, analyzed by an independent data safety monitoring board, who then made a decision to move forward to the next dose level. So from 10, we advanced up to 300. And at the end of the Part 1, the data center monitoring board then again, evaluated the data and decided that we can move to the Part 2. And in the Part 2, we recruited 12 subjects, both male and female, again, healthy volunteers. Here, we used the wording older for 50 to 64 years of age and 65 to 75 for elderly. 6 Individuals from both age groups and 6 males and females as shown by the demographic summary in the bottom. The objectives of the study were safety and tolerability of single dose in healthy subjects. This was the primary end point. The pharmacokinetics in young and elderly healthy subjects was the secondary endpoint. And this included the blood-brain barrier penetration assessment in the elderly cohort. So in the Part 1, we did not collect cerebrospinal fluid, but started that in the Part 2 with elderly individuals. And the Part 2 consisted only of 1 dose level, 200-milligram. The exploratory biomarkers include various assessments that are still going on. We will do our best to thoroughly analyze these valuable samples, plasma and CSF. I think it will take several months until this analysis is completed. So none of this data will be presented in today's top line data where we are now. So then moving on to the safety data. On the top table, you can see a summary of Part 1, the dose escalation cohort and in the bottom table is the Part 2 with the elderly individuals. In general, we can say that there were no serious adverse events. The adverse events that we saw were quite typical for clinical studies with our general events like nausea and headache occasionally. But mostly the AEs were related to the local injection site events such as redness, irritation, itching and such. Also placebo group showed some local injection site events, but these were clearly increased in number as we went higher with the dose. So overall, we can say that the safety data was very similar to what we have seen in the preclinical toxicology studies. There were no indications of systemic side effects, adverse events. It was really mostly focused on the injection site. So overall, we can say that we have a good safety and tolerability profile in young, healthy males and older and elderly healthy females and males based on the Phase 1a data. Again, there were no serious adverse events. There was 1 significant adverse event reported. This was when an incidence where the subject actually fainted during dosing, is most likely a vasovagal reaction rather than a direct pharmacodynamic effect of the drug itself. In this case, the dosing was then discontinued. Again, the local injection site adverse events were mild in nature. And there was clearly some dose dependency there. The good safety profile allows us now moving forward in clinical development with subcutaneous route of administration with HER-096. Then moving on to the secondary endpoint, the pharmacokinetics. So this slide summarizes the plasma pharmacokinetic data from Part 1. So these are the healthy young males. On the graph on the left, you can see a very nice dose proportionality as we start increasing the dose, we can see how the maximum concentration in plasma and also the overall profile is actually very nicely and dose proportionately increasing. In general, we can say that we have a relatively quick absorption, the Tmax, so the time point where the maximum plasma concentration is reached, varies between 1 to 2 hours. In this cohort, the plasma elimination half-life is about 2 hours and very much what we expected based on our preclinical studies. The exposure and the area under the curve, the plasma exposure is also nicely dose proportionally increasing and the elimination rate is not significantly changing as we go higher with the dose. So in addition to quick absorption and expected plasma elimination half-life, we also have concluded that renal excretion appears to be the main route of elimination in humans, which was also what we saw in various animal species preclinically. Importantly, the linear pharmacokinetics that we see here helps us to determine the safe and effective dose range in our future clinical studies. Then moving on to Part 2. So this is, again, plasma data. So here, the subject received a single 200-milligram dose of HER-096 and here on the graph on the left, we can see how the drug is appearing in the plasma and then eliminated over time. Again -- and now we have males and females, and we can see that there is a little bit of difference. Females seem to have a slightly higher maximum concentrations in plasma and also somewhat higher exposure overall when we look at the area under the curve. This is not very uncommon for drugs. So many drugs show similar behavior, and it's good that we have this understanding already early on in our clinical development. In the elderly individuals, we did observe a slightly longer plasma elimination half-life, which was about 2.5 hours. This is also expected as the main route of elimination is renal excretion. And as we know, [indiscernible] rate tends to decline during aging. Now moving on to the cerebrospinal fluid data. So here, as a reminder, again, this was a single 200-milligram dose. And this was an exploratory assessment. So as we didn't know what to -- how quickly the drug would appear in the CSF and how long it would take for the drug to be eliminated from the CSF. We actually tested multiple time points in this Phase 1a study. So first, we gave the elderly subjects the injection. And then did the lumbar puncture for collection of cerebrospinal fluid in 2 hours, then 4 hours, 6 hours, 8 hours, and then finally, a couple of subjects, 12 hours. Just to get a broader picture, although we did understand that we're not going to have a fully characterized CSF PK profile based on this data. Importantly, though, we now have clear evidence that HER-096 penetrates the blood-brain barrier in humans. And this is a major milestone for HER-096 development program. So all of the subjects showed detectable levels after dosing. And the range that we saw between 2 and 12 hours was between 15 and about 97 nanograms per mil. And based on our preclinical data, and we can say that this is very much in the range that we expected. This is the expected therapeutic concentration range in the CSF as we can tell based on available evidence. Interestingly, it seems that, although we don't -- we can't determine the half-life, the CSF elimination half-life, it looks like we may have a slightly longer presence of HER-096 in the CSF as we predicted by the preclinical data. Still at 12 hours, we have fairly high levels here. And of course, we don't know if it still continues to rise. But looking at the plasma half-life preclinical data, we would expect that it soon starts to decline after the 12-hour time point. Overall, a fantastic piece of news translationally. What we've seen in several animal species is clearly translating into humans, and this is a very important part of this first-in-human study. So overall, we can conclude from this Phase 1a top line data, that the primary endpoint was met. The single subcutaneous dose of HER-096 was found to be safe and well tolerated in healthy subjects, both young and elderly. Secondary endpoints were also met, we have now clearly defined plasma pharmacokinetic profile in humans, and we have clear evidence demonstrating blood-brain barrier penetration in humans. And in general, we can say that the pharmacokinetic data support moving forward with subcutaneous HER-096 dosing in humans. A little bit in a bigger picture, we believe that this very positive Phase 1a data set, strongly complements and supports our existing data package in HER-096. It certainly supports continued clinical development and will help us to advance our partnering process. Our preclinical evidence for HER-096 very strongly suggests that we have disease-modifying effects in Parkinson's disease model, an alpha-synuclein model that we have used broadly. And this includes protection of dopamine neurons effects on alpha-synuclein and also neuro information, which coincides with increased dopamine level in the brain and improved motor symptoms. Now combined with the Phase 1a data, and hopefully, we will also continue to get very positive data on the biomarker side, the exploratory endpoints that combined with our previous clinical experience with Parkinson's disease and the CDNF administration in Parkinson's patients. This really gives us a very exciting basis to go forward with the clinical development of HER-096.

Okay. Thank you, Henri. So of course, one of the topics that we have been discussing and expressing our ambition to find a development partner for HER-096, we believe that this data that we presented here will be a key to continue the discussions and hopefully advance them in a very, let's say, serious manner going forward. Let's see how those discussions continue during the next months. Happy to inform that we already have several discussions with pharma like waiting within the next month or so. The summary on the slide, I think we have already gone through basically everything that is set here. This is a great stepping stone going forward. We really want to like advance this into the patients and hope to be able to start such a study next year. And I really would like to thank all the healthy subjects participated in the study. They were elemental in getting this far and this quickly. I want to remind that we have kept the time lines during the past 18 months through the preclinical development and now with the -- starting with the clinical development, I think that's an exceptional performance for a drug development company. So really happy about all the persons, all the organization partners who have been involved in this study. And I think the whole team is committed to be able to deliver in such an efficient manner also going forward. So thank you for listening this presentation now, and I think it's time for questions and answers.

Great. Thank you guys. What a great presentation and exciting news. We are open for questions. So if you have a question, please feel free to add your question in the Q&A section of the dashboard. And with that, I will start with question number 1. Why do you need to run a Phase 1b trial? Why can't you just go directly to a Phase 2 trial?

Very good question. Henri, maybe you will take this one.

Yes. So in this Phase 1a study, we studied single doses of HER-096 in healthy subjects. So the next step, what we really need to do is to study the safety and tolerability of multiple doses. So repeated dosing over time in Parkinson's patients. And obviously, for longer term, there are also other benefits such as getting more extensive data on biomarkers, particularly looking at the pharmacodynamics, the biological response to the drug as this data, and we expect will significantly derisk the future Phase 2 study.

Okay. Thanks, Henri. There's a quick follow-up question to that. What do you mean by biomarker endpoints and why are they important?

Yes. This is a good question. So as we've seen in the past years in the fields of cancer and recently Alzheimer's, biomarkers are increasingly important in clinical development. They can significantly reduce the risks and also bring other benefits. We have started our work with biomarkers already years ago with CDNF, particularly the Phase 1 study with intracranial CDNF delivery. And we have continued on that path. And the recent EIC funding that we received, particularly for this purpose very much strengthens our abilities in this area. And for the next steps, Phase 1b, particularly Phase 2, we are looking to involve pharmacodynamic biomarkers. So basically biomarkers that help us to demonstrate the biological response to the drug. How the brain, for example, responds in Parkinson's patients, when the subjects receive a dose of HER-096. This helps to demonstrate target engagement, target pathway modulation and so on, very important steps in early clinical development to derisk the program.

Thank you, Henri. The next question is, now that you have proven that HER-096 is safe, and can reach the brain, will you start exploring HER-096 and other indications?

Henri, maybe you'll take this as well.

Okay. Thanks. Yes, this is a very exciting question and maybe perhaps some of you in the audience have followed the literature a little bit. There's a large body of literature on CDNF and CDNF therapeutic effects in various preclinical models of brain disorders, for example. So academic groups have shown that CDNF has strong effect, for example, in ALS models, Huntington's, stroke, et cetera. So there's a lot of interesting territory to be explored there. And we've been very much interested in this area as well. And we really hope that we could do more extensive work in this area in the future as we believe that this could really generate additional value for the company in the long term.

The next question is, there are no disease-modifying treatments approved for PD today. Do you foresee Parkinson's following the path of recent Alzheimer's drug approvals? And how long do you think it will take? What is the future market opportunity?

Yes. So definitely, we believe that Parkinson's would follow the path of Alzheimer's. So there are many similarities between these 2 indications in terms of the drug development and the regulatory paths and also the biomarker strategies. We believe that the research that has been done during the past decade for Parkinson's, it will convert into disease-modifying therapy soon or maybe -- well, we don't know when, of course, we want to be on the forefront of that development. But if we think about the recent development in the Alzheimer's, earlier this year, the collaboration between EISAI, Biogen and BioArctic, they were able to get a full approval from FDA for LEQEMBI, that is an immunotherapy to remove protein aggregates. Their sales forecast is approximately USD 13 billion during the next 5 years, which is huge. Parkinson's disease is maybe a slightly smaller indication, but this is truly something that we are looking at with disease-modifying treatment for Parkinson's as well. And as I said, we want to be with HER-096 in the forefront of that development.

The next question is, will you present the data in a publication or at a scientific conference?

Henri, you will probably.

Yes. We are very much a pro publication. We have already submitted some abstracts for scientific conferences for the Spring '24 with Phase 1a data. And hopefully, sooner or later after that, then also the Phase 1a data will be published in a scientific journal.

Great. Are there any differences to CDNF in terms of safety, tolerability?